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Sample records for nociceptive primary sensory

  1. 17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception.

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    Qu, Zu-Wei; Liu, Ting-Ting; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Ren, Ping; Rao, Zhiguo; Hu, Wang-Ping

    2015-12-01

    Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

  2. The primary somatosensory cortex and the insula contribute differently to the processing of transient and sustained nociceptive and non-nociceptive somatosensory inputs.

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    Hu, Li; Zhang, Li; Chen, Rui; Yu, Hongbo; Li, Hong; Mouraux, André

    2015-11-01

    Transient nociceptive stimuli elicit consistent brain responses in the primary and secondary somatosensory cortices (S1, S2), the insula and the anterior and mid-cingulate cortex (ACC/MCC). However, the functional significance of these responses, especially their relationship with sustained pain perception, remains largely unknown. Here, using functional magnetic resonance imaging, we characterize the differential involvement of these brain regions in the processing of sustained nociceptive and non-nociceptive somatosensory input. By comparing the spatial patterns of activity elicited by transient (0.5 ms) and long-lasting (15 and 30 s) stimuli selectively activating nociceptive or non-nociceptive afferents, we found that the contralateral S1 responded more strongly to the onset of non-nociceptive stimulation as compared to the onset of nociceptive stimulation and the sustained phases of nociceptive and non-nociceptive stimulation. Similarly, the anterior insula responded more strongly to the onset of nociceptive stimulation as compared to the onset of non-nociceptive stimulation and the sustained phases of nociceptive and non-nociceptive stimulation. This suggests that S1 is specifically sensitive to changes in incoming non-nociceptive input, whereas the anterior insula is specifically sensitive to changes in incoming nociceptive input. Second, we found that the MCC responded more strongly to the onsets as compared to the sustained phases of both nociceptive and non-nociceptive stimulation, suggesting that it could be involved in the detection of change regardless of sensory modality. Finally, the posterior insula and S2 responded maximally during the sustained phase of non-nociceptive stimulation but not nociceptive stimulation, suggesting that these regions are preferentially involved in processing non-nociceptive somatosensory input. © 2015 Wiley Periodicals, Inc.

  3. Resiniferatoxin combined with antidepressants preferentially prolongs sensory/nociceptive block in rat sciatic nerve.

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    Hung, Yu-Chun; Suzuki, Suzuko; Huang, Chun-Jen; Chen, Chien-Chuan; Pan, Yu-Yen; Wang, Chi-Fei; Srinavasan, Venkatesh; Gerner, Peter

    2010-07-01

    Current techniques of peripheral nerve block have major limitations, including lack of differentiation between motor and sensory fibers and potential toxicity of local anesthetics. Recent studies have suggested that a nociceptive-selective nerve block can be achieved via a transient receptor potential vanilloid type 1 activator (capsaicin) along with local anesthetics. We hypothesized that the combination of potent transient receptor potential vanilloid type 1 agonist resiniferatoxin (RTX) and selected antidepressants (amitriptyline, doxepin, and fluoxetine, also potent sodium channel blockers) would produce prolonged and predominantly sensory nerve block. Rats were anesthetized with isoflurane, and 0.2 mL of amitriptyline, doxepin, or fluoxetine was deposited next to the surgically exposed sciatic nerves (n = 8 per group). Some animals received a second injection containing RTX (n = 8 per group). The effect of nerve block was assessed by neurobehavioral tests of the motor function (extensor postural thrust) and the nocifensive reaction (mechanical pinch). A single application of RTX produced nociceptive-selective sciatic nerve block, whereas antidepressants produced nociceptive and motor block. The combined administration of RTX and antidepressant resulted in a predominantly nociceptive nerve block. Compared with antidepressants or RTX alone, the combination prolonged the nociceptive nerve block more than the motor block. The combined application of RTX and antidepressants produced a markedly prolonged nociceptive peripheral nerve block in rat sciatic nerves compared with either agent alone. However, the 2-drug regimen also elicited prolonged blockade of the motor function, although disproportionately less compared with the nociceptive modality, suggesting the existence of nontransient receptor potential vanilloid type 1-mediated mechanisms. The mechanisms through which RTX affects nociceptive signal transduction/transmission have yet to be fully elucidated.

  4. Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies

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    Aaron D. Mickle

    2016-11-01

    Full Text Available Specialized receptors belonging to the transient receptor potential (TRP family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these TRP channels are also expressed in neurons of the central nervous system, and in non-neuronal cells that communicate with sensory nerves. Nociceptive TRPs are activated by specific physico-chemical stimuli to provide the excitatory trigger in neurons. In addition, decades of research has identified a large number of immune and neuromodulators as mediators of nociceptive TRP channel activation during injury, inflammatory and other pathological conditions. These findings have led to aggressive targeting of TRP channels for the development of new-generation analgesics. This review summarizes the complex activation and/or modulation of nociceptive TRP channels under pathophysiological conditions, and how these changes underlie acute and chronic pain conditions. Furthermore, development of small-molecule antagonists for several TRP channels as analgesics, and the positive and negative outcomes of these drugs in clinical trials are discussed. Understanding the diverse functional and modulatory properties of nociceptive TRP channels is critical to function-based drug targeting for the development of evidence-based and efficacious new generation analgesics.

  5. Nociceptive Sensory Neurons Drive Interleukin-23 Mediated Psoriasiform Skin Inflammation

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    Riol-Blanco, Lorena; Ordovas-Montanes, Jose; Perro, Mario; Naval, Elena; Thiriot, Aude; Alvarez, David; Wood, John N.; von Andrian, Ulrich H.

    2014-01-01

    The skin has a dual function as a barrier and a sensory interface between the body and the environment. To protect against invading pathogens, the skin harbors specialized immune cells, including dermal dendritic cells (DDCs) and interleukin (IL)-17 producing γδ T cells (γδT17), whose aberrant activation by IL-23 can provoke psoriasis-like inflammation1–4. The skin is also innervated by a meshwork of peripheral nerves consisting of relatively sparse autonomic and abundant sensory fibers. Interactions between the autonomic nervous system and immune cells in lymphoid organs are known to contribute to systemic immunity, but how peripheral nerves regulate cutaneous immune responses remains unclear5,6. Here, we have exposed the skin of mice to imiquimod (IMQ), which induces IL-23 dependent psoriasis-like inflammation7,8. We show that a subset of sensory neurons expressing the ion channels TRPV1 and NaV1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of DDCs, the principal source of IL-23, is in close contact with these nociceptors. Upon selective pharmacological or genetic ablation of nociceptors9–11, DDCs failed to produce IL-23 in IMQ exposed skin. Consequently, the local production of IL-23 dependent inflammatory cytokines by dermal γδT17 cells and the subsequent recruitment of inflammatory cells to the skin were dramatically reduced. Intradermal injection of IL-23 bypassed the requirement for nociceptor communication with DDCs and restored the inflammatory response12. These findings indicate that TRPV1+NaV1.8+ nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway and control cutaneous immune responses. PMID:24759321

  6. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation.

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    Riol-Blanco, Lorena; Ordovas-Montanes, Jose; Perro, Mario; Naval, Elena; Thiriot, Aude; Alvarez, David; Paust, Silke; Wood, John N; von Andrian, Ulrich H

    2014-06-05

    The skin has a dual function as a barrier and a sensory interface between the body and the environment. To protect against invading pathogens, the skin harbours specialized immune cells, including dermal dendritic cells (DDCs) and interleukin (IL)-17-producing γδ T (γδT17) cells, the aberrant activation of which by IL-23 can provoke psoriasis-like inflammation. The skin is also innervated by a meshwork of peripheral nerves consisting of relatively sparse autonomic and abundant sensory fibres. Interactions between the autonomic nervous system and immune cells in lymphoid organs are known to contribute to systemic immunity, but how peripheral nerves regulate cutaneous immune responses remains unclear. We exposed the skin of mice to imiquimod, which induces IL-23-dependent psoriasis-like inflammation. Here we show that a subset of sensory neurons expressing the ion channels TRPV1 and Nav1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of DDCs, the principal source of IL-23, is in close contact with these nociceptors. Upon selective pharmacological or genetic ablation of nociceptors, DDCs failed to produce IL-23 in imiquimod-exposed skin. Consequently, the local production of IL-23-dependent inflammatory cytokines by dermal γδT17 cells and the subsequent recruitment of inflammatory cells to the skin were markedly reduced. Intradermal injection of IL-23 bypassed the requirement for nociceptor communication with DDCs and restored the inflammatory response. These findings indicate that TRPV1(+)Nav1.8(+) nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway and control cutaneous immune responses.

  7. Neonatal bee venom exposure induces sensory modality-specific enhancement of nociceptive response in adult rats.

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    Li, Mengmeng; Chen, Huisheng; Tang, Jiaguang; Chen, Jun

    2014-06-01

    Previous studies have shown that inflammatory pain at the neonatal stage can produce long-term structural and functional changes in nociceptive pathways, resulting in altered pain perception in adulthood. However, the exact pattern of altered nociceptive response and associated neurochemical changes in the spinal cord in this process is unclear. In this study, we used an experimental paradigm in which each rat first received intraplantar bee venom (BV) or saline injection on postnatal day 1, 4, 7, 14, 21, or 28. This was followed 2 months later by a second intraplantar bee venom injection in the same rats to examine the difference in nociceptive responses. We found that neonatal inflammatory pain induced by the first BV injection significantly reduced baseline paw withdrawal mechanical threshold, but not baseline paw withdrawal thermal latency, when rats were examined 2 months from the first BV injection. Neonatal inflammatory pain also exacerbated mechanical, but not thermal, hyperalgesia in response to the second BV injection in these same rats. Rats exposed to neonatal inflammation also showed up-regulation of spinal NGF, TrkA receptor, BDNF, TrkB receptor, IL-1β, and COX-2 expression following the second BV injection, especially with prior BV exposure on postnatal day 21 or 28. These results indicate that neonatal inflammation produces sensory modality-specific changes in nociceptive behavior and alters neurochemistry in the spinal cord of adult rats. These results also suggest that a prior history of inflammatory pain during the developmental period might have an impact on clinical pain in highly susceptible adult patients. Wiley Periodicals, Inc.

  8. Organization of sensory input to the nociceptive-specific cutaneous trunk muscle reflex in rat, an effective experimental system for examining nociception and plasticity

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    Petruska, Jeffrey C.; Barker, Darrell F.; Garraway, Sandra M.; Trainer, Robert; Fransen, James W.; Seidman, Peggy A.; Soto, Roy G.; Mendell, Lorne M.; Johnson, Richard D.

    2013-01-01

    Detailed characterization of neural circuitries furthers our understanding of how nervous systems perform specific functions and enables the use of those systems to test hypotheses. We have characterized the sensory input to the cutaneous trunk muscle (CTM; also cutaneus trunci (rat) or cutaneus maximus (mouse)) reflex (CTMR), which manifests as a puckering of the dorsal thoracolumbar skin and is selectively driven by noxious stimuli. CTM electromyography (EMG) and neurogram recordings in naïve rats revealed that CTMR responses were elicited by natural stimuli and electrical stimulation of all segments from C4 to L6, a much greater extent of segmental drive to the CTMR than previously described. Stimulation of some subcutaneous paraspinal tissue can also elicit this reflex. Using a selective neurotoxin, we also demonstrate differential drive of the CTMR by trkA-expressing and non-expressing small diameter afferents. These observations highlight aspects of the organization of the CTMR system which make it attractive for studies of nociception and anesthesiology and plasticity of primary afferents, motoneurons, and the propriospinal system. We use the CTMR system to qualitatively and quantitatively demonstrate that experimental pharmacological treatments can be compared to controls applied either to the contralateral side or to another segment, with the remaining segments providing controls for systemic or other treatment effects. These data indicate the potential for using the CTMR system as both an invasive and non-invasive quantitative assessment tool providing improved statistical power and reduced animal use. PMID:23983104

  9. Sensory gating in primary insomnia.

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    Hairston, Ilana S; Talbot, Lisa S; Eidelman, Polina; Gruber, June; Harvey, Allison G

    2010-06-01

    Although previous research indicates that sleep architecture is largely intact in primary insomnia (PI), the spectral content of the sleeping electroencephalographic trace and measures of brain metabolism suggest that individuals with PI are physiologically more aroused than good sleepers. Such observations imply that individuals with PI may not experience the full deactivation of sensory and cognitive processing, resulting in reduced filtering of external sensory information during sleep. To test this hypothesis, gating of sensory information during sleep was tested in participants with primary insomnia (n = 18) and good sleepers (n = 20). Sensory gating was operationally defined as (i) the difference in magnitude of evoked response potentials elicited by pairs of clicks presented during Wake and Stage II sleep, and (ii) the number of K complexes evoked by the same auditory stimulus. During wake the groups did not differ in magnitude of sensory gating. During sleep, sensory gating of the N350 component was attenuated and completely diminished in participants with insomnia. P450, which occurred only during sleep, was strongly gated in good sleepers, and less so in participants with insomnia. Additionally, participants with insomnia showed no stimulus-related increase in K complexes. Thus, PI is potentially associated with impaired capacity to filter out external sensory information, especially during sleep. The potential of using stimulus-evoked K complexes as a biomarker for primary insomnia is discussed.

  10. Human primary somatosensory cortex is differentially involved in vibrotaction and nociception.

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    Lenoir, Cédric; Huang, Gan; Vandermeeren, Yves; Hatem, Samar Marie; Mouraux, André

    2017-07-01

    The role of the primary somatosensory cortex (S1) in vibrotaction is well established. In contrast, its involvement in nociception is still debated. Here we test whether S1 is similarly involved in the processing of nonnociceptive and nociceptive somatosensory input in humans by comparing the aftereffects of high-definition transcranial direct current stimulation (HD-tDCS) of S1 on the event-related potentials (ERPs) elicited by nonnociceptive and nociceptive somatosensory stimuli delivered to the ipsilateral and contralateral hands. Cathodal HD-tDCS significantly affected the responses to nonnociceptive somatosensory stimuli delivered to the contralateral hand: both early-latency ERPs from within S1 (N20 wave elicited by transcutaneous electrical stimulation of median nerve) and late-latency ERPs elicited outside S1 (N120 wave elicited by short-lasting mechanical vibrations delivered to index fingertip, thought to originate from bilateral operculo-insular and cingulate cortices). These results support the notion that S1 constitutes an obligatory relay for the cortical processing of nonnociceptive tactile input originating from the contralateral hemibody. Contrasting with this asymmetric effect of HD-tDCS on the responses to nonnociceptive somatosensory input, HD-tDCS over the sensorimotor cortex led to a bilateral and symmetric reduction of the magnitude of the N240 wave of nociceptive laser-evoked potentials elicited by stimulation of the hand dorsum. Taken together, our results demonstrate in humans a differential involvement of S1 in vibrotaction and nociception. NEW & NOTEWORTHY Whereas the role of the primary somatosensory cortex (S1) in vibrotaction is well established, its involvement in nociception remains strongly debated. By assessing, in healthy volunteers, the effect of high-definition transcranial direct current stimulation over S1, we demonstrate a differential involvement of S1 in vibrotaction and nociception. Copyright © 2017 the American

  11. Localization of SSeCKS in unmyelinated primary sensory neurons

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    Siegel Sandra M

    2008-03-01

    % reduction in the number of SSeCKS-labeled cells. This attenuation is concomitant with a decrease in fluoride-resistant acid phosphatase labeled fibers in the spinal cord dorsal horn and small neuronal somata in sensory ganglia. Conclusion These results demonstrate that SSeCKS is primarily localized within a distinct subpopulation of small diameter, largely unmyelinated C-fiber primary sensory neurons putatively involved in nociception.

  12. The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord

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    Philip Tröster

    2018-02-01

    Full Text Available A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice. Cholera toxin labeling in digits of the hind paw demonstrated an altered shape of sensory neuron termination fields in the spinal cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes indicated that noxious heat sensation and nociception induced by chemical irritants are impaired in the mutants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are not affected. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is not due to an impaired C-fiber function. Overall, these data point to a critical role of axonal bifurcation for the processing of pain induced by heat or chemical stimuli.

  13. Thermal nociceptive threshold testing detects altered sensory processing in broiler chickens with spontaneous lameness.

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    Becky Hothersall

    Full Text Available Lameness is common in commercially reared broiler chickens but relationships between lameness and pain (and thus bird welfare have proved complex, partly because lameness is often partially confounded with factors such as bodyweight, sex and pathology. Thermal nociceptive threshold (TNT testing explores the neural processing of noxious stimuli, and so can contribute to our understanding of pain. Using an acute model of experimentally induced articular pain, we recently demonstrated that TNT was reduced in lame broiler chickens, and was subsequently attenuated by administration of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs. This study extended these findings to a large sample of commercial broilers. It examined factors affecting thermal threshold (Part 1 and the effect of an NSAID drug (meloxicam, 5 mg/kg and of an opioid (butorphanol; 4 mg/kg (Part 2. Spontaneously lame and matched non-lame birds (n=167 from commercial farms were exposed to ramped thermal stimulations via a probe attached to the lateral aspect of the tarsometatarsus. Baseline skin temperature and temperature at which a behavioural avoidance response occurred (threshold were recorded. In Part 1 bird characteristics influencing threshold were modelled; In Part 2 the effect of subcutaneous administration of meloxicam or butorphanol was investigated. Unexpectedly, after accounting for other influences, lameness increased threshold significantly (Part 1. In Part 2, meloxicam affected threshold differentially: it increased further in lame birds and decreased in non-lame birds. No effect of butorphanol was detected. Baseline skin temperature was also consistently a significant predictor of threshold. Overall, lameness significantly influenced threshold after other bird characteristics were taken into account. This, and a differential effect of meloxicam on lame birds, suggests that nociceptive processing may be altered in lame birds, though mechanisms for this require further

  14. Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons.

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    Stéphanie Ventéo

    Full Text Available Dorsal root ganglia (DRGs contain the cell bodies of sensory neurons which relay nociceptive, thermoceptive, mechanoceptive and proprioceptive information from peripheral tissues toward the central nervous system. These neurons establish constant communication with their targets which insures correct maturation and functioning of the somato-sensory nervous system. Interfering with this two-way communication leads to cellular, electrophysiological and molecular modifications that can eventually cause neuropathic conditions. In this study we reveal that FXYD2, which encodes the gamma-subunit of the Na,K-ATPase reported so far to be mainly expressed in the kidney, is induced in the mouse DRGs at postnatal stages where it is restricted specifically to the TrkB-expressing mechanoceptive and Ret-positive/IB4-binding non-peptidergic nociceptive neurons. In non-peptidergic nociceptors, we show that the transcription factor Runx1 controls FXYD2 expression during the maturation of the somato-sensory system, partly through regulation of the tyrosine kinase receptor Ret. Moreover, Ret signaling maintains FXYD2 expression in adults as demonstrated by the axotomy-induced down-regulation of the gene that can be reverted by in vivo delivery of GDNF family ligands. Altogether, these results establish FXYD2 as a specific marker of defined sensory neuron subtypes and a new target of the Ret signaling pathway during normal maturation of the non-peptidergic nociceptive neurons and after sciatic nerve injury.

  15. Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain.

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    Berta, Temugin; Qadri, Yawar; Tan, Ping-Heng; Ji, Ru-Rong

    2017-07-01

    Currently the treatment of chronic pain is inadequate and compromised by debilitating central nervous system side effects. Here we discuss new therapeutic strategies that target dorsal root ganglia (DRGs) in the peripheral nervous system for a better and safer treatment of chronic pain. Areas covered: The DRGs contain the cell bodies of primary sensory neurons including nociceptive neurons. After painful injuries, primary sensory neurons demonstrate maladaptive molecular changes in DRG cell bodies and in their axons. These changes result in hypersensitivity and hyperexcitability of sensory neurons (peripheral sensitization) and are crucial for the onset and maintenance of chronic pain. We discuss the following new strategies to target DRGs and primary sensory neurons as a means of alleviating chronic pain and minimizing side effects: inhibition of sensory neuron-expressing ion channels such as TRPA1, TRPV1, and Nav1.7, selective blockade of C- and Aβ-afferent fibers, gene therapy, and implantation of bone marrow stem cells. Expert opinion: These peripheral pharmacological treatments, as well as gene and cell therapies, aimed at DRG tissues and primary sensory neurons can offer better and safer treatments for inflammatory, neuropathic, cancer, and other chronic pain states.

  16. [Sensory integration function in children with primary nocturnal enuresis].

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    Tian, Yu-Hong; Cheng, Huan

    2008-10-01

    To assess the sensory integration function of children with primary nocturnal enuresis (PNE) and explore the role of sensory integration dysfunction in the pathogenesis of PNE. Sensory integration function was assessed by the Childhood Sensory Integration Ability Development Checklist in 46 children with PNE and 46 normal children (control). The incidence of sensory integration dysfunction in the PNE group (82.6%) was significantly higher than that in the control group (43.5%)(Psensory integration dysfunction in the PNE group but only 1 (2.1%) in the control group (Psensory integration indexes revealed by sensory integration function testing in the PNE group were significantly lower than those in the control group (Psensory integration dysfunction. Sensory integration dysfunction may be associated with the pathogenesis of PNE.

  17. Early sensory experience influences the development of multisensory thalamocortical and intracortical connections of primary sensory cortices.

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    Henschke, Julia U; Oelschlegel, Anja M; Angenstein, Frank; Ohl, Frank W; Goldschmidt, Jürgen; Kanold, Patrick O; Budinger, Eike

    2018-04-01

    The nervous system integrates information from multiple senses. This multisensory integration already occurs in primary sensory cortices via direct thalamocortical and corticocortical connections across modalities. In humans, sensory loss from birth results in functional recruitment of the deprived cortical territory by the spared senses but the underlying circuit changes are not well known. Using tracer injections into primary auditory, somatosensory, and visual cortex within the first postnatal month of life in a rodent model (Mongolian gerbil) we show that multisensory thalamocortical connections emerge before corticocortical connections but mostly disappear during development. Early auditory, somatosensory, or visual deprivation increases multisensory connections via axonal reorganization processes mediated by non-lemniscal thalamic nuclei and the primary areas themselves. Functional single-photon emission computed tomography of regional cerebral blood flow reveals altered stimulus-induced activity and higher functional connectivity specifically between primary areas in deprived animals. Together, we show that intracortical multisensory connections are formed as a consequence of sensory-driven multisensory thalamocortical activity and that spared senses functionally recruit deprived cortical areas by an altered development of sensory thalamocortical and corticocortical connections. The functional-anatomical changes after early sensory deprivation have translational implications for the therapy of developmental hearing loss, blindness, and sensory paralysis and might also underlie developmental synesthesia.

  18. Identifying local and descending inputs for primary sensory neurons.

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    Zhang, Yi; Zhao, Shengli; Rodriguez, Erica; Takatoh, Jun; Han, Bao-Xia; Zhou, Xiang; Wang, Fan

    2015-10-01

    Primary pain and touch sensory neurons not only detect internal and external sensory stimuli, but also receive inputs from other neurons. However, the neuronal derived inputs for primary neurons have not been systematically identified. Using a monosynaptic rabies viruses-based transneuronal tracing method combined with sensory-specific Cre-drivers, we found that sensory neurons receive intraganglion, intraspinal, and supraspinal inputs, the latter of which are mainly derived from the rostroventral medulla (RVM). The viral-traced central neurons were largely inhibitory but also consisted of some glutamatergic neurons in the spinal cord and serotonergic neurons in the RVM. The majority of RVM-derived descending inputs were dual GABAergic and enkephalinergic (opioidergic). These inputs projected through the dorsolateral funiculus and primarily innervated layers I, II, and V of the dorsal horn, where pain-sensory afferents terminate. Silencing or activation of the dual GABA/enkephalinergic RVM neurons in adult animals substantially increased or decreased behavioral sensitivity, respectively, to heat and mechanical stimuli. These results are consistent with the fact that both GABA and enkephalin can exert presynaptic inhibition of the sensory afferents. Taken together, this work provides a systematic view of and a set of tools for examining peri- and extrasynaptic regulations of pain-afferent transmission.

  19. Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

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    Wassila Ouelaa

    Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

  20. Low-dimensional sensory feature representation by trigeminal primary afferents.

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    Bale, Michael R; Davies, Kyle; Freeman, Oliver J; Ince, Robin A A; Petersen, Rasmus S

    2013-07-17

    In any sensory system, the primary afferents constitute the first level of sensory representation and fundamentally constrain all subsequent information processing. Here, we show that the spike timing, reliability, and stimulus selectivity of primary afferents in the whisker system can be accurately described by a simple model consisting of linear stimulus filtering combined with spike feedback. We fitted the parameters of the model by recording the responses of primary afferents to filtered, white noise whisker motion in anesthetized rats. The model accurately predicted not only the response of primary afferents to white noise whisker motion (median correlation coefficient 0.92) but also to naturalistic, texture-induced whisker motion. The model accounted both for submillisecond spike-timing precision and for non-Poisson spike train structure. We found substantial diversity in the responses of the afferent population, but this diversity was accurately captured by the model: a 2D filter subspace, corresponding to different mixtures of position and velocity sensitivity, captured 94% of the variance in the stimulus selectivity. Our results suggest that the first stage of the whisker system can be well approximated as a bank of linear filters, forming an overcomplete representation of a low-dimensional feature space.

  1. Primary sensory cortices contain distinguishable spatial patterns of activity for each sense.

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    Liang, M; Mouraux, A; Hu, L; Iannetti, G D

    2013-01-01

    Whether primary sensory cortices are essentially multisensory or whether they respond to only one sense is an emerging debate in neuroscience. Here we use a multivariate pattern analysis of functional magnetic resonance imaging data in humans to demonstrate that simple and isolated stimuli of one sense elicit distinguishable spatial patterns of neuronal responses, not only in their corresponding primary sensory cortex, but in other primary sensory cortices. These results indicate that primary sensory cortices, traditionally regarded as unisensory, contain unique signatures of other senses and, thereby, prompt a reconsideration of how sensory information is coded in the human brain.

  2. Learning Enhances Sensory and Multiple Non-sensory Representations in Primary Visual Cortex.

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    Poort, Jasper; Khan, Adil G; Pachitariu, Marius; Nemri, Abdellatif; Orsolic, Ivana; Krupic, Julija; Bauza, Marius; Sahani, Maneesh; Keller, Georg B; Mrsic-Flogel, Thomas D; Hofer, Sonja B

    2015-06-17

    We determined how learning modifies neural representations in primary visual cortex (V1) during acquisition of a visually guided behavioral task. We imaged the activity of the same layer 2/3 neuronal populations as mice learned to discriminate two visual patterns while running through a virtual corridor, where one pattern was rewarded. Improvements in behavioral performance were closely associated with increasingly distinguishable population-level representations of task-relevant stimuli, as a result of stabilization of existing and recruitment of new neurons selective for these stimuli. These effects correlated with the appearance of multiple task-dependent signals during learning: those that increased neuronal selectivity across the population when expert animals engaged in the task, and those reflecting anticipation or behavioral choices specifically in neuronal subsets preferring the rewarded stimulus. Therefore, learning engages diverse mechanisms that modify sensory and non-sensory representations in V1 to adjust its processing to task requirements and the behavioral relevance of visual stimuli. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Extinction reveals that primary sensory cortex predicts reinforcement outcome.

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    Bieszczad, Kasia M; Weinberger, Norman M

    2012-02-01

    Primary sensory cortices are traditionally regarded as stimulus analysers. However, studies of associative learning-induced plasticity in the primary auditory cortex (A1) indicate involvement in learning, memory and other cognitive processes. For example, the area of representation of a tone becomes larger for stronger auditory memories and the magnitude of area gain is proportional to the degree that a tone becomes behaviorally important. Here, we used extinction to investigate whether 'behavioral importance' specifically reflects a sound's ability to predict reinforcement (reward or punishment) vs. to predict any significant change in the meaning of a sound. If the former, then extinction should reverse area gains as the signal no longer predicts reinforcement. Rats (n = 11) were trained to bar-press to a signal tone (5.0 kHz) for water-rewards, to induce signal-specific area gains in A1. After subsequent withdrawal of reward, A1 was mapped to determine representational areas. Signal-specific area gains, estimated from a previously established brain-behavior quantitative function, were reversed, supporting the 'reinforcement prediction' hypothesis. Area loss was specific to the signal tone vs. test tones, further indicating that withdrawal of reinforcement, rather than unreinforced tone presentation per se, was responsible for area loss. Importantly, the amount of area loss was correlated with the amount of extinction (r = 0.82, P reinforcement, and that the number of cells tuned to a stimulus can dictate its ability to command behavior. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  4. Axotomy depletes intracellular calcium stores in primary sensory neurons.

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    Rigaud, Marcel; Gemes, Geza; Weyker, Paul D; Cruikshank, James M; Kawano, Takashi; Wu, Hsiang-En; Hogan, Quinn H

    2009-08-01

    The cellular mechanisms of neuropathic pain are inadequately understood. Previous investigations have revealed disrupted Ca signaling in primary sensory neurons after injury. The authors examined the effect of injury on intracellular Ca stores of the endoplasmic reticulum, which critically regulate the Ca signal and neuronal function. Intracellular Ca levels were measured with Fura-2 or mag-Fura-2 microfluorometry in axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent L4 neurons isolated from hyperalgesic rats after L5 spinal nerve ligation, compared to neurons from control animals. Endoplasmic reticulum Ca stores released by the ryanodine-receptor agonist caffeine decreased by 46% in axotomized small neurons. This effect persisted in Ca-free bath solution, which removes the contribution of store-operated membrane Ca channels, and after blockade of the mitochondrial, sarco-endoplasmic Ca-ATPase and the plasma membrane Ca ATPase pathways. Ca released by the sarco-endoplasmic Ca-ATPase blocker thapsigargin and by the Ca-ionophore ionomycin was also diminished by 25% and 41%, respectively. In contrast to control neurons, Ca stores in axotomized neurons were not expanded by neuronal activation by K depolarization, and the proportionate rate of refilling by sarco-endoplasmic Ca-ATPase was normal. Luminal Ca concentration was also reduced by 38% in axotomized neurons in permeabilized neurons. The adjacent neurons of the L4 dorsal root ganglia showed modest and inconsistent changes after L5 spinal nerve ligation. Painful nerve injury leads to diminished releasable endoplasmic reticulum Ca stores and a reduced luminal Ca concentration. Depletion of Ca stores may contribute to the pathogenesis of neuropathic pain.

  5. Sensory integration and neuromodulatory feedback facilitate Drosophila mechanonociceptive behavior.

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    Hu, Chun; Petersen, Meike; Hoyer, Nina; Spitzweck, Bettina; Tenedini, Federico; Wang, Denan; Gruschka, Alisa; Burchardt, Lara S; Szpotowicz, Emanuela; Schweizer, Michaela; Guntur, Ananya R; Yang, Chung-Hui; Soba, Peter

    2017-08-01

    Nociception is an evolutionarily conserved mechanism to encode and process harmful environmental stimuli. Like most animals, Drosophila melanogaster larvae respond to a variety of nociceptive stimuli, including noxious touch and temperature, with stereotyped escape responses through activation of multimodal nociceptors. How behavioral responses to these different modalities are processed and integrated by the downstream network remains poorly understood. By combining trans-synaptic labeling, ultrastructural analysis, calcium imaging, optogenetics and behavioral analyses, we uncovered a circuit specific for mechanonociception but not thermonociception. Notably, integration of mechanosensory input from innocuous and nociceptive sensory neurons is required for robust mechanonociceptive responses. We further show that neurons integrating mechanosensory input facilitate primary nociceptive output by releasing short neuropeptide F, the Drosophila neuropeptide Y homolog. Our findings unveil how integration of somatosensory input and neuropeptide-mediated modulation can produce robust modality-specific escape behavior.

  6. Crossmodal Connections of Primary Sensory Cortices Largely Vanish During Normal Aging

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    Henschke, Julia U.; Ohl, Frank W.; Budinger, Eike

    2018-01-01

    During aging, human response times (RTs) to unisensory and crossmodal stimuli decrease. However, the elderly benefit more from crossmodal stimulus representations than younger people. The underlying short-latency multisensory integration process is mediated by direct crossmodal connections at the level of primary sensory cortices. We investigate the age-related changes of these connections using a rodent model (Mongolian gerbil), retrograde tracer injections into the primary auditory (A1), somatosensory (S1), and visual cortex (V1), and immunohistochemistry for markers of apoptosis (Caspase-3), axonal plasticity (Growth associated protein 43, GAP 43), and a calcium-binding protein (Parvalbumin, PV). In adult animals, primary sensory cortices receive a substantial number of direct thalamic inputs from nuclei of their matched, but also from nuclei of non-matched sensory modalities. There are also direct intracortical connections among primary sensory cortices and connections with secondary sensory cortices of other modalities. In very old animals, the crossmodal connections strongly decrease in number or vanish entirely. This is likely due to a retraction of the projection neuron axonal branches rather than ongoing programmed cell death. The loss of crossmodal connections is also accompanied by changes in anatomical correlates of inhibition and excitation in the sensory thalamus and cortex. Together, the loss and restructuring of crossmodal connections during aging suggest a shift of multisensory processing from primary cortices towards other sensory brain areas in elderly individuals. PMID:29551970

  7. Crossmodal Connections of Primary Sensory Cortices Largely Vanish During Normal Aging

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    Julia U. Henschke

    2018-03-01

    Full Text Available During aging, human response times (RTs to unisensory and crossmodal stimuli decrease. However, the elderly benefit more from crossmodal stimulus representations than younger people. The underlying short-latency multisensory integration process is mediated by direct crossmodal connections at the level of primary sensory cortices. We investigate the age-related changes of these connections using a rodent model (Mongolian gerbil, retrograde tracer injections into the primary auditory (A1, somatosensory (S1, and visual cortex (V1, and immunohistochemistry for markers of apoptosis (Caspase-3, axonal plasticity (Growth associated protein 43, GAP 43, and a calcium-binding protein (Parvalbumin, PV. In adult animals, primary sensory cortices receive a substantial number of direct thalamic inputs from nuclei of their matched, but also from nuclei of non-matched sensory modalities. There are also direct intracortical connections among primary sensory cortices and connections with secondary sensory cortices of other modalities. In very old animals, the crossmodal connections strongly decrease in number or vanish entirely. This is likely due to a retraction of the projection neuron axonal branches rather than ongoing programmed cell death. The loss of crossmodal connections is also accompanied by changes in anatomical correlates of inhibition and excitation in the sensory thalamus and cortex. Together, the loss and restructuring of crossmodal connections during aging suggest a shift of multisensory processing from primary cortices towards other sensory brain areas in elderly individuals.

  8. [Comparative study on sensory integration function in children with primary nocturnal enuresis].

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    Liu, Fang; Ma, Hong-Wei; Dai, Xiao-Mei; Tian, Xiao-Bo; Wang, Li-Bo; Ma, Jian

    2010-05-01

    To study the sensory integration function in children with primary nocturnal enuresis (PNE). The sensory integration function was assessed by the Childhood Sensory Integration Ability Development Checklist in 70 children with PNE and was compared with that in 74 normal children(control group). The incidence of sensory integration dysfunction (76%) in the PNE group were significantly higher than that in the control group (35%; Psensory integration dysfunction occurred in more children in the PNE group compared with the control group (39% vs 18%; Psensory integration indexes revealed by sensory integration function testing in the PNE group were significantly lower than those in the control group (Psensory integrative dysfunction which presents in various aspects. It is necessary to assess the sensory integration function in children with PNE.

  9. Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

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    Jimmy eStehberg

    2014-09-01

    Full Text Available Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI and primary visual (VI. It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA and retrograde (CTb tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging and cortical parcellation are discussed.

  10. Shielding cognition from nociception with working memory.

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    Legrain, Valéry; Crombez, Geert; Plaghki, Léon; Mouraux, André

    2013-01-01

    Because pain often signals the occurrence of potential tissue damage, nociceptive stimuli have the capacity to capture attention and interfere with ongoing cognitive activities. Working memory is known to guide the orientation of attention by maintaining goal priorities active during the achievement of a task. This study investigated whether the cortical processing of nociceptive stimuli and their ability to capture attention are under the control of working memory. Event-related brain potentials (ERPs) were recorded while participants performed primary tasks on visual targets that required or did not require rehearsal in working memory (1-back vs 0-back conditions). The visual targets were shortly preceded by task-irrelevant tactile stimuli. Occasionally, in order to distract the participants, the tactile stimuli were replaced by novel nociceptive stimuli. In the 0-back conditions, task performance was disrupted by the occurrence of the nociceptive distracters, as reflected by the increased reaction times in trials with novel nociceptive distracters as compared to trials with standard tactile distracters. In the 1-back conditions, such a difference disappeared suggesting that attentional capture and task disruption induced by nociceptive distracters were suppressed by working memory, regardless of task demands. Most importantly, in the conditions involving working memory, the magnitude of nociceptive ERPs, including ERP components at early latency, were significantly reduced. This indicates that working memory is able to modulate the cortical processing of nociceptive input already at its earliest stages, and could explain why working memory reduces consequently ability of nociceptive stimuli to capture attention and disrupt performance of the primary task. It is concluded that protecting cognitive processing against pain interference is best guaranteed by keeping out of working memory pain-related information. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. The Glutamatergic System in Primary Somatosensory Neurons and Its Involvement in Sensory Input-Dependent Plasticity.

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    Fernández-Montoya, Julia; Avendaño, Carlos; Negredo, Pilar

    2017-12-27

    Glutamate is the most common neurotransmitter in both the central and the peripheral nervous system. Glutamate is present in all types of neurons in sensory ganglia, and is released not only from their peripheral and central axon terminals but also from their cell bodies. Consistently, these neurons express ionotropic and metabotropic receptors, as well as other molecules involved in the synthesis, transport and release of the neurotransmitter. Primary sensory neurons are the first neurons in the sensory channels, which receive information from the periphery, and are thus key players in the sensory transduction and in the transmission of this information to higher centers in the pathway. These neurons are tightly enclosed by satellite glial cells, which also express several ionotropic and metabotropic glutamate receptors, and display increases in intracellular calcium accompanying the release of glutamate. One of the main interests in our group has been the study of the implication of the peripheral nervous system in sensory-dependent plasticity. Recently, we have provided novel evidence in favor of morphological changes in first- and second-order neurons of the trigeminal system after sustained alterations of the sensory input. Moreover, these anatomical changes are paralleled by several molecular changes, among which those related to glutamatergic neurotransmission are particularly relevant. In this review, we will describe the state of the art of the glutamatergic system in sensory ganglia and its involvement in input-dependent plasticity, a fundamental ground for advancing our knowledge of the neural mechanisms of learning and adaptation, reaction to injury, and chronic pain.

  12. Tachykinin acts upstream of autocrine Hedgehog signaling during nociceptive sensitization in Drosophila.

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    Im, Seol Hee; Takle, Kendra; Jo, Juyeon; Babcock, Daniel T; Ma, Zhiguo; Xiang, Yang; Galko, Michael J

    2015-11-17

    Pain signaling in vertebrates is modulated by neuropeptides like Substance P (SP). To determine whether such modulation is conserved and potentially uncover novel interactions between nociceptive signaling pathways we examined SP/Tachykinin signaling in a Drosophila model of tissue damage-induced nociceptive hypersensitivity. Tissue-specific knockdowns and genetic mutant analyses revealed that both Tachykinin and Tachykinin-like receptor (DTKR99D) are required for damage-induced thermal nociceptive sensitization. Electrophysiological recording showed that DTKR99D is required in nociceptive sensory neurons for temperature-dependent increases in firing frequency upon tissue damage. DTKR overexpression caused both behavioral and electrophysiological thermal nociceptive hypersensitivity. Hedgehog, another key regulator of nociceptive sensitization, was produced by nociceptive sensory neurons following tissue damage. Surprisingly, genetic epistasis analysis revealed that DTKR function was upstream of Hedgehog-dependent sensitization in nociceptive sensory neurons. Our results highlight a conserved role for Tachykinin signaling in regulating nociception and the power of Drosophila for genetic dissection of nociception.

  13. Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

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    Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

    2014-01-01

    Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

  14. Distinct Computational Principles Govern Multisensory Integration in Primary Sensory and Association Cortices.

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    Rohe, Tim; Noppeney, Uta

    2016-02-22

    Human observers typically integrate sensory signals in a statistically optimal fashion into a coherent percept by weighting them in proportion to their reliabilities. An emerging debate in neuroscience is to which extent multisensory integration emerges already in primary sensory areas or is deferred to higher-order association areas. This fMRI study used multivariate pattern decoding to characterize the computational principles that define how auditory and visual signals are integrated into spatial representations across the cortical hierarchy. Our results reveal small multisensory influences that were limited to a spatial window of integration in primary sensory areas. By contrast, parietal cortices integrated signals weighted by their sensory reliabilities and task relevance in line with behavioral performance and principles of statistical optimality. Intriguingly, audiovisual integration in parietal cortices was attenuated for large spatial disparities when signals were unlikely to originate from a common source. Our results demonstrate that multisensory interactions in primary and association cortices are governed by distinct computational principles. In primary visual cortices, spatial disparity controlled the influence of non-visual signals on the formation of spatial representations, whereas in parietal cortices, it determined the influence of task-irrelevant signals. Critically, only parietal cortices integrated signals weighted by their bottom-up reliabilities and top-down task relevance into multisensory spatial priority maps to guide spatial orienting. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Trafficking regulates the subcellular distribution of voltage-gated sodium channels in primary sensory neurons.

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    Bao, Lan

    2015-09-30

    Voltage-gated sodium channels (Navs) comprise at least nine pore-forming α subunits. Of these, Nav1.6, Nav1.7, Nav1.8 and Nav1.9 are the most frequently studied in primary sensory neurons located in the dorsal root ganglion and are mainly localized to the cytoplasm. A large pool of intracellular Navs raises the possibility that changes in Nav trafficking could alter channel function. The molecular mediators of Nav trafficking mainly consist of signals within the Navs themselves, interacting proteins and extracellular factors. The surface expression of Navs is achieved by escape from the endoplasmic reticulum and proteasome degradation, forward trafficking and plasma membrane anchoring, and it is also regulated by channel phosphorylation and ubiquitination in primary sensory neurons. Axonal transport and localization of Navs in afferent fibers involves the motor protein KIF5B and scaffold proteins, including contactin and PDZ domain containing 2. Localization of Nav1.6 to the nodes of Ranvier in myelinated fibers of primary sensory neurons requires node formation and the submembrane cytoskeletal protein complex. These findings inform our understanding of the molecular and cellular mechanisms underlying Nav trafficking in primary sensory neurons.

  16. Enhanced Nociception in Angelman Syndrome Model Mice.

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    McCoy, Eric S; Taylor-Blake, Bonnie; Aita, Megumi; Simon, Jeremy M; Philpot, Benjamin D; Zylka, Mark J

    2017-10-18

    Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutation or deletion of the maternal UBE3A allele. The maternal UBE3A allele is expressed in nearly all neurons of the brain and spinal cord, whereas the paternal UBE3A allele is repressed by an extremely long antisense transcript ( UBE3A-ATS ). Little is known about expression of UBE3A in the peripheral nervous system, where loss of maternal UBE3A might contribute to AS phenotypes. Here we sought to examine maternal and paternal Ube3a expression in DRGs neurons and to evaluate whether nociceptive responses were affected in AS model mice (global deletion of maternal Ube3a allele; Ube3a m -/ p + ). We found that most large-diameter proprioceptive and mechanosensitive DRG neurons expressed maternal Ube3a and paternal Ube3a-ATS In contrast, most small-diameter neurons expressed Ube3a biallelically and had low to undetectable levels of Ube3a-ATS Analysis of single-cell DRG transcriptomes further suggested that Ube3a is expressed monoallelically in myelinated large-diameter neurons and biallelically in unmyelinated small-diameter neurons. Behavioral responses to some noxious thermal and mechanical stimuli were enhanced in male and female AS model mice; however, nociceptive responses were not altered by the conditional deletion of maternal Ube3a in the DRG. These data suggest that the enhanced nociceptive responses in AS model mice are due to loss of maternal Ube3a in the central, but not peripheral, nervous system. Our study provides new insights into sensory processing deficits associated with AS. SIGNIFICANCE STATEMENT Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss or mutation of the maternal UBE3A allele. While sensory processing deficits are frequently associated with AS, it is currently unknown whether Ube3a is expressed in peripheral sensory neurons or whether maternal deletion of Ube3a affects somatosensory responses. Here, we found that Ube3a is primarily expressed

  17. Controlling attention to nociceptive stimuli with working memory.

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    Valéry Legrain

    Full Text Available BACKGROUND: Because pain often signals the occurrence of potential tissue damage, a nociceptive stimulus has the capacity to involuntarily capture attention and take priority over other sensory inputs. Whether distraction by nociception actually occurs may depend upon the cognitive characteristics of the ongoing activities. The present study tested the role of working memory in controlling the attentional capture by nociception. METHODOLOGY AND PRINCIPAL FINDINGS: Participants performed visual discrimination and matching tasks in which visual targets were shortly preceded by a tactile distracter. The two tasks were chosen because of the different effects the involvement of working memory produces on performance, in order to dissociate the specific role of working memory in the control of attention from the effect of general resource demands. Occasionally (i.e. 17% of the trials, tactile distracters were replaced by a novel nociceptive stimulus in order to distract participants from the visual tasks. Indeed, in the control conditions (no working memory, reaction times to visual targets were increased when the target was preceded by a novel nociceptive distracter as compared to the target preceded by a frequent tactile distracter, suggesting attentional capture by the novel nociceptive stimulus. However, when the task required an active rehearsal of the visual target in working memory, the novel nociceptive stimulus no longer induced a lengthening of reaction times to visual targets, indicating a reduction of the distraction produced by the novel nociceptive stimulus. This effect was independent of the overall task demands. CONCLUSION AND SIGNIFICANCE: Loading working memory with pain-unrelated information may reduce the ability of nociceptive input to involuntarily capture attention, and shields cognitive processing from nociceptive distraction. An efficient control of attention over pain is best guaranteed by the ability to maintain active goal

  18. Comparative biology of pain: What invertebrates can tell us about how nociception works.

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    Burrell, Brian D

    2017-04-01

    The inability to adequately treat chronic pain is a worldwide health care crisis. Pain has both an emotional and a sensory component, and this latter component, nociception, refers specifically to the detection of damaging or potentially damaging stimuli. Nociception represents a critical interaction between an animal and its environment and exhibits considerable evolutionary conservation across species. Using comparative approaches to understand the basic biology of nociception could promote the development of novel therapeutic strategies to treat pain, and studies of nociception in invertebrates can provide especially useful insights toward this goal. Both vertebrates and invertebrates exhibit segregated sensory pathways for nociceptive and nonnociceptive information, injury-induced sensitization to nociceptive and nonnociceptive stimuli, and even similar antinociceptive modulatory processes. In a number of invertebrate species, the central nervous system is understood in considerable detail, and it is often possible to record from and/or manipulate single identifiable neurons through either molecular genetic or physiological approaches. Invertebrates also provide an opportunity to study nociception in an ethologically relevant context that can provide novel insights into the nature of how injury-inducing stimuli produce persistent changes in behavior. Despite these advantages, invertebrates have been underutilized in nociception research. In this review, findings from invertebrate nociception studies are summarized, and proposals for how research using invertebrates can address questions about the fundamental mechanisms of nociception are presented. Copyright © 2017 the American Physiological Society.

  19. Role of NHE1 in Nociception

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    Jorge Elías Torres-López

    2013-01-01

    Full Text Available Intracellular pH is a fundamental parameter to cell function that requires tight homeostasis. In the absence of any regulation, excessive acidification of the cytosol would have the tendency to produce cellular damage. Mammalian Na+/H+ exchangers (NHEs are electroneutral Na+-dependent proteins that exchange extracellular Na+ for intracellular H+. To date, there are 9 identified NHE isoforms where NHE1 is the most ubiquitous member, known as the housekeeping exchanger. NHE1 seems to have a protective role in the ischemia-reperfusion injury and other inflammatory diseases. In nociception, NHE1 is found in neurons along nociceptive pathways, and its pharmacological inhibition increases nociceptive behavior in acute pain models at peripheral and central levels. Electrophysiological studies also show that NHE modulates electrical activity of primary nociceptive terminals. However, its role in neuropathic pain still remains controversial. In humans, NHE1 may be responsible for inflammatory bowel diseases since its expression is reduced in Crohn’s disease and ulcerative colitis. The purpose of this work is to provide a review of the evidence about participation of NHE1 in the nociceptive processing.

  20. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol.

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    Takeda, Mamoru; Takehana, Shiori; Sekiguchi, Kenta; Kubota, Yoshiko; Shimazu, Yoshihito

    2016-10-11

    Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM) candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

  1. Modulatory Mechanism of Nociceptive Neuronal Activity by Dietary Constituent Resveratrol

    Directory of Open Access Journals (Sweden)

    Mamoru Takeda

    2016-10-01

    Full Text Available Changes to somatic sensory pathways caused by peripheral tissue, inflammation or injury can result in behavioral hypersensitivity and pathological pain, such as hyperalgesia. Resveratrol, a plant polyphenol found in red wine and various food products, is known to have several beneficial biological actions. Recent reports indicate that resveratrol can modulate neuronal excitability, including nociceptive sensory transmission. As such, it is possible that this dietary constituent could be a complementary alternative medicine (CAM candidate, specifically a therapeutic agent. The focus of this review is on the mechanisms underlying the modulatory effects of resveratrol on nociceptive neuronal activity associated with pain relief. In addition, we discuss the contribution of resveratrol to the relief of nociceptive and/or pathological pain and its potential role as a functional food and a CAM.

  2. Convergence of primary sensory cortex and cerebellar nuclei pathways in the whisker system.

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    Schäfer, Carmen B; Hoebeek, Freek E

    2018-01-01

    To safely maneuver through the environment the brain needs to compare active sensory information with ongoing motor programs. This process occurs at various levels in the brain: at the lower level, i.e., in the spinal cord, reflexes are generated for the most primitive motor responses; at the intermediate level, i.e., in the brainstem, various nuclei co-process sensory- and motor-related inputs; and, at the higher level cerebellum and thalamo-cortical networks individually compute suitable commands for fine-tuned motor output. For sensorimotor processes the integrative capacities of the cerebral cortex and the cerebellum have been the topic of detailed analysis. Here, we use higher order sensorimotor integration in the whisker system as a model to evaluate the convergence pattern of primary sensory cortex projections and the cerebellar output nuclei throughout several brain nuclei. This prospective review focuses not only on the thalamus, but also incorporates extra-thalamic structures that could function as comparators of cerebellar output and sensory cortex output. Based on the literature on anatomical and physiological studies in the rodent brain and our qualitative data on the convergence of cerebellar sensory cortical projections we identify the superior colliculus as well as the zona incerta and the anterior pretectal nucleus as suitable candidates for cerebello-cortical convergence. Including these putative comparators we discuss the potential routes for sensorimotor information flow between the cerebellum and cerebral sensory cortex with a focus on the modulation of thalamic activity by extra-thalamic structures. Copyright © 2017. Published by Elsevier Ltd.

  3. Primary Sjogren’s Syndrome Presented with Sensory Ataxia Associated with Bilateral Hearing Loss and Dementia

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    Madjdinasab Nastaran

    2009-10-01

    Full Text Available Primary Sjorgen syndrome is one of the commonest autoimmune diseases with characteristic of involvement of lachrymal and salivary glands, but other organ involvements as peripheral and central nervous system are also possible. The reported case is a 23 year old lady presented with progressive sensory ataxia and weakness of four limbs, bilateral sensory hearing loss and cognitive impairment with minimental score equal to 15/30 since one year prior to admission with associated bilateral central corneal opacity, dry mouth and dry eyes. Electro physiologic studies showed sensory motor axonal polyneuropathy . A biopsy of sural nerve and salivary glands of lower lip showed lymphocytic infiltration. Serologic evidence showed positive Anti Ro (SS-B, negative HCV and HIV antibody, thereafter the diagnosis was confirmed and according to this diagnosis she received high dose of intravenous methyl prednisolon then both hearing loss and cognitive impairment improved partially (minimental score 21/30 . At last, she underwent plasmapheresis and her sensory ataxia improved greatly.

  4. Peptidergic CGRPα primary sensory neurons encode heat and itch and tonically suppress sensitivity to cold

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    McCoy, Eric S.; Taylor-Blake, Bonnie; Street, Sarah E.; Pribisko, Alaine L.; Zheng, Jihong; Zylka, Mark J.

    2013-01-01

    SUMMARY Calcitonin gene-related peptide (CGRP) is a classic molecular marker of peptidergic primary somatosensory neurons. Despite years of research, it is unknown if these neurons are required to sense pain or other sensory stimuli. Here, we found that genetic ablation of CGRPα-expressing sensory neurons reduced sensitivity to noxious heat, capsaicin and itch (histamine and chloroquine) and impaired thermoregulation but did not impair mechanosensation or β-alanine itch—stimuli associated with nonpeptidergic sensory neurons. Unexpectedly, ablation enhanced behavioral responses to cold stimuli and cold mimetics without altering peripheral nerve responses to cooling. Mechanistically, ablation reduced tonic and evoked activity in postsynaptic spinal neurons associated with TRPV1/heat, while profoundly increasing tonic and evoked activity in spinal neurons associated with TRPM8/cold. Our data reveal that CGRPα sensory neurons encode heat and itch and tonically cross-inhibit cold-responsive spinal neurons. Disruption of this crosstalk unmasks cold hypersensitivity, with mechanistic implications for neuropathic pain and temperature perception. PMID:23523592

  5. Possible anatomical pathways for short-latency multisensory integration processes in primary sensory cortices.

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    Henschke, Julia U; Noesselt, Tömme; Scheich, Henning; Budinger, Eike

    2015-03-01

    Multisensory integration does not only recruit higher-level association cortex, but also low-level and even primary sensory cortices. Here, we will describe and quantify two types of anatomical pathways, a thalamocortical and a corticocortical that possibly underlie short-latency multisensory integration processes in the primary auditory (A1), somatosensory (S1), and visual cortex (V1). Results were obtained from Mongolian gerbils, a common model-species in neuroscience, using simultaneous injections of different retrograde tracers into A1, S1, and V1. Several auditory, visual, and somatosensory thalamic nuclei project not only to the primary sensory area of their own (matched) but also to areas of other (non-matched) modalities. The crossmodal output ratios of these nuclei, belonging to both core and non-core sensory pathways, vary between 0.4 and 63.5 % of the labeled neurons. Approximately 0.3 % of the sensory thalamic input to A1, 5.0 % to S1, and 2.1 % to V1 arise from non-matched nuclei. V1 has most crossmodal corticocortical connections, projecting strongest to S1 and receiving a similar amount of moderate inputs from A1 and S1. S1 is mainly interconnected with V1. A1 has slightly more projections to V1 than S1, but gets just faint inputs from there. Concerning the layer-specific distribution of the retrogradely labeled somata in cortex, V1 provides the most pronounced feedforward-type outputs and receives (together with S1) most pronounced feedback-type inputs. In contrast, A1 has most pronounced feedback-type outputs and feedforward-type inputs in this network. Functionally, the different sets of thalamocortical and corticocortical connections could underlie distinctive types of integration mechanisms for different modality pairings.

  6. Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.

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    G Gregory Neely

    Full Text Available The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species.

  7. Delayed onset of changes in soma action potential genesis in nociceptive A-beta DRG neurons in vivo in a rat model of osteoarthritis

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    Henry James L

    2009-09-01

    Full Text Available Abstract Background Clinical data on osteoarthritis (OA suggest widespread changes in sensory function that vary during the progression of OA. In previous studies on a surgically-induced animal model of OA we have observed that changes in structure and gene expression follow a variable trajectory over the initial days and weeks. To investigate mechanisms underlying changes in sensory function in this model, the present electrophysiological study compared properties of primary sensory nociceptive neurons at one and two months after model induction with properties in naïve control animals. Pilot data indicated no difference in C- or Aδ-fiber associated neurons and therefore the focus is on Aβ-fiber nociceptive neurons. Results At one month after unilateral derangement of the knee by cutting the anterior cruciate ligament and removing the medial meniscus, the only changes observed in Aβ-fiber dorsal root ganglion (DRG neurons were in nociceptor-like unresponsive neurons bearing a hump on the repolarization phase; these changes consisted of longer half width, reflecting slowed dynamics of AP genesis, a depolarized Vm and an increased AP amplitude. At two months, changes observed were in Aβ-fiber high threshold mechanoreceptors, which exhibited shorter AP duration at base and half width, shorter rise time and fall time, and faster maximum rising rate/maximum falling rate, reflecting accelerated dynamics of AP genesis. Conclusion These data indicate that Aβ nociceptive neurons undergo significant changes that vary in time and occur later than changes in structure and in nociceptive scores in this surgically induced OA model. Thus, if changes in Aβ-fiber nociceptive neurons in this model reflect a role in OA pain, they may relate to mechanisms underlying pain associated with advanced OA.

  8. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro

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    Brianna K. Swartwout

    2017-10-01

    Full Text Available Zika virus (ZIKV has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  9. Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro.

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    Swartwout, Brianna K; Zlotnick, Marta G; Saver, Ashley E; McKenna, Caroline M; Bertke, Andrea S

    2017-10-13

    Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

  10. CGRPα within the Trpv1-Cre population contributes to visceral nociception.

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    Spencer, Nick J; Magnúsdóttir, Elín I; Jakobsson, Jon E T; Kestell, Garreth; Chen, Bao Nan; Morris, David; Brookes, Simon J; Lagerström, Malin C

    2018-02-01

    The role of calcitonin gene-related peptide (CGRP) in visceral and somatic nociception is incompletely understood. CGRPα is highly expressed in sensory neurons of dorsal root ganglia and particularly in neurons that also express the transient receptor potential cation channel subfamily V member 1 (Trpv1). Therefore, we investigated changes in visceral and somatic nociception following deletion of CGRPα from the Trpv1-Cre population using the Cre/lox system. In control mice, acetic acid injection (0.6%, ip) caused significant immobility (time stationary), an established indicator of visceral pain. In CGRPα-mCherry lx/lx ;Trpv1-Cre mice, the duration of immobility was significantly less than controls, and the distance CGRPα-mCherry lx/lx ;Trpv1-Cre mice traveled over 20 min following acetic acid was significantly greater than controls. However, following acetic acid injection, there was no difference between genotypes in the writhing reflex, number of abdominal licks, or forepaw wipes of the cheek. CGRPα-mCherry lx/lx ;Trpv1-Cre mice developed more pronounced inflammation-induced heat hypersensitivity above baseline values compared with controls. However, analyses of noxious acute heat or cold transmission revealed no difference between genotypes. Also, odor avoidance test, odor preference test, and buried food test for olfaction revealed no differences between genotypes. Our findings suggest that CGRPα-mediated transmission within the Trpv1-Cre population plays a significant role in visceral nociceptive pathways underlying voluntary movement. Monitoring changes in movement over time is a sensitive parameter to identify differences in visceral nociception, compared with writhing reflexes, abdominal licks, or forepaw wipes of the cheek that were unaffected by deletion of CGRPα- from Trpv1-Cre population and likely utilize different mechanisms. NEW & NOTEWORTHY The neuropeptide calcitonin gene-related peptide (CGRP) is highly colocalized with transient receptor

  11. Intraneural Injection of ATP Stimulates Regeneration of Primary Sensory Axons in the Spinal Cord.

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    Wu, Dongsheng; Lee, Sena; Luo, Juan; Xia, Haijian; Gushchina, Svetlana; Richardson, Peter M; Yeh, John; Krügel, Ute; Franke, Heike; Zhang, Yi; Bo, Xuenong

    2018-02-07

    Injury to the peripheral axons of sensory neurons strongly enhances the regeneration of their central axons in the spinal cord. It remains unclear on what molecules that initiate such conditioning effect. Because ATP is released extracellularly by nerve and other tissue injury, we hypothesize that injection of ATP into a peripheral nerve might mimic the stimulatory effect of nerve injury on the regenerative state of the primary sensory neurons. We found that a single injection of 6 μl of 150 μm ATP into female rat sciatic nerve quadrupled the number of axons growing into a lesion epicenter in spinal cord after a concomitant dorsal column transection. A second boost ATP injection 1 week after the first one markedly reinforced the stimulatory effect of a single injection. Single ATP injection increased expression of phospho-STAT3 and GAP43, two markers of regenerative activity, in sensory neurons. Double ATP injections sustained the activation of phospho-STAT3 and GAP43, which may account for the marked axonal growth across the lesion epicenter. Similar studies performed on P2X7 or P2Y2 receptor knock-out mice indicate P2Y2 receptors are involved in the activation of STAT3 after ATP injection or conditioning lesion, whereas P2X7 receptors are not. Injection of ATP at 150 μm caused little Wallerian degeneration and behavioral tests showed no significant long-term adverse effects on sciatic nerve functions. The results in this study reveal possible mechanisms underlying the stimulation of regenerative programs and suggest a practical strategy for stimulating axonal regeneration following spinal cord injury. SIGNIFICANCE STATEMENT Injury of peripheral axons of sensory neurons has been known to strongly enhance the regeneration of their central axons in the spinal cord. In this study, we found that injection of ATP into a peripheral nerve can mimic the effect of peripheral nerve injury and significantly increase the number of sensory axons growing across lesion

  12. Development of primary sensory neurons in the trigeminal nervous system; dependency on neurotrophins and other substances

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    Hiroyuki Ichikawa

    2012-02-01

    Full Text Available This review presents information about the development of primary sensory neurons in the trigeminal nervous system. The deficiency of high affinity receptors for nerve growth factor (trkA and neurotrophin-3 (trk-C causesa reduction of primary nociceptors in the trigeminal ganglion (TG. The disruption of trkB, a receptor for brain-derived neurotrophic factor and neurotrophin-4, causes a loss of Meissner endings in the palate and Ruffini endings in the periodontal ligament. The number of Merkel cells in palatal rugae is also severely reduced by the absence of trkA, trkB or trkC. In the mesencephalic trigeminal tract nucleus (Mes5, primary proprioceptors are decreased by 50% in trkC null mutant mice. On the other hand, the deficiency of Brn-3a, a member of the POU family of transcription factors, decreases primary nociceptors and low-threshold mechanoreceptors in the TG. In the Mes5 of Brn-3a knockout mice, primary proprioceptors are completely lost. In addition, the disruption of dystonin which is a member of the plakin family of high molecular weight cytoskeletal linker proteins causes a reduction of nociceptors in the TG but not proprioceptors in the Mes5. The dependency of primary nociceptors, low-threshold mechanoreceptors and proprioceptors on neurotrophins, Brn-3a and dystonin in the trigeminal nervous system is discussed.

  13. Temporal association between changes in primary sensory cortex and corticomotor output during muscle pain.

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    Schabrun, S M; Jones, E; Kloster, J; Hodges, P W

    2013-04-03

    Integration of information between multiple cortical regions is thought to underpin the experience of pain. Yet studies tend to focus on pain related changes in discrete cortical regions. Although altered processing in the primary motor (M1) and sensory cortex (S1) is implicated in pain, the temporal relationship between these regions is unknown and may provide insight into the interaction between them. We used recordings of somatosensory-evoked potentials (SEPs) and transcranial magnetic stimulation to investigate the temporal relationship between altered excitability of the primary sensory cortex and corticomotor output during and after muscle pain induced by hypertonic saline infusion into the right first dorsal interosseous. SEPs and motor-evoked potentials (MEPs) were recorded in 12 healthy individuals. Participants reported an average pain intensity of 5.4 (0.5) on a 10-cm visual analogue scale. The area of the N20-P25-N33 complex of the SEP was reduced during and after pain, but MEP amplitudes were suppressed only after pain had resolved. Our data show that pain reduces sensory processing before motor output is altered. This temporal dispersion, coupled with the lack of correlation between pain-induced changes in S1 and M1 excitability, imply either that independent processes are involved, or that reduced excitability of S1 during acute experimental muscle pain mediates latent reductions in motor output via processes that are non-linear and potentially involve activation of a wider brain network. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  14. Primary Cesarean Delivery Patterns among Women with Physical, Sensory, or Intellectual Disabilities.

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    Darney, Blair G; Biel, Frances M; Quigley, Brian P; Caughey, Aaron B; Horner-Johnson, Willi

    Little is known about the relationship between disability and mode of delivery. Prior research has indicated elevated risk of cesarean delivery among women with certain disabilities, but has not examined patterns across multiple types of disability or by parity. This study sought to determine whether physical, sensory, or intellectual and developmental disabilities are independently associated with primary cesarean delivery. We conducted a retrospective cohort study of all deliveries in California from 2000 to 2010 using linked birth certificate and hospital discharge data. We identified physical, sensory, and intellectual and developmental disabilities using International Classification of Diseases, 9th revision, clinical modification codes. We used logistic regression to examine the association of these disabilities and primary cesarean delivery, controlling for sociodemographic characteristics and comorbidities, and stratified by parity. In our sample, 0.45% of deliveries (20,894/4,610,955) were to women with disabilities. A greater proportion of women with disabilities were nulliparous, had public insurance, and had comorbidities (e.g., gestational diabetes) compared with women without disabilities (p disabilities was twice that in women without disabilities (32.7% vs. 16.3%; p disabilities due to injuries compared with women without disabilities (57.8% vs. 16.3%; p type. More attention is needed to this population to ensure better understanding of care practices that may impact maternal and perinatal outcomes. Copyright © 2017 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  15. Distribution of TTX-sensitive voltage-gated sodium channels in primary sensory endings of mammalian muscle spindles.

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    Carrasco, Dario I; Vincent, Jacob A; Cope, Timothy C

    2017-04-01

    Knowledge of the molecular mechanisms underlying signaling of mechanical stimuli by muscle spindles remains incomplete. In particular, the ionic conductances that sustain tonic firing during static muscle stretch are unknown. We hypothesized that tonic firing by spindle afferents depends on sodium persistent inward current (INaP) and tested for the necessary presence of the appropriate voltage-gated sodium (NaV) channels in primary sensory endings. The NaV 1.6 isoform was selected for both its capacity to produce INaP and for its presence in other mechanosensors that fire tonically. The present study shows that NaV 1.6 immunoreactivity (IR) is concentrated in heminodes, presumably where tonic firing is generated, and we were surprised to find NaV 1.6 IR strongly expressed also in the sensory terminals, where mechanotransduction occurs. This spatial pattern of NaV 1.6 IR distribution was consistent for three mammalian species (rat, cat, and mouse), as was tonic firing by primary spindle afferents. These findings meet some of the conditions needed to establish participation of INaP in tonic firing by primary sensory endings. The study was extended to two additional NaV isoforms, selected for their sensitivity to TTX, excluding TTX-resistant NaV channels, which alone are insufficient to support firing by primary spindle endings. Positive immunoreactivity was found for NaV 1.1 , predominantly in sensory terminals together with NaV 1.6 and for NaV 1.7 , mainly in preterminal axons. Differential distribution in primary sensory endings suggests specialized roles for these three NaV isoforms in the process of mechanosensory signaling by muscle spindles. NEW & NOTEWORTHY The molecular mechanisms underlying mechanosensory signaling responsible for proprioceptive functions are not completely elucidated. This study provides the first evidence that voltage-gated sodium channels (NaVs) are expressed in the spindle primary sensory ending, where NaVs are found at every site

  16. Ontogeny of the serotonergic projection to rat neocortex: transient expression of a dense innervation to primary sensory areas

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    D' Amato, R.J.; Blue, M.E.; Largent, B.L.; Lynch, D.R.; Ledbetter, D.J.; Molliver, M.E.; Snyder, S.H.

    1987-06-01

    The development of serotonergic innervation to rat cerebral cortex was characterized by immunohistochemical localization of serotonin combined with autoradiographic imaging of serotonin-uptake sites. In neonatal rat, a transient, dense, serotonergic innervation appears in all primary sensory areas of cortex. In somatosensory cortex, dense patches of serotonergic innervation are aligned with specialized cellular aggregates called barrels. The dense patches are not apparent after 3 weeks of age, and the serotonergic innervation becomes more uniform in adult neocortex. This precocious neonatal serotonergic innervation may play a transient physiologic role in sensory areas of cortex or may exert a trophic influence on the development of cortical circuitry and thalamocortical connections.

  17. Prolactin potentiates the activity of acid-sensing ion channels in female rat primary sensory neurons.

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    Liu, Ting-Ting; Qu, Zu-Wei; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Hu, Wang-Ping

    2016-04-01

    Prolactin (PRL) is a polypeptide hormone produced and released from the pituitary and extrapituitary tissues. It regulates activity of nociceptors and causes hyperalgesia in pain conditions, but little is known the molecular mechanism. We report here that PRL can exert a potentiating effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons. First, PRL dose-dependently increased the amplitude of ASIC currents with an EC50 of (5.89 ± 0.28) × 10(-8) M. PRL potentiation of ASIC currents was also pH dependent. Second, PRL potentiation of ASIC currents was blocked by Δ1-9-G129R-hPRL, a PRL receptor antagonist, and removed by intracellular dialysis of either protein kinase C inhibitor GF109203X, protein interacting with C-kinase 1(PICK1) inhibitor FSC-231, or PI3K inhibitor AS605240. Third, PRL altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Four, PRL exacerbated nociceptive responses to injection of acetic acid in female rats. Finally, PRL displayed a stronger effect on ASIC mediated-currents and nociceptive behavior in intact female rats than OVX female and male rats and thus modulation of PRL may be gender-dependent. These results suggest that PRL up-regulates the activity of ASICs and enhances ASIC mediated nociceptive responses in female rats, which reveal a novel peripheral mechanism underlying PRL involvement in hyperalgesia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

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    Onozawa Kitaro

    2011-11-01

    Full Text Available Abstract Background We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC. The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS delivered to the BLA on nociceptive responses in the rat PFC. Results HFS induced long lasting suppression (LLS of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA receptor antagonists (2-amino-5-phosphonovaleric acid (APV, dizocilpine (MK-801 and also metabotropic glutamate receptor (mGluR group antagonists (α-methyl-4-carboxyphenylglycine (MCPG, and 2-[(1S,2S-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl-D-alanine (LY341495, prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride and D4 (3-{[4-(4-chlorophenyl piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870, microinjected into the PFC, inhibited LLS of nociceptive responses. Conclusions Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.

  19. Bilateral Neuropathy of Primary Sensory Neurons by the Chronic Compression of Multiple Unilateral DRGs

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    Xie, Ya-Bin; Zhao, Huan; Wang, Ying; Song, Kai; Zhang, Ming; Meng, Fan-Cheng; Yang, Yu-Jie; He, Yang-Song; Kuang, Fang; You, Si-Wei; You, Hao-Jun; Xu, Hui

    2016-01-01

    To mimic multilevel nerve root compression and intervertebral foramina stenosis in human, we established a new animal model of the chronic compression of unilateral multiple lumbar DRGs (mCCD) in the rat. A higher occurrence of signs of spontaneous pain behaviors, such as wet-dog shaking and spontaneous hind paw shrinking behaviors, was firstly observed from day 1 onward. In the meantime, the unilateral mCCD rat exhibited significant bilateral hind paw mechanical and cold allodynia and hyperalgesia, as well as a thermal preference to 30°C plate between 30 and 35°C. The expression of activating transcription factor 3 (ATF3) was significantly increased in the ipsilateral and contralateral all-sized DRG neurons after the mCCD. And the expression of CGRP was significantly increased in the ipsilateral and contralateral large- and medium-sized DRG neurons. ATF3 and CGRP expressions correlated to evoked pain hypersensitivities such as mechanical and cold allodynia on postoperative day 1. The results suggested that bilateral neuropathy of primary sensory neurons might contribute to bilateral hypersensitivity in the mCCD rat. PMID:26819761

  20. Bilateral Neuropathy of Primary Sensory Neurons by the Chronic Compression of Multiple Unilateral DRGs

    Directory of Open Access Journals (Sweden)

    Ya-Bin Xie

    2016-01-01

    Full Text Available To mimic multilevel nerve root compression and intervertebral foramina stenosis in human, we established a new animal model of the chronic compression of unilateral multiple lumbar DRGs (mCCD in the rat. A higher occurrence of signs of spontaneous pain behaviors, such as wet-dog shaking and spontaneous hind paw shrinking behaviors, was firstly observed from day 1 onward. In the meantime, the unilateral mCCD rat exhibited significant bilateral hind paw mechanical and cold allodynia and hyperalgesia, as well as a thermal preference to 30°C plate between 30 and 35°C. The expression of activating transcription factor 3 (ATF3 was significantly increased in the ipsilateral and contralateral all-sized DRG neurons after the mCCD. And the expression of CGRP was significantly increased in the ipsilateral and contralateral large- and medium-sized DRG neurons. ATF3 and CGRP expressions correlated to evoked pain hypersensitivities such as mechanical and cold allodynia on postoperative day 1. The results suggested that bilateral neuropathy of primary sensory neurons might contribute to bilateral hypersensitivity in the mCCD rat.

  1. Gliotransmission modulates baseline mechanical nociception

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    Foley Jeannine C

    2011-12-01

    Full Text Available Abstract Pain is a physiological and adaptive process which occurs to protect organisms from tissue damage and extended injury. Pain sensation beyond injury, however, is a pathological process which is poorly understood. Experimental models of neuropathic pain demonstrate that reactive astrocytes contribute to reduced nociceptive thresholds. Astrocytes release "gliotransmitters" such as D-serine, glutamate, and ATP, which is extracellularly hydrolyzed to adenosine. Adenosine 1 receptor activation in the spinal cord has anti-nociceptive effects on baseline pain threshold, but the source of the endogenous ligand (adenosine in the spinal cord is unknown. In this study we used a transgenic mouse model in which SNARE-mediated gliotransmission was selectively attenuated (called dnSNARE mice to investigate the role of astrocytes in mediating baseline nociception and the development of neuropathic pain. Under baseline conditions, immunostaining in the dorsal horn of the spinal cord showed astrocyte-specific transgene expression in dnSNARE mice, and no difference in expression levels of the astrocyte marker GFAP and the microglia marker Iba1 relative to wild-type mice. The Von Frey filament test was used to probe sensitivity to baseline mechanical pain thresholds and allodynia following the spared nerve injury model of neuropathic pain. DnSNARE mice exhibit a reduced nociceptive threshold in response to mechanical stimulation compared to wild-type mice under baseline conditions, but nociceptive thresholds following spared nerve injury were similar between dnSNARE and wild-types. This study is the first to provide evidence that gliotransmission contributes to basal mechanical nociception.

  2. Interhemispheric Inhibition Induced by Transcranial Magnetic Stimulation Over Primary Sensory Cortex.

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    Iwata, Yasuyuki; Jono, Yasutomo; Mizusawa, Hiroki; Kinoshita, Atsushi; Hiraoka, Koichi

    2016-01-01

    The present study investigated whether the long-interval interhemispheric inhibition (LIHI) is induced by the transcranial magnetic stimulation over the primary sensory area (S1-TMS) without activation of the conditioning side of the primary motor area (M1) contributing to the contralateral motor evoked potential (MEP), whether the S1-TMS-induced LIHI is dependent on the status of the S1 modulated by the tactile input, and whether the pathways mediating the LIHI are different from those mediating the M1-TMS-induced LIHI. In order to give the TMS over the S1 without eliciting the MEP, the intensity of the S1-TMS was adjusted to be the sub-motor-threshold level and the trials with the MEP response elicited by the S1-TMS were discarded online. The LIHI was induced by the S1-TMS given 40 ms before the test TMS in the participants with the attenuation of the tactile perception of the digit stimulation (TPDS) induced by the S1-TMS, indicating that the LIHI is induced by the S1-TMS without activation of the conditioning side of the M1 contributing to the contralateral MEP in the participants in which the pathways mediating the TPDS is sensitive to the S1-TMS. The S1-TMS-induced LIHI was positively correlated with the attenuation of the TPDS induced by the S1-TMS, indicating that the S1-TMS-induced LIHI is dependent on the effect of the S1-TMS on the pathways mediating the TPDS at the S1. In another experiment, the effect of the digit stimulation given before the conditioning TMS on the S1- or M1-TMS-induced LIHI was examined. The digit stimulation produces tactile input to the S1 causing change in the status of the S1. The S1-TMS-induced LIHI was enhanced when the S1-TMS was given in the period in which the tactile afferent volley produced by the digit stimulation just arrived at the S1, while the LIHI induced by above-motor-threshold TMS over the contralateral M1 was not enhanced by the tactile input. Thus, the S1-TMS-induced LIHI is dependent on the status of the S1

  3. Pain and Nociception

    DEFF Research Database (Denmark)

    Falk, Sarah; Dickenson, Anthony H

    2014-01-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditiona...... spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.......Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional...... therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain...

  4. Ecto-5’-nucleotidase (CD73) inhibits nociception by hydrolyzing AMP to adenosine in nociceptive circuits

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    Sowa, Nathaniel A.; Taylor-Blake, Bonnie; Zylka, Mark J.

    2010-01-01

    Ecto-5’-nucleotidase (NT5E, CD73) is a membrane-anchored protein that hydrolyzes extracellular adenosine 5’-monophosphate (AMP) to adenosine in diverse tissues but has not been directly studied in nociceptive neurons. We found that NT5E was located on peptidergic and nonpeptidergic nociceptive neurons in dorsal root ganglia (DRG) and on axon terminals in lamina II (the substantia gelatinosa) of spinal cord. NT5E was also located on epidermal keratinocytes, cells of the dermis and on nociceptive axon terminals in the epidermis. Following nerve injury, NT5E protein and AMP histochemical staining were coordinately reduced in lamina II. In addition, AMP hydrolytic activity was reduced in DRG neurons and spinal cord of Nt5e−/− mice. The antinociceptive effects of AMP, when combined with the adenosine kinase inhibitor 5-iodotubericidin, were reduced by ~50% in Nt5e−/− mice and were eliminated in Adenosine A1 receptor (A1R, Adora1) knockout mice. Additionally, Nt5e−/− mice displayed enhanced sensitivity in the tail immersion assay, in the complete Freund's adjuvant (CFA) model of inflammatory pain and in the spared nerve injury (SNI) model of neuropathic pain. Collectively, our data indicate that the ectonucleotidase NT5E regulates nociception by hydrolyzing AMP to adenosine in nociceptive circuits and represents a new molecular target for the treatment of chronic pain. Moreover, our data suggest NT5E is well localized to regulate nucleotide signaling between skin cells and sensory axons. PMID:20147550

  5. Continuous theta-burst stimulation to primary motor cortex reveals asymmetric compensation for sensory attenuation in bimanual repetitive force production.

    Science.gov (United States)

    Therrien, Amanda S; Lyons, James; Balasubramaniam, Ramesh

    2013-08-01

    Studies of fingertip force production have shown that self-produced forces are perceived as weaker than externally generated forces. This is due to mechanisms of sensory reafference where the comparison between predicted and actual sensory feedback results in attenuated perceptions of self-generated forces. Without an external reference to calibrate attenuated performance judgments, a compensatory overproduction of force is exhibited. It remains unclear whether the force overproduction seen in the absence of visual reference stimuli differs when forces are produced bimanually. We studied performance of two versions of a bimanual sequential force production task compared with each hand performing the task unimanually. When the task goal was shared, force series produced by each hand in bimanual conditions were found to be uncorrelated. When the bimanual task required each hand to reach a target force level, we found asymmetries in the degree of force overproduction between the hands following visual feedback removal. Unilateral continuous theta-burst stimulation of the left primary motor cortex yielded a selective reduction of force overproduction in the hand contralateral to stimulation by disrupting sensory reafference processes. While variability was lower in bimanual trials when the task goal was shared, this influence of hand condition disappeared when the target force level was to be reached by each hand simultaneously. Our findings strengthen the notion that force control in bimanual action is less tightly coupled than other mechanisms of bimanual motor control and show that this effector specificity may be extended to the processing and compensation for mechanisms of sensory reafference.

  6. Evidence for glutamate as a neuroglial transmitter within sensory ganglia.

    Science.gov (United States)

    Kung, Ling-Hsuan; Gong, Kerui; Adedoyin, Mary; Ng, Johnson; Bhargava, Aditi; Ohara, Peter T; Jasmin, Luc

    2013-01-01

    This study examines key elements of glutamatergic transmission within sensory ganglia of the rat. We show that the soma of primary sensory neurons release glutamate when depolarized. Using acute dissociated mixed neuronal/glia cultures of dorsal root ganglia (DRG) or trigeminal ganglia and a colorimetric assay, we show that when glutamate uptake by satellite glial cells (SGCs) is inhibited, KCl stimulation leads to simultaneous increase of glutamate in the culture medium. With calcium imaging we see that the soma of primary sensory neurons and SGCs respond to AMPA, NMDA, kainate and mGluR agonists, and selective antagonists block this response. Using whole cell patch-clamp technique, inward currents were recorded from small diameter (ganglion preparation) in response to local application of the above glutamate receptor agonists. Following a chronic constriction injury (CCI) of either the inferior orbital nerve or the sciatic nerve, glutamate expression increases in the trigeminal ganglia and DRG respectively. This increase occurs in neurons of all diameters and is present in the somata of neurons with injured axons as well as in somata of neighboring uninjured neurons. These data provides additional evidence that glutamate can be released within the sensory ganglion, and that the somata of primary sensory neurons as well as SGCs express functional glutamate receptors at their surface. These findings, together with our previous gene knockdown data, suggest that glutamatergic transmission within the ganglion could impact nociceptive threshold.

  7. Computational modeling of Adelta-fiber-mediated nociceptive detection of electrocutaneous stimulation

    NARCIS (Netherlands)

    Yang, H.; Meijer, Hil Gaétan Ellart; Doll, Robert; Buitenweg, Jan R.; van Gils, Stephanus A.

    2015-01-01

    Sensitization is an example of malfunctioning of the nociceptive pathway in either the peripheral or central nervous system. Using quantitative sensory testing, one can only infer sensitization, but not determine the defective subsystem. The states of the subsystems may be characterized using

  8. New Insights in Trigeminal Anatomy: A Double Orofacial Tract for Nociceptive Input

    NARCIS (Netherlands)

    Henssen, D.J.H.A.; Kurt, E.; Kozicz, L.T.; Dongen, R.T.M. van; Bartels, R.H.M.A.; Cappellen van Walsum, A.M. van

    2016-01-01

    Orofacial pain in patients relies on the anatomical pathways that conduct nociceptive information, originating from the periphery towards the trigeminal sensory nucleus complex (TSNC) and finally, to the thalami and the somatosensorical cortical regions. The anatomy and function of the so-called

  9. Nociceptive behavior and physiology of molluscs: animal welfare implications.

    Science.gov (United States)

    Crook, Robyn J; Walters, Edgar T

    2011-01-01

    Molluscs have proven to be invaluable models for basic neuroscience research, yielding fundamental insights into a range of biological processes involved in action potential generation, synaptic transmission, learning, memory, and, more recently, nociceptive biology. Evidence suggests that nociceptive processes in primary nociceptors are highly conserved across diverse taxa, making molluscs attractive models for biomedical studies of mechanisms that may contribute to pain in humans but also exposing them to procedures that might produce painlike sensations. We review the physiology of nociceptors and behavioral responses to noxious stimulation in several molluscan taxa, and discuss the possibility that nociception may result in painlike states in at least some molluscs that possess more complex nervous systems. Few studies have directly addressed possible emotionlike concomitants of nociceptive responses in molluscs. Because the definition of pain includes a subjective component that may be impossible to gauge in animals quite different from humans, firm conclusions about the possible existence of pain in molluscs may be unattainable. Evolutionary divergence and differences in lifestyle, physiology, and neuroanatomy suggest that painlike experiences in molluscs, if they exist, should differ from those in mammals. But reports indicate that some molluscs exhibit motivational states and cognitive capabilities that may be consistent with a capacity for states with functional parallels to pain. We therefore recommend that investigators attempt to minimize the potential for nociceptor activation and painlike sensations in experimental invertebrates by reducing the number of animals subjected to stressful manipulations and by administering appropriate anesthetic agents whenever practicable, welfare practices similar to those for vertebrate subjects.

  10. Association of activity changes in the primary sensory cortex with successful motor rehabilitation of the hand following stroke.

    Science.gov (United States)

    Laible, Mona; Grieshammer, Steven; Seidel, Gundula; Rijntjes, Michel; Weiller, Cornelius; Hamzei, Farsin

    2012-09-01

    Previous studies demonstrated a posterior shift of activation toward the primary sensory cortex (S1) following stroke; however, any relationship between this posterior shift and clinical outcome measures for the affected hand function were unclear. The authors investigated the possible role of S1 in motor recovery. Assuming that previous studies examined inhomogeneous groups of patients, the authors selected participants with chronic stroke who had moderate hand paresis, normal sensory examination and somatosensory-evoked potentials, and no lesion within the S1, thalamus, or brain stem. Constraint-induced movement therapy (CIMT) was used to train the impaired hand. To relate fMRI (functional MRI) activation changes from baseline to post-CIMT, a correlation analysis was performed with changes of the Wolf Motor Function Test (WMFT) as a test for the hand function. A close relationship was found between increases in hand function and peak changes in activation within the ipsilesional S1. With a better outcome, greater increases in activation within the S1 were evident (P < .03; r = 0.73). In selected patients, the sensory network influences training-induced motor gains. This predictive knowledge of plasticity when applying CIMT may suggest strategies to enhance the effect of therapy, such as the addition of electrical stimulation to enhance S1 excitability.

  11. Significant reduction in phantom limb pain after low-frequency repetitive transcranial magnetic stimulation to the primary sensory cortex.

    Science.gov (United States)

    Grammer, Geoffrey G; Williams-Joseph, Sonya; Cesar, Ashley; Adkinson, David K; Spevak, Christopher

    2015-01-01

    Phantom limb pain (PLP) is believed to be linked to the reorganization of the deafferented sensory cortex. We present a case of a patient with upper extremity PLP who was successfully treated with repetitive transcranial magnetic stimulation (rTMS). We treated an active duty service member who suffered an amputation of his right upper extremity after sustaining a blast injury in Afghanistan. He had 28 sessions of alternating sequences of rTMS to the left dorsolateral prefrontal cortex and primary sensory cortex of the left cerebral hemisphere. Pain intensity was assessed with the Visual Analogue Scale. We delivered 1 Hz stimulation to the sensory cortex corresponding to the area of amputation five times a week. After 4 sessions, the patient's pain decreased from a Visual Analogue Scale of 5 to 2. Left 10 Hz stimulation was added and after 28 sessions, the pain decreased from 2 to 1. Our findings support that rTMS was an effective modality for this patient in treating his PLP. The significance of 10 Hz stimulation is unknown because of the lack of an effect size and is possibly associated with a floor effect. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  12. Imaging tactile imagery: changes in brain connectivity support perceptual grounding of mental images in primary sensory cortices.

    Science.gov (United States)

    Schmidt, Timo Torsten; Ostwald, Dirk; Blankenburg, Felix

    2014-09-01

    Constructing mental representations in the absence of sensory stimulation is a fundamental ability of the human mind and has been investigated in numerous brain imaging studies. However, it is still unclear how brain areas facilitating mental construction processes interact with brain regions related to specific sensory representations. In this fMRI study subjects formed mental representations of tactile stimuli either from memory (imagery) or from presentation of actual corresponding vibrotactile patterned stimuli. First our analysis addressed the question of whether tactile imagery recruits primary somatosensory cortex (SI), because the activation of early perceptual areas is classically interpreted as perceptual grounding of the mental image. We also tested whether a network, referred to as 'core construction system', is involved in the generation of mental representations in the somatosensory domain. In fact, we observed imagery-induced activation of SI. We further found support for the notion of a modality independent construction network with the retrosplenial cortices and the precuneus as core components, which were supplemented with the left inferior frontal gyrus (IFG). Finally, psychophysiological interaction (PPI) analyses revealed robust imagery-modulated changes in the connectivity of these construction related areas, which suggests that they orchestrate the assembly of an abstract mental representation. Interestingly, we found increased coupling between prefrontal cortex (left IFG) and SI during mental imagery, indicating the augmentation of an abstract mental representation by reactivating perceptually grounded sensory details. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Participation of calbindin-D28K in nociception: results from calbindin-D28K knockout mice.

    Science.gov (United States)

    Egea, Javier; Malmierca, Eduardo; Rosa, Angelo O; del Barrio, Laura; Negredo, Pilar; Nuñez, Angel; López, Manuela G

    2012-03-01

    Since calbindin-D(28K) (CB-D(28K))-positive neurons have been related to nociceptive sensory processing, we have hypothesized that altered CB-D(28K) expression could alter nociceptive transmission. We have used +/+ and -/- knockout (KO) mice for CB-D(28k) in different behavioral models of pain and sensory responses at the caudalis subdivision of the trigeminal spinal nucleus in order to understand how this protein may participate in nociception. Behavioral responses to formalin injection in the hind paw or at the whisker pad or in the hind paw glutamate or i.p. acetic acid tests showed an increase of the pain threshold in CB-D(28k) -/- mice. KO mice showed a diminution of the inhibitory activity at Sp5C nucleus and a marked reduction of GABA content. Sp5C neurons from CB-D(28k) -/- mice did not change their spontaneous activity or tactile response after formalin injection in the whisker pad. In contrast, Sp5C neurons increased their spontaneous firing rate and tactile response after formalin injection in their receptive field in CB-D(28k) +/+ mice. The results of this study demonstrate the active role played by CB-D(28k) in nociceptive sensory transmission. The lack of this calcium binding protein, associated to deficient GABAergic neurotransmission, translates into dysfunction of sensory processing of nociceptive stimuli.

  14. CORTICAL RESPONSES TO SALIENT NOCICEPTIVE AND NOT NOCICEPTIVE STIMULI IN VEGETATIVE AND MINIMAL CONSCIOUS STATE

    Directory of Open Access Journals (Sweden)

    MARINA eDE TOMMASO

    2015-01-01

    Full Text Available Aims Questions regarding perception of pain in non-communicating patients and the management of pain continue to raise controversy both at a clinical and ethical level. The aim of this study was to examine the cortical response to salient multimodal visual, acoustic, somatosensory electric non nociceptive and nociceptive laser stimuli and their correlation with the clinical evaluation.Methods: Five Vegetative State (VS, 4 Minimally Conscious State (MCS patients and 11 age- and sex-matched controls were examined. Evoked responses were obtained by 64 scalp electrodes, while delivering auditory, visual, non-noxious electrical and noxious laser stimulation, which were randomly presented every 10 sec. Laser, somatosensory, auditory and visual evoked responses were identified as a negative-positive (N2-P2 vertex complex in the 500 msec post-stimulus time. We used Nociception Coma Scale-Revised (NCS-R and Coma Recovery Scale (CRS-R for clinical evaluation of pain perception and consciousness impairment.Results: The laser evoked potentials (LEPs were recognizable in all cases. Only one MCS patient showed a reliable cortical response to all the employed stimulus modalities. One VS patient did not present cortical responses to any other stimulus modality. In the remaining participants, auditory, visual and electrical related potentials were inconstantly present. Significant N2 and P2 latency prolongation occurred in both VS and MCS patients. The presence of a reliable cortical response to auditory, visual and electric stimuli was able to correctly classify VS and MCS patients with 90% accuracy. Laser P2 and N2 amplitudes were not correlated with the CRS-R and NCS-R scores, while auditory and electric related potentials amplitude were associated with the motor response to pain and consciousness recovery. Discussion: pain arousal may be a primary function also in vegetative state patients while the relevance of other stimulus modalities may indicate the

  15. Altered functional magnetic resonance imaging responses to nonpainful sensory stimulation in fibromyalgia patients.

    Science.gov (United States)

    López-Solà, Marina; Pujol, Jesus; Wager, Tor D; Garcia-Fontanals, Alba; Blanco-Hinojo, Laura; Garcia-Blanco, Susana; Poca-Dias, Violant; Harrison, Ben J; Contreras-Rodríguez, Oren; Monfort, Jordi; Garcia-Fructuoso, Ferran; Deus, Joan

    2014-11-01

    Fibromyalgia (FM) is a disorder characterized by chronic pain and enhanced responses to acute noxious events. However, the sensory systems affected in FM may extend beyond pain itself, as FM patients show reduced tolerance to non-nociceptive sensory stimulation. Characterizing the neural substrates of multisensory hypersensitivity in FM may thus provide important clues about the underlying pathophysiology of the disorder. The aim of this study was to characterize brain responses to non-nociceptive sensory stimulation in FM patients and their relationship to subjective sensory sensitivity and clinical pain severity. Functional magnetic resonance imaging (MRI) was used to assess brain response to auditory, visual, and tactile motor stimulation in 35 women with FM and 25 matched controls. Correlation and mediation analyses were performed to establish the relationship between brain responses and 3 types of outcomes: subjective hypersensitivity to daily sensory stimulation, spontaneous pain, and functional disability. Patients reported increased subjective sensitivity (increased unpleasantness) in response to multisensory stimulation in daily life. Functional MRI revealed that patients showed reduced task-evoked activation in primary/secondary visual and auditory areas and augmented responses in the insula and anterior lingual gyrus. Reduced responses in visual and auditory areas were correlated with subjective sensory hypersensitivity and clinical severity measures. FM patients showed strong attenuation of brain responses to nonpainful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. These abnormalities are associated with core FM symptoms, suggesting that they may be part of the pathophysiology of the disease. Copyright © 2014 by the American College of Rheumatology.

  16. Enhanced behavioral responses to cold stimuli following CGRPα sensory neuron ablation are dependent on TRPM8.

    Science.gov (United States)

    McCoy, Eric S; Zylka, Mark J

    2014-11-19

    Calcitonin gene-related peptide-α (CGRPα) is a classic marker of peptidergic nociceptive neurons and is expressed in myelinated and unmyelinated dorsal root ganglia (DRG) neurons. Recently, we found that ablation of Cgrpα-expressing sensory neurons reduced noxious heat sensitivity and enhanced sensitivity to cold stimuli in mice. These studies suggested that the enhanced cold responses were due to disinhibition of spinal neurons that receive inputs from cold-sensing/TRPM8 primary afferents; although a direct role for TRPM8 was not examined at the time. Here, we ablated Cgrpα-expressing sensory neurons in mice lacking functional TRPM8 and evaluated sensory responses to noxious heat, cold temperatures, and cold mimetics (acetone evaporative cooling and icilin). We also evaluated thermoregulation in these mice following an evaporative cold challenge. We found that ablation of Cgrpα-expressing sensory neurons in a Trpm8-/- background reduced sensitivity to noxious heat but did not enhance sensitivity to cold stimuli. Thermoregulation following the evaporative cold challenge was not affected by deletion of Trpm8 in control or Cgrpα-expressing sensory neuron-ablated mice. Our data indicate that the enhanced behavioral responses to cold stimuli in CGRPα sensory neuron-ablated mice are dependent on functional TRPM8, whereas the other sensory and thermoregulatory phenotypes caused by CGRPα sensory neuron ablation are independent of TRPM8.

  17. Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons

    Directory of Open Access Journals (Sweden)

    Andy A. Yanez

    2017-02-01

    Full Text Available Herpes simplex viruses (HSV1 and HSV2 establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs. Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG and sympathetic superior cervical ganglia (SCG after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons.

  18. The primary cilium is a sensory organelle that regulates growth control and tissue homeostasis

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Schneider, Linda; Clement, Christian Alexandro

    2006-01-01

    The growth-arrest specific receptor tyrosine kinase, PDGFRa, is up-regulated and targeted to the primary cilium during growth arrest in NIH3T3 cells and primary cultures of mouse embryonic fibroblasts (MEFs), and PDGF-AA-stimulated fibroblast cycle entrance is regulated through activation of cili...... fibroblasts might be to interact with growth factors and extracellular matrix to control cell survival and growth, and likely migration, and to continuously monitor the mechanical stress on the tissue through modulation of Ca2+-dependent signaling in the primary cilium....

  19. Biofortified cassava with pro-vitamin A is sensory and culturally acceptable for consumption by primary school children in Kenya.

    Science.gov (United States)

    Talsma, Elise F; Melse-Boonstra, Alida; de Kok, Brenda P H; Mbera, Gloria N K; Mwangi, Alice M; Brouwer, Inge D

    2013-01-01

    Biofortification of cassava with pro-vitamin A can potentially reduce vitamin A deficiency in low-income countries. However, little is known about consumer acceptance of this deep yellow variety of cassava compared to the commonly available white varieties. We aimed to determine the sensory and cultural acceptability of the consumption of pro-vitamin A rich cassava in order to identify key factors predicting the intention to consume pro-vitamin A rich cassava by families with school-aged children in Eastern Kenya. Sensory acceptability was measured by replicated discrimination tests and paired preference tests among 30 children (7-12 yr) and 30 caretakers (18-45 yr) in three primary schools. Cultural acceptability was assessed with a questionnaire based on the combined model of The Theory of Planned Behavior and The Health Belief Model in one primary school among 140 caretakers of children aged 6 to 12 years. Correlations and multivariate analyses were used to determine associations between summed scores for model constructs. Caretakers and children perceived a significant difference in taste between white and pro-vitamin A rich cassava. Both preferred pro-vitamin A rich cassava over white cassava because of its soft texture, sweet taste and attractive color. Knowledge about pro-vitamin A rich cassava and it's relation to health ('Knowledge' ((β = 0.29, P = behavior identity'. Worries related to bitter taste and color ('Perceived barriers 1' (β = -0.21, P = .02)), the belief of the caretaker about having control to prepare cassava ('Control beliefs' (β = 0.18, P = .02)) and activities like information sessions about pro-vitamin A rich cassava and recommendations from health workers ('Cues to action'(β = 0.51, P = consume pro-vitamin A rich cassava. Pro-vitamin A rich cassava is well accepted by school children in our study population.

  20. Alleviation of Trigeminal Nociception Using p75 Neurotrophin Receptor Targeted Lentiviral Interference Therapy.

    Science.gov (United States)

    O'Leary, Valerie B; O'Connell, Marie; Antyborzec, Inga; Ntziachristos, Vasilis; Oliver Dolly, J; Ovsepian, Saak V

    2018-02-09

    Acute and chronic trigeminal (TG) neuropathies are the cause of considerable distress, with limited treatments available at present. Nociceptive neurons enriched with the vanilloid type 1 receptor (VR1) partake in pain sensation and sensitization in the TG system. While VR1 blockers with anti-nociceptive potential are of substantial medical interest, their use remains limited due to poor selectivity and lack of cell-targeting capabilities. This study describes a methodology for the alleviation of nociception via targeted depletion of VR1 in TG sensory neurons in rats. In cultured TG ganglion neurons, VR1 expression was virtually abolished by lentiviral short hairpin RNA (LV-VR1). By decorating GFP encoding LV (LV-GFP) and LV-VR1 with IgG192 for targeting TG sensory neurons enriched with the p75 neurotrophin receptor (p75NTR), transduction of a reporter GFP and VR1 depletion was achieved after injection of targeted vectors into the whisker pad. In IgG192/LV-VR1-injected rats, the behavioral response to capsaicin exposure as well as Erk 1/2 phosphorylation and VR1 current activation by capsaicin were significantly reduced. This pioneering investigation, thus, provides a proof of principle for a means of attenuating TG nociception, revealing therapeutic potential.

  1. Subsecond Sensory Modulation of Serotonin Levels in a Primary Sensory Area and Its Relation to Ongoing Communication Behavior in a Weakly Electric Fish.

    Science.gov (United States)

    Fotowat, Haleh; Harvey-Girard, Erik; Cheer, Joseph F; Krahe, Rüdiger; Maler, Leonard

    2016-01-01

    Serotonergic neurons of the raphe nuclei of vertebrates project to most regions of the brain and are known to significantly affect sensory processing. The subsecond dynamics of sensory modulation of serotonin levels and its relation to behavior, however, remain unknown. We used fast-scan cyclic voltammetry to measure serotonin release in the electrosensory system of weakly electric fish, Apteronotus leptorhynchus . These fish use an electric organ to generate a quasi-sinusoidal electric field for communicating with conspecifics. In response to conspecific signals, they frequently produce signal modulations called chirps. We measured changes in serotonin concentration in the hindbrain electrosensory lobe (ELL) with a resolution of 0.1 s concurrently with chirping behavior evoked by mimics of conspecific electric signals. We show that serotonin release can occur phase locked to stimulus onset as well as spontaneously in the ELL region responsible for processing these signals. Intense auditory stimuli, on the other hand, do not modulate serotonin levels in this region, suggesting modality specificity. We found no significant correlation between serotonin release and chirp production on a trial-by-trial basis. However, on average, in the trials where the fish chirped, there was a reduction in serotonin release in response to stimuli mimicking similar-sized same-sex conspecifics. We hypothesize that the serotonergic system is part of an intricate sensory-motor loop: serotonin release in a sensory area is triggered by sensory input, giving rise to motor output, which can in turn affect serotonin release at the timescale of the ongoing sensory experience and in a context-dependent manner.

  2. [A case report of bilateral trigeminal sensory neuropathy as one of the initial manifestation of systemic scleroderma (the difficulties of early diagnosis of the primary disease)].

    Science.gov (United States)

    Grachev, Ju V; Anan'eva, L P; Tjurnikov, V M; Zaharova, A Ju

    2015-01-01

    The article describes the case of a patient with bilateral trigeminal sensory neuropathy (TSN), as a possible neurological manifestation of systemic scleroderma (SS). In this patient, intense non-paroxysmal facial pain caused by TSN, subjectively dominated over other manifestations of SS, including Raynaud's syndrome, for at least 1.5 years, thus hampering the diagnosis of the primary disease. In addition to pain, which was not relieved by analgesic medication, TSN was manifested by marked sensory deficit on the face (hypoesthesia / anesthesia) and bilateral sensory deficits in the oral cavity, including the anterior third of the tongue. TSN was also combined with disorders of taste perception. The assumption of rheumatic origin of TSN occurred during a primary neurological examination: a standard examination revealed generalized sensory polyneuropathy with bilateral involvement of the trigeminal nerve; the additional study identified no neurological signs of rheumatic diseases, including Raynaud's phenomenon. SS met all the criteria for the diagnosis (2013), high titers of nuclear ribonucleoprotein were determined as well. Thus, TSN as early and subjectively dominant manifestation of SS can complicate the diagnosis of primary rheumatic diseases. Therefore, in cases of distal sensory polyneuropathy with bilateral involvement of the trigeminal nerve, it is necessary to conduct an additional survey to identify the signs of possible rheumatic diseases: signs of vascular lesion (Raynaud's syndrome), lesions of skin, joints and muscles.

  3. Mechanisms of G Protein-Coupled Estrogen Receptor-Mediated Spinal Nociception

    DEFF Research Database (Denmark)

    Deliu, Elena; Brailoiu, G. Cristina; Arterburn, Jeffrey B.

    2012-01-01

    Human and animal studies suggest that estrogens are involved in the processing of nociceptive sensory information and analgesic responses in the central nervous system. Rapid pronociceptive estrogenic effects have been reported, some of which likely involve G protein-coupled estrogen receptor (GPER...... in spinal nociceptive processing. Intrathecal challenging of mice with the GPER agonist G-1 results in pain-related behaviors. GPER antagonism with G15 reduces the G-1-induced response. Electrophysiological recordings from superficial dorsal horn neurons indicate neuronal membrane depolarization with G-1...... application, which is G15 sensitive. In cultured spinal sensory neurons, G-1 increases intracellular calcium concentration and induces mitochondrial and cytosolic ROS accumulation. In the presence of G15, G-1 does not elicit the calcium and ROS responses, confirming specific GPER involvement in this process...

  4. Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

    Directory of Open Access Journals (Sweden)

    Wang Ying-Wei

    2010-01-01

    Full Text Available Abstract Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist and parecoxib (a selective cyclooxygenase-2 inhibitor on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity, while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect.

  5. Neonatal morphine enhances nociception and decreases analgesia in young rats.

    Science.gov (United States)

    Zhang, Guo Hua; Sweitzer, Sarah M

    2008-03-14

    The recognition of the impact of neonatal pain experience on subsequent sensory processing has led to the increased advocacy for the use of opioids for pain relief in infants. However, following long-term opioid exposure in intensive care units more than 48% of infants exhibited behaviors indicative of opioid abstinence syndrome, a developmentally equivalent set of behaviors to opioid withdrawal as seen in adults. Little is known about the long-term influence of repeated neonatal morphine exposure on nociception and analgesia. To investigate this, we examined mechanical and thermal nociception on postnatal days 11, 13, 15, 19, 24, 29, 39 and 48 following subcutaneous administration of morphine (3 mg/kg) once daily on postnatal days 1-9. The cumulative morphine dose-response was assessed on postnatal days 20 and 49, and stress-induced analgesia was assessed on postnatal days 29 and 49. Both basal mechanical and thermal nociception in neonatal, morphine-exposed rats were significantly lower than those in saline-exposed, handled-control rats and naive rats until P29. A rightward-shift of cumulative dose-response curves for morphine analgesia upon chronic neonatal morphine was observed both on P20 and P49. The swim stress-induced analgesia was significantly decreased in neonatal morphine-exposed rats on P29, but not on P49. These data indicate that morphine exposure equivalent to the third trimester of gestation produced prolonged pain hypersensitivity, decreased morphine antinociception, and decreased stress-induced analgesia. The present study illustrates the need to examine the long-term influence of prenatal morphine exposure on pain and analgesia in the human pediatric population.

  6. Cortical responses to salient nociceptive and not nociceptive stimuli in vegetative and minimal conscious state

    Science.gov (United States)

    de Tommaso, Marina; Navarro, Jorge; Lanzillotti, Crocifissa; Ricci, Katia; Buonocunto, Francesca; Livrea, Paolo; Lancioni, Giulio E.

    2015-01-01

    Aims: Questions regarding perception of pain in non-communicating patients and the management of pain continue to raise controversy both at a clinical and ethical level. The aim of this study was to examine the cortical response to salient visual, acoustic, somatosensory electric non-nociceptive and nociceptive laser stimuli and their correlation with the clinical evaluation. Methods: Five Vegetative State (VS), 4 Minimally Conscious State (MCS) patients and 11 age- and sex-matched controls were examined. Evoked responses were obtained by 64 scalp electrodes, while delivering auditory, visual, non-noxious electrical and noxious laser stimulation, which were randomly presented every 10 s. Laser, somatosensory, auditory and visual evoked responses were identified as a negative-positive (N2-P2) vertex complex in the 500 ms post-stimulus time. We used Nociception Coma Scale-Revised (NCS-R) and Coma Recovery Scale (CRS-R) for clinical evaluation of pain perception and consciousness impairment. Results: The laser evoked potentials (LEPs) were recognizable in all cases. Only one MCS patient showed a reliable cortical response to all the employed stimulus modalities. One VS patient did not present cortical responses to any other stimulus modality. In the remaining participants, auditory, visual and electrical related potentials were inconstantly present. Significant N2 and P2 latency prolongation occurred in both VS and MCS patients. The presence of a reliable cortical response to auditory, visual and electric stimuli was able to correctly classify VS and MCS patients with 90% accuracy. Laser P2 and N2 amplitudes were not correlated with the CRS-R and NCS-R scores, while auditory and electric related potentials amplitude were associated with the motor response to pain and consciousness recovery. Discussion: pain arousal may be a primary function also in vegetative state patients while the relevance of other stimulus modalities may indicate the degree of cognitive and motor

  7. Quantification of Nociceptive Escape Response in C.elegans

    Science.gov (United States)

    Leung, Kawai; Mohammadi, Aylia; Ryu, William; Nemenman, Ilya

    2013-03-01

    Animals cannot rank and communicate their pain consciously. Thus in pain studies on animal models, one must infer the pain level from high precision experimental characterization of behavior. This is not trivial since behaviors are very complex and multidimensional. Here we explore the feasibility of C.elegans as a model for pain transduction. The nematode has a robust neurally mediated noxious escape response, which we show to be partially decoupled from other sensory behaviors. We develop a nociceptive behavioral response assay that allows us to apply controlled levels of pain by locally heating worms with an IR laser. The worms' motions are captured by machine vision programming with high spatiotemporal resolution. The resulting behavioral quantification allows us to build a statistical model for inference of the experienced pain level from the behavioral response. Based on the measured nociceptive escape of over 400 worms, we conclude that none of the simple characteristics of the response are reliable indicators of the laser pulse strength. Nonetheless, a more reliable statistical inference of the pain stimulus level from the measured behavior is possible based on a complexity-controlled regression model that takes into account the entire worm behavioral output. This work was partially supported by NSF grant No. IOS/1208126 and HFSP grant No. RGY0084/2011.

  8. New tachykinin peptides and nociception

    Directory of Open Access Journals (Sweden)

    Toshikazu Nishimori

    2013-02-01

    Full Text Available Hemokinin-1 (HK-1 and endokinins are peptides predicted from a new mammalian tachykinin gene, TAC4. The amino acid sequences derived from rat/mouse HK-1 and human HK-1 are not identical; however, the effects induced by intracerebroventricular or intrathecal administration of HK-1 are attenuated by treatment with antagonists of neurokinin 1 (NK1 receptor, substance P (SP receptor, indicating that HK-1 is an agonist of the NK1 receptor. On the other hand, a growing body of evidence indicates that pharmacological characteristics of HK-1 and SP are always not identical, suggesting that the HK-1-preferred receptor may be involved in the effects of HK-1. Endokinins are derived from human TAC4 and consist of four endokinins, endokinin A (EKA, endokinin B (EKB, endokinin C (EKC and endokinin D (EKD. Effects induced by intrathecal administration of EKA/B (the common C-terminal decapeptide in EKA and EKB and SP were very similar, while the effects of SP and EKA/B were inhibited by EKC/D (the common C-terminal duodecapeptide in EKC and EKD. This inhibitory effect of EKC/D was derived from leucine at the carboxyl-terminus. These findings suggest that HK-1 and EKA/B have an agonistic effect, while EKC/D has an antagonistic effect on the NK1 receptor in nociceptive processing.

  9. Nociceptive responses to thermal and mechanical stimulations in awake pigs

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S.

    2013-01-01

    body sizes (30 and 60 kg) were exposed to thermal (CO(2) laser) and mechanical (pressure application measurement device) stimulations to the flank and the hind legs in a balanced order. The median response latency and the type of behavioural response were recorded. RESULTS: Small pigs exhibited...... animal studies in a large species require further examination. This manuscript describes the initial development of a porcine model of cutaneous nociception and focuses on interactions between the sensory modality, body size and the anatomical location of the stimulation site. METHODS: Pigs of different...... significantly lower pain thresholds (shorter latency to response) than large pigs to thermal and mechanical stimulations. Stimulations at the two anatomical locations elicited very distinct sets of behavioural responses, with different levels of sensitivity between the flank and the hind legs. Furthermore...

  10. Biofortified cassava with pro-vitamin A is sensory and culturally acceptable for consumption by primary school children in Kenya.

    Directory of Open Access Journals (Sweden)

    Elise F Talsma

    Full Text Available BACKGROUND: Biofortification of cassava with pro-vitamin A can potentially reduce vitamin A deficiency in low-income countries. However, little is known about consumer acceptance of this deep yellow variety of cassava compared to the commonly available white varieties. We aimed to determine the sensory and cultural acceptability of the consumption of pro-vitamin A rich cassava in order to identify key factors predicting the intention to consume pro-vitamin A rich cassava by families with school-aged children in Eastern Kenya. METHODS: Sensory acceptability was measured by replicated discrimination tests and paired preference tests among 30 children (7-12 yr and 30 caretakers (18-45 yr in three primary schools. Cultural acceptability was assessed with a questionnaire based on the combined model of The Theory of Planned Behavior and The Health Belief Model in one primary school among 140 caretakers of children aged 6 to 12 years. Correlations and multivariate analyses were used to determine associations between summed scores for model constructs. RESULTS: Caretakers and children perceived a significant difference in taste between white and pro-vitamin A rich cassava. Both preferred pro-vitamin A rich cassava over white cassava because of its soft texture, sweet taste and attractive color. Knowledge about pro-vitamin A rich cassava and it's relation to health ('Knowledge' ((β = 0.29, P = <.01 was a strong predictor of 'Health behavior identity'. Worries related to bitter taste and color ('Perceived barriers 1' (β = -0.21, P = .02, the belief of the caretaker about having control to prepare cassava ('Control beliefs' (β = 0.18, P = .02 and activities like information sessions about pro-vitamin A rich cassava and recommendations from health workers ('Cues to action'(β = 0.51, P = <.01 were the best predictors of intention to consume pro-vitamin A rich cassava. CONCLUSIONS: Pro-vitamin A rich cassava is well

  11. Quantitative sensory test for primary restless legs syndrome/Willis-Ekbom disease using the current perception threshold test.

    Science.gov (United States)

    Cho, Yong Won; Kang, Min-Sung; Kim, Keun Tae; Do, So Young; Lim, Jung-Geun; Lee, So Young; Motamedi, Gholam K

    2017-02-01

    Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sensorimotor neurological disorder, and it is especially aggravated at night. The purpose of this study was to investigate the diurnal sensory dysfunction in primary RLS/WED using the current perception threshold (CPT) test, compared to healthy controls. Thirty primary RLS/WED subjects and 30 healthy controls were enrolled. The severity of RLS/WED and sleep problems were evaluated in all subjects. Peripheral polyneuropathy was excluded through neurological examination and nerve conduction study. We used the Neurometer ® system for the CPT test and applied three different parameters (2000 Hz, 250 Hz, and 5 Hz), to stimulate both big toes. The CPT test was performed twice, once during the asymptomatic daytime period and again in the evening, when the patients were symptomatic. The mean ages of the RLS/WED group and controls were 50.5 ± 11.7 (22; 73.3% female), and 46.3 ± 11.4 (24; 80.0% female), respectively. The mean international RLS/WED study group severity scale score was 28.6 ± 4.25. There was no significant difference in the current perception thresholds between the RLS/WED patients and controls in daytime. However, the RLS/WED patients had lower mean CPT measurements for all three stimulation protocols in the evening (2000 Hz: 393.2 ± 93.7 vs 430.8 ± 79.6, 250 Hz: 172.0 ± 48.4 vs 198.5 ± 38.2, and 5 Hz: 98.0 ± 34.1 vs 124.6 ± 31.3), while the healthy controls showed no difference. RLS patients showed a lower CPT in the evening. The diurnal variation of hyperalgesia in RLS/WED patients indicates a central (circadian) sensory processing disturbance rather than a peripheral disturbance. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Neurotrophin selectivity in organizing topographic regeneration of nociceptive afferents.

    Science.gov (United States)

    Kelamangalath, Lakshmi; Tang, Xiaoqing; Bezik, Kathleen; Sterling, Noelle; Son, Young-Jin; Smith, George M

    2015-09-01

    Neurotrophins represent some of the best candidates to enhance regeneration. In the current study, we investigated the effects of artemin, a member of the glial derived neurotrophic factor (GDNF) family, on sensory axon regeneration following a lumbar dorsal root injury and compared these effects with that observed after either NGF or GDNF expression in the rat spinal cord. Unlike previously published data, artemin failed to induce regeneration of large-diameter myelinated sensory afferents when expressed within either the spinal cord or DRG. However, artemin or NGF induced regeneration of calcitonin gene related peptide positive (CGRP(+)) axons only when expressed within the spinal cord. Accordingly, artemin or NGF enhanced recovery of only nociceptive behavior and showed a cFos distribution similar to the topography of regenerating axons. Artemin and GDNF signaling requires binding to different co-receptors (GFRα3 or GFRα1, respectively) prior to binding to the signaling receptor, cRet. Approximately 70% of DRG neurons express cRet, but only 35% express either co-receptor. To enhance artemin-induced regeneration, we co-expressed artemin with either GFRα3 or GDNF. Co-expression of artemin and GFRα3 only slightly enhanced regeneration of IB4(+) non-peptidergic nociceptive axons, but not myelinated axons. Interestingly, this co-expression also disrupted the ability of artemin to produce topographic targeting and lead to significant increases in cFos immunoreactivity within the deep dorsal laminae. This study failed to demonstrate artemin-induced regeneration of myelinated axons, even with co-expression of GFRα3, which only promoted mistargeted regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Gestational Valproate Alters BOLD Activation in Response to Complex Social and Primary Sensory Stimuli

    Science.gov (United States)

    Felix-Ortiz, Ada C.; Febo, Marcelo

    2012-01-01

    Valproic acid (VPA) has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD) exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2), animals were examined for physical and behavior abnormalities. Functional MRI studies were carried out after PND60. VPA and control animals were given vehicle or a central infusion of a V1a antagonist 90 minutes before imaging. During imaging sessions, rats were presented with a juvenile test male followed by a primary visual stimulus (2 Hz pulsed light) to examine the effects of prenatal VPA on neural processing. VPA rats showed greater increases in BOLD signal response to the social stimulus compared to controls in the temporal cortex, thalamus, midbrain and the hypothalamus. Blocking the V1a receptor reduced the BOLD response in VPA animals only. Neural responses to the visual stimulus, however, were lower in VPA animals. Blockade with the V1a antagonist did not revert this latter effect. Our data suggest that prenatal VPA affects the processing of social stimuli and perhaps social memory, partly through a mechanism that may involve vasopressin V1a neurotransmission. PMID:22615973

  14. Gestational valproate alters BOLD activation in response to complex social and primary sensory stimuli.

    Directory of Open Access Journals (Sweden)

    Ada C Felix-Ortiz

    Full Text Available Valproic acid (VPA has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2, animals were examined for physical and behavior abnormalities. Functional MRI studies were carried out after PND60. VPA and control animals were given vehicle or a central infusion of a V(1a antagonist 90 minutes before imaging. During imaging sessions, rats were presented with a juvenile test male followed by a primary visual stimulus (2 Hz pulsed light to examine the effects of prenatal VPA on neural processing. VPA rats showed greater increases in BOLD signal response to the social stimulus compared to controls in the temporal cortex, thalamus, midbrain and the hypothalamus. Blocking the V(1a receptor reduced the BOLD response in VPA animals only. Neural responses to the visual stimulus, however, were lower in VPA animals. Blockade with the V(1a antagonist did not revert this latter effect. Our data suggest that prenatal VPA affects the processing of social stimuli and perhaps social memory, partly through a mechanism that may involve vasopressin V(1a neurotransmission.

  15. An unavoidable modulation? Sensory attention and human primary motor cortex excitability.

    Science.gov (United States)

    Ruge, Diane; Muggleton, Neil; Hoad, Damon; Caronni, Antonio; Rothwell, John C

    2014-09-01

    The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task-specific dystonia, widely lack laboratory-based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation-induced GABA-related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use-dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Sensory stimulation for lowering intraocular pressure, improving blood flow to the optic nerve and neuroprotection in primary open-angle glaucoma.

    Science.gov (United States)

    Rom, Edith

    2013-12-01

    Primary open-angle glaucoma is a group of optic neuropathies that can lead to irreversible blindness. Sensory stimulation in the form of acupuncture or ear acupressure may contribute to protecting patients from blindness when used as a complementary method to orthodox treatment in the form of drops, laser or surgery. The objective of this article is to provide a narrative overview of the available literature up to July 2012. It summarises reported evidence on the potential beneficial effects of sensory stimulation for glaucoma. Sensory stimulation appears to significantly enhance the pressure-lowering effect of orthodox treatments. Studies suggest that it may also improve blood flow to the eye and optic nerve head. Furthermore, it may play a role in neuroprotection through regulating nerve growth factor and brain-derived neurotrophic factor and their receptors, thereby encouraging the survival pathway in contrast to the pathway to apoptosis. Blood flow and neuroprotection are areas that are not directly influenced by orthodox treatment modalities. Numerous different treatment protocols were used to investigate the effect of sensory stimulation on intraocular pressure, blood flow or neuroprotection of the retina and optic nerve in the animal model and human pilot studies. Objective outcomes were reported to have been evaluated with Goldmann tonometry, Doppler ultrasound techniques and electrophysiology (pattern electroretinography, visually evoked potentials), and supported with histological studies in the animal model. Taken together, reported evidence from these studies strongly suggests that sensory stimulation is worthy of further research.

  17. Tracking of nociceptive thresholds using adaptive psychophysical methods

    NARCIS (Netherlands)

    Doll, Robert; Buitenweg, Jan R.; Meijer, Hil Gaétan Ellart; Veltink, Petrus H.

    Psychophysical thresholds reflect the state of the underlying nociceptive mechanisms. For example, noxious events can activate endogenous analgesic mechanisms that increase the nociceptive threshold. Therefore, tracking thresholds over time facilitates the investigation of the dynamics of these

  18. Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats.

    Science.gov (United States)

    Chen, Yu-Wen; Chiu, Chong-Chi; Liu, Kuo-Sheng; Hung, Ching-Hsia; Wang, Jhi-Joung

    2015-12-01

    Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  19. Cognitive aspects of nociception and pain: bridging neurophysiology with cognitive psychology.

    Science.gov (United States)

    Legrain, V; Mancini, F; Sambo, C F; Torta, D M; Ronga, I; Valentini, E

    2012-10-01

    The event-related brain potentials (ERPs) elicited by nociceptive stimuli are largely influenced by vigilance, emotion, alertness, and attention. Studies that specifically investigated the effects of cognition on nociceptive ERPs support the idea that most of these ERP components can be regarded as the neurophysiological indexes of the processes underlying detection and orientation of attention toward the eliciting stimulus. Such detection is determined both by the salience of the stimulus that makes it pop out from the environmental context (bottom-up capture of attention) and by its relevance according to the subject's goals and motivation (top-down attentional control). The fact that nociceptive ERPs are largely influenced by information from other sensory modalities such as vision and proprioception, as well as from motor preparation, suggests that these ERPs reflect a cortical system involved in the detection of potentially meaningful stimuli for the body, with the purpose to respond adequately to potential threats. In such a theoretical framework, pain is seen as an epiphenomenon of warning processes, encoded in multimodal and multiframe representations of the body, well suited to guide defensive actions. The findings here reviewed highlight that the ERPs elicited by selective activation of nociceptors may reflect an attentional gain apt to bridge a coherent perception of salient sensory events with action selection processes. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  20. Primary sensory neurons regulate Toll-like receptor-4-dependent activity of glial cells in dorsal root ganglia.

    Science.gov (United States)

    Tse, K-H; Chow, K B S; Leung, W K; Wong, Y H; Wise, H

    2014-10-24

    Toll-like receptor-4 (TLR4) has been identified in primary sensory neurons, both in vivo and in vitro, but is reportedly absent from satellite glial cells (SGCs). Herein we reveal that, in rat dorsal root ganglia (DRG), SGCs do express TLR4 but this expression is inhibited by direct contact with neurons. Thus, TLR4 mRNA and protein is strongly up-regulated in isolated DRG glial cells in the absence of neurons. Lipopolysaccharide (LPS) increased cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNFα) mRNA expression with greater efficacy in DRG glial cell cultures than in mixed DRG cell cultures containing TLR4-positive neurons. Using an insert co-culture system, we have shown that neuronal inhibition of glial cell TLR4 is likely to be dependent on cell-cell contact rather than diffusible factors from neurons. LPS stimulated prostaglandin E2 (PGE2) production from DRG glial cells in a TLR4- and COX-2-dependent manner. In addition, exogenous PGE2 potentiated LPS-stimulated COX-2 mRNA while inhibiting TNFα mRNA expression by DRG cells, suggestive of a complex regulatory system to control inflammation within the DRG. In addition to LPS, conditioned medium from heat-shocked DRG neurons also increased COX-2 mRNA expression in DRG glial cells in a partially TLR4-dependent manner. We therefore hypothesize that neuronal suppression of glial TLR4 activity is a protective mechanism to prevent uncontrolled inflammation within the DRG. Under conditions where DRG neuronal viability is compromised, DRG glial cells become responsive to PAMPs (pathogen-associated molecular patterns) and DAMPs (danger-associated molecular patterns) and generate a range of classical inflammatory responses. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Characteristics of sensori-motor interaction in the primary and secondary somatosensory cortices in humans: a magnetoencephalography study.

    Science.gov (United States)

    Wasaka, T; Kida, T; Nakata, H; Akatsuka, K; Kakigi, R

    2007-10-26

    We studied sensori-motor interaction in the primary (SI) and secondary somatosensory cortex (SII) using magnetoencephalography. Since SII in both hemispheres was activated following unilateral stimulation, we analyzed SIIc (contralateral to stimulation) as well as SIIi (ipsilateral to stimulation). Four tasks were performed in human subjects in which a voluntary thumb movement of the left or right hand was combined with electrical stimulation applied to the index finger of the left or right hand: L(M)-L(S) (movement of the left thumb triggered stimulation to the left finger), L(M)-R(S) (movement of the left thumb triggered electrical stimulation to the right finger), R(M)-R(S) (movement of the right thumb triggered electrical stimulation to the right finger), and R(M)-L(S) (movement of the right thumb triggered electrical stimulation to the left finger). Stimulation to the index finger only (S condition) was also recorded. In SI, the amplitude of N20m and P35m was significantly attenuated in the R(M)-R(S) and L(M)-L(S) tasks compared with the S condition, but that for other tasks showed no change, corresponding to a conventional gating phenomenon. In SII, the R(M)-L(S) task significantly enhanced the amplitude of SIIc but reduced that of SIIi compared with the S condition. The L(M)-L(S) and R(M)-R(S) tasks caused a significant enhancement only in SIIi. The L(M)-R(S) task enhanced the amplitude only in SIIc. The laterality index showed that SII modulation with voluntary movement was more dominant in the hemisphere ipsilateral to movement but was not affected by the side of stimulation. These results provided the characteristics of activities in somatosensory cortices, a simple inhibition in SI but complicated changes in SII depending on the side of movement and stimulation, which may indicate the higher cognitive processing in SII.

  2. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

    OpenAIRE

    Birol Muhammet Er; İsmail Serhat Kocamanoğlu; Ayhan Bozkurt; Sırrı Bilge; Erhan Çetin Çetinoğlu

    2016-01-01

    Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. ...

  3. Kv4 channels underlie the subthreshold-operating A-type K+-current in nociceptive dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Thanawath R Na Phuket

    2009-07-01

    Full Text Available The dorsal root ganglion (DRG contains heterogeneous populations of sensory neurons including primary nociceptive neurons and C-fibers implicated in pain signaling.  Recent studies have demonstrated DRG hyperexcitability associated with downregulation of A-type K+ channels; however, the molecular correlate of the corresponding A-type K+ current (IA has remained hypothetical.  Kv4 channels may underlie the IA in DRG neurons.  We combined electrophysiology, molecular biology (whole-tissue and single-cell RT-PCR and immunohistochemistry to investigate the molecular basis of the IA in acutely dissociated DRG neurons from 7-8 day-old rats.  Whole-cell recordings demonstrate a robust tetraethylammonium-resistant (20 mM and 4-aminopyridine-sensitive (5 mM IA.  Matching Kv4 channel properties, activation and inactivation of this IA occur in the subthreshold range of membrane potentials and the rate of recovery from inactivation is rapid and voltage-dependent.  Among Kv4 transcripts, the DRG expresses significant levels of Kv4.1 and Kv4.3 mRNAs.  Also, single small-medium diameter DRG neurons (~30 mm exhibit correlated frequent expression of mRNAs encoding Kv4.1 and Nav1.8, a known nociceptor marker.  In contrast, the expressions of Kv1.4 and Kv4.2 mRNAs at the whole-tissue and single-cell levels are relatively low and infrequent.  Kv4 protein expression in nociceptive DRG neurons was confirmed by immunohistochemistry, which demonstrates colocalization of Kv4.3 and Nav1.8, and negligible expression of Kv4.2.  Furthermore, specific dominant-negative suppression and overexpression strategies confirmed the contribution of Kv4 channels to IA in DRG neurons.  Contrasting the expression patterns of Kv4 channels in the central and peripheral nervous systems, we discuss possible functional roles of these channels in primary sensory neurons.

  4. Characterisation of a behavioural protocol for the assessment of nociception in normal and inflamed porcine skin

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo

    2012-01-01

    of behavioural cutaneous nociception was performed via the assessment of differences in cutaneous pain sensitivity as determined by the body size of the animals, the anatomical locations of interest and the sensory modalities involved. Consequently, this new protocol allowed measuring the change in cutaneous...... investigation were associated to specific behavioural responses unique to the two anatomical locations of interest and clearly discernible from spontaneous movements. Based on this approach, the behavioural assays of nociception in pigs are considered reliable assessment tools to investigate porcine cutaneous...... to ultraviolet-B irradiation and, although less consistently, to capsaicin. Although the results on thermal and mechanical hyperalgesia were affected by high levels of variability, they clearly support the value of the porcine model in future investigations of the mechanisms behind the two inflammatory processes...

  5. Differentiating nociceptive mechanisms using electrocutaneous detection thresholds

    NARCIS (Netherlands)

    Doll, Robert; Veltink, Petrus H.; Buitenweg, Jan R.

    Chronic pain after surgery is a frequent problem and difficult to treat. Persisting and chronic pain can be the result of the malfunctioning of nociceptive mechanisms; both ascending and descending pathways can, individually, attribute to chronic pain development. However, existing methodology does

  6. Information theoretic analysis of dynamical encoding by four identified primary sensory interneurons in the cricket cercal system.

    Science.gov (United States)

    Theunissen, F; Roddey, J C; Stufflebeam, S; Clague, H; Miller, J P

    1996-04-01

    1. The stimulus/response properties of four identified primary sensory interneurons in the cricket cercal sensory system were studied using electrophysiological techniques. These four cells are thought to represent a functionally discrete subunit of the cercal system: they are the only cells that encode information about stimulus direction to higher centers for low intensity stimuli. Previous studies characterized the quantity of information encoded by these cells about the direction of air currents in the horizontal plane. In the experiments reported here, we characterized the quantity and quality of information encoded in the cells' elicited responses about the dynamics of air current waveforms presented at their optimal stimulus directions. The total sample set included 22 cells. 2. This characterization was achieved by determining the cells' frequency sensitivities and encoding accuracy using the methods of stochastic systems analysis and information theory. The specific approach used for the analysis was the "stimulus reconstruction" technique in which a functional expansion was derived to transform the observed spike train responses into the optimal estimate (i.e., "reconstruction") of the actual stimulus. A novel derivation of the crucial equations is presented. The reverse approach is compared with the more traditional forward analysis, in which an expansion is derived that transforms the stimulus to a prediction of the spike train response. Important aspects of the application of these analytical approaches are considered. 3. All four interneurons were found to have identical frequency tuning, as assessed by the accuracy with which different frequency components of stimulus waveforms could be reconstructed with a linear expansion. The interneurons encoded significant information about stimulus frequencies between 5 and 80 Hz, which peak sensitivities at approximately 15 Hz. 4. All four interneurons were found to have identical stimulus/response latencies

  7. Mechanical sensibility of nociceptive and non-nociceptive fast-conducting afferents is modulated by skin temperature.

    Science.gov (United States)

    Boada, M Danilo; Eisenach, James C; Ririe, Douglas G

    2016-01-01

    The ability to distinguish mechanical from thermal input is a critical component of peripheral somatosensory function. Polymodal C fibers respond to both stimuli. However, mechanosensitive, modality-specific fast-conducting tactile and nociceptor afferents theoretically carry information only about mechanical forces independent of the thermal environment. We hypothesize that the thermal environment can nonetheless modulate mechanical force sensibility in fibers that do not respond directly to change in temperature. To study this, fast-conducting mechanosensitive peripheral sensory fibers in male Sprague-Dawley rats were accessed at the soma in the dorsal root ganglia from T11 or L4/L5. Neuronal identification was performed using receptive field characteristics and passive and active electrical properties. Neurons responded to mechanical stimuli but failed to generate action potentials in response to changes in temperature alone, except for the tactile mechanical and cold sensitive neurons. Heat and cold ramps were utilized to determine temperature-induced modulation of response to mechanical stimuli. Mechanically evoked electrical activity in non-nociceptive, low-threshold mechanoreceptors (tactile afferents) decreased in response to changes in temperature while mechanically induced activity was increased in nociceptive, fast-conducting, high-threshold mechanoreceptors in response to the same changes in temperature. These data suggest that mechanical activation does not occur in isolation but rather that temperature changes appear to alter mechanical afferent activity and input to the central nervous system in a dynamic fashion. Further studies to understand the psychophysiological implications of thermal modulation of fast-conducting mechanical input to the spinal cord will provide greater insight into the implications of these findings. Copyright © 2016 the American Physiological Society.

  8. Nociceptor-Enriched Genes Required for Normal Thermal Nociception

    Directory of Open Access Journals (Sweden)

    Ken Honjo

    2016-07-01

    Full Text Available Here, we describe a targeted reverse genetic screen for thermal nociception genes in Drosophila larvae. Using laser capture microdissection and microarray analyses of nociceptive and non-nociceptive neurons, we identified 275 nociceptor-enriched genes. We then tested the function of the enriched genes with nociceptor-specific RNAi and thermal nociception assays. Tissue-specific RNAi targeted against 14 genes caused insensitive thermal nociception while targeting of 22 genes caused hypersensitive thermal nociception. Previously uncategorized genes were named for heat resistance (i.e., boilerman, fire dancer, oven mitt, trivet, thawb, and bunker gear or heat sensitivity (firelighter, black match, eucalyptus, primacord, jet fuel, detonator, gasoline, smoke alarm, and jetboil. Insensitive nociception phenotypes were often associated with severely reduced branching of nociceptor neurites and hyperbranched dendrites were seen in two of the hypersensitive cases. Many genes that we identified are conserved in mammals.

  9. Facilitation of tactile working memory by top-down suppression from prefrontal to primary somatosensory cortex during sensory interference.

    Science.gov (United States)

    Savolainen, Petri; Carlson, Synnöve; Boldt, Robert; Neuvonen, Tuomas; Hannula, Henri; Hiltunen, Jaana; Salonen, Oili; Ma, Yuan-Ye; Pertovaara, Antti

    2011-06-01

    Tactile working memory (WM) is improved by increasing top-down suppression of interfering sensory processing in S1 via a link from the middle frontal gyrus (MFG) to S1. Here we studied in healthy subjects whether the efficacy of top-down suppression varies with submodality of sensory interference. Navigated stimulation of the MFG-S1 link significantly improved tactile WM performance when accompanied by tactile but not visual interference of memory maintenance. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms.

    Science.gov (United States)

    Kosek, E; Ekholm, J; Hansson, P

    1996-12-01

    This study, addressing etiologic and pathogenic aspects of fibromyalgia (FM), aimed at examining whether sensory abnormalities in FM patients are generalized or confined to areas with spontaneous pain. Ten female FM patients and 10 healthy, age-matched females participated. The patients were asked to rate the intensity of ongoing pain using a visual analogue scale (VAS) at the site of maximal pain, the homologous contralateral site and two homologous sites with no or minimal pain. Quantitative sensory testing was performed for assessment of perception thresholds in these four sites. Von Frey filaments were used to test low-threshold mechanoreceptive function. Pressure pain sensitivity was assessed with a pressure algometer and thermal sensitivity with a Thermotest. In addition the stimulus-response curve of pain intensity as a function of graded nociceptive heat stimulation was studied at the site of maximal pain and at the homologous contralateral site. FM patients had increased sensitivity to non-painful warmth (P painful sites and a tendency to increased sensitivity to non-painful cold (P pain (P pain (P pain (P tested sites. The stimulus-response curve was parallely shifted to the left of the curve obtained from controls (P pain (P pain compared to the homologous contralateral site. These findings could be explained in terms of sensitization of primary afferent pathways or as a dysfunction of endogenous systems modulating afferent activity. However, the generalized increase in sensitivity found in FM patients was unrelated to spontaneous pain and thus most likely due to a central nervous system (CNS) dysfunction. The additional hyperphenomena related to spontaneous pain are probably dependent on disinhibition/facilitation of nociceptive afferent input from normal (or ischemic) muscles.

  11. Behavioral changes in brain-injured critical care adults with different levels of consciousness during nociceptive stimulation: an observational study.

    Science.gov (United States)

    Roulin, Marie-José; Ramelet, Anne-Sylvie

    2014-08-01

    The primary objective of this study was to describe the frequency of behaviors observed during rest, a non-nociceptive procedure, and a nociceptive procedure in brain-injured intensive care unit (ICU) patients with different levels of consciousness (LOC). Second, it examined the inter-rater reliability and discriminant and concurrent validity of the behavioral checklist used. The non-nociceptive procedure involved calling the patient and shaking his/her shoulder. The nociceptive procedure involved turning the patient. The frequency of behaviors was recorded using a behavioral checklist. Patients with absence of movement, or stereotyped flexion or extension responses to a nociceptive stimulus displayed more behaviors during turning (median 5.5, range 0-14) than patients with localized responses (median 4, range 0-10) or able to self-report their pain (median 4, range 0-10). Face flushing, clenched teeth, clenched fist, and tremor were more frequent in patients with absence of movement, or stereotyped responses to a nociceptive stimulus. The reliability of the checklist was supported by a high intra-class correlation coefficient (0.77-0.92), and the internal consistency was acceptable in all three groups (KR 20, 0.71-0.85). Discriminant validity was supported as significantly more behaviors were observed during nociceptive stimulation than at rest. Concurrent validity was confirmed as checklist scores were correlated to the patients' self-reports of pain (r s = 0.53; 95 % CI 0.21-0.75). Brain-injured patients reacted significantly more during a nociceptive stimulus and the number of observed behaviors was higher in patients with a stereotyped response.

  12. Nociceptive Effects of Locally Treated Metoprolol

    Directory of Open Access Journals (Sweden)

    Nursima Cukadar

    2015-06-01

    Results: Metoprolol, an antagonist, significantly decreased the thermal latency and mechanical thresholds with dose and time dependent manner. However, dobutamine, an agonist, enhanced the latency and thresholds dose and time dependent. Conclusions: This results suggest that in contrast to dobutamine, locally treated metoprolol may cause hyperalgesic and allodynic actions. In addition, our results can demonstrate that peripheral beta-adrenergic receptors can play important roles in nociceptive process. [Cukurova Med J 2015; 40(2.000: 258-266

  13. Cellular mechanisms of nociception in the frog

    Czech Academy of Sciences Publication Activity Database

    Kuffler, D. P.; Lyfenko, Alla; Vyklický st., Ladislav; Vlachová, Viktorie

    2002-01-01

    Roč. 88, č. 4 (2002), s. 1843-1850 ISSN 0022-3077 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Grant - others:NATO(XX) Grant 977062 Institutional research plan: CEZ:AV0Z5011922 Keywords : cellular mechanisms of nociception * frog Subject RIV: FH - Neurology Impact factor: 3.743, year: 2002

  14. Differences in sensory processing between chronic cervical zygapophysial joint pain patients with and without cervicogenic headache

    NARCIS (Netherlands)

    Chua Hai Liang, N.; Suijlekom, H.A. van; Vissers, K.C.P.; Arendt-Nielsen, L.; Wilder-Smith, O.H.G.

    2011-01-01

    BACKGROUND: It is not known why some patients with underlying chronic nociceptive sources in the neck develop cervicogenic headache (CEH) and why others do not. This quantitative sensory testing (QST) study systematically explores the differences in sensory pain processing in 17 CEH patients with

  15. Primary Sjögren’s Syndrome with Sensory Ganglionopathy and Painful Legs and Moving Toes Syndrome

    Directory of Open Access Journals (Sweden)

    Mehmet Uğur Çevik

    2014-06-01

    Full Text Available Sjogren’s syndrome is characterized by the sicca syndrome, with dryness of the mouth (xerostomia and the eyes (xerophthalmia. Sjogren's syndrome is the only connective tissue disease that has been associated with sensory neuronopathy. The syndrome of painful legs and moving toes consisting of pain in the lower limbs with spontaneous movements of the toes or feet. The association between Sjogren’s syndrome and painful legs and moving toes syndrome is a rare condition

  16. Role of the spinal Na+/H+ exchanger in formalin-induced nociception.

    Science.gov (United States)

    Castañeda-Corral, Gabriela; Rocha-González, Héctor I; Godínez-Chaparro, Beatriz; Jiménez-Andrade, Juan Miguel; Granados-Soto, Vinicio

    2011-08-21

    This study assessed the role of the Na(+)/H(+) exchanger (NHE) in the formalin-induced nociception as well as the expression of the NHE isoform 1 (NHE1) in the rat spinal cord by using immunohistochemistry. Rats received a 50μl injection of diluted formalin (0.5%). Nociceptive behavior was quantified as the number of flinches of the injected paw. Intrathecal administration of the partially selective NHE1 inhibitors DMA, EIPA (0.3-30μM/rat) and the selective NHE1 inhibitor zoniporide (0.03-3μM/rat) significantly increased formalin-induced flinching behavior in a dose-dependent manner during both phases of the test. Immunohistochemical analysis of the rat lumbar spinal cord showed that NHE1 was mainly expressed in the lamina I of the dorsal horn of the spinal cord. Double immunofluorescence staining showed co-localization of NHE1 with the peptide-rich sensory nerve fiber markers, substance P and calcitonin gene-related peptide, but not with markers of neuronal cell bodies (NeuN), microglia (OX-42) or astroglia (GFAP). Collectively, these pharmacological and anatomical results suggest that spinal NHE1 plays a role in formalin-induced nociception acting as a protective protein extruding H(+). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

    Science.gov (United States)

    Bouwense, Stefan A W; Buscher, Hessel C J L; van Goor, Harry; Wilder-Smith, Oliver H G

    2011-01-01

    Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain control affects supraspinal and spinal sensitization. Seventeen CPP were studied preoperatively and 6 weeks after BTS. Pressure pain thresholds (PPT) were measured in clavicle and pancreatic dermatomes reflecting supraspinal and spinal central sensitization, respectively. Patients with increased PPT after BTS (hypoalgesic) were compared to those without (hyperalgesic) and PPT vs. pain numeric rating scale (NRS) changes compared. After BTS, ten patients showed C5 PPT increases (hypoalgesic; median change 87 kPa), 7 patients had unaltered/lower PPT (hyperalgesic; -135 kPa). Preoperative pain NRS was similar between groups (4 vs. 5, P = 0.2). After BTS hypoalgesic group NRS was lower (1 vs. 6; P = 0.008) and NRS change greater (-2 vs. 0; P = 0.005). Whole group NRS and C5 PPT change correlated significantly and negatively (r = 0.53; P central sensitization after BTS was associated with significantly reduced pain scores in a majority of CPP. A subgroup showed no reductions in supraspinal central sensitization after BTS, coupled to no significant pain NRS reduction. Our results suggest that a subgroup of CPP has altered pain processing that may be independent of ongoing peripheral nociceptive input, resulting in persisting pain despite BTS. If confirmed, these results indicate the importance of sensory testing for indications and management of pain treatments.

  18. Sensory input to the central nervous system from the lungs and airways: A prominent role for purinergic signalling via P2X2/3 receptors.

    Science.gov (United States)

    Adriaensen, Dirk; Brouns, Inge; Timmermans, Jean-Pierre

    2015-09-01

    Specific subpopulations of lung-related primary afferent neurons in dorsal root and vagal sensory ganglia have been reported to express P2X2 and P2X3 receptors both in the neuronal cell bodies and in their peripheral terminals. The afferent innervation of airways and lungs is organised as sensory receptor structures, of which at least seven types with a vagal origin and two with a spinal origin have been reported. In view of the recently suggested therapeutic promise of ATP antagonism - specifically at P2X3 receptor expressing nociceptive fibres - in respiratory disorders, the present work focusses on four distinct populations of pulmonary sensory receptors that have so far been reported to express P2X2/3 receptors. Three of them originate from myelinated nerve fibres that display similar mechanosensor-like morphological and neurochemical characteristics. Two of the latter concern vagal nodose sensory fibres, either related to pulmonary neuroepithelial bodies (NEBs), or giving rise to smooth muscle-associated airway receptors (SMARs); the third gives rise to visceral pleura receptors (VPRs) and most likely arises from dorsal root ganglia. The fourth population concerns C-fibre receptors (CFRs) that also derive from neuronal cell bodies located in vagal nodose ganglia. Although the majority of the airway- and lung-related sensory receptors that express P2X2/3 receptors apparently do not belong to accepted nociceptive populations, these data definitely point out that ATP may be an important player in the physiological transduction of different lung-related afferent signals from the periphery to the CNS. The observed variety within the populations of pulmonary sensory receptors that express P2X2/3 receptors argues for a critical and careful interpretation of the functional data. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Factors affecting mechanical (nociceptive) thresholds in piglets.

    Science.gov (United States)

    Janczak, Andrew M; Ranheim, Birgit; Fosse, Torunn K; Hild, Sophie; Nordgreen, Janicke; Moe, Randi O; Zanella, Adroaldo J

    2012-11-01

    To evaluate the stability and repeatability of measures of mechanical (nociceptive) thresholds in piglets and to examine potentially confounding factors when using a hand held algometer. Descriptive, prospective cohort. Forty-four piglets from four litters, weighing 4.6 ± 1.0 kg (mean ± SD) at 2 weeks of age. Mechanical thresholds were measured twice on each of 2 days during the first and second week of life. Data were analyzed using a repeated measures design to test the effects of behavior prior to testing, sex, week, day within week, and repetition within day. The effect of body weight and the interaction between piglet weight and behaviour were also tested. Piglet was entered into the model as a random effect as an additional test of repeatability. The effect of repeated testing was used to test the stability of measures. Pearson correlations between repeated measures were used to test the repeatability of measures. Variance component analysis was used to describe the variability in the data. Variance component analysis indicated that piglet explained only 17% of the variance in the data. All variables in the model (behaviour prior to testing, sex, week, day within week, repetition within day, body weight, the interaction between body weight and behaviour, piglet identity) except sex had a significant effect (p testing and measures changed with repeated testing and increased with increasing piglet weight, indicating that time (age) and animal body weight should be taken into account when measuring mechanical (nociceptive) thresholds in piglets. Mechanical (nociceptive) thresholds can be used both for testing the efficacy of anaesthetics and analgesics, and for assessing hyperalgesia in chronic pain states in research and clinical settings. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  20. The Significance of Memory in Sensory Cortex.

    Science.gov (United States)

    Muckli, Lars; Petro, Lucy S

    2017-05-01

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. The significance of memory in sensory cortex

    OpenAIRE

    Muckli, Lars; Petro, Lucy S.

    2017-01-01

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing.

  2. Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis.

    Science.gov (United States)

    Greaves, Erin; Grieve, Kelsey; Horne, Andrew W; Saunders, Philippa T K

    2014-09-01

    Ovarian suppression is a common treatment for endometriosis-associated pelvic pain. Its exact mechanism of action is poorly understood, although it is assumed to reflect reduced production/action of estrogens. The objective of the study was to measure the expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis and to investigate whether estrogens alter nociceptive gene expression in human sensory neurons. The study was performed using human tissue analysis and cell culture. The study was conducted at a university research institute. Peritoneal biopsies were obtained from women with CPP and endometriosis (n = 12), CPP and no endometriosis (n = 10), and no pain or endometriosis (n = 5). Endometriosis lesions were obtained from women with endometriosis (n = 18). mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in human tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens. TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P endometriosis lesions (P endometriosis (P endometriosis-associated pain. Strategies directly targeting ion channels may offer an alternative option for the management of CPP.

  3. A5-Positive Primary Sensory Neurons Are Nonpermissive for Productive Infection with Herpes Simplex Virus 1 In Vitro▿

    Science.gov (United States)

    Bertke, Andrea S.; Swanson, Sophia M.; Chen, Jenny; Imai, Yumi; Kinchington, Paul R.; Margolis, Todd P.

    2011-01-01

    Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) establish latency and express the latency-associated transcript (LAT) preferentially in different murine sensory neuron populations, with most HSV-1 LAT expression in A5+ neurons and most HSV-2 LAT expression in KH10+ neurons. To study the mechanisms regulating the establishment of HSV latency in specific subtypes of neurons, cultured dissociated adult murine trigeminal ganglion (TG) neurons were assessed for relative permissiveness for productive infection. In contrast to that for neonatal TG, the relative distribution of A5+ and KH10+ neurons in cultured adult TG was similar to that seen in vivo. Productive infection with HSV was restricted, and only 45% of cultured neurons could be productively infected with either HSV-1 or HSV-2. A5+ neurons supported productive infection with HSV-2 but were selectively nonpermissive for productive infection with HSV-1, a phenomenon that was not due to restricted viral entry or DNA uncoating, since HSV-1 expressing β-galactosidase under the control of the neurofilament promoter was detected in ∼90% of cultured neurons, with no preference for any neuronal subtype. Infection with HSV-1 reporter viruses expressing enhanced green fluorescent protein (EGFP) from immediate early (IE), early, and late gene promoters indicated that the block to productive infection occurred before IE gene expression. Trichostatin A treatment of quiescently infected neurons induced productive infection preferentially from non-A5+ neurons, demonstrating that the nonpermissive neuronal subtype is also nonpermissive for reactivation. Thus, HSV-1 is capable of entering the majority of sensory neurons in vitro; productive infection occurs within a subset of these neurons; and this differential distribution of productive infection is determined at or before the expression of the viral IE genes. PMID:21507969

  4. Effect of Centella asiatica extract on nociception, experimental ...

    African Journals Online (AJOL)

    This study was undertaken to determine the effect of Centella asiatica aqueous extract (CAEt) on nociception, experimental diabetes and hyperlipidemia in mice and rats. The extract was administered orally and the effects of different doses of the extract on nociception in mice, on blood glucose, glucose-6-phosphatase, and ...

  5. The Left Superior Longitudinal Fasciculus within the Primary Sensory Area of Inferior Parietal Lobe Plays a Role in Dysgraphia of Kana Omission within Sentences

    Directory of Open Access Journals (Sweden)

    Nobusada Shinoura

    2012-01-01

    Full Text Available Functional neurological changes after surgery combined with diffusion tensor imaging (DTI tractography can directly provide evidence of anatomical localization of brain function. Using these techniques, a patient with dysgraphia before surgery was analyzed at our hospital in 2011. The patient showed omission of kana within sentences before surgery, which improved after surgery. The brain tumor was relatively small and was located within the primary sensory area (S1 of the inferior parietal lobe (IPL. DTI tractography before surgery revealed compression of the branch of the superior longitudinal fasciculus (SLF by the brain tumor. These results suggest that the left SLF within the S1 of IPL plays a role in the development of dysgraphia of kana omission within sentences.

  6. The third-stimulus temporal discrimination threshold: focusing on the temporal processing of sensory input within primary somatosensory cortex.

    Science.gov (United States)

    Leodori, Giorgio; Formica, Alessandra; Zhu, Xiaoying; Conte, Antonella; Belvisi, Daniele; Cruccu, Giorgio; Hallett, Mark; Berardelli, Alfredo

    2017-10-01

    The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information, but little is known about the physiological correlates of somatosensory temporal discrimination. The objective of this study was to investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the third-stimulus temporal discrimination threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus following a pair of stimuli delivered at the STDT. The STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1 continuous theta-burst stimulation (S1-cTBS) on the STDT and ThirdDT. Results show that ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, although the latter was affected to a greater extent and for a longer period of time. We conclude that the interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1, probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination. NEW & NOTEWORTHY To investigate whether the time interval required to discriminate between stimuli varies according to changes in the stimulation pattern, we used the third-stimulus temporal discrimination threshold (ThirdDT). We found that the somatosensory temporal discrimination acuity varies according to the number of stimuli in the

  7. The ankyrin repeat domain of the TRPA protein painless is important for thermal nociception but not mechanical nociception.

    Directory of Open Access Journals (Sweden)

    Richard Y Hwang

    Full Text Available The Drosophila TRPA channel Painless is required for the function of polymodal nociceptors which detect noxious heat and noxious mechanical stimuli. These functions of Painless are reminiscent of mammalian TRPA channels that have also been implicated in thermal and mechanical nociception. A popular hypothesis to explain the mechanosensory functions of certain TRP channels proposes that a string of ankyrin repeats at the amino termini of these channels acts as an intracellular spring that senses force. Here, we describe the identification of two previously unknown Painless protein isoforms which have fewer ankyrin repeats than the canonical Painless protein. We show that one of these Painless isoforms, that essentially lacks ankyrin repeats, is sufficient to rescue mechanical nociception phenotypes of painless mutant animals but does not rescue thermal nociception phenotypes. In contrast, canonical Painless, which contains Ankyrin repeats, is sufficient to largely rescue thermal nociception but is not capable of rescuing mechanical nociception. Thus, we propose that in the case of Painless, ankryin repeats are important for thermal nociception but not for mechanical nociception.

  8. Analysis of long-standing nociceptive and neuropathic pain in patients with post-polio syndrome.

    Science.gov (United States)

    Werhagen, Lars; Borg, Kristian

    2010-06-01

    The purpose of this study was to analyze pain, both nociceptive and neuropathic, in patients with post-polio syndrome (PPS) and relate the pain to age at the initial polio infection, age at examination, to gender and disability. The study was conducted in a university hospital department. Patients with PPS were interviewed at their regular visits about pain, its character, intensity and localization. A clinical examination, including a thorough neurological examination, was performed. Data included age at time of polio infection, age at time of examination and gender. Pain intensity was measured with the VAS-scale and walking capability by the WISCI-scale. One hundred sixty-three (88 women, 75 men) patients were included in the study. Pain was present in 109 (67%). Pain was more frequently reported by women (82%) than by men (49%). 96 patients experienced nociceptive pain, 10 patients both neuropathic and nociceptive pain and three experienced pure neuropathic pain. Half of the patients with pain experienced pain in more than one body region. When neuropathic pain was present, another additional neurological disorder was diagnosed. Pain was more often found in younger patients (around 70%) than in older patients (around 50%). In summary pain is common in patients with PPS and most patients experienced nociceptive pain. Women have pain more often than men. Older patients experience pain more seldom than younger patients. Age at time of primary polio infection is important for the development of pain. When neuropathic pain is present, it is important to proceed with neurological examination to find an adequate diagnosis.

  9. Relationships among Sensory Responsiveness, Anxiety, and Ritual Behaviors in Children with and without Atypical Sensory Responsiveness.

    Science.gov (United States)

    Bart, Orit; Bar-Shalita, Tami; Mansour, Hanin; Dar, Reuven

    2017-08-01

    To explore relationships between sensory responsiveness, anxiety, and ritual behaviors in boys with typical and atypical sensory responsiveness. Forty-eight boys, ages 5-9 participated in the study (28 boys with atypical sensory responsiveness and 20 controls). Atypical sensory responsiveness was defined as a score of ≤154 on the Short Sensory Profile. Parents completed the Sensory Profile, the Screen for Child Anxiety Related Emotional Disorders, and the Childhood Routines Inventory. Children with atypical sensory responsiveness had significantly higher levels of anxiety and a higher frequency of ritual behaviors than controls. Atypical sensory responsiveness was significantly related to both anxiety and ritual behaviors, with anxiety mediating the relationship between sensory modulation and ritual behaviors. The findings elucidate the potential consequences of atypical sensory responsiveness and could support the notion that ritual behaviors develop as a coping mechanism in response to anxiety stemming from primary difficulty in modulating sensory input.

  10. DNA Methylation Modulates Nociceptive Sensitization after Incision.

    Directory of Open Access Journals (Sweden)

    Yuan Sun

    Full Text Available DNA methylation is a key epigenetic mechanism controlling DNA accessibility and gene expression. Blockade of DNA methylation can significantly affect pain behaviors implicated in neuropathic and inflammatory pain. However, the role of DNA methylation with regard to postoperative pain has not yet been explored. In this study we sought to investigate the role of DNA methylation in modulating incisional pain and identify possible targets under DNA methylation and contributing to incisional pain. DNA methyltranferase (DNMT inhibitor 5-Aza-2'-deoxycytidine significantly reduced incision-induced mechanical allodynia and thermal sensitivity. Aza-2'-deoxycytidine also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. Global DNA methylation and DNMT3b expression were increased in skin after incision, but none of DNMT1, DNMT3a or DNMT3b was altered in spinal cord or DRG. The expression of proopiomelanocortin Pomc encoding β-endorphin and Oprm1 encoding the mu-opioid receptor were upregulated peripherally after incision; moreover, Oprm1 expression was further increased under DNMT inhibitor treatment. Finally, local peripheral injection of the opioid receptor antagonist naloxone significantly exacerbated incision-induced mechanical hypersensitivity. These results suggest that DNA methylation is functionally relevant to incisional nociceptive sensitization, and that mu-opioid receptor signaling might be one methylation regulated pathway controlling sensitization after incision.

  11. Effects of Anethole in Nociception Experimental Models

    Directory of Open Access Journals (Sweden)

    Alessandra Mileni Versuti Ritter

    2014-01-01

    Full Text Available This study investigated the antinociceptive activity of anethole (anethole 1-methoxy-4-benzene (1-propenyl, major compound of the essential oil of star anise (Illicium verum, in different experimental models of nociception. The animals were pretreated with anethole (62.5, 125, 250, and 500 mg/kg one hour before the experiments. To eliminate a possible sedative effect of anethole, the open field test was conducted. Anethole (62.5, 125, 250, and 500 mg/kg showed an antinociceptive effect in the writhing model induced by acetic acid, in the second phase of the formalin test (125 and 250 mg/kg in the test of glutamate (62.5, 125, and 250 mg/kg, and expresses pain induced by ACF (250 mg/kg. In contrast, anethole was not able to increase the latency time on the hot plate and decrease the number of flinches during the initial phase of the formalin test in any of the doses tested. It was also demonstrated that anethole has no association with sedative effects. Therefore, these data showed that anethole, at all used doses, has no sedative effect and has an antinociceptive effect. This effect may be due to a decrease in the production/release of inflammatory mediators.

  12. Effects of anethole in nociception experimental models.

    Science.gov (United States)

    Ritter, Alessandra Mileni Versuti; Ames, Franciele Queiroz; Otani, Fernando; de Oliveira, Rubia Maria Weffort; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2014-01-01

    This study investigated the antinociceptive activity of anethole (anethole 1-methoxy-4-benzene (1-propenyl)), major compound of the essential oil of star anise (Illicium verum), in different experimental models of nociception. The animals were pretreated with anethole (62.5, 125, 250, and 500 mg/kg) one hour before the experiments. To eliminate a possible sedative effect of anethole, the open field test was conducted. Anethole (62.5, 125, 250, and 500 mg/kg) showed an antinociceptive effect in the writhing model induced by acetic acid, in the second phase of the formalin test (125 and 250 mg/kg) in the test of glutamate (62.5, 125, and 250 mg/kg), and expresses pain induced by ACF (250 mg/kg). In contrast, anethole was not able to increase the latency time on the hot plate and decrease the number of flinches during the initial phase of the formalin test in any of the doses tested. It was also demonstrated that anethole has no association with sedative effects. Therefore, these data showed that anethole, at all used doses, has no sedative effect and has an antinociceptive effect. This effect may be due to a decrease in the production/release of inflammatory mediators.

  13. Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade.

    Science.gov (United States)

    Sun, Wei; Yang, Fei; Wang, Yan; Fu, Han; Yang, Yan; Li, Chun-Li; Wang, Xiao-Liang; Lin, Qing; Chen, Jun

    2017-02-01

    Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (I h ) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of I h in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing I h through activation of COX-1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Urethane anesthesia depresses activities of thalamocortical neurons and alters its response to nociception in terms of dual firing modes

    Directory of Open Access Journals (Sweden)

    Yeowool eHuh

    2013-10-01

    Full Text Available Anesthetics are often used to characterize the activity of single neurons in-vivo for its advantages such as reduced noise level and convenience in noxious stimulations. Of the anesthetics, urethane had been widely used in some thalamic studies under the assumption that sensory signals are still relayed to the thalamus under urethane anesthesia and that thalamic response would therefore reflect the response of the awake state. We tested whether this assumption stands by comparing thalamic activity in terms of tonic and burst firing modes during ‘the awake state’ or under ‘urethane anesthesia’ utilizing the extracellular single unit recording technique. First we have tested how thalamic relay neurons respond to the introduction of urethane and then tested how urethane influences thalamic discharges under formalin-induced nociception. Urethane significantly depressed overall firing rates of thalamic relay neurons, which was sustained despite the delayed increase of burst activity over the 4 hour recording period. Thalamic response to nociception under anesthesia was also similar overall except for the slight and transient increase of burst activity. Overall, results demonstrated that urethane suppresses the activity of thalamic relay neurons and that, despite the slight fluctuation of burst firing, formalin-induced nociception cannot significantly change the firing pattern of thalamic relay neurons that was caused by urethane.

  15. Pain when walking: individual sensory profiles in the foot soles of torture victims - a controlled study using quantitative sensory testing

    DEFF Research Database (Denmark)

    Prip, K.; Persson, A. L.; Sjolund, B. H.

    2012-01-01

    Background: With quantitative sensory testing (QST) we recently found no differences in sensory function of the foot soles between groups of torture victims with or without exposure to falanga (beatings under the feet). Compared to matched controls the torture victims had hyperalgesia to deep...... mechano-nociceptive stimuli and hypoesthesia to non-noxious cutaneous stimuli. The purpose of the present paper was to extend the group analysis into individual sensory profiles of victims' feet to explore possible relations between external violence (torture), reported pain, sensory symptoms and QST data...... to help clarify the underlying mechanisms. Methods: We employed interviews and assessments of the pain and sensory symptoms and QST by investigators blinded to whether the patients, 32 male torture victims from the Middle East, had (n=15), or had not (n=17) been exposed to falanga. Pain intensity, area...

  16. [Changes in ingestive behavior during growth affects the functional maturation of temporomandibular joint nociceptive neurons of rats].

    Science.gov (United States)

    Hiranuma, Maya

    2013-03-01

    Temporomandibular joint (TMJ) loading during development promotes its growth and maintains normal structure/function. Continuous change in diet consistency is related to development and maturation of the peripheral nervous system, including the nociceptive system. However, the functional modulation of TMJ-nociceptive neurons under different ingestive behavior is unclear. We fed growing rats a liquid diet to investigate the effects of low TMJ loading on the response properties of neurons in the trigeminal spinal tract subnucleus caudalis (Sp5C). Forty 2-week-old male rats were used. They were fed chow pellets (n = 20, C group) or a liquid diet (n = 20, LD group) soon after weaning. Firing activities of single sensory units in response to TMJ pressure stimuli were recorded at 4, 5, 7 and 9 weeks. In TMJ-nociceptive neurons, the firing threshold (FT) in the LD group was significantly lower than that in the C group at each recording age. The FT in the C group remained unchanged throughout the recording period, whereas that in the LD group was the highest at 4 weeks, and gradually decreased. On the other hand, the initial firing frequency (IFF) was significantly higher in the LD group than in the C group at each recording age. The IFF in the C group remained unchanged throughout the experimental period, whereas that in the LD group was at its lowest at 4 weeks, and gradually increased. Based on these findings, ingestive behavior that results from continuous changes in the physical consistency of the diet during growth may affect the functional maturation of TMJ-nociceptive neurons.

  17. The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization.

    Science.gov (United States)

    Tokusumi, Yumiko; Tokusumi, Tsuyoshi; Schulz, Robert A

    2017-05-13

    In vertebrates, interaction between the nervous system and immune system is important to protect a challenged host from stress inputs from external sources. In this study, we demonstrate that sensory neurons are involved in the cellular immune response elicited by wasp infestation of Drosophila larvae. Multidendritic class IV neurons sense contacts from external stimuli and induce avoidance behaviors for host defense. Our findings show that inactivation of these sensory neurons impairs the cellular response against wasp parasitization. We also demonstrate that the nociception genes encoding the mechanosensory receptors Painless and Piezo, both expressed in class IV neurons, are essential for the normal cellular immune response to parasite challenge. Copyright © 2017. Published by Elsevier Inc.

  18. Sub-threshold cross-modal sensory interaction in the thalamus: lemniscal auditory response in the medial geniculate nucleus is modulated by somatosensory stimulation.

    Science.gov (United States)

    Donishi, T; Kimura, A; Imbe, H; Yokoi, I; Kaneoke, Y

    2011-02-03

    Recent studies have highlighted cross-modal sensory modulations in the primary sensory areas in the cortex, suggesting that cross-modal sensory interactions occur at early stages in the hierarchy of sensory processing. Multi-modal sensory inputs from non-lemniscal thalamic nuclei and cortical inputs from the secondary sensory and association areas are considered responsible for the modulations. On the other hand, there is little evidence of cross-sensory modal sensitivities in lemniscal thalamic nuclei. In the present study, we were interested in a possibility that somatosensory stimulation may affect auditory response in the ventral division (MGV) of the medial geniculate nucleus (MG), a lemniscal thalamic nucleus that is considered to be dedicated to auditory uni-modal processing. Experiments were performed on anesthetized rats. Transcutaneous electrical stimulation of the hindpaw, which is thought to evoke nociception and seems unrelated to auditory processing, modulated unit discharges in response to auditory stimulation (noise bursts). The modulation was observed in the MGV and non-lemniscal auditory thalamic nuclei such as the dorsal and medial divisions of the MG. The major effect of somatosensory stimulation was suppression. The most robust suppression was induced by electrical stimuli given simultaneously with noise bursts or preceding noise bursts by 10 to 20 ms. The results indicate that the lemniscal (MGV) and non-lemniscal auditory nuclei are subject to somatosensory influence. In everyday experience intense somatosensory stimuli such as pain interrupt our ongoing hearing or interfere with clear recognition of sound. The modulation of lemniscal auditory response by somatosensory stimulation may underlie such cross-modal disturbance of auditory perception as a form of cross-modal switching of attention. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Serotonergic Modulation Enables Pathway-Specific Plasticity in a Developing Sensory Circuit in Drosophila.

    Science.gov (United States)

    Kaneko, Takuya; Macara, Ann Marie; Li, Ruonan; Hu, Yujia; Iwasaki, Kenichi; Dunnings, Zane; Firestone, Ethan; Horvatic, Shawn; Guntur, Ananya; Shafer, Orie T; Yang, Chung-Hui; Zhou, Jie; Ye, Bing

    2017-08-02

    How experiences during development cause long-lasting changes in sensory circuits and affect behavior in mature animals are poorly understood. Here we establish a novel system for mechanistic analysis of the plasticity of developing neural circuits by showing that sensory experience during development alters nociceptive behavior and circuit physiology in Drosophila larvae. Despite the convergence of nociceptive and mechanosensory inputs on common second-order neurons (SONs), developmental noxious input modifies transmission from nociceptors to their SONs, but not from mechanosensors to the same SONs, which suggests striking sensory pathway specificity. These SONs activate serotonergic neurons to inhibit nociceptor-to-SON transmission; stimulation of nociceptors during development sensitizes nociceptor presynapses to this feedback inhibition. Our results demonstrate that, unlike associative learning, which involves inputs from two sensory pathways, sensory pathway-specific plasticity in the Drosophila nociceptive circuit is in part established through feedback modulation. This study elucidates a novel mechanism that enables pathway-specific plasticity in sensory systems. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy?

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Buscher, H.C.J.L.; Goor, H. van; Wilder-Smith, O.H.G.

    2011-01-01

    BACKGROUND AND OBJECTIVES: : Central sensitization due to visceral pancreatic nociceptive input may be important in chronic pancreatitis pain. We investigated whether bilateral thoracoscopic splanchnicectomy (BTS) to reduce nociceptive input in chronic pancreatitis patients (CPP) with poor pain

  1. Gray matter volumes of early sensory regions are associated with individual differences in sensory processing.

    Science.gov (United States)

    Yoshimura, Sayaka; Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Sawada, Reiko; Kubota, Yasutaka; Toichi, Motomi

    2017-12-01

    Sensory processing (i.e., the manner in which the nervous system receives, modulates, integrates, and organizes sensory stimuli) is critical when humans are deciding how to react to environmental demands. Although behavioral studies have shown that there are stable individual differences in sensory processing, the neural substrates that implement such differences remain unknown. To investigate this issue, structural magnetic resonance imaging scans were acquired from 51 healthy adults and individual differences in sensory processing were assessed using the Sensory Profile questionnaire (Brown et al.: Am J Occup Ther 55 (2001) 75-82). There were positive relationships between the Sensory Profile modality-specific subscales and gray matter volumes in the primary or secondary sensory areas for the visual, auditory, touch, and taste/smell modalities. Thus, the present results suggest that individual differences in sensory processing are implemented by the early sensory regions. Hum Brain Mapp 38:6206-6217, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-04-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  3. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-06-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  4. Investigation of the anti-inflammatory and anti- nociceptive activities ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-06-15

    Jun 15, 2009 ... (1998) Antinociceptive and anti-inflammatory effects of Sambucus ebulus rhizome extract in rats. J. Ethnopharmacol. 61: 229-235. Barros IMC, Lopes LDG, Borges MOR, Borges ACR, Ribeiro MNS,. Freire SMF (2006). Anti-inflammatory and anti-nociceptive activities of Pluchea quitic (D.C) ethanolic extract.

  5. Differential Contribution of TRPA1, TRPV4 and TRPM8 to Colonic Nociception in Mice.

    Directory of Open Access Journals (Sweden)

    Sonja M Mueller-Tribbensee

    Full Text Available Various transient receptor potential (TRP channels in sensory neurons contribute to the transduction of mechanical stimuli in the colon. Recently, even the cold-sensing menthol receptor TRPM(melastatin8 was suggested to be involved in murine colonic mechano-nociception.To analyze the roles of TRPM8, TRPA1 and TRPV4 in distension-induced colonic nociception and pain, TRP-deficient mice and selective pharmacological blockers in wild-type mice (WT were used. Visceromotor responses (VMR to colorectal distension (CRD in vivo were recorded and distension/pressure-induced CGRP release from the isolated murine colon ex vivo was measured by EIA.Distension-induced colonic CGRP release was markedly reduced in TRPA1-/- and TRPV4-/- mice at 90/150 mmHg compared to WT. In TRPM8-deficient mice the reduction was only distinct at 150 mmHg. Exposure to selective pharmacological antagonists (HC030031, 100 μM; RN1734, 10 μM; AMTB, 10 μM showed corresponding effects. The unselective TRP blocker ruthenium red (RR, 10 μM was as efficient in inhibiting distension-induced CGRP release as the unselective antagonists of mechanogated DEG/ENaC (amiloride, 100 μM and stretch-activated channels (gadolinium, 50 μM. VMR to CRD revealed prominent deficits over the whole pressure range (up to 90 mmHg in TRPA1-/- and TRPV4-/- but not TRPM8-/- mice; the drug effects of the TRP antagonists were again highly consistent with the results from mice lacking the respective TRP receptor gene.TRPA1 and TRPV4 mediate colonic distension pain and CGRP release and appear to govern a wide and congruent dynamic range of distensions. The role of TRPM8 seems to be confined to signaling extreme noxious distension, at least in the healthy colon.

  6. Emotional modulation of pain and spinal nociception in fibromyalgia

    Science.gov (United States)

    Rhudy, Jamie L.; DelVentura, Jennifer L.; Terry, Ellen L.; Bartley, Emily J.; Olech, Ewa; Palit, Shreela; Kerr, Kara L.

    2013-01-01

    Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (e.g., depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in four blocks; two blocks assessed only physiological-emotional reactions (i.e., pleasure/arousal ratings, corrugator EMG, startle modulation, skin conductance) in the absence of pain and two blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (e.g., reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all three groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. PMID:23622762

  7. Primary or secondary tasks? Dual-task interference between cyclist hazard perception and cadence control using cross-modal sensory aids with rider assistance bike computers.

    Science.gov (United States)

    Yang, Chao-Yang; Wu, Cheng-Tse

    2017-03-01

    This research investigated the risks involved in bicycle riding while using various sensory modalities to deliver training information. To understand the risks associated with using bike computers, this study evaluated hazard perception performance through lab-based simulations of authentic riding conditions. Analysing hazard sensitivity (d') of signal detection theory, the rider's response time, and eye glances provided insights into the risks of using bike computers. In this study, 30 participants were tested with eight hazard perception tasks while they maintained a cadence of 60 ± 5 RPM and used bike computers with different sensory displays, namely visual, auditory, and tactile feedback signals. The results indicated that synchronously using different sense organs to receive cadence feedback significantly affects hazard perception performance; direct visual information leads to the worst rider distraction, with a mean sensitivity to hazards (d') of -1.03. For systems with multiple interacting sensory aids, auditory aids were found to result in the greatest reduction in sensitivity to hazards (d' mean = -0.57), whereas tactile sensory aids reduced the degree of rider distraction (d' mean = -0.23). Our work complements existing work in this domain by advancing the understanding of how to design devices that deliver information subtly, thereby preventing disruption of a rider's perception of road hazards. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats.

    Science.gov (United States)

    Birol Muhammet, Er; Kocamanoğlu, İsmail Serhat; Bozkurt, Ayhan; Bilge, Sırrı; Çetinoğlu, Erhan Çetin

    2016-05-01

    Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Animal experimentation. Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L): Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM): Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD): Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D): Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (pdexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (pdexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.

  9. Finite element analysis of thermal laser skin stimulation for a finer characterization of the nociceptive system.

    Science.gov (United States)

    Marchandise, E; Mouraux, A; Plaghki, L; Henrotte, F

    2014-02-15

    Thermal laser stimulation of the skin is an efficient exploratory tool to characterize the nociceptive system. In the present study, finite element simulations are done to calculate the intra-cutaneous spatio-temporal temperature profiles following the delivery of such laser stimuli. The proposed computer-aided modeling considers a number of important parameters that have been disregarded in previous approaches: (i) variability of water content across the skin in both hairy and glabrous skin, (ii) temperature dependency of optical and thermal skin parameters, (iii) laser wavelength and corresponding absorption coefficient, (iv) beam shape (Gaussian vs. flat top) and (v) power emission (closed vs. open loop). Numerical simulations allow determining at each instant of time the volume and area of skin tissue whose temperature exceeds a given nociceptor activation threshold. This knowledge allows a finer characterization of the subpopulations of primary afferents that encode and convey nociceptive signals to the central nervous system. As an example, the approach is used to obtain an estimate of intraepidermal nerve fiber density in both physiological and pathological conditions. Moreover, a better knowledge of the heat distribution also reduces the risk of injury to the skin. Finally, in order to make the finite element simulations accessible to investigators with no prior background in numerical analysis, a specific open-source user-interface has been developed with the ONELAB software. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Distinct brain systems mediate the effects of nociceptive input and self-regulation on pain.

    Directory of Open Access Journals (Sweden)

    Choong-Wan Woo

    2015-01-01

    Full Text Available Cognitive self-regulation can strongly modulate pain and emotion. However, it is unclear whether self-regulation primarily influences primary nociceptive and affective processes or evaluative ones. In this study, participants engaged in self-regulation to increase or decrease pain while experiencing multiple levels of painful heat during functional magnetic resonance imaging (fMRI imaging. Both heat intensity and self-regulation strongly influenced reported pain, but they did so via two distinct brain pathways. The effects of stimulus intensity were mediated by the neurologic pain signature (NPS, an a priori distributed brain network shown to predict physical pain with over 90% sensitivity and specificity across four studies. Self-regulation did not influence NPS responses; instead, its effects were mediated through functional connections between the nucleus accumbens and ventromedial prefrontal cortex. This pathway was unresponsive to noxious input, and has been broadly implicated in valuation, emotional appraisal, and functional outcomes in pain and other types of affective processes. These findings provide evidence that pain reports are associated with two dissociable functional systems: nociceptive/affective aspects mediated by the NPS, and evaluative/functional aspects mediated by a fronto-striatal system.

  11. Transient Receptor Potential Melastatin-3 (TRPM3 Mediates Nociceptive-Like Responses in Hydra vulgaris.

    Directory of Open Access Journals (Sweden)

    Valentina Malafoglia

    Full Text Available The ability of mammals to feel noxious stimuli lies in a heterogeneous group of primary somatosensory neurons termed nociceptors, which express specific membrane receptors, such as the Transient Receptor Potential (TRP family. Here, we show that one of the most important nociceptive-like pathways is conserved in the freshwater coelenterate Hydra vulgaris, the most primitive organism possessing a nervous system. In particular, we found that H. vulgaris expresses TRPM3, a nociceptor calcium channel involved in the detection of noxious heat in mammals. Furthermore, we detected that both heat shock and TRPM3 specific agonist (i.e., pregnenolone sulfate induce the modulation of the heat shock protein 70 (HSP70 and the nitric oxide synthase (NOS, two genes activated by TRP-mediated heat painful stimuli in mammals. As expected, these effects are inhibited by a TRPM3 antagonist (i.e., mefenamic acid. Interestingly, the TRPM3 agonist and heat shock also induce the expression of nuclear transcription erythroid 2-related factor (Nrf2 and superoxide dismutase (SOD, known markers of oxidative stress; noteworthy gene expression was also inhibited by the TRPM3 antagonist. As a whole, our results demonstrate the presence of conserved molecular oxidative/nociceptive-like pathways at the primordial level of the animal kingdom.

  12. Transient Receptor Potential Melastatin-3 (TRPM3) Mediates Nociceptive-Like Responses in Hydra vulgaris.

    Science.gov (United States)

    Malafoglia, Valentina; Traversetti, Lorenzo; Del Grosso, Floriano; Scalici, Massimiliano; Lauro, Filomena; Russo, Valeria; Persichini, Tiziana; Salvemini, Daniela; Mollace, Vincenzo; Fini, Massimo; Raffaeli, William; Muscoli, Carolina; Colasanti, Marco

    2016-01-01

    The ability of mammals to feel noxious stimuli lies in a heterogeneous group of primary somatosensory neurons termed nociceptors, which express specific membrane receptors, such as the Transient Receptor Potential (TRP) family. Here, we show that one of the most important nociceptive-like pathways is conserved in the freshwater coelenterate Hydra vulgaris, the most primitive organism possessing a nervous system. In particular, we found that H. vulgaris expresses TRPM3, a nociceptor calcium channel involved in the detection of noxious heat in mammals. Furthermore, we detected that both heat shock and TRPM3 specific agonist (i.e., pregnenolone sulfate) induce the modulation of the heat shock protein 70 (HSP70) and the nitric oxide synthase (NOS), two genes activated by TRP-mediated heat painful stimuli in mammals. As expected, these effects are inhibited by a TRPM3 antagonist (i.e., mefenamic acid). Interestingly, the TRPM3 agonist and heat shock also induce the expression of nuclear transcription erythroid 2-related factor (Nrf2) and superoxide dismutase (SOD), known markers of oxidative stress; noteworthy gene expression was also inhibited by the TRPM3 antagonist. As a whole, our results demonstrate the presence of conserved molecular oxidative/nociceptive-like pathways at the primordial level of the animal kingdom.

  13. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

    Directory of Open Access Journals (Sweden)

    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  14. Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing.

    Science.gov (United States)

    Sankarasubramanian, Vishwanath; Cunningham, David A; Potter-Baker, Kelsey A; Beall, Erik B; Roelle, Sarah M; Varnerin, Nicole M; Machado, Andre G; Jones, Stephen E; Lowe, Mark J; Plow, Ela B

    2017-04-01

    The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks

  15. Pre-operative pain and sensory function in groin hernia

    DEFF Research Database (Denmark)

    Aasvang, Eske K; Hansen, Jeanette B; Kehlet, Henrik

    2009-01-01

    (rho=-0.413, p=0.049), indicating a paradoxical association between level of mechanical pain threshold and magnitude of spontaneous pain. No other sensory modality was significantly correlated to pain intensity. New/increased pain during repetitive pinprick stimulation (wind-up) was seen in 3 patients......BACKGROUND: Although persistent postherniotomy occurs in 5-10% of patients, pathogenic mechanisms remain debatable. Since pre-operative pain has been demonstrated to be a risk factor for persistent postherniotomy pain, pre-operative alterations in nociceptive function may be a potential pathogenic...... mechanism. AIMS: To investigate the correlation between pre-operative pain intensity and sensory functions in the groin hernia area. METHODS: Patients with unilateral groin hernia were examined preoperatively by quantitative sensory testing (thermal, mechanical, and pressure [detection and pain thresholds...

  16. Physiological Signal Processing for Individualized Anti-nociception Management During General Anesthesia: a Review.

    Science.gov (United States)

    De Jonckheere, J; Bonhomme, V; Jeanne, M; Boselli, E; Gruenewald, M; Logier, R; Richebé, P

    2015-08-13

    The aim of this paper is to review existing technologies for the nociception / anti-nociception balance evaluation during surgery under general anesthesia. General anesthesia combines the use of analgesic, hypnotic and muscle-relaxant drugs in order to obtain a correct level of patient non-responsiveness during surgery. During the last decade, great efforts have been deployed in order to find adequate ways to measure how anesthetic drugs affect a patient's response to surgical nociception. Nowadays, though some monitoring devices allow obtaining information about hypnosis and muscle relaxation, no gold standard exists for the nociception / anti-nociception balance evaluation. Articles from the PubMed literature search engine were reviewed. As this paper focused on surgery under general anesthesia, articles about nociception monitoring on conscious patients, in post-anesthesia care unit or in intensive care unit were not considered. In this article, we present a review of existing technologies for the nociception / anti-nociception balance evaluation, which is based in all cases on the analysis of the autonomous nervous system activity. Presented systems, based on sensors and physiological signals processing algorithms, allow studying the patients' reaction regarding anesthesia and surgery. Some technological solutions for nociception / antinociception balance monitoring were described. Though presented devices could constitute efficient solutions for individualized anti-nociception management during general anesthesia, this review of current literature emphasizes the fact that the choice to use one or the other mainly relies on the clinical context and the general purpose of the monitoring.

  17. Nociceptive Alteration by High Sucrose Diet in Hypoestrogenic Wistar Rats.

    Science.gov (United States)

    Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; Corona-Ramos, Janette Nallely; López-Muñoz, Francisco Javier

    2016-08-01

    Preclinical Research Obesity is a risk factor associated with alterations in pain perception. The aim of this study was to analyse a time-course of nociceptive responses (plantar test) in hypoestrogenic rats after the induction of obesity. Animals (hypoestrogenic and naïve) received either a hypercaloric or regular diet for 24 weeks. Thermal nociception and body weight were measured during this period. At the 4th and 17th weeks after treatment, oral glucose tolerance, blood insulin levels, abdominal fat weight, and uric acid levels were measured. The hypoestrogenic rats on a high sucrose diet had higher body weight and abdominal fat weight than control rats. A biphasic response was observed in the ovariectomized group fed with sucrose with thermal latency being decreased in the fourth week. During weeks 12-18, thermal latency increased compared to that of the hypoestrogenic control. There were no differences in basal blood glucose levels at the 4th and 17th weeks; however, oral glucose tolerance, insulin, and uric acid levels were altered. This indicated that increased body weight and fat as well as alteration sin glucose tolerance, hyperinsulinemia and hyperuricemia, may be associated with the biphasic nociceptive response. Drug Dev Res 77 : 258-266, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Chronic intrathecal cannulation enhances nociceptive responses in rats

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    Almeida F.R.C.

    2000-01-01

    Full Text Available The influence of a chronically implanted spinal cannula on the nociceptive response induced by mechanical, chemical or thermal stimuli was evaluated. The hyperalgesia in response to mechanical stimulation induced by carrageenin or prostaglandin E2 (PGE2 was significantly increased in cannulated (Cn rats, compared with naive (Nv or sham-operated (Sh rats. Only Cn animals presented an enhanced nociceptive response in the first phase of the formalin test when low doses were used (0.3 and 1%. The withdrawal latency to thermal stimulation of a paw inflamed by carrageenin was significantly reduced in Cn rats but not in Nv or Sh rats. In contrast to Nv and Sh rats, injection in Cn animals of a standard non-steroid anti-inflammatory drug, indomethacin, either intraperitoneally or into the spinal cord via an implanted cannula or by direct puncture of the intrathecal space significantly blocked the intensity of the hyperalgesia induced by PGE2. Cannulated animals treated with indomethacin also showed a significant inhibition of second phase formalin-induced paw flinches. Histopathological analysis of the spinal cord showed an increased frequency of mononuclear inflammatory cells in the Cn groups. Thus, the presence of a chronically implanted cannula seems to cause nociceptive spinal sensitization to mechanical, chemical and thermal stimulation, which can be blocked by indomethacin, thus suggesting that it may result from the spinal release of prostaglandins due to an ongoing mild inflammation.

  19. Neuropathic sensory symptoms: association with pain and psychological factors

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    Shaygan M

    2014-05-01

    Full Text Available Maryam Shaygan,1 Andreas Böger,2 Birgit Kröner-Herwig11Department of Clinical Psychology and Psychotherapy, University of Göttingen, Germany; 2Pain Management Clinic at the Red Cross Hospital, Kassel, GermanyBackground: A large number of population-based studies of chronic pain have considered neuropathic sensory symptoms to be associated with a high level of pain intensity and negative affectivity. The present study examines the question of whether this association previously found in non-selected samples of chronic pain patients can also be found in chronic pain patients with underlying pathology of neuropathic sensory symptoms.Methods: Neuropathic sensory symptoms in 306 patients with chronic pain diagnosed as typical neuropathic pain, radiculopathy, fibromyalgia, or nociceptive back pain were assessed using the Pain DETECT Questionnaire. Two separate cluster analyses were performed to identify subgroups of patients with different levels of self-reported neuropathic sensory symptoms and, furthermore, to identify subgroups of patients with distinct patterns of neuropathic sensory symptoms (adjusted for individual response bias regarding specific symptoms.Results: ANOVA (analysis of variance results in typical neuropathic pain, radiculopathy, and fibromyalgia showed no significant differences between the three levels of neuropathic sensory symptoms regarding pain intensity, pain chronicity, pain catastrophizing, pain acceptance, and depressive symptoms. However, in nociceptive back pain patients, significant differences were found for all variables except pain chronicity. When controlling for the response bias of patients in ratings of symptoms, none of the patterns of neuropathic sensory symptoms were associated with pain and psychological factors.Conclusion: Neuropathic sensory symptoms are not closely associated with higher levels of pain intensity and cognitive-emotional evaluations in chronic pain patients with underlying pathology of

  20. Sensory Science Education

    DEFF Research Database (Denmark)

    Otrel-Cass, Kathrin

    2018-01-01

    little note of the body-mind interactions we have with the material world. Utilizing examples from primary schools, it is argued that a sensory pedagogy in science requires a deliberate sensitization and validation of the senses’ presence and that a sensor pedagogy approach may reveal the unique ways...... in how we all experience the world. Troubling science education pedagogy is therefore also a reconceptualization of who we are and how we make sense of the world and the acceptance that the body-mind is present, imbalanced and complex....

  1. The effect of treatment with BRX-220, a co-inducer of heat shock proteins, on sensory fibers of the rat following peripheral nerve injury.

    Science.gov (United States)

    Kalmar, B; Greensmith, L; Malcangio, M; McMahon, S B; Csermely, P; Burnstock, G

    2003-12-01

    In this study, we examined the effect BRX-220, a co-inducer of heat shock proteins, in injury-induced peripheral neuropathy. Following sciatic nerve injury in adult rats and treatment with BRX-220, the following features of the sensory system were studied: (a) expression of calcitonin gene-related peptide (CGRP); (b) binding of isolectin B4 (IB4) in dorsal root ganglia (DRG) and spinal cord; (c) stimulation-evoked release of substance P (SP) in an in vitro spinal cord preparation and (d) nociceptive responses of partially denervated rats. BRX-220 partially reverses axotomy-induced changes in the sensory system. In vehicle-treated rats there is a decrease in IB4 binding and CGRP expression in injured neurones, while in BRX-220-treated rats these markers were better preserved. Thus, 7.0 +/- 0.6% of injured DRG neurones bound IB4 in vehicle-treated rats compared to 14.4 +/- 0.9% in BRX-220-treated animals. Similarly, 4.5 +/- 0.5% of DRG neurones expressed CGRP in the vehicle-treated group, whereas 9.0 +/- 0.3% were positive in the BRX-220-treated group. BRX-220 also partially restored SP release from spinal cord sections to electrical stimulation of primary sensory neurones. Behavioural tests carried out on partially denervated animals showed that BRX-220 treatment did not prevent the emergence of mechanical or thermal hyperalgesia. However, oral treatment for 4 weeks lead to reduced pain-related behaviour suggesting either slowly developing analgesic actions or enhancement of recovery processes. Thus, the morphological improvement seen in sensory neurone markers was accompanied by restored functional activity. Therefore, treatment with BRX-220 promotes restoration of morphological and functional properties in the sensory system following peripheral nerve injury.

  2. The sensory system of the esophagus--what do we know?

    Science.gov (United States)

    Brock, Christina; Gregersen, Hans; Gyawali, C Prakash; Lottrup, Christian; Furnari, Manuele; Savarino, Edoardo; Novais, Luis; Frøkjaer, Jens Brøndum; Bor, Serhat; Drewes, Asbjørn Mohr

    2016-09-01

    The nervous innervation and complex mechanical function of the esophagus make sensory evaluation difficult. However, during the last decades, several new techniques have made it possible to gain insight into pain processing of nociceptive signals. The current review highlights the sensory innervation and possibilities for quantitative sensory testing, the mechanosensory properties, the potential of high-resolution manometry and imaging, and the sensory system in special conditions, such as Barrett's esophagus. It is mandatory to understand the complex pathophysiology of the esophagus to enhance our understanding of esophageal disorders, but it also increases the complexity of future experimental and clinical studies. The new methods, as outlined in the current review, provide the possibility for researchers to enhance the quality of interdisciplinary research and to gain more knowledge about sensory symptoms and treatment possibilities. © 2016 New York Academy of Sciences.

  3. Intrinsic frequency response patterns in mechano-sensory neurons of the leech

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    Linda Fischer

    2017-07-01

    Full Text Available Animals employ mechano-sensory systems to detect and explore their environment. Mechano-sensation encompasses stimuli such as constant pressure, surface movement or vibrations at various intensities that need to be segregated in the central nervous system. Besides different receptor structures, sensory filtering via intrinsic response properties could provide a convenient way to solve this problem. In leech, three major mechano-sensory cell types can be distinguished, according to their stimulus sensitivity, as nociceptive, pressure and touch cells. Using intracellular recordings, we show that the different mechano-sensory neuron classes in Hirudo medicinalis differentially respond supra-threshold to distinct frequencies of sinusoidal current injections between 0.2 and 20 Hz. Nociceptive cells responded with a low-pass filter characteristic, pressure cells as high-pass filters and touch cells as an intermediate band-pass filter. Each class of mechano-sensory neurons is thus intrinsically tuned to a specific frequency range of voltage oscillation that could help segregate mechano-sensory information centrally.

  4. Intrinsic frequency response patterns in mechano-sensory neurons of the leech.

    Science.gov (United States)

    Fischer, Linda; Scherbarth, Frank; Chagnaud, Boris; Felmy, Felix

    2017-07-15

    Animals employ mechano-sensory systems to detect and explore their environment. Mechano-sensation encompasses stimuli such as constant pressure, surface movement or vibrations at various intensities that need to be segregated in the central nervous system. Besides different receptor structures, sensory filtering via intrinsic response properties could provide a convenient way to solve this problem. In leech, three major mechano-sensory cell types can be distinguished, according to their stimulus sensitivity, as nociceptive, pressure and touch cells. Using intracellular recordings, we show that the different mechano-sensory neuron classes in Hirudo medicinalis differentially respond supra-threshold to distinct frequencies of sinusoidal current injections between 0.2 and 20 Hz. Nociceptive cells responded with a low-pass filter characteristic, pressure cells as high-pass filters and touch cells as an intermediate band-pass filter. Each class of mechano-sensory neurons is thus intrinsically tuned to a specific frequency range of voltage oscillation that could help segregate mechano-sensory information centrally. © 2017. Published by The Company of Biologists Ltd.

  5. Intraplantar injection of tetrahydrobiopterin induces nociception in mice

    DEFF Research Database (Denmark)

    Nasser, Arafat; Ali, Sawsan; Wilsbech, Signe

    2015-01-01

    . Intrathecal injections of BH4 have been shown to induce and enhance pain-like behaviours in rats, suggesting that under chronic pain conditions BH4 may act by facilitating central sensitisation. So far it is unknown whether BH4 acts on peripheral sites of the somatosensory system or whether BH4 per se...... sites of the somatosensory system, proposing an as yet unexplored involvement of BH4 in peripheral nociceptive processes. However, this appears not to be mediated through nitric oxide and prostaglandin release or by activation of the transient receptor potential vanilloid 1....

  6. Evaluation of Postoperative Anti-nociceptive Efficacy of Intrathecal Dexketoprofen in Rats

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    Birol Muhammet Er

    2016-06-01

    Full Text Available Background: Some studies have suggested that the intrathecal use of cyclooxygenase enzyme inhibitors provides an anti-nociceptive effect. Therefore, the occurrence of side effects seen in systemic usage can be eliminated. Aims: The primary objective of this experimental, randomized, controlled trial was to test the hypothesis asserting that intrathecal dexketoprofen trometamol would demonstrate an analgesic effect during postoperative period. Study Design: Animal experimentation. Methods: Forty rats were randomized into 4 groups 7 days after intrathecal catheterization; the following drugs were given through catheter lumens: Group Lidocaine (Group L: Lidocaine 20 μg; Group Lidocaine-Morphine (Group LM: Lidocaine 20 μg and morphine 0.5 μgr; Group Lidocaine-Dexketoprofen (Group LD: Lidocaine 20 μg and dexketoprofen trometamol 100 μg; and Group Dexketoprofen (Group D: Dexketoprofen trometamol 100 μg. Paw incision was achieved under ether inhalation. To measure analgesic potential, hot plate and tail immersion tests were used as nociceptive tests during the postoperative period. Results: The mean reaction times detected in groups during hot plate and tail immersion tests were shortest in Group L at 15, 30, 45, 60, 75, 90, 105, and 120 minutes after start of surgery (p<0.01, all others. In the groups using dexketoprofen, as in the morphine group, longer reaction times were detected than in the lidocaine group at all measurement times except 120 minutes (p<0.01. Conclusion: Intrathecal dexketoprofen in the optimal perioperative pain management is effective, and can be administered as an adjuvant in clinics after neurotoxicity studies in animals, and effective dose studies in volunteers.

  7. Network dynamics in nociceptive pathways assessed by the neuronal avalanche model

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    Wu José

    2012-04-01

    Full Text Available Abstract Background Traditional electroencephalography provides a critical assessment of pain responses. The perception of pain, however, may involve a series of signal transmission pathways in higher cortical function. Recent studies have shown that a mathematical method, the neuronal avalanche model, may be applied to evaluate higher-order network dynamics. The neuronal avalanche is a cascade of neuronal activity, the size distribution of which can be approximated by a power law relationship manifested by the slope of a straight line (i.e., the α value. We investigated whether the neuronal avalanche could be a useful index for nociceptive assessment. Findings Neuronal activity was recorded with a 4 × 8 multichannel electrode array in the primary somatosensory cortex (S1 and anterior cingulate cortex (ACC. Under light anesthesia, peripheral pinch stimulation increased the slope of the α value in both the ACC and S1, whereas brush stimulation increased the α value only in the S1. The increase in α values was blocked in both regions under deep anesthesia. The increase in α values in the ACC induced by peripheral pinch stimulation was blocked by medial thalamic lesion, but the increase in α values in the S1 induced by brush and pinch stimulation was not affected. Conclusions The neuronal avalanche model shows a critical state in the cortical network for noxious-related signal processing. The α value may provide an index of brain network activity that distinguishes the responses to somatic stimuli from the control state. These network dynamics may be valuable for the evaluation of acute nociceptive processes and may be applied to chronic pathological pain conditions.

  8. Study of nociceptive flexion reflex in healthy subjects and patients with chronic neuropathic pain syndrome.

    Science.gov (United States)

    Gordeev, S A; Turbina, L G; Zus'man, A A; Posokhov, S I

    2012-12-01

    Nociceptive flexion reflex was measured in healthy subjects and patients with chronic neuropathic pain (diabetic distal symmetric sensorimotor polyneuropathy). The study of nociceptive flexion reflex revealed reduction of subjective pain threshold and reflex threshold in patients compared with healthy persons reflecting deficit of descending antinociceptive influences in the CNS.

  9. Influence of Stimulation Location and Posture on the Reliability and Comfort of the Nociceptive Flexion Reflex

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    Gwyn N Lewis

    2012-01-01

    Full Text Available BACKGROUND: The lower limb nociceptive flexion reflex (NFR is commonly used to assess the function of the nociceptive system. Currently, there is a lack of standardized stimulation procedures to determine the NFR threshold, making comparisons of thresholds across studies difficult.

  10. Dependence of nociceptive detection thresholds on physiological parameters and capsaicin-induced neuroplasticity: a computational study

    NARCIS (Netherlands)

    Yang, H.; Meijer, Hil Gaétan Ellart; Doll, Robert; Buitenweg, Jan R.; van Gils, Stephanus A.

    2016-01-01

    Physiological properties of peripheral and central nociceptive subsystems can be altered over time due to medical interventions. The effective change for the whole nociceptive system can be reflected in changes of psychophysical characteristics, e.g., detection thresholds. However, it is challenging

  11. Assessment of anti-nociceptive efficacy of costus speciosus rhizome in swiss albino mice.

    Science.gov (United States)

    Bhattacharya, Sanjib; Nagaich, Upendra

    2010-01-01

    Present study attempts to evaluate the anti-nociceptive activity of the aqueous and ethanol extracts of Costus speciosus rhizome (CPA and CPE) in Swiss albino mice. The maceration extracts were evaluated for anti-nociceptive activity by acetic acid-induced writhing and tail flick method in mice. The anti-nociceptive screening revealed significant peripheral anti-nociceptive actions of both extracts against acetic acid induced writhing in mice. Aqueous extract (CPA) significantly inhibited writhes at the dose of 75 and 150 mg/kg body weight, while ethanol extract (CPE) produced significant protection at the dose of 150 mg/kg body weight. However, in tail flick method only the ethanol extract (CPE) showed significant central analgesic action, while aqueous extract was totally ineffective. The present investigation demonstrates that the rhizome extracts of C. speciosus exhibited significant anti-nociceptive effects in Swiss albino mice.

  12. Assessment of anti-nociceptive efficacy of Costus Speciosus rhizome in swiss albino mice

    Directory of Open Access Journals (Sweden)

    Sanjib Bhattacharya

    2010-01-01

    Full Text Available Present study attempts to evaluate the anti-nociceptive activity of the aqueous and ethanol extracts of Costus speciosus rhizome (CPA and CPE in Swiss albino mice. The maceration extracts were evaluated for anti-nociceptive activity by acetic acid-induced writhing and tail flick method in mice. The anti-nociceptive screening revealed significant peripheral anti-nociceptive actions of both extracts against acetic acid induced writhing in mice. Aqueous extract (CPA significantly inhibited writhes at the dose of 75 and 150 mg/kg body weight, while ethanol extract (CPE produced significant protection at the dose of 150 mg/kg body weight. However, in tail flick method only the ethanol extract (CPE showed significant central analgesic action, while aqueous extract was totally ineffective. The present investigation demonstrates that the rhizome extracts of C. speciosus exhibited significant anti-nociceptive effects in Swiss albino mice.

  13. Strychnine-sensitive glycine receptors mediate analgesia induced by emulsified inhalation anaesthetics in thermal nociception but not in chemical nociception.

    Science.gov (United States)

    Chen, Yan; Dai, Ti-Jun; Zeng, Yin-Ming

    2007-03-01

    The present study was designed to investigate the role of strychnine-sensitive glycine receptors in analgesia induced by emulsified inhalation anaesthetics. After having established the mice model of analgesia by intraperitoneal or subcutaneous injections of appropriate doses of ether, enflurane, isoflurane or sevoflurane, we injected different doses of strychnine intrathecally and then observed the effects on the tail-flick latency using the tail-withdrawal test and the writhing times and acetic acid-induced writhing test. In the tail-withdrawal test, all four emulsified inhalation anaesthetics (intraperitoneally) significantly increased the tail-flick latency (P strychnine. In the acetic acid-induced writhing test, writhing times inhibition induced by subcutaneous administration of four emulsified inhalation anaesthetics was not effected by intrathecal strychnine (0.1, 0.2 and 0.4 microg). The data presented in this study suggest that glycine receptors are specifically involved in mediating the analgesic effect of ether, enflurane, isoflurane and sevoflurane on thermal-induced nociception but not chemically induced nociception.

  14. [Sensory and autonomic neuropathies and pain-related channelopathies].

    Science.gov (United States)

    Kurth, I

    2015-08-01

    Loss of pain perception can result from neurodevelopmental defects, degeneration of nociceptive fibers, or altered excitability of sensory neurons. Hereditary neurodegeneration leading to pain loss is classified as sensory and autonomic neuropathy (HSAN). Mutations in approximately 15 genes have been identified in the group of HSAN disorders. Hallmark of the disease is a liability to injury because of impaired acute pain as a warning system to prevent harm. The clinically overlapping "congenital insensitivity to pain (CIP)" is caused by mutations in voltage-gated sodium channels, which control the excitability of nociceptors. However, mutations in the latter genes can also result in disorders with increased pain susceptibility. This review summarizes the clinical presentation of HSAN and pain-related channelopathies and discusses the underlying disease mechanisms.

  15. Excitability parameters and sensitivity to anemone toxin ATX-II in rat small diameter primary sensory neurones discriminated by Griffonia simplicifolia isolectin IB4.

    Science.gov (United States)

    Snape, Alistair; Pittaway, James F; Baker, Mark D

    2010-01-01

    Sensory neurone subtypes (ATX-II might also discriminate neurones and report that 1 microm has negligible or small effects on action potentials in IB4 +ve, but dramatically increased action potential duration in IB4 ve, neurones. The toxin did not act on tetrodotoxin-resistant (TTX-r) Na(V)1.8 currents; discrimination was based on tetrodotoxin-sensitive (TTX-s) Na(+) channel expression. We also explored the effects of varying the holding potential on current threshold, and the effect of repetitive activation on action currents in IB4 +ve and ve neurones. IB4 +ve neurones became more excitable with depolarization over the range 100 to 20 mV, but IB4 ve neurones exhibited peak excitability near 55 mV, and were inexcitable at 20 mV. Eliciting action potentials at 2 Hz, we found that peak inward action current in IB4 +ve neurones was reduced, whereas changes in the current amplitude were negligible in most IB4 ve neurones. Our findings are consistent with relatively toxin-insensitive channels including Na(V)1.7 being expressed in IB4 +ve neurones, whereas toxin sensitivity indicates that IB4 ve neurones may express Na(V)1.1 or Na(V)1.2, or both. The retention of excitability at low membrane potentials, and the responses to repetitive stimulation are explained by the known preferential expression of Na(V)1.8 in IB4 +ve neurones, and the reduction in action current in IB4 +ve neurones with repetitive stimulation supports a novel hypothesis explaining the slowing of conduction velocity in C-fibres by the build-up of Na(+) channel inactivation.

  16. Cerebral processing of pain in school-aged children with neonatal nociceptive input: an exploratory fMRI study.

    Science.gov (United States)

    Hohmeister, Johanna; Kroll, Alexander; Wollgarten-Hadamek, Iris; Zohsel, Katrin; Demirakça, Süha; Flor, Herta; Hermann, Christiane

    2010-08-01

    Due to maturation-related plasticity of the developing nociceptive system, neonatal nociceptive input, as induced by medical procedures in the neonatal intensive care unit (NICU), may cause long-term alterations in pain processing. Using functional magnetic resonance imaging, this study investigated the cerebral pain response in school-aged children and adolescents (11-16 yr) with experience in a NICU after preterm (or=37 weeks gestational age, N=9) as compared to fullterm control children without early hospitalization (N=9). NICU children had been recruited retrospectively among former patients of the Children's University Hospital Mannheim. All children had participated in our previous studies [46,49] entailing psychophysical measurements. In response to tonic (30s) heat stimuli of individually adjusted moderate pain intensity, which were of comparable temperature across groups, the preterm but not the fullterm NICU children exhibited significant activations in a number of brain regions (thalamus, anterior cingulate cortex, cerebellum, basal ganglia, and periaquaeductal gray) that were not significantly activated in controls. The preterms showed significantly higher activations than controls in primary somatosensory cortex, anterior cingulate cortex, and insula. This exaggerated brain response was pain-specific and was not observed during non-painful warmth stimulation. Preterms' continuous pain ratings revealed a tendency for increased sensitization within and a lack of habituation across trials. In highly vulnerable children such as preterms, neonatal nociceptive input may, aside from other neurodevelopmental consequences, persistently increase the gain within pain pathways. Copyright (c) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  17. Prenatal VPA exposure and changes in sensory processing by the superior colliculus

    Directory of Open Access Journals (Sweden)

    Georgia eDendrinos

    2011-10-01

    Full Text Available Disorders involving dysfunctional sensory processing are characterized by an inability to filter sensory information, particularly simultaneously arriving multimodal inputs. We examined the effects of prenatal exposure to valproic acid (VPA, a teratogen linked to sensory dysfunction, on the behavior of juvenile and adult rats, and on the anatomy of the superior colliculus, a critical multisensory integration center in the brain. VPA-exposed rats showed deficits in colliculus-dependent behaviors including startle response, prepulse inhibition and nociceptive responses. Some deficits reversed with age. Stereological analyses revealed that colliculi of VPA-treated rats had significantly fewer parvalbumin-positive neurons, a subset of GABAergic cells. These results suggest that prenatal VPA treatment affects the development of the superior colliculus and leads to persistent anatomical changes evidenced by aberrant behavior in tasks that require sensory processing.

  18. Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release.

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    Seungwon Choi

    2015-07-01

    Full Text Available C. elegans undergoes periods of behavioral quiescence during larval molts (termed lethargus and as adults. Little is known about the circuit mechanisms that establish these quiescent states. Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1. Here, we show that the aroused locomotion of npr-1 mutants results from the exaggerated activity in multiple classes of sensory neurons, including nociceptive (ASH, touch sensitive (ALM and PLM, and stretch sensing (DVA neurons. These sensory neurons accelerate locomotion via both neuropeptide and glutamate release. The relative contribution of these sensory neurons to arousal differs between larval molts and adults. Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states.

  19. Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release

    Science.gov (United States)

    Chatzigeorgiou, Marios; Hu, Zhitao; Schafer, William R.; Kaplan, Joshua M.

    2015-01-01

    C. elegans undergoes periods of behavioral quiescence during larval molts (termed lethargus) and as adults. Little is known about the circuit mechanisms that establish these quiescent states. Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide receptor NPR-1. Here, we show that the aroused locomotion of npr-1 mutants results from the exaggerated activity in multiple classes of sensory neurons, including nociceptive (ASH), touch sensitive (ALM and PLM), and stretch sensing (DVA) neurons. These sensory neurons accelerate locomotion via both neuropeptide and glutamate release. The relative contribution of these sensory neurons to arousal differs between larval molts and adults. Our results suggest that a broad network of sensory neurons dictates transitions between aroused and quiescent behavioral states. PMID:26154367

  20. The nociceptive withdrawal reflex does not adapt to joint position change and short-term motor practice [v2; ref status: indexed, http://f1000r.es/2lr

    Directory of Open Access Journals (Sweden)

    Nathan Eckert

    2013-12-01

    Full Text Available The nociceptive withdrawal reflex is a protective mechanism to mediate interactions within a potentially dangerous environment. The reflex is formed by action-based sensory encoding during the early post-natal developmental period, and it is unknown if the protective motor function of the nociceptive withdrawal reflex in the human upper-limb is adaptable based on the configuration of the arm or if it can be modified by short-term practice of a similar or opposing motor action. In the present study, nociceptive withdrawal reflexes were evoked by a brief train of electrical stimuli applied to digit II, 1 in five different static arm positions and, 2 before and after motor practice that was opposite (EXT or similar (FLEX to the stereotyped withdrawal response, in 10 individuals. Withdrawal responses were quantified by the electromyography (EMG reflex response in several upper limb muscles, and by the forces and moments recorded at the wrist. EMG onset latencies and response amplitudes were not significantly different across the arm positions or between the EXT and FLEX practice conditions, and the general direction of the withdrawal response was similar across arm positions. In addition, the force vectors were not different after practice in either the practice condition or between EXT and FLEX conditions. We conclude the withdrawal response is insensitive to changes in elbow or shoulder joint angles as well as remaining resistant to short-term adaptations from the practice of motor actions, resulting in a generalized limb withdrawal in each case. It is further hypothesized that the multisensory feedback is weighted differently in each arm position, but integrated to achieve a similar withdrawal response to safeguard against erroneous motor responses that could cause further harm. The results remain consistent with the concept that nociceptive withdrawal reflexes are shaped through long-term and not short-term action based sensory encoding.

  1. Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

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    Heike L Rittner

    2009-04-01

    Full Text Available In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR and/or toll like receptor (TLR agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively. Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim

  2. Anatomy, physiology and neurobiology of the nociception: a focus on low back pain (part A).

    Science.gov (United States)

    Mertens, P; Blond, S; David, R; Rigoard, P

    2015-03-01

    The treatment of Failed Back Surgery Syndrome (FBSS) remains a challenge for pain medicine due to the complexity in the interactions between [1] a residual mechanical pain after surgery and, [2] a progressive transition into chronic pain involving central nervous system plasticity and molecular reorganization. The aim of this paper is to provide a fundamental overview of the pain pathway supporting the nociceptive component of the back pain. Literature searches included an exhaustive review of 643 references and 74 book chapters updated by searching the major electronic databases from 1930 to August 2013. Pain input is gathered by the peripheral fibre from the innervated tissue's environment and relayed by two contiguous central axons to the brain, via the spinal cord. At this level, it is possible to characterize physical pain and emotional pain. These are supported by two different pathways, encoding two dimensions of pain perception: In Neo-spino-thalamic pathway, the wide dynamic range neuron system is able to provide the information needed for mapping the "sensory-discriminative" dimension of pain. The second projection system (Paleo-spino-thalamic pathway) also involves the ventromedial thalamus but projects to the amygdala, the insula and the anterior cingulate cortex. These areas are associated with emotionality and affect. The mechanical component of FBSS cannot be understood unless the functioning of the pain system is known. But ultimately, the highly variable nature of back pain expression among individuals would require a careful pathophysiological dissection of the potential generators of back pain to guide pain management strategies. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. The Interface of Mechanics and Nociception in Joint Pathophysiology: Insights From the Facet and Temporomandibular Joints

    Science.gov (United States)

    Sperry, Megan M.; Ita, Meagan E.; Kartha, Sonia; Zhang, Sijia; Yu, Ya-Hsin; Winkelstein, Beth

    2017-01-01

    Chronic joint pain is a widespread problem that frequently occurs with aging and trauma. Pain occurs most often in synovial joints, the body's load bearing joints. The mechanical and molecular mechanisms contributing to synovial joint pain are reviewed using two examples, the cervical spinal facet joints and the temporomandibular joint (TMJ). Although much work has focused on the macroscale mechanics of joints in health and disease, the combined influence of tissue mechanics, molecular processes, and nociception in joint pain has only recently become a focus. Trauma and repeated loading can induce structural and biochemical changes in joints, altering their microenvironment and modifying the biomechanics of their constitutive tissues, which themselves are innervated. Peripheral pain sensors can become activated in response to changes in the joint microenvironment and relay pain signals to the spinal cord and brain where pain is processed and perceived. In some cases, pain circuitry is permanently changed, which may be a potential mechanism for sustained joint pain. However, it is most likely that alterations in both the joint microenvironment and the central nervous system (CNS) contribute to chronic pain. As such, the challenge of treating joint pain and degeneration is temporally and spatially complicated. This review summarizes anatomy, physiology, and pathophysiology of these joints and the sensory pain relays. Pain pathways are postulated to be sensitized by many factors, including degeneration and biochemical priming, with effects on thresholds for mechanical injury and/or dysfunction. Initiators of joint pain are discussed in the context of clinical challenges including the diagnosis and treatment of pain. PMID:28056123

  4. Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

    Science.gov (United States)

    Casey, Kenneth L.

    1999-07-01

    Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

  5. Sertraline inhibits formalin-induced nociception and cardiovascular responses

    Energy Technology Data Exchange (ETDEWEB)

    Santuzzi, C.H. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Futuro Neto, H.A. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Escola de Medicina da Empresa Brasileira de Ensino, Pesquisa e Extensão, Vitória, ES (Brazil); Escola Superior de Ciências da Saúde, Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil); Pires, J.G.P. [Escola de Medicina da Empresa Brasileira de Ensino, Pesquisa e Extensão, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Gonçalves, W.L.S. [Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Tiradentes, R.V.; Gouvea, S.A.; Abreu, G.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2011-11-18

    The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8 per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg{sup −1}·day{sup −1}, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5% (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7%), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9%, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.

  6. Supraspinal modulation of neuronal synchronization by nociceptive stimulation induces an enduring reorganization of dorsal horn neuronal connectivity.

    Science.gov (United States)

    Contreras-Hernández, E; Chávez, D; Hernández, E; Velázquez, E; Reyes, P; Béjar, J; Martín, M; Cortés, U; Glusman, S; Rudomin, P

    2018-02-16

    weak mechanical stimulation of the skin in the region of secondary but not primary hyperalgesia. The effects of both intradermic capsaicin and systemic lidocaine on the segmental correlation and coherence between ongoing cord dorsum potentials and on the responses evoked by tactile stimulation in the region of secondary hyperalgesia are greatly attenuated in spinalized preparations, showing that supraspinal influences are involved in the reorganization of the nociceptive-induced structured patterns of dorsal horn neuronal connectivity. We conclude that the structured reorganization of the functional connectivity between the dorsal horn neurones induced by capsaicin nociceptive stimulation results from cooperative interactions between supraspinal and spinal networks, a process that may have a relevant role in the shaping of the spinal state in the pathogenesis of chronic pain and analgesia. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

  7. TRPA1, substance P, histamine and 5-hydroxytryptamine interact in an interdependent way to induce nociception.

    Science.gov (United States)

    Fischer, Luana; Lavoranti, Maria Isabel; de Oliveira Borges, Mariana; Miksza, Alana Farias; Sardi, Natalia Fantin; Martynhak, Bruno Jacson; Tambeli, Claudia H; Parada, Carlos Amílcar

    2017-04-01

    Although TRPA1, SP, histamine and 5-hydroxytryptamine (5-HT) have recognized contribution to nociceptive mechanisms, little is known about how they interact with each other to mediate inflammatory pain in vivo. In this study we evaluated whether TRPA1, SP, histamine and 5-HT interact, in an interdependent way, to induce nociception in vivo. The subcutaneous injection of the TRPA1 agonist allyl isothiocyanate (AITC) into the rat's hind paw induced a dose-dependent and short lasting behavioral nociceptive response that was blocked by the co-administration of the TRPA1 antagonist, HC030031, or by the pretreatment with antisense ODN against TRPA1. AITC-induced nociception was significantly decreased by the co-administration of selective antagonists for the NK1 receptor for substance P, the H1 receptor for histamine and the 5-HT 1A or 3 receptors for 5-HT. Histamine- or 5-HT-induced nociception was decreased by the pretreatment with antisense ODN against TRPA1. These findings suggest that AITC-induced nociception depends on substance P, histamine and 5-HT, while histamine- or 5-HT-induced nociception depends on TRPA1. Most important, AITC interact in a synergistic way with histamine, 5-HT or substance P, since their combination at non-nociceptive doses induced a nociceptive response much higher than that expected by the sum of the effect of each one alone. This synergistic effect is dependent on the H1, 5-HT 1A or 3 receptors. Together, these findings suggest a self-sustainable cycle around TRPA1, no matter where the cycle is initiated each step is achieved and even subeffective activation of more than one step results in a synergistic activation of the overall cycle.

  8. Learning from sensory and reward prediction errors during motor adaptation.

    Science.gov (United States)

    Izawa, Jun; Shadmehr, Reza

    2011-03-01

    Voluntary motor commands produce two kinds of consequences. Initially, a sensory consequence is observed in terms of activity in our primary sensory organs (e.g., vision, proprioception). Subsequently, the brain evaluates the sensory feedback and produces a subjective measure of utility or usefulness of the motor commands (e.g., reward). As a result, comparisons between predicted and observed consequences of motor commands produce two forms of prediction error. How do these errors contribute to changes in motor commands? Here, we considered a reach adaptation protocol and found that when high quality sensory feedback was available, adaptation of motor commands was driven almost exclusively by sensory prediction errors. This form of learning had a distinct signature: as motor commands adapted, the subjects altered their predictions regarding sensory consequences of motor commands, and generalized this learning broadly to neighboring motor commands. In contrast, as the quality of the sensory feedback degraded, adaptation of motor commands became more dependent on reward prediction errors. Reward prediction errors produced comparable changes in the motor commands, but produced no change in the predicted sensory consequences of motor commands, and generalized only locally. Because we found that there was a within subject correlation between generalization patterns and sensory remapping, it is plausible that during adaptation an individual's relative reliance on sensory vs. reward prediction errors could be inferred. We suggest that while motor commands change because of sensory and reward prediction errors, only sensory prediction errors produce a change in the neural system that predicts sensory consequences of motor commands.

  9. Epilepsy and the Sensory Systems

    OpenAIRE

    Wolf, Peter

    2016-01-01

    The relations of epilepsy and the sensory systems are bidirectional. Epilepsy may act on sensory systems by producing sensory seizure symptoms, by altering sensory performance, and by epilepsy treatment causing sensory side effects. Sensory system activity may have an important role in both generation and inhibition of seizures.

  10. Emergent spatial patterns of excitatory and inhibitory synaptic strengths drive somatotopic representational discontinuities and their plasticity in a computational model of primary sensory cortical area 3b

    Directory of Open Access Journals (Sweden)

    Kamil A. Grajski

    2016-07-01

    Full Text Available Mechanisms underlying the emergence and plasticity of representational discontinuities in the mammalian primary somatosensory cortical representation of the hand are investigated in a computational model. The model consists of an input lattice organized as a three-digit hand forward-connected to a lattice of cortical columns each of which contains a paired excitatory and inhibitory cell. Excitatory and inhibitory synaptic plasticity of feedforward and lateral connection weights is implemented as a simple covariance rule and competitive normalization. Receptive field properties are computed independently for excitatory and inhibitory cells and compared within and across columns. Within digit representational zones intracolumnar excitatory and inhibitory receptive field extents are concentric, single-digit, small, and unimodal. Exclusively in representational boundary-adjacent zones, intracolumnar excitatory and inhibitory receptive field properties diverge: excitatory cell receptive fields are single-digit, small, and unimodal; and the paired inhibitory cell receptive fields are bimodal, double-digit, and large. In simulated syndactyly (webbed fingers, boundary-adjacent intracolumnar receptive field properties reorganize to within-representation type; divergent properties are reacquired following syndactyly release. This study generates testable hypotheses for assessment of cortical laminar-dependent receptive field properties and plasticity within and between cortical representational zones. For computational studies, present results suggest that concurrent excitatory and inhibitory plasticity may underlie novel emergent properties.

  11. Identifying brain nociceptive information transmission in patients with chronic somatic pain

    Directory of Open Access Journals (Sweden)

    Don A. Davis

    2016-10-01

    Conclusion:. Collectively, the results suggest that, across 2 types of chronic pain, nociceptive-specific information is relayed through the spinothalamic pathway to the lateral thalamus, potentiated by pronociceptive descending modulation, and interrupting cortical cognitive processes.

  12. Vagus nerve stimulation inhibits trigeminal nociception in a rodent model of episodic migraine

    Directory of Open Access Journals (Sweden)

    Jordan L. Hawkins

    2017-12-01

    Conclusion:. Our findings demonstrate that nVNS inhibits mechanical nociception and represses expression of proteins associated with peripheral and central sensitization of trigeminal neurons in a novel rodent model of episodic migraine.

  13. Electrophysiological assessment of nociception in patients with Parkinson's disease : A multi-methods approach

    NARCIS (Netherlands)

    Priebe, Janosch A.; Kunz, Miriam; Morcinek, Christian; Rieckmann, Peter; Lautenbacher, Stefan

    2016-01-01

    Objective: Nociceptive abnormalities indicating increased pain sensitivity have been reported in patients with Parkinson's disease (PD). The disturbances are mostly responsive to dopaminergic (DA) treatment; yet, there are conflicting results. The objective of the present study was to investigate

  14. Comparing intensities and modalities within the sensory attenuation paradigm: Preliminary evidence

    Directory of Open Access Journals (Sweden)

    Dalila Burin

    2017-11-01

    Full Text Available It is well-documented that the intensity of a self-generated somatosensory stimulus is perceived to be attenuated in respect to an identical stimulus generated by others. At present, it is not clear whether such a phenomenon, known as somatosensory attenuation, is based not only on feedforward motor signals but also on re-afferences towards the body. To answer this question, in the present pilot investigation on twelve healthy subjects, three types of stimulations (sensory non-nociceptive electrical – ES, nociceptive electrical – NES, and vibrotactile – VTS and intensities (1 = sensory threshold ∗ 2.5 + 2 mA, 2 = sensory threshold ∗ 2.5 + 3 mA, 3 = sensory threshold ∗ 2.5 + 4 mA for ES and NES; 1 = sensory threshold ∗ 2 Hz, 2 = sensory threshold ∗ 3 Hz, 3 = sensory threshold ∗ 4 Hz for VTS have been directly compared in a somatosensory attenuation paradigm. The results show that the attenuation effect emerged only with electrical stimuli and that it increased with higher intensities. These pilot findings suggest that, depending on the type and the intensity of stimulation, re-afferences can have a role in somatosensory attenuation. Additionally, it is possible to speculate the effect is present only with electrical stimuli because those stimuli are prospectively judged as potentially dangerous. This, in turn, would optimize planning successful reactions to incoming threatening stimuli.

  15. Neuronal nitric oxide synthase is involved in the induction of NGF induced neck muscle nociception

    OpenAIRE

    Isaak, Andreas

    2011-01-01

    BACKGROUND: Neck muscle nociception mediated by nitric oxide may play a role in the pathophysiology of tension-type headache.OBJECTIVE: The present study addresses the involvement of neuronal nitric oxide synthase (nNOS) in the facilitation of neck muscle nociception after local application of nerve growth factor (NGF).METHODS: After administration of NGF into semispinal neck muscles, the impact of neck muscle noxious input on brainstem processing was monitored by the jaw-opening reflex in an...

  16. Measuring persistent temporomandibular joint nociception in rats and two mice strains

    OpenAIRE

    Kramer, Phillip R.; Kerins, Carolyn A.; Schneiderman, Emet; Bellinger, Larry L.

    2010-01-01

    Temporomandibular joint (TMJ) pain has been reported to last for prolonged periods in humans. In rodents a variety of methods have been used to measure TMJ nociception, but for most of these methods the period of measurement has been minutes to a couple of hours. In addition, most measurement protocols required restraint or training of the animal. Previous studies from our laboratory demonstrated that feeding behavior, particularly meal duration, was an indicator of TMJ nociception in unrestr...

  17. Anti-nociceptive and anti-inflammatory effects of the methanolic extract of Opuntia humifusa stem

    OpenAIRE

    Bhesh Raj Sharma; Chul Min Park; Jong Choi; Dong Young Rhyu

    2017-01-01

    Objective: Opuntia humifusa (O. humifusa) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). Materials and Methods: The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular...

  18. The relationship between nociceptive brain activity, spinal reflex withdrawal and behaviour in newborn infants

    Science.gov (United States)

    Hartley, Caroline; Goksan, Sezgi; Poorun, Ravi; Brotherhood, Kelly; Mellado, Gabriela Schmidt; Moultrie, Fiona; Rogers, Richard; Adams, Eleri; Slater, Rebeccah

    2015-01-01

    Measuring infant pain is complicated by their inability to describe the experience. While nociceptive brain activity, reflex withdrawal and facial grimacing have been characterised, the relationship between these activity patterns has not been examined. As cortical and spinally mediated activity is developmentally regulated, it cannot be assumed that they are predictive of one another in the immature nervous system. Here, using a new experimental paradigm, we characterise the nociceptive-specific brain activity, spinal reflex withdrawal and behavioural activity following graded intensity noxious stimulation and clinical heel lancing in 30 term infants. We show that nociceptive-specific brain activity and nociceptive reflex withdrawal are graded with stimulus intensity (p < 0.001), significantly correlated (r = 0.53, p = 0.001) and elicited at an intensity that does not evoke changes in clinical pain scores (p = 0.55). The strong correlation between reflex withdrawal and nociceptive brain activity suggests that movement of the limb away from a noxious stimulus is a sensitive indication of nociceptive brain activity in term infants. This could underpin the development of new clinical pain assessment measures. PMID:26228435

  19. [Postsynaptic reactions of cerebral cortex neurons, activated by nociceptive afferents during stimulation of the Raphe nuclei].

    Science.gov (United States)

    Labakhua, T Sh; Dzhanashiia, T K; Gedevanishvili, G I; Dzhokhadze, L D; Tkemaladze, T T; Abzianidze, I V

    2012-01-01

    On cats, we studied the influence of stimulation of the Raphe nuclei (RN) on postsynaptic processes evoked in neurons of the somatosensory cortex by stimulation of nociceptive (intensive stimulation of the tooth pulp) and non-nociceptive (moderate stimulation of the ventroposteromedial--VPN--nucleus of the thalamus) afferent inputs. 6 cells, selectively excited by stimulation of nocciceptors and 9 cells, activated by both the above nociceptive and non-nociceptive influences (nociceptive and convergent neurons, respectively) were recorded intracellular. In neurons of both groups, responses to nociceptive stimulation (of sufficient intensity) looked like an EPSP-spike-IPSP (the letter of significant duration, up to 200-300 ms) compleх. Conditioning stimulation of the RN which preceded test stimulus applied to the tooth pulp or VPM nucleus by 100 to 800 ms, induced 40-60 % decrease of the IPSP amplitude only, while maхimal effect of influence, in both cases, was noted within intervals of 300-800 ms between conditioning and test stimulus. During stimulation of the RN, serotonin released via receptor and second messengers, provides postsynaptic modulation of GABAergic system, decreasing the IPSP amplitude which occurs after stimulation of both the tooth pulp and VPM thalamic nucleus. This process may be realized trough either pre- or postsynaptic mechanisms.

  20. Habituation and sensitization in primary headaches

    Science.gov (United States)

    2013-01-01

    The phenomena of habituation and sensitization are considered most useful for studying the neuronal substrates of information processing in the CNS. Both were studied in primary headaches, that are functional disorders of the brain characterized by an abnormal responsivity to any kind of incoming innocuous or painful stimuli and it’s cycling pattern over time (interictal, pre-ictal, ictal). The present review summarizes available data on stimulus responsivity in primary headaches obtained with clinical neurophysiology. In migraine, the majority of electrophysiological studies between attacks have shown that, for a number of different sensory modalities, the brain is characterised by a lack of habituation of evoked responses to repeated stimuli. This abnormal processing of the incoming information reaches its maximum a few days before the beginning of an attack, and normalizes during the attack, at a time when sensitization may also manifest itself. An abnormal rhythmic activity between thalamus and cortex, namely thalamocortical dysrhythmia, may be the pathophysiological mechanism subtending abnormal information processing in migraine. In tension-type headache (TTH), only few signs of deficient habituation were observed only in subgroups of patients. By contrast, using grand-average responses indirect evidence for sensitization has been found in chronic TTH with increased nociceptive specific reflexes and evoked potentials. Generalized increased sensitivity to pain (lower thresholds and increased pain rating) and a dysfunction in supraspinal descending pain control systems may contribute to the development and/or maintenance of central sensitization in chronic TTH. Cluster headache patients are chrarcterized during the bout and on the headache side by a pronounced lack of habituation of the brainstem blink reflex and a general sensitization of pain processing. A better insight into the nature of these ictal/interictal electrophysiological dysfunctions in primary

  1. Factors affecting mechanical nociceptive thresholds in healthy sows.

    Science.gov (United States)

    Nalon, Elena; Maes, Dominiek; Piepers, Sofie; Taylor, Polly; van Riet, Miriam M J; Janssens, Geert P J; Millet, Sam; Tuyttens, Frank A M

    2016-05-01

    To describe anatomical and methodological factors influencing mechanical nociceptive thresholds (MNTs) and intra-site variability in healthy sows. Prospective, randomized validation. Eight pregnant, healthy, mixed-parity sows (176-269 kg). Repeated MNT measurements were taken: 1) with a hand-held probe and a limb-mounted actuator connected to a digital algometer; 2) at nine landmarks on the limbs and tail; and 3) at 1 and 3 minute intervals. Data were analysed using linear mixed regression models. The MNTs (±SEM) of the limbs were lower with the probe (14.7 ± 1.2 N) than with the actuator (21.3 ± 1.2 N; p testing compared with day 1 (p < 0.001). The mean CV (±SE) was 38.9% (±1.1%). MNTs and intra-site variability in healthy sows were affected by several factors, indicating that this methodology requires considerable attention to detail. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  2. Regulation of Wnt signaling by nociceptive input in animal models

    Directory of Open Access Journals (Sweden)

    Shi Yuqiang

    2012-06-01

    Full Text Available Abstract Background Central sensitization-associated synaptic plasticity in the spinal cord dorsal horn (SCDH critically contributes to the development of chronic pain, but understanding of the underlying molecular pathways is still incomplete. Emerging evidence suggests that Wnt signaling plays a crucial role in regulation of synaptic plasticity. Little is known about the potential function of the Wnt signaling cascades in chronic pain development. Results Fluorescent immunostaining results indicate that β-catenin, an essential protein in the canonical Wnt signaling pathway, is expressed in the superficial layers of the mouse SCDH with enrichment at synapses in lamina II. In addition, Wnt3a, a prototypic Wnt ligand that activates the canonical pathway, is also enriched in the superficial layers. Immunoblotting analysis indicates that both Wnt3a a β-catenin are up-regulated in the SCDH of various mouse pain models created by hind-paw injection of capsaicin, intrathecal (i.t. injection of HIV-gp120 protein or spinal nerve ligation (SNL. Furthermore, Wnt5a, a prototypic Wnt ligand for non-canonical pathways, and its receptor Ror2 are also up-regulated in the SCDH of these models. Conclusion Our results suggest that Wnt signaling pathways are regulated by nociceptive input. The activation of Wnt signaling may regulate the expression of spinal central sensitization during the development of acute and chronic pain.

  3. Brief report: Further evidence of sensory subtypes in autism.

    Science.gov (United States)

    Lane, Alison E; Dennis, Simon J; Geraghty, Maureen E

    2011-06-01

    Distinct sensory processing (SP) subtypes in autism have been reported previously. This study sought to replicate the previous findings in an independent sample of thirty children diagnosed with an Autism Spectrum Disorder. Model-based cluster analysis of parent-reported sensory functioning (measured using the Short Sensory Profile) confirmed the triad of sensory subtypes reported earlier. Subtypes were differentiated from each other based on degree of SP dysfunction, taste/smell sensitivity and vestibular/proprioceptive processing. Further elucidation of two of the subtypes was also achieved in this study. Children with a primary pattern of sensory-based inattention could be further described as sensory seekers or non-seekers. Children with a primary pattern of vestibular/proprioceptive dysfunction were also differentiated on movement and tactile sensitivity.

  4. The Chemical Background for Sensory Quality

    DEFF Research Database (Denmark)

    Zhang, Shujuan

    or consumer panels. Sensory evaluation is a primary measurement for providing immediate information of human perception on the products. Instrumental methods give objective analysis of compounds that potentially contribute to food flavour. These two kinds of analysis, basically, give different types...... of information about food flavour but correlate to each other. The exploration of relationships between sensory and instrumental data is one important aspect for fundamental understanding of the mechanisms of sensory perception. This thesis has investigated the importance and limitation of aroma analysis...... closer towards the direct link between volatiles and sensory sensation. In Study 5, GC-O results showed that esters were the main odour active compounds which contribute to fruity notes of Solaris wine. An optimized APCI-MS/MS method in monitoring in nose (in vivo) aroma release for select odour active...

  5. Cellular mechanisms for presynaptic inhibition of sensory afferents

    DEFF Research Database (Denmark)

    Perrier, Jean-Francois Marie; delgado-lezama, rodolfo; Christensen, Rasmus Kordt

    (DRP) by stimulating one dorsal root and recording another one. In the presence of a low concentration of tetrodotoxin (100nM) nerve impulses are abolished centrally but remain in nociceptive afferents. Under these conditions, a DRP generated by a non-spiking microcircuit remained. In the presence...... with a 2-photon microscope. Stimulation of primary afferents evoked a transient increase in calcium concentration in a subset of cells. The response disappeared after addition of CNQX. This showed that primary afferents activate astrocytes. In a thin slice preparation, we recorded astrocytes with the whole...

  6. Onset timing of cross-sensory activations and multisensory interactions in auditory and visual sensory cortices.

    Science.gov (United States)

    Raij, Tommi; Ahveninen, Jyrki; Lin, Fa-Hsuan; Witzel, Thomas; Jääskeläinen, Iiro P; Letham, Benjamin; Israeli, Emily; Sahyoun, Cherif; Vasios, Christos; Stufflebeam, Steven; Hämäläinen, Matti; Belliveau, John W

    2010-05-01

    Here we report early cross-sensory activations and audiovisual interactions at the visual and auditory cortices using magnetoencephalography (MEG) to obtain accurate timing information. Data from an identical fMRI experiment were employed to support MEG source localization results. Simple auditory and visual stimuli (300-ms noise bursts and checkerboards) were presented to seven healthy humans. MEG source analysis suggested generators in the auditory and visual sensory cortices for both within-modality and cross-sensory activations. fMRI cross-sensory activations were strong in the visual but almost absent in the auditory cortex; this discrepancy with MEG possibly reflects the influence of acoustical scanner noise in fMRI. In the primary auditory cortices (Heschl's gyrus) the onset of activity to auditory stimuli was observed at 23 ms in both hemispheres, and to visual stimuli at 82 ms in the left and at 75 ms in the right hemisphere. In the primary visual cortex (Calcarine fissure) the activations to visual stimuli started at 43 ms and to auditory stimuli at 53 ms. Cross-sensory activations thus started later than sensory-specific activations, by 55 ms in the auditory cortex and by 10 ms in the visual cortex, suggesting that the origins of the cross-sensory activations may be in the primary sensory cortices of the opposite modality, with conduction delays (from one sensory cortex to another) of 30-35 ms. Audiovisual interactions started at 85 ms in the left auditory, 80 ms in the right auditory and 74 ms in the visual cortex, i.e., 3-21 ms after inputs from the two modalities converged.

  7. Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures.

    Science.gov (United States)

    Ayzenberg, I; Obermann, M; Nyhuis, P; Gastpar, M; Limmroth, V; Diener, H C; Kaube, H; Katsarava, Z

    2006-09-01

    Trigeminal and somatic nociceptive systems were studied in controls (n=15), episodic migraine (n=16), analgesics (n=14) and triptan-induced medication overuse headache (MOH) (n=15) before and after withdrawal. Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression. Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials (PREP) and nociceptive blink reflex (nBR) following nociceptive-specific electrical stimulation of the forehead. Somatic nociception was evaluated using PREP of upper limbs. We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH, which normalized after withdrawal. No differences were found comparing analgesics vs. triptan MOH. No differences were observed between controls and patients with episodic migraine and depression without headache. A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH, which was more pronounced on a supraspinal level.

  8. The nociceptive and anti-nociceptive effects of bee venom injection and therapy: a double-edged sword.

    Science.gov (United States)

    Chen, Jun; Lariviere, William R

    2010-10-01

    Bee venom injection as a therapy, like many other complementary and alternative medicine approaches, has been used for thousands of years to attempt to alleviate a range of diseases including arthritis. More recently, additional theraupeutic goals have been added to the list of diseases making this a critical time to evaluate the evidence for the beneficial and adverse effects of bee venom injection. Although reports of pain reduction (analgesic and antinociceptive) and anti-inflammatory effects of bee venom injection are accumulating in the literature, it is common knowledge that bee venom stings are painful and produce inflammation. In addition, a significant number of studies have been performed in the past decade highlighting that injection of bee venom and components of bee venom produce significant signs of pain or nociception, inflammation and many effects at multiple levels of immediate, acute and prolonged pain processes. This report reviews the extensive new data regarding the deleterious effects of bee venom injection in people and animals, our current understanding of the responsible underlying mechanisms and critical venom components, and provides a critical evaluation of reports of the beneficial effects of bee venom injection in people and animals and the proposed underlying mechanisms. Although further studies are required to make firm conclusions, therapeutic bee venom injection may be beneficial for some patients, but may also be harmful. This report highlights key patterns of results, critical shortcomings, and essential areas requiring further study. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Functional sensory symptoms

    NARCIS (Netherlands)

    Stone, J.; Vermeulen, M.

    2017-01-01

    Functional (psychogenic) sensory symptoms are those in which the patient genuinely experiences alteration or absence of normal sensation in the absence of neurologic disease. The hallmark of functional sensory symptoms is the presence of internal inconsistency revealing a pattern of symptoms

  10. A new role of growth hormone and insulin growth factor receptor type 1 in neonatal inflammatory nociception

    Directory of Open Access Journals (Sweden)

    Alfredo Manzano-García

    2017-08-01

    Full Text Available Abstract. Growth hormone (GH and insulin growth factor 1 (IGF1 are implicated in nociceptive processing; it has been reported that the latter participates in neonatal inflammatory nociception. In the target article, the authors propose that local inflammation evoked by carrageenan administration in mice produces a decrease in the local GH levels and an increment of IGF1 receptors type 1 expression, this produces behavioral nociception and peripheral sensitization that can be prevented by GH systemic administration pretreatment.

  11. Changes in thermal nociceptive responses in dairy cows following experimentally induced Esherichia coli mastitis

    DEFF Research Database (Denmark)

    Rasmussen, Ditte B.; Fogsgaard, Katrine; Røntved, Christine Maria

    2011-01-01

    Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NL......) in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables....

  12. Sensory correlations in autism.

    Science.gov (United States)

    Kern, Janet K; Trivedi, Madhukar H; Grannemann, Bruce D; Garver, Carolyn R; Johnson, Danny G; Andrews, Alonzo A; Savla, Jayshree S; Mehta, Jyutika A; Schroeder, Jennifer L

    2007-03-01

    This study examined the relationship between auditory, visual, touch, and oral sensory dysfunction in autism and their relationship to multisensory dysfunction and severity of autism. The Sensory Profile was completed on 104 persons with a diagnosis of autism, 3 to 56 years of age. Analysis showed a significant correlation between the different processing modalities using total scores. Analysis also showed a significant correlation between processing modalities for both high and low thresholds, with the exception that auditory high threshold processing did not correlate with oral low threshold or touch low threshold processing. Examination of the different age groups suggests that sensory disturbance correlates with severity of autism in children, but not in adolescents and adults. Evidence from this study suggests that: all the main modalities and multisensory processing appear to be affected; sensory processing dysfunction in autism is global in nature; and sensory processing problems need to be considered part of the disorder.

  13. Probabilistic sensory recoding.

    Science.gov (United States)

    Jazayeri, Mehrdad

    2008-08-01

    A hallmark of higher brain functions is the ability to contemplate the world rather than to respond reflexively to it. To do so, the nervous system makes use of a modular architecture in which sensory representations are dissociated from areas that control actions. This flexibility however necessitates a recoding scheme that would put sensory information to use in the control of behavior. Sensory recoding faces two important challenges. First, recoding must take into account the inherent variability of sensory responses. Second, it must be flexible enough to satisfy the requirements of different perceptual goals. Recent progress in theory, psychophysics, and neurophysiology indicate that cortical circuitry might meet these challenges by evaluating sensory signals probabilistically.

  14. Alfaxalone Anaesthesia Facilitates Electrophysiological Recordings of Nociceptive Withdrawal Reflexes in Dogs (Canis familiaris.

    Directory of Open Access Journals (Sweden)

    James Hunt

    Full Text Available Naturally occurring canine osteoarthritis represents a welfare issue for affected dogs (Canis familiaris, but is also considered very similar to human osteoarthritis and has therefore been proposed as a model of disease in humans. Central sensitisation is recognized in human osteoarthritis sufferers but identification in dogs is challenging. Electromyographic measurement of responses to nociceptive stimulation represents a potential means of investigating alterations in central nociceptive processing, and has been evaluated in conscious experimental dogs, but is likely to be aversive. Development of a suitable anaesthetic protocol in experimental dogs, which facilitated electrophysiological nociceptive withdrawal reflex assessment, may increase the acceptability of using the technique in owned dogs with naturally occurring osteoarthritis. Seven purpose bred male hound dogs underwent electromyographic recording sessions in each of three states: acepromazine sedation, alfaxalone sedation, and alfaxalone anaesthesia. Electromyographic responses to escalating mechanical and electrical, and repeated electrical, stimuli were recorded. Subsequently the integral of both early and late rectified responses was calculated. Natural logarithms of the integral values were analysed within and between the three states using multi level modeling. Alfaxalone increased nociceptive thresholds and decreased the magnitude of recorded responses, but characteristics of increasing responses with increasing stimulus magnitude were preserved. Behavioural signs of anxiety were noted in two out of seven dogs during recordings in the acepromazine sedated state. There were few significant differences in response magnitude or nociceptive threshold between the two alfaxalone states. Following acepromazine premedication, induction of anaesthesia with 1-2 mg kg-1 alfaxalone, followed by a continuous rate infusion in the range 0.075-0.1 mg kg-1 min-1 produced suitable conditions

  15. Mechanisms underlying the nociceptive responses induced by platelet-activating factor (PAF) in the rat paw.

    Science.gov (United States)

    Marotta, Denise M; Costa, Robson; Motta, Emerson M; Fernandes, Elizabeth S; Medeiros, Rodrigo; Quintão, Nara L M; Campos, Maria M; Calixto, João B

    2009-04-01

    Platelet-activating factor (PAF) is an inflammatory mediator widely known to exert relevant pathophysiological functions. However, the relevance of PAF in nociception has received much less attention. Herein, we have investigated the mechanisms underlying PAF-induced spontaneous nociception and mechanical hypersensitivity in the rat paw. PAF injection (1- 30 nmol/paw) resulted in a dose-related overt nociception, whilst only the dose of 10 nmol/ paw produced a significant and time-related mechanical hypersensitivity. Local coinjection of PAF antagonist WEB2086 significantly inhibited both spontaneous nociception and mechanical hypersensitivity. Moreover, the coinjection of the natural IL-1beta receptor antagonist (IRA) notably prevented both PAF-induced nociceptive responses, whilst these responses were not altered by anti-TNFalpha coinjection. Interestingly, pretreatment with the ultrapotent vaniloid agonist resiniferotoxin, coinjection of the TRPV1 receptor antagonist SB366791, or mast cell depletion with compound 48/80 markedly prevented PAF-induced spontaneous nociception. Conversely, PAF-elicited mechanical hypersensitivity was strikingly susceptible to distinct antineutrophil-related strategies, namely the antineutrophil antibody, the selectin blocker fucoidin, the chemokine CXCR2 receptor antagonist SB225002, and the C5a receptor antibody anti-CD88. Notably, the same antineutrophil migration strategies significantly prevented the increase of myeloperoxidase activity induced by PAF. The mechanical hypersensitivity caused by PAF was also prevented by the cyclooxygenase inhibitors indomethacin or celecoxib, and by the selective beta(1) adrenergic receptor antagonist atenolol. Collectively, the present results provide consistent evidence indicating that distinct mechanisms are involved in the spontaneous nociception and mechanical hypersensitivity caused by PAF. They also support the concept that selective PAF receptor antagonists might constitute interesting

  16. Alfaxalone Anaesthesia Facilitates Electrophysiological Recordings of Nociceptive Withdrawal Reflexes in Dogs (Canis familiaris)

    Science.gov (United States)

    Hunt, James; Murrell, Jo; Knazovicky, David; Harris, John; Kelly, Sara; Knowles, Toby G.; Lascelles, B. Duncan X.

    2016-01-01

    Naturally occurring canine osteoarthritis represents a welfare issue for affected dogs (Canis familiaris), but is also considered very similar to human osteoarthritis and has therefore been proposed as a model of disease in humans. Central sensitisation is recognized in human osteoarthritis sufferers but identification in dogs is challenging. Electromyographic measurement of responses to nociceptive stimulation represents a potential means of investigating alterations in central nociceptive processing, and has been evaluated in conscious experimental dogs, but is likely to be aversive. Development of a suitable anaesthetic protocol in experimental dogs, which facilitated electrophysiological nociceptive withdrawal reflex assessment, may increase the acceptability of using the technique in owned dogs with naturally occurring osteoarthritis. Seven purpose bred male hound dogs underwent electromyographic recording sessions in each of three states: acepromazine sedation, alfaxalone sedation, and alfaxalone anaesthesia. Electromyographic responses to escalating mechanical and electrical, and repeated electrical, stimuli were recorded. Subsequently the integral of both early and late rectified responses was calculated. Natural logarithms of the integral values were analysed within and between the three states using multi level modeling. Alfaxalone increased nociceptive thresholds and decreased the magnitude of recorded responses, but characteristics of increasing responses with increasing stimulus magnitude were preserved. Behavioural signs of anxiety were noted in two out of seven dogs during recordings in the acepromazine sedated state. There were few significant differences in response magnitude or nociceptive threshold between the two alfaxalone states. Following acepromazine premedication, induction of anaesthesia with 1–2 mg kg-1 alfaxalone, followed by a continuous rate infusion in the range 0.075–0.1 mg kg-1 min-1 produced suitable conditions to enable

  17. Alfaxalone Anaesthesia Facilitates Electrophysiological Recordings of Nociceptive Withdrawal Reflexes in Dogs (Canis familiaris).

    Science.gov (United States)

    Hunt, James; Murrell, Jo; Knazovicky, David; Harris, John; Kelly, Sara; Knowles, Toby G; Lascelles, B Duncan X

    2016-01-01

    Naturally occurring canine osteoarthritis represents a welfare issue for affected dogs (Canis familiaris), but is also considered very similar to human osteoarthritis and has therefore been proposed as a model of disease in humans. Central sensitisation is recognized in human osteoarthritis sufferers but identification in dogs is challenging. Electromyographic measurement of responses to nociceptive stimulation represents a potential means of investigating alterations in central nociceptive processing, and has been evaluated in conscious experimental dogs, but is likely to be aversive. Development of a suitable anaesthetic protocol in experimental dogs, which facilitated electrophysiological nociceptive withdrawal reflex assessment, may increase the acceptability of using the technique in owned dogs with naturally occurring osteoarthritis. Seven purpose bred male hound dogs underwent electromyographic recording sessions in each of three states: acepromazine sedation, alfaxalone sedation, and alfaxalone anaesthesia. Electromyographic responses to escalating mechanical and electrical, and repeated electrical, stimuli were recorded. Subsequently the integral of both early and late rectified responses was calculated. Natural logarithms of the integral values were analysed within and between the three states using multi level modeling. Alfaxalone increased nociceptive thresholds and decreased the magnitude of recorded responses, but characteristics of increasing responses with increasing stimulus magnitude were preserved. Behavioural signs of anxiety were noted in two out of seven dogs during recordings in the acepromazine sedated state. There were few significant differences in response magnitude or nociceptive threshold between the two alfaxalone states. Following acepromazine premedication, induction of anaesthesia with 1-2 mg kg-1 alfaxalone, followed by a continuous rate infusion in the range 0.075-0.1 mg kg-1 min-1 produced suitable conditions to enable assessment

  18. NEUROPHYSIOLOGICAL EVALUATION OF SENSORY SYSTEMS'

    Science.gov (United States)

    Exposure to many neurotoxic compounds has been shown to produce a sensory system dysfunction. Neurophysiological assessment of sensory function in humans and animal models often uses techniques known as sensory evoked potentials. Because both humans and animals show analogous res...

  19. Spinal nociceptive transmission by mechanical stimulation of bone marrow.

    Science.gov (United States)

    Ishida, Takashi; Tanaka, Satoshi; Sekiguchi, Takemi; Sugiyama, Daisuke; Kawamata, Mikito

    2016-01-01

    Since bone marrow receives innervation from A-delta and C-fibers and since an increase in intramedullary pressure in bone marrow may induce acute pain in orthopedic patients during surgery and chronic pain in patients with bone marrow edema, skeletal pain may partly originate from bone marrow. Intraosseous lesions, such as osteomyelitis and bone cancer, are also known to produce cutaneous hypersensitivity, which might be referred pain from bone. However, little is known about pain perception in bone marrow and referred pain induced by bone disease. Thus, we carried out an in vivo electrophysiological study and behavioral study to determine whether increased intraosseous pressure of the femur induces acute pain and whether increased intraosseous pressure induces referred pain in the corresponding receptive fields of the skin. Intraosseous balloon inflation caused spontaneous pain-related behavior and mechanical hyperalgesia and allodynia in the lumbosacral region. Single neuronal activities of spinal dorsal horn neurons were extracellularly isolated, and then evoked responses to non-noxious and noxious cutaneous stimuli and intraosseous balloon inflation were recorded. Ninety-four spinal dorsal horn neurons, which had somatic receptive fields at the lower back and thigh, were obtained. Sixty-two percent of the wide-dynamic-range neurons (24/39) and 86% of the high-threshold neurons (12/14) responded to intraosseous balloon inflation, while none of the low-threshold neurons (0/41) responded to intraosseous balloon inflation. Spinally administered morphine (1 µg) abolished balloon inflation-induced spontaneous pain-related behavior and mechanical hyperalgesia in awake rats and also suppressed evoked activities of wide-dynamic-range neurons to noxious cutaneous stimulation and intraosseous balloon inflation. The results suggest that mechanical stimulation to bone marrow produces nociception, concomitantly producing its referred pain in the corresponding skin fields

  20. Effects of salt-loading hypertension on nociception in rats

    Directory of Open Access Journals (Sweden)

    Afolabi AO

    2013-05-01

    Full Text Available Ayobami Oladele Afolabi,1 Saheed Kolade Mudashiru,1 Isiaka Abdullateef Alagbonsi21Department of Physiology, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Oyo, Nigeria; 2Department of Physiology, Faculty of Medicine, Kogi State University, PMB 1008, Anyigba, Kogi, NigeriaBackground: There is on going controversy on the effect of experimentally induced hypertension on nociception. The effect of salt-loading-induced hypertension on pain was studied in male rats.Method: Twenty-four male Sprague-Dawley rats (160–280 g were divided into two groups. Group A (n = 12 was treated with normal-feed diet (control, while group B (n = 12 was treated with 8% salt-loaded diet for 10 weeks. After 10 weeks of the treatment, six rats each from groups A and B were used for blood pressure measurement, while the remaining six rats were used for both the tail-flick and formalin tests. Thermal and chemical pain test were assessed using tail immersion test (tail flick and formalin test pain paradigms at onset of salt-loading diet and after 10 weeks of salt loading.Results: Chronic administration of salt-loading diet caused significant increases (P < 0.001 in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Moreover, salt-loading-induced hypertension was found to significantly reduce pain sensitivity in the tail-immersion test (P < 0.001 and in the early and late phase of the formalin test (P < 0.01. However, the hypoalgesia was higher in the late phase (94.8% than in the early phase (56.8% of the formalin test.Conclusion: The present study suggests that high salt-loading-induced hypertension causes hypoalgesia in rats, which might be due more to reduction in inflammatory response.Keywords: formalin test, tail-flick test

  1. Central nervous system mast cells in peripheral inflammatory nociception

    Directory of Open Access Journals (Sweden)

    Ellmeier Wilfried

    2011-06-01

    Full Text Available Abstract Background Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation. Results Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia. Conclusion The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.

  2. [Pain and sensory disturbance in Parkinson disease].

    Science.gov (United States)

    Yoshii, Fumihito

    2012-04-01

    Pain or sensory symptoms are a frequent complaint in Parkinson disease (PD), which reduce health-related quality of life (QOL) and interfere with patient's ability to participate in activities of daily living, thus contributing to sleep disturbance or major depression. The frequency of pain is thought to have a bimodal distribution. The initial peak seems to occur before, or at the onset of PD and a second peak occurs later in the disease course in conjunction with the development of motor fluctuations or dyskinesia. The spectrum of sensory symptoms is wide, and the most common sites that experience pain are the back, legs, and shoulders. In cases, pain occurs on the side that is more affected by parkinsonism; however unusual distributions, such as oral or genital pain syndrome, chest pain, and upper or lower abdominal discomfort may be observed. The etiological basis of PD-related pain is multifactorial, with varying degrees of contribution from peripheral and central sources. Central mechanisms include derangement of the intrinsic pain-modulating monoaminergic mechanism in addition to plastic central nervous system changes induced by chronic anti-parkinsonian medication. The importance of dopaminergic deficits as a causal factor in PD-related pain is supported by the normalization of these abnormalities after L-dopa administration, which suggests that the human striatum plays a central role in processing nociceptive information. Nevertheless, the lack of response to dopaminergic agents in some patients suggests the involvement of non-dopaminergic structures in PD. Abnormalities of noradrenergic and serotonergic pathways descending to the spinal cord are assumed to play a role in pain perception in PD. Some reports have highlighted the problem of delayed diagnosis in PD patients with an initial presentation of pain. Greater awareness of this possibility among physicians is important. Physicians also should bear in mind that psychological factors are major

  3. Early compensatory sensory re-education.

    Science.gov (United States)

    Daniele, Hugo R; Aguado, Leda

    2003-02-01

    After a neurorrhaphy, there will be a distal disconnection between the cortex and skin receptors, along with interruption of sensibility information. This report demonstrates the efficacy of a new sensory re-education program for achieving optimal sensation in a relatively short time. Between 1999 and 2001, in the authors' Hand Rehabilitation Department, 11 patients with previous neurorrhaphy were subjected to a program of early "compensatory sensory re-education." Lesions were caused by clean cut. There were 13 primary digital nerve procedures, 12 at the distal palmar MP level, and one at the radial dorsal branch of the index (just after emerging from the common digital nerve). The technique of compensatory sensory re-education was based on a previous, but modified, sensory re-education method. In order to evaluate the results in the compensatory sensory re-education series described, additional tests for evaluation of achieved functional sensibility were used. The authors' best results were achieved in a maximum of 8 weeks (4-8 weeks), much less time than with the original method (1-2 years). Using the British classification, it was possible to compare the achieved levels of sensibility and the time required for optimal results. The different methods of sensibility re-education may be similar, but with the authors' compensatory sensory re-education method, substantial time is saved.

  4. Low back pain: guidelines for the clinical classification of predominant neuropathic, nociceptive, or central sensitization pain.

    Science.gov (United States)

    Nijs, Jo; Apeldoorn, Adri; Hallegraeff, Hank; Clark, Jacqui; Smeets, Rob; Malfliet, Annaleen; Girbes, Enrique L; De Kooning, Margot; Ickmans, Kelly

    2015-01-01

    Low back pain (LBP) is a heterogeneous disorder including patients with dominant nociceptive (e.g., myofascial low back pain), neuropathic (e.g., lumbar radiculopathy), and central sensitization pain. In order to select an effective and preferably also efficient treatment in daily clinical practice, LBP patients should be classified clinically as either predominantly nociceptive, neuropathic, or central sensitization pain. To explain how clinicians can differentiate between nociceptive, neuropathic, and central sensitization pain in patients with LBP. Narrative review and expert opinion Universities, university hospitals and private practices Recently, a clinical method for the classification of central sensitization pain versus neuropathic and nociceptive pain was developed. It is based on a body of evidence of original research papers and expert opinion of 18 pain experts from 7 different countries. Here we apply this classification algorithm to the LBP population. The first step implies examining the presence of neuropathic low back pain. Next, the differential diagnosis between predominant nociceptive and central sensitization pain is done using a clinical algorithm. The classification criteria are substantiated by several original research findings including a Delphi survey, a study of a large group of LBP patients, and validation studies of the Central Sensitization Inventory. Nevertheless, these criteria require validation in clinical settings. The pain classification system for LBP should be an addition to available classification systems and diagnostic procedures for LBP, as it is focussed on pain mechanisms solely.

  5. Inhibition of spinal MAPKs by scorpion venom peptide BmK AGAP produces a sensory-specific analgesic effect.

    Science.gov (United States)

    Ruan, Jia-Ping; Mao, Qing-Hong; Lu, Wu-Guang; Cai, Xue-Ting; Chen, Jiao; Li, Qing-; Fu, Qun-; Yan, Huai-Jiang; Cao, Jun-Li; Cao, Peng

    2018-01-01

    Background Several studies have shown that scorpion venom peptide BmK AGAP has an analgesic activity. Our previous study also demonstrated that intraplantar injection of BmK AGAP ameliorates formalin-induced spontaneous nociceptive behavior. However, the effect of intrathecal injection of BmK AGAP on nociceptive processing is poorly understood. Methods We investigated the effects of intrathecal injection of BmK AGAP on spinal nociceptive processing induced by chronic constrictive injury or formalin. Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and the von Frey filaments test. Formalin-induced spontaneous nociceptive behavior was also investigated. C-Fos expression was assessed by immunohistochemistry. Phosphorylated mitogen-activated protein kinase (p-MAPK) expression was monitored by Western blot assay. Results Intrathecal injection of BmK AGAP reduced chronic constrictive injury-induced neuropathic pain behavior and pain from formalin-induced inflammation, accompanied by decreased expression of spinal p-MAPKs and c-Fos protein. The results of combining low doses of different MAPK inhibitor (U0126, SP600125, or SB203580; 0.1 µg for each inhibitor) with a low dose of BmK AGAP (0.2 µg) suggested that BmK AGAP could potentiate the effects of MAPK inhibitors on inflammation-associated pain. Conclusion Our results demonstrate that intrathecal injection of BmK AGAP produces a sensory-specific analgesic effect via a p-MAPK-dependent mechanism.

  6. Accessibility and sensory experiences

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2010-01-01

    and accessibility. Sensory accessibility accommodates aspects of a sensory disability and describes architectural design requirements needed to ensure access to architectural experiences. In the context of architecture accessibility has become a design concept of its own. It is generally described as ensuring...... physical access to the built environment by accommodating physical disabilities. While the existing concept of accessibility ensures the physical access of everyone to a given space, sensory accessibility ensures the choice of everyone to stay and be able to participate and experience....

  7. Pain when walking: individual sensory profiles in the foot soles of torture victims - a controlled study using quantitative sensory testing

    Science.gov (United States)

    2012-01-01

    Background With quantitative sensory testing (QST) we recently found no differences in sensory function of the foot soles between groups of torture victims with or without exposure to falanga (beatings under the feet). Compared to matched controls the torture victims had hyperalgesia to deep mechano-nociceptive stimuli and hypoesthesia to non-noxious cutaneous stimuli. The purpose of the present paper was to extend the group analysis into individual sensory profiles of victims’ feet to explore possible relations between external violence (torture), reported pain, sensory symptoms and QST data to help clarify the underlying mechanisms. Methods We employed interviews and assessments of the pain and sensory symptoms and QST by investigators blinded to whether the patients, 32 male torture victims from the Middle East, had (n=15), or had not (n=17) been exposed to falanga. Pain intensity, area and stimulus dependence were used to characterize the pain. QST included thresholds for touch, cold, warmth, cold-pain, heat-pain, deep pressure pain and wind-up to cutaneous noxious stimuli. An ethnically matched control group was available.The normality criterion, from our control group data, was set as the mean +/− 1.28SD, thus including 80% of all values.QST data were transformed into three categories in relation to our normality range; hypoesthesia, normoesthesia or hyperesthesia/hyperalgesia. Results Most patients, irrespective of having been exposed to falanga or not, reported severe pain when walking. This was often associated with hyperalgesia to deep mechanical pressure. Hypoesthesia to mechanical stimuli co-occurred with numbness, burning and with deep mechanical hyperalgesia more often than not, but otherwise, a hypoesthesia to cutaneous sensory modalities did not co-occur systematically to falanga, pain or sensory symptoms. Conclusion In torture victims, there seem to be overriding mechanisms, manifested by hyperalgesia to pressure pain, which is usually

  8. Pain when walking: individual sensory profiles in the foot soles of torture victims - a controlled study using quantitative sensory testing

    Directory of Open Access Journals (Sweden)

    Prip Karen

    2012-12-01

    Full Text Available Abstract Background With quantitative sensory testing (QST we recently found no differences in sensory function of the foot soles between groups of torture victims with or without exposure to falanga (beatings under the feet. Compared to matched controls the torture victims had hyperalgesia to deep mechano-nociceptive stimuli and hypoesthesia to non-noxious cutaneous stimuli. The purpose of the present paper was to extend the group analysis into individual sensory profiles of victims’ feet to explore possible relations between external violence (torture, reported pain, sensory symptoms and QST data to help clarify the underlying mechanisms. Methods We employed interviews and assessments of the pain and sensory symptoms and QST by investigators blinded to whether the patients, 32 male torture victims from the Middle East, had (n=15, or had not (n=17 been exposed to falanga. Pain intensity, area and stimulus dependence were used to characterize the pain. QST included thresholds for touch, cold, warmth, cold-pain, heat-pain, deep pressure pain and wind-up to cutaneous noxious stimuli. An ethnically matched control group was available.The normality criterion, from our control group data, was set as the mean +/− 1.28SD, thus including 80% of all values.QST data were transformed into three categories in relation to our normality range; hypoesthesia, normoesthesia or hyperesthesia/hyperalgesia. Results Most patients, irrespective of having been exposed to falanga or not, reported severe pain when walking. This was often associated with hyperalgesia to deep mechanical pressure. Hypoesthesia to mechanical stimuli co-occurred with numbness, burning and with deep mechanical hyperalgesia more often than not, but otherwise, a hypoesthesia to cutaneous sensory modalities did not co-occur systematically to falanga, pain or sensory symptoms. Conclusion In torture victims, there seem to be overriding mechanisms, manifested by hyperalgesia to pressure pain

  9. Mapping sensory circuits by anterograde trans-synaptic transfer of recombinant rabies virus

    Science.gov (United States)

    Zampieri, Niccolò; Jessell, Thomas M.; Murray, Andrew J.

    2014-01-01

    Summary Primary sensory neurons convey information from the external world to relay circuits within the central nervous system (CNS), but the identity and organization of the neurons that process incoming sensory information remains sketchy. Within the CNS viral tracing techniques that rely on retrograde trans-synaptic transfer provide a powerful tool for delineating circuit organization. Viral tracing of the circuits engaged by primary sensory neurons has, however, been hampered by the absence of a genetically tractable anterograde transfer system. In this study we demonstrate that rabies virus can infect sensory neurons in the somatosensory system, is subject to anterograde trans-synaptic transfer from primary sensory to spinal target neurons, and can delineate output connectivity with third-order neurons. Anterograde trans-synaptic transfer is a feature shared by other classes of primary sensory neurons, permitting the identification and potentially the manipulation of neural circuits processing sensory feedback within the mammalian CNS. PMID:24486087

  10. Whole body static magnetic field exposure increases thermal nociceptive threshold in the snail, Helix pomatia.

    Science.gov (United States)

    László, J F; Hernádi, L

    2012-12-01

    We investigated the effect of homogeneous and inhomogeneous static magnetic field (SMF) exposure on the thermal nociceptive threshold of snail in the hot plate test (43 °C). Both homogeneous (hSMF) and inhomogeneous (iSMF) SMF increased the thermo-nociceptive threshold: 40.2%, 29.2%, or 41.7% after an exposure of 20, 30, or 40 min hSMF by p snail. On the other hand, naloxone as an atypical opioid antagonist in an amount of 1 μg/g was found to significantly decrease the thermo-nociceptive threshold (41.9% by p < 0.002), which could be antagonized by hSMF exposure implying that hSMF exerts its antinociceptive effect partly via opioid receptors.

  11. Anti-nociceptive and anti-inflammatory effects of some Jordanian medicinal plant extracts.

    Science.gov (United States)

    Atta, A H; Alkofahi, A

    1998-03-01

    The anti-nociceptive effect of ethanolic extract of 11 traditionally used Jordanian plants was studied by using the acetic acid-induced writhing and hot-plate test in mice. The anti-inflammatory effect of these plants was determined by xylene-induced ear oedema in mice and cotton pellet granuloma test in rats. Mentha piperita, Cinnamomum zeylanicum, Apium graveolens, Eucalyptus camaldulentis, and Ruta graveolens possess an anti-nociceptive effect against both acetic acid-induced writhing and hot plate-induced thermal stimulation. M. piperita, Jasminum officinale, Commiphora molmol, and Beta vulgaris possess an anti-inflammatory effect against acute (xylene-induced ear oedema) and chronic (cotton-pellet granuloma) inflammation. The anti-nociceptive and anti-inflammatory effects were dose dependent. These data affirm the traditional use of some of these plants for painful and inflammatory conditions.

  12. Non-nociceptive pain in rheumatoid arthritis is frequent and affects disease activity estimation

    DEFF Research Database (Denmark)

    Christensen, A W; Rifbjerg-Madsen, Signe; Christensen, R

    2016-01-01

    independently associated with the PDQ score. CONCLUSIONS: In patients initiating or intensifying medical treatment for their RA, non-nociceptive pain (PDQ score ≥ 13) is common. In these patients, the pain mechanisms result in increased disease activity scores on a non-inflammatory basis.......BACKGROUND: The painDETECT questionnaire (PDQ) is a mechanism-based pain classification tool assigning patients to one of three categories depending on the quality of the experienced pain. Patients with non-nociceptive pain score high on the PDQ. The objective was to assess the proportions...... score 13-18), and high (PDQ score > 18) scores indicate nociceptive, unclear/possible neuropathic, or neuropathic pain mechanisms, respectively. RESULTS: The 102 included patients were classified into the following PDQ classification groups: low = 65%, medium = 23%, and high = 12%. Patients...

  13. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

    Directory of Open Access Journals (Sweden)

    Yelena Nersesyan

    2017-11-01

    Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

  14. Attentive, Affective, and Adaptive Behavior in the Cat: Sensory deprivation of the forebrain by lesions in the brain stem results in striking behavioral abnormalities.

    Science.gov (United States)

    Sprague, J M; Chambers, W W; Stellar, E

    1961-01-20

    Lesions of the lateral portion of the upper midbrain, involving medial, lateral, spinal, and trigeminal lemnisci primarily, result in a consistent syndrome of symptoms in the cat. (i) There is a marked sensory deficit, characterized mainly by sensory inattention and poor localization in the tactile, proprioceptive, auditory, gustatory, and nociceptive modalities, where direct pathways are interrupted. Similar defectsappear in vision and olfaction where no known direct or primary paths are interrupted. (ii) These cats are characterized by a lack of affect, showing little or no defensive and aggressive reaction to noxious and aversive situations and no response to pleasurable stimulation or solicitation of affection or petting. The animals are mute, lack facial expression, and show minimal autonomic responses. (iii) They show a hyperexploratory activity characterized by incessant, stereotyped wandering, sniffing, and visual searching, as though hallucinating. This behavior appears to be centrally directed and is very difficult to interrupt with environmental stimuli. (iv) They also demonstrate exaggerated oral activities: they snap in response to tactile stimulation of the lips, seizing and swallowing small objects even if inedible; they overeat; they hold objects too large to swallow (a mouse, a catnip ball) firmly clamped in the mouth for long periods of time; they mount and seize other animals (rat, cat, dog, monkey) by the back or the neck; they lick and chew the hair and skin of the back or tail incessantly when confined in a cage. In interpreting these results we emphasize the view that the syndrome is due chiefly to the extensive, specific, sensory deprivation produced by interruption of the lemnisci at the rostral midbrain. The relation of these findings to the effects of sensory isolation in man and animals, to the effects of midbrain lesions and neodecortication, to parietal lobe syndrome in primates, and to the behavior of autistic children is discussed

  15. Sensory evaluation techniques

    National Research Council Canada - National Science Library

    Meilgaard, Morten; Civille, Gail Vance; Carr, B. Thomas

    1991-01-01

    ..., #2 as a textbook for courses at the academic level, it aims to provide just enough theoretical background to enable the student to understand which sensory methods are best suited to particular...

  16. Neuromorphic sensory systems.

    Science.gov (United States)

    Liu, Shih-Chii; Delbruck, Tobi

    2010-06-01

    Biology provides examples of efficient machines which greatly outperform conventional technology. Designers in neuromorphic engineering aim to construct electronic systems with the same efficient style of computation. This task requires a melding of novel engineering principles with knowledge gleaned from neuroscience. We discuss recent progress in realizing neuromorphic sensory systems which mimic the biological retina and cochlea, and subsequent sensor processing. The main trends are the increasing number of sensors and sensory systems that communicate through asynchronous digital signals analogous to neural spikes; the improved performance and usability of these sensors; and novel sensory processing methods which capitalize on the timing of spikes from these sensors. Experiments using these sensors can impact how we think the brain processes sensory information. 2010 Elsevier Ltd. All rights reserved.

  17. Midazolam as an active placebo in 3 fentanyl-validated nociceptive pain models.

    Science.gov (United States)

    Prosenz, Julian; Gustorff, Burkhard

    2017-07-01

    The use of inactive placebos in early translational trials of potentially analgesic compounds is discouraged because of the side-effect profiles of centrally acting analgesics. Therefore, benzodiazepines are used, although their use has not been validated in this context. Whether benzodiazepines confound the results of acute pain tests is unknown. Midazolam (0.06 mg/kg) as an active placebo was investigated in 3 nociceptive models that included contact heat, electrical pain, and pressure pain thresholds in 24 healthy volunteers. Fentanyl (1 μg/kg) served as an internal validator in this randomized, placebo (saline) controlled, 3-way cross-over trial. The primary outcome parameter (contact heat pain) was analyzed using a one-way, repeated measures analysis of variance and Tukey's post test. Midazolam did not reduce pain ([numeric rating scale], 0-100) in a statistically significant manner compared with placebo for the contact heat (mean difference -1.7, 95% confidence interval -10.6 to 7.3; P = 0.89) or electrical pain (4.3, -5.1 to 13.7; P = 0.51) test, nor did it raise the pressure pain thresholds (-28 kPa, -122; 64 kPa, P = 0.73). The width of the confidence intervals suggested that there were no clinically meaningful analgesic effects compared with the placebo. In contrast, the analgesic efficacy of fentanyl was effectively demonstrated in all 3 models (P < 0.01 vs midazolam and placebo). The findings of this study show that midazolam can be used as an active placebo in analgesic drug trials. Furthermore, the proposed models were simple to implement and very effective in detecting analgesia. The test battery can be used in translational trials for new compounds and comes with an active placebo and an optional active comparator.

  18. From a Somatotopic to a Spatiotopic Frame of Reference for the Localization of Nociceptive Stimuli.

    Directory of Open Access Journals (Sweden)

    Annick L De Paepe

    Full Text Available To react efficiently to potentially threatening stimuli, we have to be able to localize these stimuli in space. In daily life we are constantly moving so that our limbs can be positioned at the opposite side of space. Therefore, a somatotopic frame of reference is insufficient to localize nociceptive stimuli. Here we investigated whether nociceptive stimuli are mapped into a spatiotopic frame of reference, and more specifically a peripersonal frame of reference, which takes into account the position of the body limbs in external space, as well as the occurrence of external objects presented near the body. Two temporal order judgment (TOJ experiments were conducted, during which participants had to decide which of two nociceptive stimuli, one applied to either hand, had been presented first while their hands were either uncrossed or crossed over the body midline. The occurrence of the nociceptive stimuli was cued by uninformative visual cues. We found that the visual cues prioritized the perception of nociceptive stimuli applied to the hand laying in the cued side of space, irrespective of posture. Moreover, the influence of the cues was smaller when they were presented far in front of participants' hands as compared to when they were presented in close proximity. Finally, participants' temporal sensitivity was reduced by changing posture. These findings are compatible with the existence of a peripersonal frame of reference for the localization of nociceptive stimuli. This allows for the construction of a stable representation of our body and the space closely surrounding our body, enabling a quick and efficient reaction to potential physical threats.

  19. From a Somatotopic to a Spatiotopic Frame of Reference for the Localization of Nociceptive Stimuli.

    Science.gov (United States)

    De Paepe, Annick L; Crombez, Geert; Legrain, Valéry

    2015-01-01

    To react efficiently to potentially threatening stimuli, we have to be able to localize these stimuli in space. In daily life we are constantly moving so that our limbs can be positioned at the opposite side of space. Therefore, a somatotopic frame of reference is insufficient to localize nociceptive stimuli. Here we investigated whether nociceptive stimuli are mapped into a spatiotopic frame of reference, and more specifically a peripersonal frame of reference, which takes into account the position of the body limbs in external space, as well as the occurrence of external objects presented near the body. Two temporal order judgment (TOJ) experiments were conducted, during which participants had to decide which of two nociceptive stimuli, one applied to either hand, had been presented first while their hands were either uncrossed or crossed over the body midline. The occurrence of the nociceptive stimuli was cued by uninformative visual cues. We found that the visual cues prioritized the perception of nociceptive stimuli applied to the hand laying in the cued side of space, irrespective of posture. Moreover, the influence of the cues was smaller when they were presented far in front of participants' hands as compared to when they were presented in close proximity. Finally, participants' temporal sensitivity was reduced by changing posture. These findings are compatible with the existence of a peripersonal frame of reference for the localization of nociceptive stimuli. This allows for the construction of a stable representation of our body and the space closely surrounding our body, enabling a quick and efficient reaction to potential physical threats.

  20. Effect of chronic stress on capsaicin-induced dental nociception in a model of pulpitis in rats.

    Science.gov (United States)

    Raoof, Maryam; Ashrafganjoui, Ehsan; Kooshki, Razieh; Abbasnejad, Mehdi; Haghani, Jahangir; Amanpour, Sara; Zarei, Mohammad-Reza

    2018-01-01

    Chronic stress can alter nociceptive sensitivity. However, the effect of stress exposure on dental nociception has been less addressed. Therefore, the present study investigated the effects of chronic exposures to some social and psychological stresses on pulpal nociceptive responses. The stress groups were constructed as follows: forced swimming (n=6), restraint (n=6), and mild (n=10) and severe (n=15) crowding stresses. Rats were subjected to stress for 1h per day for a week. At the end of the stress session, pulp irritation was induced by intradental application of capsaicin (100μg). There were another capsaicin or capsaicin plus stress training groups that received articaine 5min before the administration of capsaicin. Nociceptive responses were recorded for 40min. The time (ins) of continuous shaking of the lower jaw and excessive grooming and rubbing of the mouth near the procedure site was measured as nociceptive behaviors. Data was analyzed using one-way analysis of variance (ANOVA) followed by post hoc Tukey's test. Significant nociceptive responses were evoked by the administration of capsaicin. Exposures to forced swimming (pstresses (pstress groups. Articaine buccal infiltration attenuated nociceptive time in capsaicin and capsaicin plus stress training groups (pstress exposures and nociceptive behavior following intradental capsaicin administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Cutaneous TRPM8-expressing sensory afferents are a small population of neurons with unique firing properties.

    Science.gov (United States)

    Jankowski, Michael P; Rau, Kristofer K; Koerber, H Richard

    2017-04-01

    It has been well documented that the transient receptor potential melastatin 8 (TRPM8) receptor is involved in environmental cold detection. The role that this receptor plays in nociception however, has been somewhat controversial since conflicting reports have shown different neurochemical identities and responsiveness of TRPM8 neurons. In order to functionally characterize cutaneous TRMP8 fibers, we used two ex vivo somatosensory recording preparations to functionally characterize TRPM8 neurons that innervate the hairy skin in mice genetically engineered to express GFP from the TRPM8 locus. We found several types of cold-sensitive neurons that innervate the hairy skin of the mouse but the TRPM8-expressing neurons were found to be of two specific populations that responded with rapid firing to cool temperatures. The first group was mechanically insensitive but the other did respond to high threshold mechanical deformation of the skin. None of these fibers were found to contain calcitonin gene-related peptide, transient receptor potential vanilloid type 1 or bind isolectin B4. These results taken together with other reports suggest that TRPM8 containing sensory neurons are environmental cooling detectors that may be nociceptive or non-nociceptive depending on the sensitivity of individual fibers to different combinations of stimulus modalities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  2. Nociception and role of immune system in pain.

    Science.gov (United States)

    Verma, Vivek; Sheikh, Zeeshan; Ahmed, Ahad S

    2015-09-01

    Both pain and inflammation are protective responses. However, these self-limiting conditions (with well-established negative feedback loops) become pathological if left uncontrolled. Both pain and inflammation can interact with each other in a multi-dimensional manner. These interactions are known to create an array of 'difficult to manage' pathologies. This review explains in detail the role of immune system and the related cells in peripheral sensitization and neurogenic inflammation. Various neuro-immune interactions are analyzed at peripheral, sensory and central nervous system levels. Innate immunity plays a critical role in central sensitization and in establishing acute pain as chronic condition. Moreover, inflammatory mediators also exhibit psychological effects, thus contributing towards the emotional elements associated with pain. However, there is also a considerable anti-inflammatory and analgesic role of immune system. This review also attempts to enlist various novel pharmacological approaches that exhibit their actions through modification of neuro-immune interface.

  3. Age differences in visual sensory memory.

    Science.gov (United States)

    Walsh, D A; Thompson, L W

    1978-05-01

    Age differences in visual sensory memory were studied using the direct measure procedure of Haber and Standing (1969) -- the longest interstimulus interval at which subjects reported a single stimulus as continuous was measured. The visual storage of the young (mean age 24 years) was found to persist for 289 msec compared to 248 for the old (mean age 67 years). Similar estimates of sensory memory duration were obtained when either monoptic or dichoptic stimulus presentations were employed, supporting the idea that visual storage is centrally mediated for both age groups. The relevance of these findings for age differences in the registration of information into primary and secondary memory and their implications for the stimulus persistence hypothesis are considered. The appropriateness and validity of the persistence of form task for studies of sensory memory and aging are also discussed.

  4. c-fos expression in the trigeminal sensory complex and pontine parabrachial areas following experimental tooth movement.

    Science.gov (United States)

    Yamashiro, T; Nakagawa, K; Satoh, K; Moriyama, H; Takada, K

    1997-07-07

    Ortodontic tooth movement causes continuous pain. However, it does not appear immediately, usually appearing after the application of orthodontic force to the teeth. Mechanically induced inflammatory responses in the periodontal membrane are assumed to be related to the mechanism of the later pain sensation. In the present study, we investigated Fos-like immunoreactivity in the trigeminal sensory complex and pontine parabrachial areas 24 h after the commencement of experimental tooth movement. An orthodontic elastic module was unilaterally inserted between upper molars. Following experimental tooth movement, Fos-like immunoreactive neurons appeared ipsilaterally in the trigeminal subnucleus caudalis and bilaterally in the lateral parabrachial nucleus. These results indicate that experimental tooth movement evokes delayed and continuous nociception after application of orthodontic force to the teeth and that the nociceptive information would be conveyed to the ipsilateral trigeminal subnucleus caudalis and further processed, at least in part, to the lateral parabrachial nucleus.

  5. Conversion of sensory signals into perceptual decisions.

    Science.gov (United States)

    Romo, Ranulfo; de Lafuente, Victor

    2013-04-01

    A fundamental problem in neurobiology is to understand how brain circuits represent sensory information and how such representations give rise to perception, memory and decision-making. We demonstrate that a sensory stimulus engages multiple areas of the cerebral cortex, including primary sensory, prefrontal, premotor and motor cortices. As information transverses the cortical circuits it shows progressively more relation to perception, memory and decision reports. In particular, we show how somatosensory areas on the parietal lobe generate a parameterized representation of a tactile stimulus. This representation is maintained in working memory by prefrontal and premotor areas of the frontal lobe. The presentation of a second stimulus, that monkeys are trained to compare with the first, generates decision-related activity reflecting which stimulus had the higher frequency. Importantly, decision-related activity is observed across several cortical circuits including prefrontal, premotor and parietal cortices. Sensory information is encoded by neuronal populations with opposite tuning, and suggests that a simple subtraction operation could be the underlying mechanism by which past and present sensory information is compared to generate perceptual decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Measurement in Sensory Modulation: The Sensory Processing Scale Assessment

    Science.gov (United States)

    Miller, Lucy J.; Sullivan, Jillian C.

    2014-01-01

    OBJECTIVE. Sensory modulation issues have a significant impact on participation in daily life. Moreover, understanding phenotypic variation in sensory modulation dysfunction is crucial for research related to defining homogeneous groups and for clinical work in guiding treatment planning. We thus evaluated the new Sensory Processing Scale (SPS) Assessment. METHOD. Research included item development, behavioral scoring system development, test administration, and item analyses to evaluate reliability and validity across sensory domains. RESULTS. Items with adequate reliability (internal reliability >.4) and discriminant validity (p sensory modulation (scale reliability >.90; discrimination between group effect sizes >1.00). This scale has the potential to aid in differential diagnosis of sensory modulation issues. PMID:25184464

  7. Response characteristics of pruriceptive and nociceptive trigeminoparabrachial tract neurons in the rat

    NARCIS (Netherlands)

    N.A. Jansen (Nico A.); G.J. Giesler (Glenn J.)

    2015-01-01

    textabstractWe tested the possibility that the trigeminoparabrachial tract (VcPbT), a projection thought to be importantly involved in nociception, might also contribute to sensation of itch. In anesthetized rats, 47 antidromically identified VcPbT neurons with receptive fields involving the cheek

  8. Anti-nociceptive effect of total alkaloids isolated from the seeds of ...

    African Journals Online (AJOL)

    The antinociceptive effect of the extract in mice was evaluated by acetic acid writhing reflex test, hot plate test, capsaicin-induced nociception test, tail-flick test and formalin-induced pain test in mice. Furthermore, pretreatment of the animals with naloxone (2 mg/kg) was performed to investigate whether the antinociceptive ...

  9. Anti-nociceptive and anti-inflammatory properties of the ethanolic ...

    African Journals Online (AJOL)

    Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice. ... Its effect was comparable especially at 200mg/kg body weight to those of diclofenac, indomethacin and ibuprofen. It could be suggested from the findings of this experiment that the extract may be ...

  10. Pain sensation and nociceptive reflex excitability in surgical patients and human volunteers

    DEFF Research Database (Denmark)

    Dahl, J B; Erichsen, C J; Fuglsang-Frederiksen, A

    1992-01-01

    Pain threshold, nociceptive flexion reflex (NFR) threshold and responses to suprathreshold stimulation were investigated in 15 female patients (mean age 32 yr (range 22-48 yr)) before and 68 (range 48-96) h after gynaecological laparotomy. Control measurements were performed in 17 healthy human v...

  11. Anti-nociceptive and anti-inflammatory properties of the leaf extracts ...

    African Journals Online (AJOL)

    Anti-nociceptive and anti-inflammatory properties of the leaf extracts of Hedranthera barteri in rats and mice. SA Onasanwo, RA Elegbe. Abstract. Hedranthera barteri, HB (Apocynaceae) is a shrub in the closed-forest in some parts of West Africa and used among the natives for inflammatory pain relief. This study was carried ...

  12. The anti-inflammatory and anti-nociceptive activities of Patrinia ...

    African Journals Online (AJOL)

    This study explores the anti-inflammatory and anti-nociceptive activities of Patrinia villosa, a Chinese medicinal plant, and to explore its effects on the proinflammatory cytokines of the rats with pelvic inflammation model. The animals were randomly divided into Patrinia villosa group (PV group), dexamethasone group (DEX ...

  13. Exposure to intermittent nociceptive stimulation under pentobarbital anesthesia disrupts spinal cord function in rats

    Science.gov (United States)

    Patton, Brianne C.; Ferguson, Adam R.; Hudson, Kara L.; Grau, James W.

    2011-01-01

    Rationale Spinal cord plasticity can be assessed in spinal rats using an instrumental learning paradigm in which subjects learn an instrumental response, hindlimb flexion, to minimize shock exposure. Prior exposure to uncontrollable intermittent stimulation blocks learning in spinal rats but has no effect if given before spinal transection, suggesting that supraspinal systems modulate nociceptive input to the spinal cord, rendering it less susceptible to the detrimental consequences of uncontrollable stimulation. Objective The present study examines whether disrupting brain function with pentobarbital blocks descending inhibitory systems that normally modulate nociceptive input, making the spinal cord more sensitive to the adverse effect of uncontrollable intermittent stimulation. Materials and methods Male Sprague–Dawley rats received uncontrollable intermittent stimulation during pentobarbital anesthesia after (experiment 1) or before (experiment 2) spinal cord transection. They were then tested for instrumental learning at a later time point. Experiment 3 examined whether these manipulations affected nociceptive (thermal) thresholds. Results Experiment 1 showed that pentobarbital had no effect on the induction of the learning deficit after spinal cord transection. Experiment 2 showed that intact rats anesthetized during uncontrollable intermittent stimulation failed to learn when later transected and tested for instrumental learning. Experiment 3 found that uncontrollable intermittent stimulation induced an antinociception in intact subjects that was blocked by pentobarbital. Conclusions The results suggest a surgical dose of pentobarbital (50 mg/kg) suppresses supraspinal (experiment 2) but not spinal (experiment 1) systems that modulate nociceptive input to the spinal cord by blocking the antinociception that is induced by this input (experiment 3). PMID:17297638

  14. Changes in thermal nociceptive responses in dairy cows following experimentally induced Escherichia coli mastitis

    Directory of Open Access Journals (Sweden)

    Klaas Ilka C

    2011-05-01

    Full Text Available Abstract Background Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables. Methods Seven Danish Holstein-Friesian cows were kept in tie-stalls, where the E. coli associated mastitis was induced and laser stimulations were conducted. Measurements of rectal temperature, somatic cell counts, white blood cell counts and E. coli counts were conducted. Furthermore, scores were given for anorexia, local udder inflammation and milk appearance to quantify the local and systemic disease response. In order to quantify the nociceptive threshold, behavioral responses toward cutaneous NLS applied to six skin areas at the tarsus/metatarsus and udder hind quarters were registered at evening milking on day 0 (control and days 1, 2, 3, 6 and 10 after experimental induction of mastitis. Results All clinical and paraclinical variables were affected by the induced mastitis. All cows were clinically ill on days 1 and 2. The cows responded behaviorally toward the NLS. For hind leg stimulation, the proportion of cows responding by stepping was higher on day 0 than days 3 and 6, and the frequency of leg movements after laser stimulation tended to decrease on day 1 compared to the other days. After udder stimulation, the proportion of cows responding by stepping was higher on day 1 than on all other days of testing. Significant correlations between the clinical and paraclinical variables of disease and the behavioral responses toward nociceptive stimulation were found. Conclusions Changes in behavioral responses coincide with peaks in local and systemic signs of E

  15. Effects of antagonists and heat on TRPM8 channel currents in dorsal root ganglion neuron activated by nociceptive cold stress and menthol.

    Science.gov (United States)

    Naziroğlu, Mustafa; Ozgül, Cemil

    2012-02-01

    Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperature and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of environmental cold stress such as cold allodynia in dorsal root ganglion (DRG) neuron; however, the underlying mechanisms of action are unclear. We tested the effects of physiological heat (37°C), anthralic acid (ACA and 0.025 mM), 2-aminoethyl diphenylborinate (2-APB and 0.05) on noxious cold (10°C) and menthol (0.1 mM)-induced TRPM8 cation channel currents in the DRG neurons of rats. DRG neurons were freshly isolated from rats. In whole-cell patch clamp experiments, TRPM8 currents were consistently induced by noxious cold or menthol. TRPM8 channels current densities of the neurons were higher in cold and menthol groups than in control. When the physiological heat is introduced by chamber TRPM8 channel currents were inhibited by the heat. Noxious cold-induced Ca(2+) gates were blocked by the ACA although menthol-induced TRPM8 currents were not blocked by ACA and 2-APB. In conclusion, the results suggested that activation of TRPM8 either by menthol or nociceptive cold can activate TRPM8 channels although we observed the protective role of heat, ACA and 2-APB through a TRPM8 channel in nociceptive cold-activated DRG neurons. Since cold allodynia is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in DRG neurons.

  16. Immobilization contributes to exaggerated neuropeptide signaling, inflammatory changes, and nociceptive sensitization after fracture in rats.

    Science.gov (United States)

    Guo, Tian-Zhi; Wei, Tzuping; Li, Wen-Wu; Li, Xiang-Qi; Clark, J David; Kingery, Wade S

    2014-10-01

    A tibia fracture cast immobilized for 4 weeks can induce exaggerated substance P and calcitonin gene-related peptide signaling and neuropeptide-dependent nociceptive and inflammatory changes in the hind limbs of rats similar to those seen in complex regional pain syndrome (CRPS). Four weeks of hind limb cast immobilization can also induce nociceptive and vascular changes resembling CRPS. To test our hypothesis that immobilization alone could cause exaggerated neuropeptide signaling and inflammatory changes, we tested 5 cohorts of rats: 1) controls; 2) tibia fracture and hind limb casted; 3) hind limb casted, no fracture; 4) tibia fracture with intramedullary pinning, no cast; and 5) tibia fracture with intramedullary pinning and hind limb casting. After 4 weeks, the casts were removed and hind limb allodynia, unweighting, warmth, edema, sciatic nerve neuropeptide content, cutaneous and spinal cord inflammatory mediator levels, and spinal c-Fos activation were measured. After fracture with casting, there was allodynia, unweighting, warmth, edema, increased sciatic nerve substance P and calcitonin gene-related peptide, increased skin neurokinin 1 receptors and keratinocyte proliferation, increased inflammatory mediator expression in the hind paw skin (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, nerve growth factor) and cord (IL-1β, nerve growth factor), and increased spinal c-Fos activation. These same changes were observed after cast immobilization alone, except that spinal IL-1β levels were not increased. Treating cast-only rats with a neurokinin 1 receptor antagonist inhibited development of nociceptive and inflammatory changes. Four weeks after fracture with pinning, all nociceptive and vascular changes had resolved and there were no increases in neuropeptide signaling or inflammatory mediator expression. Collectively, these data indicate that immobilization alone increased neuropeptide signaling and caused nociceptive and inflammatory changes similar

  17. Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.

    Science.gov (United States)

    Huang, Yung-Jen; Lee, Kuan H; Murphy, Lauren; Garraway, Sandra M; Grau, James W

    2016-11-01

    Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. In spinally transected rats, noxious electrical stimulation and inflammation induce enhanced mechanical reactivity (EMR), a behavioral index of nociceptive sensitization. Pretreatment with the GABA A receptor antagonist bicuculline blocked these effects. Peripheral application of an irritant (capsaicin) also induced EMR. Both the induction and maintenance of this effect were blocked by bicuculline. Cellular indices of central sensitization [c-fos expression and ERK phosphorylation (pERK)] were also attenuated. In intact (sham operated) rats, bicuculline had the opposite effect. Pretreatment with a GABA agonist (muscimol) attenuated nociceptive sensitization in intact, but not spinally injured, rats. The effect of SCI on GABA function was linked to a reduction in the Cl - transporter, KCC2, leading to a reduction in intracellular Cl - that would attenuate GABA-mediated inhibition. Pharmacologically blocking the KCC2 channel (with i.t. DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl - levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Caenorhabditis elegans nicotinic acetylcholine receptors are required for nociception.

    Science.gov (United States)

    Cohen, Emiliano; Chatzigeorgiou, Marios; Husson, Steven J; Steuer-Costa, Wagner; Gottschalk, Alexander; Schafer, William R; Treinin, Millet

    2014-03-01

    Polymodal nociceptors sense and integrate information on injurious mechanical, thermal, and chemical stimuli. Chemical signals either activate nociceptors or modulate their responses to other stimuli. One chemical known to activate or modulate responses of nociceptors is acetylcholine (ACh). Across evolution nociceptors express subunits of the nicotinic acetylcholine receptor (nAChR) family, a family of ACh-gated ion channels. The roles of ACh and nAChRs in nociceptor function are, however, poorly understood. Caenorhabditis elegans polymodal nociceptors, PVD, express nAChR subunits on their sensory arbor. Here we show that mutations reducing ACh synthesis and mutations in nAChR subunits lead to defects in PVD function and morphology. A likely cause for these defects is a reduction in cytosolic calcium measured in ACh and nAChR mutants. Indeed, overexpression of a calcium pump in PVD mimics defects in PVD function and morphology found in nAChR mutants. Our results demonstrate, for the first time, a central role for nAChRs and ACh in nociceptor function and suggest that calcium permeating via nAChRs facilitates activity of several signaling pathways within this neuron. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Caenorhabditis elegans nicotinic acetylcholine receptors are required for nociception

    Science.gov (United States)

    Cohen, Emiliano; Chatzigeorgiou, Marios; Husson, Steven J.; Steuer-Costa, Wagner; Gottschalk, Alexander; Schafer, William R.; Treinin, Millet

    2014-01-01

    Polymodal nociceptors sense and integrate information on injurious mechanical, thermal, and chemical stimuli. Chemical signals either activate nociceptors or modulate their responses to other stimuli. One chemical known to activate or modulate responses of nociceptors is acetylcholine (ACh). Across evolution nociceptors express subunits of the nicotinic acetylcholine receptor (nAChR) family, a family of ACh-gated ion channels. The roles of ACh and nAChRs in nociceptor function are, however, poorly understood. Caenorhabditis elegans polymodal nociceptors, PVD, express nAChR subunits on their sensory arbor. Here we show that mutations reducing ACh synthesis and mutations in nAChR subunits lead to defects in PVD function and morphology. A likely cause for these defects is a reduction in cytosolic calcium measured in ACh and nAChR mutants. Indeed, overexpression of a calcium pump in PVD mimics defects in PVD function and morphology found in nAChR mutants. Our results demonstrate, for the first time, a central role for nAChRs and ACh in nociceptor function and suggest that calcium permeating via nAChRs facilitates activity of several signaling pathways within this neuron. PMID:24518198

  20. Studying Sensory Perception.

    Science.gov (United States)

    Ackerly, Spafford C.

    2001-01-01

    Explains the vestibular organ's role in balancing the body and stabilizing the visual world using the example of a hunter. Describes the relationship between sensory perception and learning. Recommends using optical illusions to illustrate the distinctions between external realities and internal perceptions. (Contains 13 references.) (YDS)

  1. Understanding Sensory Integration. ERIC Digest.

    Science.gov (United States)

    DiMatties, Marie E.; Sammons, Jennifer H.

    This brief paper summarizes what is known about sensory integration and sensory integration dysfunction (DSI). It outlines evaluation of DSI, treatment approaches, and implications for parents and teachers, including compensatory strategies for minimizing the impact of DSI on a child's life. Review of origins of sensory integration theory in the…

  2. The evolution of sensory divergence in the context of limited gene flow in the bumblebee bat.

    Science.gov (United States)

    Puechmaille, Sébastien J; Gouilh, Meriadeg Ar; Piyapan, Piyathip; Yokubol, Medhi; Mie, Khin Mie; Bates, Paul J; Satasook, Chutamas; Nwe, Tin; Bu, Si Si Hla; Mackie, Iain J; Petit, Eric J; Teeling, Emma C

    2011-12-06

    The sensory drive theory of speciation predicts that populations of the same species inhabiting different environments can differ in sensory traits, and that this sensory difference can ultimately drive speciation. However, even in the best-known examples of sensory ecology driven speciation, it is uncertain whether the variation in sensory traits is the cause or the consequence of a reduction in levels of gene flow. Here we show strong genetic differentiation, no gene flow and large echolocation differences between the allopatric Myanmar and Thai populations of the world's smallest mammal, Craseonycteris thonglongyai, and suggest that geographic isolation most likely preceded sensory divergence. Within the geographically continuous Thai population, we show that geographic distance has a primary role in limiting gene flow rather than echolocation divergence. In line with sensory-driven speciation models, we suggest that in C. thonglongyai, limited gene flow creates the suitable conditions that favour the evolution of sensory divergence via local adaptation.

  3. Characterization of the functional near-infrared spectroscopy response to nociception in a pediatric population.

    Science.gov (United States)

    Olbrecht, Vanessa A; Jiang, Yifei; Viola, Luigi; Walter, Charlotte M; Liu, Hanli; Kurth, Charles D

    2018-02-01

    Near-infrared spectroscopy can interrogate functional optical signal changes in regional brain oxygenation and blood volume to nociception analogous to functional magnetic resonance imaging. This exploratory study aimed to characterize the near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin from the brain in response to nociceptive stimulation of varying intensity and duration, and after analgesic and neuromuscular paralytic in a pediatric population. We enrolled children 6 months-21 years during propofol sedation before surgery. The near-infrared spectroscopy sensor was placed on the forehead and nociception was produced from an electrical current applied to the wrist. We determined the near-infrared spectroscopy signal response to increasing current intensity and duration, and after fentanyl, sevoflurane, and neuromuscular paralytic. Heart rate and arm movement during electrical stimulation was also recorded. The near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin were calculated as optical density*time (area under curve). During electrical stimulation, nociception was evident: tachycardia and arm withdrawal was observed that disappeared after fentanyl and sevoflurane, whereas after paralytic, tachycardia persisted while arm withdrawal disappeared. The near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin increased during stimulation and decreased after stimulation; the areas under the curves were greater for stimulations 30 mA vs 15 mA (13.9 [5.6-22.2], P = .0021; 5.6 [0.8-10.5], P = .0254, and 19.8 [10.5-29.1], P = .0002 for HbO 2 , Hb, and Hb T , respectively), 50 Hz vs 1 Hz (17.2 [5.8-28.6], P = .0046; 7.5 [0.7-14.3], P = .0314, and 21.9 [4.2-39.6], P = .0177 for HbO 2 , Hb, and Hb T , respectively) and 45 seconds vs 15 seconds (16.3 [3.4-29.2], P = .0188 and 22.0 [7.5-36.5], P = .0075 for HbO 2 and Hb T , respectively); the areas under the curves were attenuated by

  4. Glial activation in the collagenase model of nociception associated with osteoarthritis.

    Science.gov (United States)

    Adães, Sara; Almeida, Lígia; Potes, Catarina S; Ferreira, Ana Rita; Castro-Lopes, José M; Ferreira-Gomes, Joana; Neto, Fani L

    2017-01-01

    Background Experimental osteoarthritis entails neuropathic-like changes in dorsal root ganglia (DRG) neurons. Since glial activation has emerged as a key player in nociception, being reported in numerous models of neuropathic pain, we aimed at evaluating if glial cell activation may also occur in the DRG and spinal cord of rats with osteoarthritis induced by intra-articular injection of collagenase. Methods Osteoarthritis was induced by two injections, separated by three days, of 500 U of type II collagenase into the knee joint of rats. Movement-induced nociception was evaluated by the Knee-Bend and CatWalk tests during the following six weeks. Glial fibrillary acidic protein (GFAP) expression in satellite glial cells of the DRG was assessed by immunofluorescence and Western Blot analysis; the pattern of GFAP and activating transcription factor-3 (ATF-3) expression was also compared through double immunofluorescence analysis. GFAP expression in astrocytes and IBA-1 expression in microglia of the L3-L5 spinal cord segments was assessed by immunohistochemistry and Western Blot analysis. The effect of the intrathecal administration of fluorocitrate, an inhibitor of glial activation, on movement-induced nociception was evaluated six weeks after the first collagenase injection. Results GFAP expression in satellite glial cells of collagenase-injected animals was significantly increased six weeks after osteoarthritis induction. Double immunofluorescence showed GFAP upregulation in satellite glial cells surrounding ATF-3-positive neurons. In the spinal cord of collagenase-injected animals, an ipsilateral upregulation of GFAP and IBA-1 was also observed. The inhibition of glial activation with fluorocitrate decreased movement- and loading-induced nociception. Conclusion Collagenase-induced knee osteoarthritis leads to the development of nociception associated with movement of the affected joint and to the activation of glial cells in both the DRG and the spinal cord

  5. Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence.

    Science.gov (United States)

    Lai, N Y; Mills, K; Chiu, I M

    2017-07-01

    Sensory neurons in the gastrointestinal tract have multifaceted roles in maintaining homeostasis, detecting danger and initiating protective responses. The gastrointestinal tract is innervated by three types of sensory neurons: dorsal root ganglia, nodose/jugular ganglia and intrinsic primary afferent neurons. Here, we examine how these distinct sensory neurons and their signal transducers participate in regulating gastrointestinal inflammation and host defence. Sensory neurons are equipped with molecular sensors that enable neuronal detection of diverse environmental signals including thermal and mechanical stimuli, inflammatory mediators and tissue damage. Emerging evidence shows that sensory neurons participate in host-microbe interactions. Sensory neurons are able to detect pathogenic and commensal bacteria through specific metabolites, cell-wall components, and toxins. Here, we review recent work on the mechanisms of bacterial detection by distinct subtypes of gut-innervating sensory neurons. Upon activation, sensory neurons communicate to the immune system to modulate tissue inflammation through antidromic signalling and efferent neural circuits. We discuss how this neuro-immune regulation is orchestrated through transient receptor potential ion channels and sensory neuropeptides including substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Recent studies also highlight a role for sensory neurons in regulating host defence against enteric bacterial pathogens including Salmonella typhimurium, Citrobacter rodentium and enterotoxigenic Escherichia coli. Understanding how sensory neurons respond to gastrointestinal flora and communicate with immune cells to regulate host defence enhances our knowledge of host physiology and may form the basis for new approaches to treat gastrointestinal diseases. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  6. Effects of Arousal on Mouse Sensory Cortex Depend on Modality

    Directory of Open Access Journals (Sweden)

    Daisuke Shimaoka

    2018-03-01

    Full Text Available Summary: Changes in arousal modulate the activity of mouse sensory cortex, but studies in different mice and different sensory areas disagree on whether this modulation enhances or suppresses activity. We measured this modulation simultaneously in multiple cortical areas by imaging mice expressing voltage-sensitive fluorescent proteins (VSFP. VSFP imaging estimates local membrane potential across large portions of cortex. We used temporal filters to predict local potential from running speed or from pupil dilation, two measures of arousal. The filters provided good fits and revealed that the effects of arousal depend on modality. In the primary visual cortex (V1 and auditory cortex (Au, arousal caused depolarization followed by hyperpolarization. In the barrel cortex (S1b and a secondary visual area (LM, it caused only hyperpolarization. In all areas, nonetheless, arousal reduced the phasic responses to trains of sensory stimuli. These results demonstrate diverse effects of arousal across sensory cortex but similar effects on sensory responses. : Shimaoka et al. use voltage-sensitive imaging to show that the effects of arousal on the mouse cortex are markedly different across areas and over time. In all the sensory areas studied, nonetheless, arousal reduced the phasic voltage responses to trains of sensory stimuli. Keywords: cerebral cortex, cortical state, locomotion, sensory processing, widefield imaging

  7. Possible effects of mobilisation on acute post-operative pain and nociceptive function after total knee arthroplasty

    DEFF Research Database (Denmark)

    Lunn, T H; Kristensen, B B; Gaarn-Larsen, L

    2012-01-01

    BACKGROUND: Experimental studies in animals, healthy volunteers, and patients with chronic pain suggest exercise to provide analgesia in several types of pain conditions and after various nociceptive stimuli. To our knowledge, there is no data on the effects of exercise on pain and nociceptive...... function in surgical patients despite early mobilisation being an important factor to enhance recovery. We therefore investigated possible effects of mobilisation on post-operative pain and nociceptive function after total knee arthroplasty (TKA). METHODS: Thirty patients undergoing TKA under standardised...... anaesthesia and analgesia underwent an exercise (mobilisation) strategy on the first post-operative morning consisting of 25-m walking twice, with a 20-min interval. Pain was assessed at rest and during passive hip and knee flexion before, and 5 and 20 min after walk, as well as during walk. Nociceptive...

  8. Measuring cutaneous thermal nociception in group-housed pigs using laser technique - effects of laser power output

    DEFF Research Database (Denmark)

    Herskin, Mette S.; Ladevig, Jan; Arendt-Nielsen, Lars

    2009-01-01

    nociceptive stimulation from a computer-controlled CO2-laser beam applied to either the caudal part of the metatarsus on the hind legs or the shoulder region of gilts. In Exp. 1, effects of laser power output (0, 0.5, 1, 1.5 and 2 W) on nociceptive responses toward stimulation on the caudal aspects...... lifting leg (P laser stimulation was increased (P laser power output (0, 0.8, 1.5, 2.2 and 3 W) on nociceptive responses toward stimulation on the shoulder region were examined in 10...... are available, especially methodology which is applicable for pigs kept in group-housing without disturbing the daily routines of the animals. To validate a laser-based method to measure thermal nociception in group-housed pigs, we performed two experiments observing the behavioural responses toward cutaneous...

  9. Anti-Nociceptive Effect of Tricyclic Anti-Depressants Following Intrathecal Administration

    Science.gov (United States)

    Kehl, Lois J.; Wilcox, George L.

    1984-01-01

    The anti-nociceptive effects of three tricyclic anti-depressants (desipramine, protriptyline, fluoxetine) were evaluated in mice following intrathecal administration. Nociceptive behavior was produced by intrathecal administration of Substance P and measured for 60 seconds following subcutaneous and intrathecal administration of vehicle and increasing doses of the drugs being tested. Systemically administered protriptyline produced dose related antinociception in this paradigm. A similar effect was seen following systemic desipramine; while fluoxetine was inactive systemically. Both protriptyline and desipramine given intrathecally were antinociceptive while fluoxetine had a biphasic effect, being analgesic only at low doses. These results indicate that tricyclic antidepressants may produce analgesia at the spinal level in rodents. This action may be related to the therapeutic success of tricyclic antidepressants in chronic pain syndromes. PMID:6335632

  10. Anti-nociceptive and anti-inflammatory effects of the methanolic extract of Opuntia humifusa stem

    Science.gov (United States)

    Sharma, Bhesh Raj; Park, Chul Min; Choi, Jong Won; Rhyu, Dong Young

    2017-01-01

    Objective: Opuntia humifusa (O. humifusa) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). Materials and Methods: The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular permeability and carrageenan and serotonin-induced paw edema tests in rats. Furthermore, anti-inflammatory effect was also measured using macrophage-like LPS-induced RAW 264.7 cells. Results: OHS extract inhibited acetic acid-induced writhing (pdiseases. PMID:28884086

  11. Anti-nociceptive and anti-inflammatory effects of the methanolic extract ofOpuntia humifusastem.

    Science.gov (United States)

    Sharma, Bhesh Raj; Park, Chul Min; Choi, Jong Won; Rhyu, Dong Young

    2017-01-01

    Opuntia humifusa ( O. humifusa ) Raf. has been used for the prevention and treatment of rheumatoid arthritis, inflammation, and cancer. Our study was designed to unveil the anti-nociceptive and anti-inflammatory effects of the methanolic extract of O. humifusa Raf stem (OHS). The anti-nociceptive effect was measured by hot plate, acetic acid-induced writhing, and tail flick assays in mice and rats. Moreover, the anti-inflammatory effect was measured by vascular permeability and carrageenan and serotonin-induced paw edema tests in rats. Furthermore, anti-inflammatory effect was also measured using macrophage-like LPS-induced RAW 264.7 cells. OHS extract inhibited acetic acid-induced writhing (pdiseases.

  12. Cortical and spinal assessment - a comparative study using encephalography and the nociceptive withdrawal reflex

    DEFF Research Database (Denmark)

    Fischer, I W; Gram, M; Hansen, T M

    2017-01-01

    BACKGROUND: Standardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels...... solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded. RESULTS: Data from thirty...... morphine administration (P>0.05). CONCLUSIONS: Cold pressor EEG and the nociceptive reflex were more sensitive to morphine analgesia than resting EEG and can be used as standardized objective methods to assess opioid effects. However, no correlation between the analgesic effect of morphine on the spinal...

  13. Vagus nerve stimulation inhibits trigeminal nociception in a rodent model of episodic migraine

    Science.gov (United States)

    Hawkins, Jordan L.; Cornelison, Lauren E.; Blankenship, Brian A.; Durham, Paul L.

    2017-01-01

    Abstract Introduction: Although neck muscle tension is considered a risk factor for migraine, pungent odors can act as a trigger to initiate an attack in sensitized individuals. Although noninvasive vagus nerve stimulation (nVNS) is now an approved treatment for chronic migraine, how it functions to inhibit trigeminal nociception in an episodic migraine model is not known. Objectives: The objectives of this study were to determine if nVNS could inhibit trigeminal nociception in a novel model of episodic migraine and investigate changes in the expression of proteins implicated in peripheral and central sensitization. Methods: Sprague-Dawley male rats were injected with an inflammatory agent in the trapezius muscle before exposure to pungent volatile compounds, which was used to initiate trigeminal nociceptor activation. The vagus nerve was stimulated transdermally by a 1-ms pulse of 5 kHz sine waves, repeated at 25 Hz for 2 minutes. Nocifensive head withdrawal response to von Frey filaments was determined and immunoreactive protein levels in the spinal cord and trigeminal ganglion (TG) were investigated. Results: Exposure to the pungent odor significantly increased the number of nocifensive withdrawals in response to mechanical stimulation of sensitized TG neurons mediated by neck muscle inflammation. Noninvasive vagus nerve stimulation inhibited nociception and repressed elevated levels of P-ERK in TG, Iba1 in microglia, and GFAP in astrocytes from sensitized animals exposed to the pungent odor. Conclusion: Our findings demonstrate that nVNS inhibits mechanical nociception and represses expression of proteins associated with peripheral and central sensitization of trigeminal neurons in a novel rodent model of episodic migraine. PMID:29392242

  14. Citronellal, a monoterpene present in Java citronella oil, attenuates mechanical nociception response in mice.

    Science.gov (United States)

    de Santana, Marilia Trindade; de Oliveira, Makson Gleydson Brito; Santana, Michele Fraga; De Sousa, Damião Pergentino; Santana, Danielle Gomes; Camargo, Enilton Aparecido; de Oliveira, Aldeídia Pereira; Almeida, Jackson Roberto Guedes da Silva; Quintans-Júnior, Lucindo José

    2013-09-01

    Citronellal is a monoterpene present in the oil of many species, including Cymbopogon winterianus Jowitt (Poaceae). The present study investigated the effect of citronellal on inflammatory nociception induced by different stimuli and examined the involvement of the NO-cGMP-ATP-sensitive K⁺ channel pathway. We used male Swiss mice (n = 6 per group) that were treated intraperitoneally with citronellal (25, 50 or 100 mg/kg) 0.5 h after the subplantar injection of 20 μl of carrageenan (CG; 300 µg/paw), tumor necrosis factor-α (TNF-α; 100 pg/paw), prostaglandin E₂ (PGE₂; 100 ng/paw) or dopamine (DA; 30 μg/paw). The mechanical nociception was evaluated at 0.5, 1, 2 and 3 h after the injection of the agents, using a digital analgesimeter (von Frey). The effects of citronellal were also evaluated in the presence of L-NAME (30 mg/kg) or glibenclamide (5 mg/kg). At all times, citronellal in all doses inhibited the development of mechanical nociception induced by CG (p < 0.001 and p < 0.01) and TNF-α (p < 0.001, p < 0.01, and p < 0.05). The citronellal was able to increase the pain threshold in the DA test (p < 0.001, p < 0.01, and p < 0.05) and in the PGE₂ test at all times (p < 0.001 and p < 0.05). L-NAME and glibenclamide reversed the antinociceptive effects of the citronellal at higher doses in the PGE₂ test. These data suggest that citronellal attenuated mechanical nociception, mediated in part by the NO-cGMP-ATP-sensitive K⁺ channel pathway.

  15. Ovariectomy results in variable changes in nociception, mood and depression in adult female rats.

    Directory of Open Access Journals (Sweden)

    Li-Hong Li

    Full Text Available Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX, a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%-induced nociceptive responses (such as elevating and licking or biting during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact. Using formalin-induced conditioned place avoidance (F-CPA, which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA. In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way.

  16. Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture

    OpenAIRE

    Li, Wen-Wu; Guo, Tian-Zhi; Shi, Xiaoyou; Sun, Yuan; Wei, Tzuping; Clark, David J; Kingery, Wade S

    2015-01-01

    Tibia fracture in rodents induces substance P (SP)-dependent keratinocyte activation and inflammatory changes in the hindlimb, similar to those seen in complex regional pain syndrome (CRPS). In animal pain models spinal glial cell activation results in nociceptive sensitization. This study tested the hypothesis that limb fracture triggers afferent C-fiber SP release in the dorsal horn, resulting in chronic glia activation and central sensitization. At 4 weeks after tibia fracture and casting ...

  17. Molecular Basis of TRPA1 Regulation in Nociceptive Neurons. A Review

    Czech Academy of Sciences Publication Activity Database

    Kádková, Anna; Synytsya, Viktor; Krůšek, Jan; Zímová, Lucie; Vlachová, Viktorie

    2017-01-01

    Roč. 66, č. 3 (2017), s. 425-439 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA15-15839S; GA MZd(CZ) NV16-28784A Institutional support: RVO:67985823 Keywords : transient receptor potential ankyrin 1 * bradykinin * structure- function * nociception * post-translational modifications * signaling pathways Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 1.461, year: 2016

  18. Surgical incision can alter capsaicin-induced central sensitization in rat brainstem nociceptive neurons.

    Science.gov (United States)

    Lam, D K; Sessle, B J; Hu, J W

    2008-10-15

    Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central

  19. Glial activation in the collagenase model of nociception associated with osteoarthritis

    OpenAIRE

    Ad?es, Sara; Almeida, L?gia; Potes, Catarina S; Ferreira, Ana Rita; Castro-Lopes, Jos? M; Ferreira-Gomes, Joana; Neto, Fani L

    2017-01-01

    Background Experimental osteoarthritis entails neuropathic-like changes in dorsal root ganglia (DRG) neurons. Since glial activation has emerged as a key player in nociception, being reported in numerous models of neuropathic pain, we aimed at evaluating if glial cell activation may also occur in the DRG and spinal cord of rats with osteoarthritis induced by intra-articular injection of collagenase. Methods Osteoarthritis was induced by two injections, separated by three days, of 500 U of typ...

  20. Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Komatsu, Takaaki; Iwata, Yoko; Watanabe, Chizuko; Watanabe, Hiroyuki; Orito, Tohru; Katsuyama, Soh; Yonezawa, Akihiko; Onodera, Kenji; Sakurada, Tsukasa; Sakurada, Shinobu

    2011-05-16

    The involvement of spinal glial cells in the nociceptive behaviors induced by 800 pmol of histamine was determined in mice. Histamine at 800 pmol injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with tachykinin NK(1) receptor antagonist CP99,994 or competitive antagonist for N-methyl-d-aspartate (NMDA) receptor d-(-)-2-amino-5-phosphonovaleric acid (d-APV). The i.t. pretreatment with the glial cell inhibitor dl-fluorocitric acid or minocycline failed to affect the nociceptive behaviors induced by histamine. However, in mice pretreated i.t. with dl-fluorocitric acid or minocycline, the nociceptive behaviors induced by histamine were significantly suppressed by i.t. co-administration with CP99,994 but not d-APV. In Western blot analysis using lumbar spinal cords, i.t. treatment with 800 pmol of histamine increased the phosphorylation of the NR1 subunit of NMDA receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with dl-fluorocitric acid or minocycline. The present results suggest that histamine at 800 pmol elicits nociceptive behaviors through activation of the neuronal NK(1) receptor and the NR1 subunit-containing NMDA receptors on glial cells in the spinal cord. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Serotonin enhances urinary bladder nociceptive processing via a 5-HT3 receptor mechanism.

    Science.gov (United States)

    Hall, Jason D; DeWitte, Cary; Ness, Timothy J; Robbins, Meredith T

    2015-09-14

    Serotonin from the descending pain modulatory pathway is critical to nociceptive processing. Its effects on pain modulation may either be inhibitory or facilitatory, depending on the type of pain and which receptors are involved. Little is known about the role of serotonergic systems in bladder nociceptive processing. These studies examined the effect of systemic administration of the serotonin precursor, 5-hydroxytryptophan (5-HTP), on normal bladder and somatic sensation in rats. ELISA was used to quantify peripheral and central changes in serotonin and its major metabolite following 5-HTP administration, and the potential role of the 5-HT3 receptor on changes in bladder sensation elicited by 5-HTP was investigated. 5-HTP produced bladder hypersensitivity and somatic analgesia. The pro-nociceptive effect of 5-HTP was attenuated by intrathecal, but not systemic, ondansetron. Peripheral increases in serotonin, its metabolism and rate of turnover were detectable within 30min of 5-HTP administration. Significant enhancement of serotonin metabolism was observed centrally. These findings suggest that 5-HTP increases serotonin, which may then affect descending facilitatory systems to produce bladder hypersensitivity via activation of spinal 5-HT3 receptors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Phytochemical Screening and Anti-nociceptive Properties of the Ethanolic Leaf Extract of Trema Cannabina Lour

    Directory of Open Access Journals (Sweden)

    Hira Arpona

    2013-02-01

    Full Text Available Purpose: The present study was designed to investigate the anti-nociceptive activity of ethanolic leaf extract of Trema cannabina Lour (family: Cannabaceae in experimental animal models. Methods: The anti-nociceptive action was carried out against two types of noxious stimuli, thermal (hot plate and tail immersion tests and chemical (acetic acid-induced writhing in mice. Results: Phytochemical analysis of crude extract indicated the presence of reducing sugar, tannins, steroid and alkaloid types of secondary metabolites. Crude extract of T. cannabina (500 mg/kg dose showed maximum time needed for the response against thermal stimuli (6.79±0.15 seconds which is comparable to diclofenac sodium (8.26±0.14 seconds in the hot plate test. Hot tail immersion test also showed similar results as in hot plate test. At the dose of 250 and 500 mg/kg body weight, the extract showed significantly and in a dose-dependent (p<0.001 reduction in acetic acid induced writhing in mice with a maximum effect of 47.56% reduction at 500 mg/kg dose comparable to that of diclofenac sodium (67.07% at 25 mg/kg. Conclusion: The obtained results tend to suggest the Anti-nociceptive activity of ethanolic leaf extract of Trema cannabina and thus provide the scientific basis for the traditional uses of this plant part as a remedy for pain.

  3. Variations of the analgesia nociception index during general anaesthesia for laparoscopic abdominal surgery.

    Science.gov (United States)

    Jeanne, M; Clément, C; De Jonckheere, J; Logier, R; Tavernier, B

    2012-08-01

    The analgesia nociception index (ANI) is an online heart rate variability analysis proposed for assessment of the antinociception/nociception balance. In this observational study, we compared ANI with heart rate (HR) and systolic blood pressure (SBP) during various noxious stimuli in anaesthetized patients. 15 adult patients undergoing laparoscopic appendectomy or cholecystectomy were studied. Patients received target controlled infusions of propofol (adjusted to maintain the Bispectral index in the range [40-60]) and remifentanil (with target increase in case of haemodynamic reactivity [increase in HR and/or SBP >20% of baseline]), and cisatracurium. Medical staff was blind to the ANI monitor. ANI and haemodynamic data were recorded at predefined times before and during surgery, including tetanic stimulation of the ulnar nerve before start of surgery. Anaesthesia induction decreased HR and SBP, while high ANI values (88 [17]) were recorded, indicating parasympathetic predominance. In 10 out of 11 patients, tetanic stimulation led to a transient (surgery, ANI decreased to 60 (39) and decreased further to 50 (15) after the pneumoperitoneum was inflated, while there was no significant change in HR or SBP. When haemodynamic reactivity occurred, ANI had further decreased to 40 (15). After completion of surgery, ANI returned to 90 (34). ANI seems more sensitive than HR and SBP to moderate nociceptive stimuli in propofol-anaesthetized patients. Whether ANI monitoring may allow preventing haemodynamic reactivity to noxious stimuli remains to be demonstrated.

  4. Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Mark S. Cooper

    2011-01-01

    Full Text Available Electrophysiological conversion of chloride-dependent synapses from inhibitory to excitatory function, as a result of aberrant neuronal chloride homeostasis, is a known mechanism for the genesis of neuropathic pain. This paper examines theoretically how this type of synaptic conversion can disrupt circuit logic in spinal nociceptive circuits. First, a mathematical scaling factor is developed to represent local aberration in chloride electrochemical driving potential. Using this mathematical scaling factor, electrophysiological symbols are developed to represent the magnitude of synaptic conversion within nociceptive circuits. When inserted into a nociceptive circuit diagram, these symbols assist in understanding the generation of neuropathic pain associated with the collapse of transmembrane chloride gradients. A more generalized scaling factor is also derived to represent the interplay of chloride and bicarbonate driving potentials on the function of GABAergic and glycinergic synapses. These mathematical and symbolic representations of synaptic conversion help illustrate the critical role that anion driving potentials play in the transduction of pain. Using these representations, we discuss ramifications of glial-mediated synaptic conversion in the genesis, and treatment, of neuropathic pain.

  5. Prediction of immediate postoperative pain using the analgesia/nociception index: a prospective observational study.

    Science.gov (United States)

    Boselli, E; Bouvet, L; Bégou, G; Dabouz, R; Davidson, J; Deloste, J-Y; Rahali, N; Zadam, A; Allaouchiche, B

    2014-04-01

    The analgesia/nociception index (ANI) is derived from heart rate variability, ranging from 0 (maximal nociception) to 100 (maximal analgesia), to reflect the analgesia/nociception balance during general anaesthesia. This should be correlated with immediate postoperative pain in the post-anaesthesia care unit (PACU). The aim of this study was to evaluate the performance of ANI measured at arousal from general anaesthesia to predict immediate postoperative pain on arrival in PACU. Two hundred patients undergoing ear, nose, and throat or lower limb orthopaedic surgery with general anaesthesia using an inhalational agent and remifentanil were included in this prospective observational study. The ANI was measured immediately before tracheal extubation and pain intensity was assessed within 10 min of arrival in PACU using a 0-10 numerical rating scale (NRS). The relationship between ANI and NRS was assessed using linear regression. A receiver-operating characteristic (ROC) curve was used to evaluate the performance of ANI to predict NRS>3. A negative linear relationship was observed between ANI immediately before extubation and NRS on arrival in PACU. Using a threshold of 3 were both 86% with 92% negative predictive value, corresponding to an area under the ROC curve of 0.89. The measurement of ANI immediately before extubation after inhalation-remifentanil anaesthesia was significantly associated with pain intensity on arrival in PACU. The performance of ANI for the prediction of immediate postoperative pain is good and may assist physicians in optimizing acute pain management. ClinicalTrials.gov NCT01796249.

  6. [Contribution of the sensitization of supraspinal nociceptive transmission in chronic pain].

    Science.gov (United States)

    Ohsawa, Masahiro; Yamamoto, Shohei; Ono, Hideki

    2014-01-01

    Central sensitization in the spinal cord is well known to be involved in chronic pain. Recent investigations indicated that the protein expressions involving the synaptic plasticity are changed in several brain areas under a chronic pain condition. These changes in supraspinal neural function might cause the emotional and memory dysfunction. It is also possible that these changes are involved in the chronic pain. Indeed, since the improvement of spinal and peripheral sensitization showed limited relief in the neuropathic pain, the sensitization of supraspinal nociceptive transmission might be involved in the expression of chronic pain. We recently found that intra-thalamic treatment with excitatory neurotransmitter glutamate caused hyperalgesia, which is mediated by the stimulation of glutamate N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Moreover, intracerebroventricular treatment with gabapentin, a calcium channel alpha2delta-1 subunit blocker, attenuated the hyperalgesia in the nerve-injury model of mice. These results suggest that the sensitization of supraspinal nociceptive transmission is involved in neuropathic pain. It is also indicated that neuropathic pain is resulted from the activations of spinal glial cells. Likewise, the supraspinal glial activation was observed in the neuropathic pain. Therefore, the sensitization of supraspinal nociceptive transmission might be important for a chronic pain. In this review, we would like to discuss the possible involvement of the supraspinal sensitization in neuropathic pain and in its application for the curative treatment in chronic pain.

  7. Ensemble encoding of nociceptive stimulus intensity in the rat medial and lateral pain systems

    Directory of Open Access Journals (Sweden)

    Woodward Donald J

    2011-08-01

    Full Text Available Abstract Background The ability to encode noxious stimulus intensity is essential for the neural processing of pain perception. It is well accepted that the intensity information is transmitted within both sensory and affective pathways. However, it remains unclear what the encoding patterns are in the thalamocortical brain regions, and whether the dual pain systems share similar responsibility in intensity coding. Results Multichannel single-unit recordings were used to investigate the activity of individual neurons and neuronal ensembles in the rat brain following the application of noxious laser stimuli of increasing intensity to the hindpaw. Four brain regions were monitored, including two within the lateral sensory pain pathway, namely, the ventral posterior lateral thalamic nuclei and the primary somatosensory cortex, and two in the medial pathway, namely, the medial dorsal thalamic nuclei and the anterior cingulate cortex. Neuron number, firing rate, and ensemble spike count codings were examined in this study. Our results showed that the noxious laser stimulation evoked double-peak responses in all recorded brain regions. Significant correlations were found between the laser intensity and the number of responsive neurons, the firing rates, as well as the mass spike counts (MSCs. MSC coding was generally more efficient than the other two methods. Moreover, the coding capacities of neurons in the two pathways were comparable. Conclusion This study demonstrated the collective contribution of medial and lateral pathway neurons to the noxious intensity coding. Additionally, we provide evidence that ensemble spike count may be the most reliable method for coding pain intensity in the brain.

  8. Spinal sensory projection neuron responses to spinal cord stimulation are mediated by circuits beyond gate control.

    Science.gov (United States)

    Zhang, Tianhe C; Janik, John J; Peters, Ryan V; Chen, Gang; Ji, Ru-Rong; Grill, Warren M

    2015-07-01

    Spinal cord stimulation (SCS) is a therapy used to treat intractable pain with a putative mechanism of action based on the Gate Control Theory. We hypothesized that sensory projection neuron responses to SCS would follow a single stereotyped response curve as a function of SCS frequency, as predicted by the Gate Control circuit. We recorded the responses of antidromically identified sensory projection neurons in the lumbar spinal cord during 1- to 150-Hz SCS in both healthy rats and neuropathic rats following chronic constriction injury (CCI). The relationship between SCS frequency and projection neuron activity predicted by the Gate Control circuit accounted for a subset of neuronal responses to SCS but could not account for the full range of observed responses. Heterogeneous responses were classifiable into three additional groups and were reproduced using computational models of spinal microcircuits representing other interactions between nociceptive and nonnociceptive sensory inputs. Intrathecal administration of bicuculline, a GABAA receptor antagonist, increased spontaneous and evoked activity in projection neurons, enhanced excitatory responses to SCS, and reduced inhibitory responses to SCS, suggesting that GABAA neurotransmission plays a broad role in regulating projection neuron activity. These in vivo and computational results challenge the Gate Control Theory as the only mechanism underlying SCS and refine our understanding of the effects of SCS on spinal sensory neurons within the framework of contemporary understanding of dorsal horn circuitry. Copyright © 2015 the American Physiological Society.

  9. Cutaneous lesions sensory impairment recovery and nerve regeneration in leprosy patients

    Directory of Open Access Journals (Sweden)

    Ximena Illarramendi

    2012-12-01

    Full Text Available It is important to understand the mechanisms that enable peripheral neurons to regenerate after nerve injury in order to identify methods of improving this regeneration. Therefore, we studied nerve regeneration and sensory impairment recovery in the cutaneous lesions of leprosy patients (LPs before and after treatment with multidrug therapy (MDT. The skin lesion sensory test results were compared to the histopathological and immunohistochemical protein gene product (PGP 9.5 and the p75 nerve growth factor receptors (NGFr findings. The cutaneous neural occupation ratio (CNOR was evaluated for both neural markers. Thermal and pain sensations were the most frequently affected functions at the first visit and the most frequently recovered functions after MDT. The presence of a high cutaneous nerve damage index did not prevent the recovery of any type of sensory function. The CNOR was calculated for each biopsy, according to the presence of PGP and NGFr-immunostained fibres and it was not significantly different before or after the MDT. We observed a variable influence of MDT in the recovery from sensory impairment in the cutaneous lesions of LPs. Nociception and cold thermosensation were the most recovered sensations. The recovery of sensation in the skin lesions appeared to be associated with subsiding inflammation rather than with the regenerative activity of nerve fibres.

  10. ASIC3, an acid-sensing ion channel, is expressed in metaboreceptive sensory neurons

    Directory of Open Access Journals (Sweden)

    Fierro Leonardo

    2005-11-01

    Full Text Available Abstract Background ASIC3, the most sensitive of the acid-sensing ion channels, depolarizes certain rat sensory neurons when lactic acid appears in the extracellular medium. Two functions have been proposed for it: 1 ASIC3 might trigger ischemic pain in heart and muscle; 2 it might contribute to some forms of touch mechanosensation. Here, we used immunocytochemistry, retrograde labelling, and electrophysiology to ask whether the distribution of ASIC3 in rat sensory neurons is consistent with either of these hypotheses. Results Less than half (40% of dorsal root ganglion sensory neurons react with anti-ASIC3, and the population is heterogeneous. They vary widely in cell diameter and express different growth factor receptors: 68% express TrkA, the receptor for nerve growth factor, and 25% express TrkC, the NT3 growth factor receptor. Consistent with a role in muscle nociception, small ( Conclusion Our data indicates that: 1 ASIC3 is expressed in a restricted population of nociceptors and probably in some non-nociceptors; 2 co-expression of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a class of sensory neurons, some of which innervate blood vessels. We suggest that these latter afferents may be muscle metaboreceptors, neurons that sense the metabolic state of muscle and can trigger pain when there is insufficient oxygen.

  11. Mechanisms-based classifications of musculoskeletal pain: part 3 of 3: symptoms and signs of nociceptive pain in patients with low back (± leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-08-01

    As a mechanisms-based classification of pain \\'nociceptive pain\\' (NP) refers to pain attributable to the activation of the peripheral receptive terminals of primary afferent neurones in response to noxious chemical, mechanical or thermal stimuli. The symptoms and signs associated with clinical classifications of NP have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of NP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol after which their pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various symptoms and signs. A regression analysis identified a cluster of seven clinical criteria predictive of NP, including: \\'Pain localised to the area of injury\\/dysfunction\\

  12. The changing sensory room

    DEFF Research Database (Denmark)

    2018-01-01

    In 2017 the kindergarten The Milky Way in the city Vejle in Denmark made a sensory room that has the special ability change whenever wanted by the children and social educators. Kjetil Sandvik (to the right) from Copenhagen University and Klaus Thestrup from Aarhus University reflects upon what...... they saw, took part in and talked with the social educators about. Jacob Knudsen from VIFIN filmed the two gentlemen and organised the project. it is a room composed around common experiments, many self-made objects, open narrative structures. and a combination of digital and analogue elements....

  13. Transcendence and Sensoriness

    DEFF Research Database (Denmark)

    Protestant theology and culture are known for a reserved, at times skeptical, attitude to the use of art and aesthetic forms of expression in a religious context. In Transcendence and Sensoriness, this attitude is analysed and discussed both theoretically and through case studies considered...... in a broad theological and philosophical framework of religious aesthetics. Nordic scholars of theology, philosophy, art, music, and architecture, discuss questions of transcendence, the human senses, and the arts in order to challenge established perspectives within the aesthetics of religion and theology....

  14. Size structures sensory hierarchy in ocean life

    DEFF Research Database (Denmark)

    Martens, Erik Andreas; Wadhwa, Navish; Jacobsen, Nis Sand

    2015-01-01

    the use of remote sensing. In this study, we explore how sensing mode and range depend on body size. We reveal a hierarchy of sensing modes (chemosensing, mechanosensing, vision, hearing, and echolocation) where body size determines the available battery of sensing modes and where larger body size means...... a longer sensing range. The size-dependent hierarchy and the transitions between primary sensory modes are explained on the grounds of limiting factors set by physiology and the physical laws governing signal generation, transmission and reception. We characterize the governing mechanisms and theoretically...... predict the body size limits for various sensory modes, which align very well with size ranges found in literature. The treatise of all ocean life, from unicellular organisms to whales, demonstrates how body size determines available sensing modes, and thereby acts as a major structuring factor of aquatic...

  15. Approximate Sensory Data Collection: A Survey

    Directory of Open Access Journals (Sweden)

    Siyao Cheng

    2017-03-01

    Full Text Available With the rapid development of the Internet of Things (IoTs, wireless sensor networks (WSNs and related techniques, the amount of sensory data manifests an explosive growth. In some applications of IoTs and WSNs, the size of sensory data has already exceeded several petabytes annually, which brings too many troubles and challenges for the data collection, which is a primary operation in IoTs and WSNs. Since the exact data collection is not affordable for many WSN and IoT systems due to the limitations on bandwidth and energy, many approximate data collection algorithms have been proposed in the last decade. This survey reviews the state of the art of approximatedatacollectionalgorithms. Weclassifythemintothreecategories: themodel-basedones, the compressive sensing based ones, and the query-driven ones. For each category of algorithms, the advantages and disadvantages are elaborated, some challenges and unsolved problems are pointed out, and the research prospects are forecasted.

  16. Approximate Sensory Data Collection: A Survey.

    Science.gov (United States)

    Cheng, Siyao; Cai, Zhipeng; Li, Jianzhong

    2017-03-10

    With the rapid development of the Internet of Things (IoTs), wireless sensor networks (WSNs) and related techniques, the amount of sensory data manifests an explosive growth. In some applications of IoTs and WSNs, the size of sensory data has already exceeded several petabytes annually, which brings too many troubles and challenges for the data collection, which is a primary operation in IoTs and WSNs. Since the exact data collection is not affordable for many WSN and IoT systems due to the limitations on bandwidth and energy, many approximate data collection algorithms have been proposed in the last decade. This survey reviews the state of the art of approximatedatacollectionalgorithms. Weclassifythemintothreecategories: themodel-basedones, the compressive sensing based ones, and the query-driven ones. For each category of algorithms, the advantages and disadvantages are elaborated, some challenges and unsolved problems are pointed out, and the research prospects are forecasted.

  17. Parasympathetic functions in children with sensory processing disorder

    Directory of Open Access Journals (Sweden)

    Roseann C Schaaf

    2010-03-01

    Full Text Available The overall goal of this study was to determine if Parasympathetic Nervous System Activity (PsNS is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS functioning affects sensory reactivity in children who have a type of condition associated with Sensory Processing Disorders (SPD termed Sensory Modulation Dysfunction (SMD. If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children. The primary aims of this project were to: (1 evaluate PsNS activity in children with SMD compared to typically developing (TYP children, and (2 determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that the children with severe SMD demonstrated a trend for low baseline parasympathetic activity, compared to TYP children, suggesting this may be a biomarker for severe SMD. In addition, children with SMD demonstrated significantly poorer adaptive behavior. These results provide preliminary evidence that children who demonstrate SMD may have physiological responses that are different from children without SMD, and that these physiological and behavioral manifestations of SMD may affect a child’s ability to engage in everyday social, communication, and daily living skills.

  18. Sensory processing disorder: any of a nurse practitioner's business?

    Science.gov (United States)

    Byrne, Mary W

    2009-06-01

    Children who exhibit the confusing symptom patterns associated with sensory processing deficits are often seen first by primary care providers, including family and pediatric nurse practitioners (NPs). The purpose of this article is to alert NPs to the state of the science for these disorders and to the roles NPs could play in filling the knowledge gaps in assessment, treatment, education, and research. Literature searches using PubMed and MedLine databases and clinical practice observations. Sensory integration disorders have only begun to be defined during the past 35 years. They are not currently included in the DSM IV standard terminology, and are not yet substantively incorporated into most health disciplines' curricula or practice, including those of the NP. NPs are in a unique position to test hypothesized terminology for Sensory Processing Disorder (SPD) by contributing precise clinical descriptions of children who match as well as deviate from the criteria for three proposed diagnostic groups: Sensory Modulation Disorder (SMD), Sensory Discrimination Disorder (SDD), and Sensory-Based Motor Disorder (SBMD). Beyond the SPD diagnostic debate, for children with sensory deficit patterns the NP role can incorporate participating in interdisciplinary treatment plans, refining differential diagnoses, providing frontline referral and support for affected children and their families, and making both secondary prevention and critical causal research possible through validation of consistently accepted diagnostic criteria.

  19. Modularity in Sensory Auditory Memory

    OpenAIRE

    Clement, Sylvain; Moroni, Christine; Samson, Séverine

    2004-01-01

    The goal of this paper was to review various experimental and neuropsychological studies that support the modular conception of auditory sensory memory or auditory short-term memory. Based on initial findings demonstrating that verbal sensory memory system can be dissociated from a general auditory memory store at the functional and anatomical levels. we reported a series of studies that provided evidence in favor of multiple auditory sensory stores specialized in retaining eit...

  20. The impact of atypical sensory processing on social impairments in autism spectrum disorder.

    Science.gov (United States)

    Thye, Melissa D; Bednarz, Haley M; Herringshaw, Abbey J; Sartin, Emma B; Kana, Rajesh K

    2017-05-17

    Altered sensory processing has been an important feature of the clinical descriptions of autism spectrum disorder (ASD). There is evidence that sensory dysregulation arises early in the progression of ASD and impacts social functioning. This paper reviews behavioral and neurobiological evidence that describes how sensory deficits across multiple modalities (vision, hearing, touch, olfaction, gustation, and multisensory integration) could impact social functions in ASD. Theoretical models of ASD and their implications for the relationship between sensory and social functioning are discussed. Furthermore, neural differences in anatomy, function, and connectivity of different regions underlying sensory and social processing are also discussed. We conclude that there are multiple mechanisms through which early sensory dysregulation in ASD could cascade into social deficits across development. Future research is needed to clarify these mechanisms, and specific focus should be given to distinguish between deficits in primary sensory processing and altered top-down attentional and cognitive processes. Published by Elsevier Ltd.

  1. Comparison of voiding function and nociceptive behavior in two rat models of cystitis induced by cyclophosphamide or acetone

    Science.gov (United States)

    Saitoh, Chikashi; Yokoyama, Hitoshi; Chancellor, Michael B.; de Groat, William C.; Yoshimura, Naoki

    2009-01-01

    Aims Nociceptive behavior and its relationship with bladder dysfunction were investigated in two cystitis models, which were induced by intraperitoneal (ip) injection of cyclophosphamide (CYP) or intravesical instillation of acetone, using freely moving, non-catheterized conscious rats. Methods Female Sprague-Dawley rats were used. Cystitis was induced by ip injection of CYP (100 and 200mg/kg) or intravesical instillation of acetone (10, 30 and 50%) via a polyethylene catheter temporarily inserted into the bladder through the urethra. Then the incidence of nociceptive behavior (immobility with decreased breathing rates) was scored. Voided urine was collected simultaneously and continuously to measure bladder capacity. The plasma extravasation in the bladder was quantified by an evans blue (EB) dye leakage technique. Results CYP (100mg/kg, ip) induced nociceptive behavior without affecting bladder capacity or EB concentration in the bladder. A higher dose of CYP (200mg/kg, ip) decreased bladder capacity and increased EB levels as well as nociceptive behavior. In contrast, intravesical instillation of acetone (30%) decreased bladder capacity and increased EB levels, but evoked nociceptive behavior less frequently compared with CYP-treated animals. In capsaicin pretreated rats, nociceptive behavior induced by CYP or acetone was reduced; however, the overall effects of CYP or acetone on bladder capacity and bladder EB levels were unaffected. Conclusions These results suggest that there is a difference in the induction process of nociceptive behavior and small bladder capacity after two different types of bladder irritation and that C-fiber sensitization is more directly involved in pain sensation than reduced bladder capacity. PMID:19618450

  2. Endocannabinoids in the brainstem modulate dural trigeminovascular nociceptive traffic via CB1 and "triptan" receptors: implications in migraine.

    Science.gov (United States)

    Akerman, Simon; Holland, Philip R; Lasalandra, Michele P; Goadsby, Peter J

    2013-09-11

    Activation and sensitization of trigeminovascular nociceptive pathways is believed to contribute to the neural substrate of the severe and throbbing nature of pain in migraine. Endocannabinoids, as well as being physiologically analgesic, are known to inhibit dural trigeminovascular nociceptive responses. They are also involved in the descending modulation of cutaneous-evoked C-fiber spinal nociceptive responses from the brainstem. The purpose of this study was to determine whether endocannabinoids are involved in the descending modulation of dural and/or cutaneous facial trigeminovascular nociceptive responses, from the brainstem ventrolateral periaqueductal gray (vlPAG). CB1 receptor activation in the vlPAG attenuated dural-evoked Aδ-fiber neurons (maximally by 19%) and basal spontaneous activity (maximally by 33%) in the rat trigeminocervical complex, but there was no effect on cutaneous facial receptive field responses. This inhibitory vlPAG-mediated modulation was inhibited by specific CB1 receptor antagonism, given via the vlPAG, and with a 5-HT1B/1D receptor antagonist, given either locally in the vlPAG or systemically. These findings demonstrate for the first time that brainstem endocannabinoids provide descending modulation of both basal trigeminovascular neuronal tone and Aδ-fiber dural-nociceptive responses, which differs from the way the brainstem modulates spinal nociceptive transmission. Furthermore, our data demonstrate a novel interaction between serotonergic and endocannabinoid systems in the processing of somatosensory nociceptive information, suggesting that some of the therapeutic action of triptans may be via endocannabinoid containing neurons in the vlPAG.

  3. SENSORY AND CONSUMER TESTING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — These laboratories conduct a wide range of studies to characterize the sensory properties of and consumer responses to foods, beverages, and other consumer products....

  4. Multi-sensory Sculpting (MSS)

    DEFF Research Database (Denmark)

    von Wallpach, Sylvia; Kreuzer, Maria

    2013-01-01

    -conscious and modality-specific level and use multi-sensory metaphors to express embodied knowledge. Retrieving embodied brand knowledge requires methods that (a) stimulate various senses that have been involved in brand knowledge formation and (b) give consumers the opportunity to express themselves metaphorically...... in a format similar to their cognitive representations. This article introduces multi-sensory sculpting (MSS) as a method that allows retrieving embodied brand knowledge via multi-sensory metaphors and proposes a multi-layered metaphor analysis procedure to interpret these multi-sensory data. The paper...

  5. Upregulation of Ih expressed in IB4-negative Aδ nociceptive DRG neurons contributes to mechanical hypersensitivity associated with cervical radiculopathic pain

    OpenAIRE

    Da-Lu Liu; Na Lu; Wen-Juan Han; Rong-Gui Chen; Rui Cong; Rou-Gang Xie; Yu-Fei Zhang; Wei-Wei Kong; San-Jue Hu; Ceng Luo

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron?s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensit...

  6. Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans

    OpenAIRE

    Mukhopadhyay, Saikat; Lu, Yun; Shaham, Shai; Sengupta, Piali

    2008-01-01

    Non-motile primary cilia are sensory organelles comprised of a microtubular axoneme and a surrounding membrane sheath that houses signaling molecules. Optimal cellular function requires the precise regulation of axoneme assembly, membrane biogenesis and signaling protein targeting and localization via as yet poorly understood mechanisms. Here we show that sensory signaling is required to maintain the architecture of the specialized AWB olfactory neuron cilia in C. elegans. Decreased sensory s...

  7. The NA(v)1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive processing

    Czech Academy of Sciences Publication Activity Database

    Torres-Pérez, J. V.; Adámek, Pavel; Paleček, Jiří; Vizcaychipi, M.; Nagy, I.; Varga, A.

    2018-01-01

    Roč. 96, č. 1 (2018), s. 75-84 ISSN 0946-2716 R&D Projects: GA ČR(CZ) GA15-11138S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) LH15279; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : pain * p-ERK1/2 * primary sensory neuron * p-S10H3 * spinal cord Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.686, year: 2016

  8. Dendritic spine dysgenesis in superficial dorsal horn sensory neurons after spinal cord injury.

    Science.gov (United States)

    Cao, Xiaoyu C; Pappalardo, Laura W; Waxman, Stephen G; Tan, Andrew M

    2017-01-01

    Neuropathic pain is a major complication of spinal cord injury, and despite aggressive efforts, this type of pain is refractory to available clinical treatment. Our previous work has demonstrated a structure-function link between dendritic spine dysgenesis on nociceptive sensory neurons in the intermediate zone, laminae IV/V, and chronic pain in central nervous system and peripheral nervous system injury models of neuropathic pain. To extend these findings, we performed a follow-up structural analysis to assess whether dendritic spine remodeling occurs on superficial dorsal horn neurons located in lamina II after spinal cord injury. Lamina II neurons are responsible for relaying deep, delocalized, often thermally associated pain commonly experienced in spinal cord injury pathologies. We analyzed dendritic spine morphometry and localization in tissue obtained from adult rats exhibiting neuropathic pain one-month following spinal cord injury. Although the total density of dendritic spines on lamina II neurons did not change after spinal cord injury, we observed an inverse relationship between the densities of thin- and mushroom-shaped spines: thin-spine density decreased while mushroom-spine density increased. These structural changes were specifically noted along dendritic branches within 150 µm from the soma, suggesting a possible adverse contribution to nociceptive circuit function. Intrathecal treatment with NSC23766, a Rac1-GTPase inhibitor, significantly reduced spinal cord injury-induced changes in both thin- and mushroom-shaped dendritic spines. Overall, these observations demonstrate that dendritic spine remodeling occurs in lamina II, regulated in part by the Rac1-signaling pathway, and suggests that structural abnormalities in this spinal cord region may also contribute to abnormal nociception after spinal cord injury.

  9. Decoding Subjective Intensity of Nociceptive Pain from Pre-stimulus and Post-stimulus Brain Activities

    Directory of Open Access Journals (Sweden)

    Yiheng eTu

    2016-04-01

    Full Text Available Pain is a highly subjective experience. Self-report is the gold standard for pain assessment in clinical practice, but it may not be available or reliable in some populations. Neuroimaging data, such as electroencephalography (EEG and functional magnetic resonance imaging (fMRI, have the potential to be used to provide physiology-based and quantitative nociceptive pain assessment tools that complements self-report. However, existing neuroimaging-based nociceptive pain assessments only rely on the information in pain-evoked brain activities, but neglect the fact that the perceived intensity of pain is also encoded by ongoing brain activities prior to painful stimulation. Here, we proposed to use machine learning algorithms to decode pain intensity from both pre-stimulus ongoing and post-stimulus evoked brain activities. Neural features that were correlated with intensity of laser-evoked nociceptive pain were extracted from high-dimensional pre- and post-stimulus EEG and fMRI activities using partial least-squares regression (PLSR. Further, we used support vector machine (SVM to predict the intensity of pain from pain-related time-frequency EEG patterns and BOLD-fMRI patterns. Results showed that combining predictive information in pre- and post-stimulus brain activities can achieve significantly better performance in classifying high-pain and low-pain and in predicting the rating of perceived pain than only using post-stimulus brain activities. Therefore, the proposed pain prediction method holds great potential in basic research and clinical applications.

  10. Experimental hypothyroidism during pregnancy affects nociception and locomotor performance of offspring in rats.

    Science.gov (United States)

    Alves, I G N; da Cruz, K M L; Mota, C M D; de Santana, D S; Gaujac, D P; de Carvalho, V C B; Reis, L C; Sluka, K A; Quintans-Junior, L J; Antoniolli, A R; Desantana, J M; Badauê-Passos, D; de Santana-Filho, V J

    2013-10-01

    Thyroid hormones (THs) play a crucial role in the development of several organic systems. An adequate support of maternal THs may be required to ensure a normal nociceptive function of offspring into adulthood. We investigated the impact of experimental gestational hypothyroidism (EGH) on nociceptive threshold and motor performance in the offspring at different post-natal days (PND) in both male and female rats. EGH was induced by the administration of 0.02% methimazole (MMI) in the drinking water from the ninth day of gestation until birth. The offspring from MMI-treated dams (OMTDs) or from water-treated dams (OWTDs) were assessed for thermal and mechanical nociception using the tail-flick test and von Frey filaments, respectively. Both rota-rod and grip strength were used to assess motor function. OMTD had reduced thermal (p<0.05) but not mechanical threshold at all studied ages (60 and 120 PND). Sixty-day-old OMTD presented reduced latency to the tail-flick test (p=0.01). Grip strength in 120-day-old OMTD was reduced (p<0.01). However, only male OMTD presented a lower locomotor performance on the rota-rod test when analysed on the 60th PND (p<0.01). EGH promotes hypersensitivity to noxious thermal but not mechanical stimulus. Moreover, motor force is similarly reduced in male and female OMTDs, whereas motor performance is reduced only in mature male OMTD, suggesting the presence of a protective factor in females. © 2013 European Federation of International Association for the Study of Pain Chapters.

  11. Central neural alterations predominate in an insect model of nociceptive sensitization.

    Science.gov (United States)

    Tabuena, Dennis R; Solis, Allan; Geraldi, Ken; Moffatt, Christopher A; Fuse, Megumi

    2017-04-01

    Many organisms respond to noxious stimuli with defensive maneuvers. This is noted in the hornworm, Manduca sexta, as a defensive strike response. After tissue damage, organisms typically display sensitized responses to both noxious or normally innocuous stimuli. To further understand this phenomenon, we used novel in situ and in vitro preparations based on paired extracellular nerve recordings and videography to identify central and peripheral nerves responsible for nociception and sensitization of the defensive behavior in M. sexta. In addition, we used the in vivo defensive strike response threshold assayed with von Frey filaments to examine the roles that N-methyl-D-aspartate receptor (NMDAR) and hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels play in this nociceptive sensitization using the inhibitors MK-801 and AP5 (NMDAR), and ivabradine and ZD7288 (HCN). Using our new preparations, we found that afferent activity evoked by noxious pinch in these preparations was conveyed to central ganglia by axons in the anterior- and lateral-dorsal nerve branches, and that sensitization induced by tissue damage was mediated centrally. Furthermore, sensitization was blocked by all inhibitors tested except the inactive isomer L-AP5, and reversed by ivabradine both in vivo and in vitro. Our findings suggest that M. sexta's sensitization occurs through central signal amplification. Due to the relatively natural sensitization method and conserved molecular actions, we suggest that M. sexta may be a valuable model for studying the electrophysiological properties of nociceptive sensitization and potentially related conditions such as allodynia and hyperalgesia in a comparative setting that offers unique experimental advantages. J. Comp. Neurol. 525:1176-1191, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Induction of muscle cramps by nociceptive stimulation of latent myofascial trigger points.

    Science.gov (United States)

    Ge, Hong-You; Zhang, Yang; Boudreau, Shellie; Yue, Shou-Wei; Arendt-Nielsen, Lars

    2008-06-01

    The aim of this present study is to test the hypothesis that nociceptive stimulation of latent myofascial trigger points (MTrPs) increases the occurrence of local muscle cramps. Nociceptive muscle stimulation was obtained by a bolus injection of glutamate (0.1 ml, 0.5 M) into a latent MTrP and a control point (a non-MTrP) located in the right or left gastrocnemius medialis muscles in 14 healthy subjects. A bolus of isotonic saline (0.9%, 0.1 ml) injection served as a control. The injections were guided by intramuscular electromyography (EMG) showing resting spontaneous electrical activity at a latent MTrP and no such activity at a non-MTrP. Intramuscular and surface EMG activities in the gastrocnemius medialis muscle were recorded pre-, during-, and post-injection for a period of 8 min to monitor the occurrence of muscle cramps, which are characterized by a brief episodic burst of high levels of EMG activity. The results showed that glutamate and isotonic saline injections into the latent MTrPs induced higher peak pain intensity than into the non-MTrPs (both P < 0.05). Glutamate injection induced higher peak pain intensity than isotonic saline injection into either latent MTrPs or non-MTrPs (both P < 0.05). Muscle camps were observed in 92.86% of the subjects following glutamate injection into the latent MTrPs, but not into the non-MTrPs (P < 0.001). No muscle cramps were recorded following isotonic saline injection into either the latent MTrPs or the non-MTrPs. These results suggest that latent MTrPs could be involved in the genesis of muscle cramps. Focal increase in nociceptive sensitivity at MTrPs constitutes one of the mechanisms underlying muscle cramps.

  13. Psychophysics of a nociceptive test in the mouse: ambient temperature as a key factor for variation.

    Directory of Open Access Journals (Sweden)

    Ivanne Pincedé

    Full Text Available The mouse is increasingly used in biomedical research, notably in behavioral neurosciences for the development of tests or models of pain. Our goal was to provide the scientific community with an outstanding tool that allows the determination of psychophysical descriptors of a nociceptive reaction, which are inaccessible with conventional methods: namely the true threshold, true latency, conduction velocity of the peripheral fibers that trigger the response and latency of the central decision-making process.Basically, the procedures involved heating of the tail with a CO(2 laser, recording of tail temperature with an infrared camera and stopping the heating when the animal reacted. The method is based mainly on the measurement of three observable variables, namely the initial temperature, the heating rate and the temperature reached at the actual moment of the reaction following random variations in noxious radiant heat. The initial temperature of the tail, which itself depends on the ambient temperature, very markedly influenced the behavioral threshold, the behavioral latency and the conduction velocity of the peripheral fibers but not the latency of the central decision-making.We have validated a psychophysical approach to nociceptive reactions for the mouse, which has already been described for rats and Humans. It enables the determination of four variables, which contribute to the overall latency of the response. The usefulness of such an approach was demonstrated by providing new fundamental findings regarding the influence of ambient temperature on nociceptive processes. We conclude by challenging the validity of using as "pain index" the reaction time of a behavioral response to an increasing heat stimulus and emphasize the need for a very careful control of the ambient temperature, as a prevailing environmental source of variation, during any behavioral testing of mice.

  14. Descriptive sensory evaluations

    DEFF Research Database (Denmark)

    Dehlholm, Christian

    in projective mapping frame geometry and restrictions on the reported semantics. Two rapid descriptive evaluation techniques were proposed to represent a consensus evaluation. One of the approaches, ‘consensus attribute rating’ (CAR), allows a group of assessors to rate products on a list of pre......-selected attributes. The other approach, ‘consensus Napping’, allows a group of assessors to project products according to an agreed consensus placement on a paper sheet. Evaluations were performed either by groups of experienced sensory assessors or by product experts. Compared with conventional profiling techniques......, the evaluations showed significant correlations between some product configurations, but no consistent and systematic similarities. On average, product expert groups had less in common with the reference profiles than the trained panellist groups and the semantic descriptions of products varied to a large degree...

  15. Descriptive sensory evaluations

    DEFF Research Database (Denmark)

    Dehlholm, Christian

    A recent trend in descriptive sensory evaluation methodology has been the application of rapid evaluation techniques. The ease in use makes the techniques extremely easy to implement by industry and university environments. Thus, one might not consider validity in the choice of method. The overall...... in projective mapping frame geometry and restrictions on the reported semantics. Two rapid descriptive evaluation techniques were proposed to represent a consensus evaluation. One of the approaches, ‘consensus attribute rating’ (CAR), allows a group of assessors to rate products on a list of pre...... for all groups. Hence, consensus profiling with untrained assessors should not be used for the purpose of considering consistency between panels, while assessors trained in the product may perform more reliably. As for projective mapping variations of frame geometry, evaluations in a rectangular...

  16. Sensory properties and preferences.

    Science.gov (United States)

    Risvik, E

    1994-01-01

    Common mistakes are frequent in sensory evaluation of meats and meat products. Conceptual confusion is often observed in triangular tests when add-on questions are included in the testing procedures, and when descriptive and hedonic scales are mixed in profiling exercises. Similar consumer responses are often recorded from trained, and thus biased, panels. Preference for meats seems to be most strongly affected by changes in colour/appearance and texture, and to a lesser extent by changes in flavour (that is when off-flavours are not present). It is difficult to generalise as to whether appearance/colour attributes or texture attributes are the most important. A simplified model for texture understanding is suggested, where water/fat perception and structure perception (described by juiciness and tenderness) are orthogonal phenomena and where most other textural attributes can be explained by this structure. Copyright © 1993. Published by Elsevier Ltd.

  17. Tic Modulation Using Sensory Tricks

    Directory of Open Access Journals (Sweden)

    Rebecca W. Gilbert

    2013-04-01

    Full Text Available Background: A sensory trick, or geste antagoniste, is defined as a physical gesture (such as a touch on a particular body part that mitigates the production of an involuntary movement. This phenomenon is most commonly described as a feature of dystonia. Here we present a case of successful modulation of tics using sensory tricks.Case Report:: A case report and video are presented. The case and video demonstrate a 19-year-old male who successfully controlled his tics with various sensory tricks.Discussion: It is underappreciated by movement disorder physicians that sensory tricks can play a role in tics. Introducing this concept to patients could potentially help in tic control. In addition, understanding the pathophysiological underpinnings of sensory tricks could help in the understanding of the pathophysiology of tics.

  18. Sensory aspects of movement disorders

    Science.gov (United States)

    Patel, Neepa; Jankovic, Joseph; Hallett, Mark

    2016-01-01

    Movement disorders, which include disorders such as Parkinson’s disease, dystonia, Tourette’s syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed. PMID:24331796

  19. Sensory analysis of pet foods.

    Science.gov (United States)

    Koppel, Kadri

    2014-08-01

    Pet food palatability depends first and foremost on the pet and is related to the pet food sensory properties such as aroma, texture and flavor. Sensory analysis of pet foods may be conducted by humans via descriptive or hedonic analysis, pets via acceptance or preference tests, and through a number of instrumental analysis methods. Sensory analysis of pet foods provides additional information on reasons behind palatable and unpalatable foods as pets lack linguistic capabilities. Furthermore, sensory analysis may be combined with other types of information such as personality and environment factors to increase understanding of acceptable pet foods. Most pet food flavor research is proprietary and, thus, there are a limited number of publications available. Funding opportunities for pet food studies would increase research and publications and this would help raise public awareness of pet food related issues. This mini-review addresses current pet food sensory analysis literature and discusses future challenges and possibilities. © 2014 Society of Chemical Industry.

  20. Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

    Science.gov (United States)

    Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

    2015-07-01

    Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Measuring persistent temporomandibular joint nociception in rats and two mice strains.

    Science.gov (United States)

    Kramer, Phillip R; Kerins, Carolyn A; Schneiderman, Emet; Bellinger, Larry L

    2010-04-19

    Temporomandibular joint (TMJ) pain has been reported to last for prolonged periods in humans. In rodents a variety of methods have been used to measure TMJ nociception, but for most of these methods the period of measurement has been minutes to a couple of hours. In addition, most measurement protocols required restraint or training of the animal. Previous studies from our laboratory demonstrated that feeding behavior, particularly meal duration, was an indicator of TMJ nociception in unrestrained and untrained male and female Sprague-Dawley rats for up to two days. In this study, we first found that injection of complete Freund's adjuvant (CFA) into the TMJ of rats significantly lengthened meal duration for 19 days and also decreased meal frequency for 42 days. Interestingly, the meal duration varied significantly from day to day within the 19 day period. TMJ interleukin-1 beta (IL-1 beta) and calcitonin gene-related peptide (CGRP) were significantly elevated in the TMJ tissues of CFA-injected animals and the level of these markers was attenuated as the meal duration decreased with time. Control animals injected with saline into the TMJ or CFA into the knee did not show a significant lengthening in meal duration but did show a decrease in meal frequency. In a second study, DBA/1LacJ mice given TMJ CFA injections showed a significantly lengthened meal duration on four of the seven days measured using end-of-the meal definition of 5 or 10 min. No other meal pattern changed significantly. Two days post-CFA injection, the DBA/1LacJ mice showed significantly elevated interleukin-6 (IL-6), but not elevated IL-1 beta. Seven days post-injection, both IL-6 and IL-1 beta were significantly elevated. No change in CGRP was detected. In this study C57Bl/6 mice also received TMJ CFA injections, but they did not show a lengthening in any meal pattern or significant increases in IL-1 beta, IL-6 or CGRP. Our data show, for the first time, that meal duration can be used to measure

  2. Cutaneous nociception and neurogenic inflammation evoked by PACAP38 and VIP

    DEFF Research Database (Denmark)

    Schytz, Henrik Winther; Holst, Helle; Arendt-Nielsen, Lars

    2010-01-01

    Pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) belong to the same secretin-glucagon superfamily and are present in nerve fibers in dura and skin. Using a model of acute cutaneous pain we explored differences in pain perception and vasomotor.......002). In conclusion, we found that peripheral nociceptive cutaneous responses elicited by PACAP38 and VIP are similar in healthy volunteers. This suggests that acute pain and vasomotor responses following intradermal injections of PACAP38 and VIP are primarily mediated by VPAC receptors....

  3. The role of protease-activated receptor type 2 in nociceptive signaling and pain

    Czech Academy of Sciences Publication Activity Database

    Mrózková, Petra; Paleček, Jiří; Špicarová, Diana

    2016-01-01

    Roč. 65, č. 3 (2016), s. 357-367 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH12058; GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA15-11138S; GA MŠk(CZ) LH15279; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : protease-activated receptor (PAR2) * signaling pathways * nociception * pain * spinal cord Subject RIV: FH - Neurology Impact factor: 1.461, year: 2016

  4. Tramadol effects on clinical variables and the mechanical nociceptive threshold in horses

    OpenAIRE

    Franco,Leandro Guimarães; Moreno,Juan Carlos Duque; Teixeira Neto,Antônio Raphael; Souza,Moisés Caetano e; Silva,Luiz Antônio Franco da

    2014-01-01

    This study assessed the clinical effects and the mechanical antinociceptive potential of intravenous (IV) tramadol in horses.A blinded and randomized study was designed with 7 horses treated with 1 (Tr1), 2 (Tr2) or 3 (Tr3) mg kg-1 of tramadol IV. The heart rate, respiratory rate (fR), arterial pressure, degree of sedation, gastrointestinal motility (GI), behavior changes and the mechanical nociceptive threshold (MNT) were evaluated. The MNT was determined with von Frey device method.Tr3 had ...

  5. Extracting Neural Oscillation Signatures of Laser-Induced Nociception in Pain-Related Regions in Rats

    Directory of Open Access Journals (Sweden)

    Xuezhu Li

    2017-10-01

    Full Text Available Previous studies have shown that multiple brain regions are involved in pain perception and pain-related neural processes by forming a functionally connected pain network. It is still unclear how these pain-related brain areas actively work together to generate the experience of pain. To get a better insight into the pain network, we implanted electrodes in four pain-related areas of rats including the anterior cingulate cortex (ACC, orbitofrontal cortex (OFC, primary somatosensory cortex (S1 and periaqueductal gray (PAG. We analyzed the pattern of local field potential (LFP oscillations under noxious laser stimulations and innoxious laser stimulations. A high-dimensional feature matrix was built based on the LFP characters for both experimental conditions. Generalized linear models (GLMs were trained to classify recorded LFPs under noxious vs. innoxious condition. We found a general power decrease in α and β bands and power increase in γ band in the recorded areas under noxious condition. After noxious laser stimulation, there was a consistent change in LFP power and correlation in all four brain areas among all 13 rats. With GLM classifiers, noxious laser trials were distinguished from innoxious laser trials with high accuracy (86% using high-dimensional LFP features. This work provides a basis for further research to examine which aspects (e.g., sensory, motor or affective processes of noxious stimulation should drive distinct neural activity across the pain network.

  6. Bilateral Pathways from the Basal Forebrain to Sensory Cortices May Contribute to Synchronous Sensory Processing

    Directory of Open Access Journals (Sweden)

    Irene Chaves-Coira

    2018-01-01

    Full Text Available Sensory processing in the cortex should integrate inputs arriving from receptive fields located on both sides of the body. This role could be played by the corpus callosum through precise projections between both hemispheres. However, different studies suggest that cholinergic projections from the basal forebrain (BF could also contribute to the synchronization and integration of cortical activities. Using tracer injections and optogenetic techniques in transgenic mice, we investigated whether the BF cells project bilaterally to sensory cortical areas, and have provided anatomical evidence to support a modulatory role for the cholinergic projections in sensory integration. Application of the retrograde tracer Fluor-Gold or Fast Blue in both hemispheres of the primary somatosensory (S1, auditory or visual cortical areas showed labeled neurons in the ipsi- and contralateral areas of the diagonal band of Broca and substantia innominata. The nucleus basalis magnocellularis only showed ipsilateral projections to the cortex. Optogenetic stimulation of the horizontal limb of the diagonal band of Broca facilitated whisker responses in the S1 cortex of both hemispheres through activation of muscarinic cholinergic receptors and this effect was diminished by atropine injection. In conclusion, our findings have revealed that specific areas of the BF project bilaterally to sensory cortices and may contribute to the coordination of neuronal activity on both hemispheres.

  7. Speciation through sensory drive in cichlid fish

    NARCIS (Netherlands)

    Seehausen, Ole; Terai, Yohey; Magalhaes, Isabel S.; Carleton, Karen L.; Mrosso, Hillary D. J.; Miyagi, Ryutaro; van der Sluijs, Inke; Schneider, Maria V.; Maan, Martine E.; Tachida, Hidenori; Imai, Hiroo; Okada, Norihiro

    2008-01-01

    Theoretically, divergent selection on sensory systems can cause speciation through sensory drive. However, empirical evidence is rare and incomplete. Here we demonstrate sensory drive speciation within island populations of cichlid fish. We identify the ecological and molecular basis of divergent

  8. Neurophysiology and new techniques to assess esophageal sensory function: an update.

    Science.gov (United States)

    Brock, Christina; McCallum, Richard W; Gyawali, C Prakash; Farmer, Adam D; Frøkjaer, Jens Brøndum; McMahon, Barry P; Drewes, Asbjørn Mohr

    2016-09-01

    This review aims to discuss the neurophysiology of the esophagus and new methods to assess esophageal nociception. Pain and other symptoms can be caused by diseases in the mucosa or muscular or sphincter dysfunction, together with abnormal pain processing, either in the peripheral or central nervous systems. Therefore, we present new techniques in the assessment of esophageal function and the potential role of the mucosal barrier in the generation and propagation of pain. We discuss the assessment and role of esophageal sphincters in nociception, as well as imaging and electrophysiological techniques, with examples of their use in understanding the sensory system following noxious stimuli to the esophagus. Additionally, we discuss the mechanisms behind functional diseases of the esophagus. We conclude that the new methods have identified many of the mechanisms behind malfunction of the mucosa, disturbances of muscular and sphincter functions, and the central response to different stimuli. Taken together, this has increased our understanding of esophageal disorders and may lead to new treatment modalities. © 2016 New York Academy of Sciences.

  9. Intraoperative "Analgesia Nociception Index"-Guided Fentanyl Administration During Sevoflurane Anesthesia in Lumbar Discectomy and Laminectomy: A Randomized Clinical Trial.

    Science.gov (United States)

    Upton, Henry D; Ludbrook, Guy L; Wing, Andrew; Sleigh, Jamie W

    2017-07-01

    The "Analgesia Nociception Index" (ANI; MetroDoloris Medical Systems, Lille, France) is a proposed noninvasive guide to analgesia derived from an electrocardiogram trace. ANI is scaled from 0 to 100; with previous studies suggesting that values ≥50 can indicate adequate analgesia. This clinical trial was designed to investigate the effect of intraoperative ANI-guided fentanyl administration on postoperative pain, under anesthetic conditions optimized for ANI functioning. Fifty patients aged 18 to 75 years undergoing lumbar discectomy or laminectomy were studied. Participants were randomly allocated to receive intraoperative fentanyl guided either by the anesthesiologist's standard clinical practice (control group) or by maintaining ANI ≥50 with boluses of fentanyl at 5-minute intervals (ANI group). A standardized anesthetic regimen (sevoflurane, rocuronium, and nonopioid analgesia) was utilized for both groups. The primary outcome was Numerical Rating Scale pain scores recorded from 0 to 90 minutes of recovery room stay. Secondary outcomes included those in the recovery room period (total fentanyl administration, nausea, vomiting, shivering, airway obstruction, respiratory depression, sedation, emergence time, and time spent in the recovery room) and in the intraoperative period (total fentanyl administration, intraoperative-predicted fentanyl effect-site concentrations over time [CeFent], the correlation between ANI and predicted CeFent and the incidence of movement). Statistical analysis was performed with 2-tailed Student t tests, χ tests, ordinal logistic generalized estimating equation models, and linear mixed-effects models. Bonferroni corrections for multiple comparisons were made for primary and secondary outcomes. Over the recovery room period (0-90 minutes) Numerical Rating Scale pain scores were on average 1.3 units lower in ANI group compared to the control group (95% confidence interval [CI], -0.4 to 2.4; P= .01). Patients in the ANI group

  10. Sensitization of the nociceptive system in patients with low back pain and sickness absence: Disc degeneration disease or pain syndrome

    DEFF Research Database (Denmark)

    Jensen, Ole Kudsk; Nielsen, Claus Vinther; Stengaard-Pedersen, Kristian

    Department of Rheumatology, Aarhus University Hospital, Denmark Background: Measuring the number of Tender Points (TPs) is a simple standardized and validated method to estimate diffuse tenderness in the locomoter system and has been helpful in the diagnosis of fibromyalgia, a chronic pain condition......SENSITIZATION OF THE NOCICEPTIVE SYSTEM IN PATIENTS WITH LOW BACK PAIN AND SICKNESS ABSENCE O.K. Jensen1, C.V. Nielsen2, K. Stengaard-Pedersen3 1The Spine Center, Department of Internal Medicine, Region Hospital Silkeborg, 2Department of Clinical Social Medicine, University of Aarhus, and 3...... characterized by sensitization of the nociceptive system. Purpose: To assess sensitization of the nociceptive system in low back pain (LBP) patients by means of TP examination and measure of Pressure Pain Threshold (PPT) on the thumb nails. To search for associations between the number of TPs and structural...

  11. The effect of social isolation, gender and familiarity with the experimental procedure on tests of porcine nociceptive thresholds

    DEFF Research Database (Denmark)

    di Giminiani, Pierpaolo; Stausholm, Julie S.; Viitasaari, Eliina

    2015-01-01

    Objective To investigate the effects of habituation and isolation on mechanical nociceptive thresholds in pigs at the pelvic limbs and at the tail. Study design Prospective randomized multifactorial study. Animals Thirty-two healthy castrated male (experiment 1), and 12 castrated male and 12 female...... pigs. The presence of a companion animal was also evaluated in pigs receiving stimuli at the pelvic limbs. Results Pigs tested inside the cage were affected by the habituation to the procedure as indicated by the increase in willingness and time spent by the animals in the test cage. This effect...... was reflected in the lower mechanical nociceptive thresholds (medians with 25–75 percentiles) recorded for familiar pigs compared with naïve animals [495 g (302–675) versus 745 g (479–1000), respectively; p = 0.026]. Mechanical nociceptive thresholds measured at the tail of the pigs in the open arena were...

  12. Application of a handheld Pressure Application Measurement device for the characterisation of mechanical nociceptive thresholds in intact pig tails

    DEFF Research Database (Denmark)

    Di Giminiani, Pierpaolo; Sandercock, Dale A.; Malcolm, Emma M.

    2016-01-01

    The assessment of nociceptive thresholds is employed in animals and humans to evaluate changes in sensitivity potentially arising from tissue damage. Its application on the intact pig tail might represent a suitable method to assess changes in nociceptive thresholds arising from tail injury......, such as tail docking or tail biting. The Pressure Application Measurement (PAM) device is used here for the first time on the tail of pigs to determine the reliability of the methods and to provide novel data on mechanical nociceptive thresholds (MNT) associated with four different age groups (9, 17, 24 and 32......) was significantly higher (P tail regions 2 and 3 (more distal). Age had a significant effect (P tail region...

  13. Anti-nociceptive properties of the xanthine oxidase inhibitor allopurinol in mice: role of A1 adenosine receptors

    Science.gov (United States)

    Schmidt, AP; Böhmer, AE; Antunes, C; Schallenberger, C; Porciúncula, LO; Elisabetsky, E; Lara, DR; Souza, DO

    2009-01-01

    Background and purpose Allopurinol is a potent inhibitor of the enzyme xanthine oxidase, used primarily in the treatment of hyperuricemia and gout. It is well known that purines exert multiple effects on pain transmission. We hypothesized that the inhibition of xanthine oxidase by allopurinol, thereby reducing purine degradation, could be a valid strategy to enhance purinergic activity. The aim of this study was to investigate the anti-nociceptive profile of allopurinol on chemical and thermal pain models in mice. Experimental approach Mice received an intraperitoneal (i.p.) injection of vehicle (Tween 10%) or allopurinol (10–400 mg kg−1). Anti-nociceptive effects were measured with intraplantar capsaicin, intraplantar glutamate, tail-flick or hot-plate tests. Key results Allopurinol presented dose-dependent anti-nociceptive effects in all models. The opioid antagonist naloxone did not affect these anti-nociceptive effects. The non-selective adenosine-receptor antagonist caffeine and the selective A1 adenosine-receptor antagonist, DPCPX, but not the selective A2A adenosine-receptor antagonist, SCH58261, completely prevented allopurinol-induced anti-nociception. No obvious motor deficits were produced by allopurinol, at doses up to 200 mg kg−1. Allopurinol also caused an increase in cerebrospinal fluid levels of purines, including the nucleosides adenosine and guanosine, and decreased cerebrospinal fluid concentration of uric acid. Conclusions and implications Allopurinol-induced anti-nociception may be related to adenosine accumulation. Allopurinol is an old and extensively used compound and seems to be well tolerated with no obvious central nervous system toxic effects at high doses. This drug may be useful to treat pain syndromes in humans. PMID:19133997

  14. Suppression of thermal and chemical nociception in rats by methanol extract and its sub-fraction from lantana camara

    International Nuclear Information System (INIS)

    Simjee, S.U.; Perveen, H.; Zehra, S.Q.

    2016-01-01

    The traditional use of Lantana camara (Verbenaceae) is reported to include anti-nociceptive, antimicrobial, and immunosuppressant activity. To our knowledge no systematic study has been carried out on the anti-nociceptive activity of L. camara. The present study was designed to delineate the analgesic activity of L. camara extract and its fractions to elucidate the traditional belief in the painkilling effects. Experimental models employed were thermal and chemical-induced nociception assays. After initial screening of the methanol extract and its fractions prepared from the aerial parts of the plant, the dose of 50,100 and 200 mg/kg were selected and route of administration was i.p. The test samples were tested against a reference drug indomethacine (i.p. 5 mg/kg). The observations were made at 15, 30, 60, and 120 seconds following the administration of the samples or reference drug. Experiments on naloxone antagonism were conducted to determine involvement of opioid receptors. Compared to concurrent controls, a significant anti-nociceptive activity was observed in methanol extract LC (ED50 50 mg/kg, P < 0.002) and its sub-fractions LCEA-AQ (ED50 50 mg/kg, P < 0.004), LCEA (ED50 100 mg/kg, P < 0.004) and LCEA-PEI (ED50 100 mg/kg, P < 0.005). No apparent acute toxicity was observed in any test groups. The anti-nociceptive activity was not precipitated by naloxone antagonism indicating that these fractions do not act through opioid receptors. The methanol extract and active fractions of Lantana camara possess anti-nociceptive activity. Further investigations are needed to elucidate the mechanism of its action. (author)

  15. A digital wireless system for closed-loop inhibition of nociceptive signals

    Science.gov (United States)

    Zuo, Chao; Yang, Xiaofei; Wang, Yang; Hagains, Christopher E.; Li, Ai-Ling; Peng, Yuan B.; Chiao, J.-C.

    2012-10-01

    Neurostimulation of the spinal cord or brain has been used to inhibit nociceptive signals in pain management applications. Nevertheless, most of the current neurostimulation models are based on open-loop system designs. There is a lack of closed-loop systems for neurostimulation in research with small freely-moving animals and in future clinical applications. Based on our previously developed analog wireless system for closed-loop neurostimulation, a digital wireless system with real-time feedback between recorder and stimulator modules has been developed to achieve multi-channel communication. The wireless system includes a wearable recording module, a wearable stimulation module and a transceiver connected to a computer for real-time and off-line data processing, display and storage. To validate our system, wide dynamic range neurons in the spinal cord dorsal horn have been recorded from anesthetized rats in response to graded mechanical stimuli (brush, pressure and pinch) applied in the hind paw. The identified nociceptive signals were used to automatically trigger electrical stimulation at the periaqueductal gray in real time to inhibit their own activities by the closed-loop design. Our digital wireless closed-loop system has provided a simplified and efficient method for further study of pain processing in freely-moving animals and potential clinical application in patients. Groups 1, 2 and 3 contributed equally to this project.

  16. Metabotropic glutamate receptor 5 (mGluR5 regulates bladder nociception

    Directory of Open Access Journals (Sweden)

    Crock Lara W

    2012-03-01

    Full Text Available Abstract Background Interstitial cystitis/painful bladder syndrome (IC/PBS, is a severely debilitating chronic condition that is frequently unresponsive to conventional pain medications. The etiology is unknown, however evidence suggests that nervous system sensitization contributes to enhanced pain in IC/PBS. In particular, central nervous system plasticity of glutamatergic signaling involving NMDA and metabotropic glutamate receptors (mGluRs has been implicated in a variety of chronic pain conditions. Here, we test the hypothesis that mGluR5 mediates both non-inflammatory and inflammatory bladder pain or nociception in a mouse model by monitoring the visceromotor response (VMR during graded bladder distention. Results Using a combination of genetic and pharmacologic approaches, we provide evidence indicating that mGluR5 is necessary for the full expression of VMR in response to bladder distention in the absence of inflammation. Furthermore, we observed that mice infected with a uropathogenic strain of Escherichia coli (UPEC develop inflammatory hyperalgesia to bladder distention, and that the selective mGluR5 antagonist fenobam [N-(3-chlorophenyl-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl urea], reduces the VMR to bladder distention in UPEC-infected mice. Conclusions Taken together, these data suggest that mGluR5 modulates both inflammatory and non-inflammatory bladder nociception, and highlight the therapeutic potential for mGluR5 antagonists in the alleviation of bladder pain.

  17. Respiratory hypoalgesia? Breath-holding, but not respiratory phase modulates nociceptive flexion reflex and pain intensity.

    Science.gov (United States)

    Jafari, Hassan; Van de Broek, Karlien; Plaghki, Léon; Vlaeyen, Johan W S; Van den Bergh, Omer; Van Diest, Ilse

    2016-03-01

    Several observations suggest that respiratory phase (inhalation vs. exhalation) and post-inspiratory breath-holds could modulate pain and the nociceptive reflex. This experiment aimed to investigate the role of both mechanisms. Thirty-two healthy participants received supra-threshold electrocutaneous stimulations to elicit both the Nociceptive Flexion Reflex (NFR) and pain, either during spontaneous inhalations or exhalations, or during three types of instructed breath-holds: following exhalation, at mid-inhalation and at full-capacity inhalation. Whether the electrocutaneous stimulus was applied during inhalation or exhalation did not affect the NFR or pain. Self-reported pain was reduced and the NFR was increased during breath-holding compared to spontaneous breathing. Whereas the type of breath-hold did not impact on self-reported pain, breath-holds at full-capacity inhalation and following exhalation were associated with a lower NFR amplitude compared to breath-holds at mid-inhalation. The present findings confirm that breath-holding can modulate pain (sensitivity) and suggest that both attentional distraction and changes in vagal activity may underlie the observed effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Dragon's blood from Croton urucurana (Baill.) attenuates visceral nociception in mice.

    Science.gov (United States)

    Rao, Vietla S; Gurgel, Luilma A; Lima-Júnior, Roberto C P; Martins, Domingos T O; Cechinel-Filho, Valdir; Santos, Flávia A

    2007-09-05

    Dragon's blood, the red sap from Croton urucurana Baill. (Euphorbiaceae) has a profound history of traditional use in conditions such as inflammation, diarrhoea and gastrointestinal distress. Previous studies established its anti-inflammatory, antidiarrhoeal and analgesic properties and in this study we verified its potential to suppress visceral pain, using capsaicin- and cyclophosphamide-induced models of visceral nociception. Mice that received intra-colonic capsaicin (0.3%, 50 microl/animal) or intraperitoneal injection of cyclophosphamide (400 mg/kg) manifested spontaneous nociceptive behaviors or crises, which were significantly suppressed in animal groups treated with red sap (200 and 400 mg/kg, p.o.) or that received N-acetylcysteine (750 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.), as positive controls. In capsaicin model, the antinociception produced by 200 mg/kg red sap was found to be naloxone-sensitive (2 mg/kg, i.p.), suggesting an opioid mechanism. In tests of open-field and pentobarbital-sleeping time, mice received 200mg/kg red sap showed no significant alterations in either locomotion frequency or on sleeping time, indicating that the observed antinociception is not a consequence of sedation or motor abnormality. These findings highlight the visceral antinociceptive property of Croton urucurana sap and further support its ethno-medical use to alleviate pain associated with gastrointestinal and other related disorders.

  19. Studies on the anti-inflammatory and anti-nociceptive properties of Blepharis maderaspatensis leaves

    Directory of Open Access Journals (Sweden)

    Abimbola Sowemimo

    Full Text Available Blepharis maderaspatensis(L. B. Heyne ex Roth, Acanthaceae, is a procumbent or scrambling perennial herb used traditionally for treatment of snakebites, wounds, edema and gout. The anti-inflammatory and anti-nociceptive properties of the ethanol extract of the whole plant of B. maderaspatensis was investigated using carrageenan-induced paw edema in rats, xyleneinduced edema in mice, mouse writhing and tail clip tests respectively. The effect of the extract on inflammatory mediators, serotonin and histamine, using the most active dose (75 mg/kg was also carried out. The results showed that the extract of B. maderaspatensis in carrageenan-induced test caused a significant inhibition (84.5%, 90 min of paw edema at a dose of 75 mg/kg while the xylene-induced test caused a significant inhibition (62.65% at 50 mg/kg. The histamine-induced test showed significant inhibition (90.9%, 90 min while serotonin-induced test showed moderate inhibition (54.10%, 180 min. In the mouse writhing and tail clip tests, the extract produced a significant inhibition of 66.21% and 15.81% at 75 mg/kg, respectively. These results collectively demonstrate that the ethanol extract of B. maderaspatensis possesses anti-inflammatory and anti-nociceptive properties, and this supports the ethnopharmacological use of the plant in the treatment of inflammation.

  20. Compression of the trigeminal ganglion produces prolonged nociceptive behavior in rats.

    Science.gov (United States)

    Ahn, Dong K; Lim, Eun J; Kim, Byung C; Yang, Gwi Y; Lee, Min K; Ju, Jin S; Han, Seung R; Bae, Yong C

    2009-07-01

    The present study is the first demonstration of prolonged nociceptive behavior in the trigeminal region following compression of the trigeminal ganglion in rats. Experiments were carried out on male Sprague-Dawley rats mounted onto a stereotaxic frame under pentobarbital sodium anesthesia. For compression of the trigeminal ganglion, a 4% agar solution (8microl) was injected into the trigeminal ganglion through a stainless steel injector (24 gauge), which extended 2mm beyond the end of a guide cannula (21 gauge). Following agar injection, the injector and guide cannula were removed. In the control group, rats were sham operated without agar injection. Air-puff thresholds (mechanical allodynia), pin prick responses (mechanical hyperalgesia), and spontaneous scratching behavior were examined 3 days before surgery and at 3, 7, 10, 14, 17, 21, 24, 30, and 40 days after surgery. Data were analyzed using a repeated measures ANOVA followed by multiple group comparisons using the LSD post-hoc test. Air-puff thresholds significantly decreased after compression of the trigeminal ganglion. Mechanical allodynia was established within 3 days and lasted beyond postoperative day 24. Mechanical hyperalgesia was also evident 3 days after compression and persisted until the 40th postoperative day. Although mechanical allodynia and hyperalgesia appeared bilaterally, the ipsilateral side was significantly more sensitive. Intraperitoneal treatment with carbamazepine significantly blocked mechanical allodynia produced by compression of the trigeminal ganglion. These findings suggest that prolonged nociceptive behavior following compression of the trigeminal ganglion may mimic trigeminal neuralgia in this animal model.

  1. [Participation of melatonin in change of nociception of snails and mice under influence of long-term electromagnetic shielding].

    Science.gov (United States)

    Temur'iants, N A; Kostiuk, A S; Tumaniants, K N

    2013-11-01

    Long-term electromagnetic shielding causes three-phase changes in nociception of snails and mice: an initial phase of the antinociceptive effect ofhyperalgesia is replaced with a further normalization of the parameters of nociception. These changes in snails develop slowly and phase of hyperalgesia expressed more vividly than in mice. Daily injections of melatonin in animals eliminate shielding-induced hyperalgesia causes an earlier and more pronounced antinociceptive effect. Such changes are due, apparently, with the initial depression ofmelatonin secretion under the influence of the electromagnetic shielding, which leads to the development ofhyperalgesia. In the future, the secretion of melatonin increases, that is shown in the growth of antinociceptive effect.

  2. Edema and Nociception Induced byPhilodryas patagoniensisVenom in Mice: A Pharmacological Evaluation with Implications for the Accident Treatment.

    Science.gov (United States)

    Lopes, Priscila Hess; Rocha, Marisa M T; Kuniyoshi, Alexandre Kazuo; Portaro, Fernanda Calheta Vieira; Gonçalves, Luís Roberto C

    2017-06-01

    We have investigated the mechanisms involved in the genesis of edema and nociception induced by Philodryas patagoniensis venom (PpV) injected into the footpad of mice. PpV induced dose-related edema and nociceptive effects. Pretreatment of mice with cyclooxygenase inhibitor (indomethacin), but not with cyclooxygenase 2 inhibitor (celecoxib) markedly inhibited both effects. Pretreatments with H 1 receptor antagonist (promethazine) or with dual histamine-serotonin inhibitor (cyproheptadine) failed in inhibiting both effects. In groups pretreated with captopril (angiotensin-converting enzyme inhibitor) the edema was unaltered, but nociception was clearly increased, suggesting the participation of kinins in the pathophysiology of the nociception but not of the edema-forming effect of PpV. When PpV was treated with EDTA, the nociception was similar to the one induced by untreated venom, but edema was markedly reduced. We concluded that PpV-induced edema and nociception have cyclooxygenase eicosanoids as the main mediators and no participation of vasoactive amines. Kinins seem to participate in nociception but not in edema induced by PpV. The results also suggest that metalloproteinases are the main compounds responsible for the edema, but not for the nociception induced by this venom. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair

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    Natalia Perussi Biscola

    2016-01-01

    Full Text Available Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons.

  4. Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization

    Science.gov (United States)

    Smith, Cody J.; O’Brien, Timothy; Chatzigeorgiou, Marios; Spencer, W. Clay; Feingold-Link, Elana; Husson, Steven J.; Hori, Sayaka; Mitani, Shohei; Gottschalk, Alexander; Schafer, William R.; Miller, David M.

    2013-01-01

    SUMMARY Sensory neurons adopt distinct morphologies and functional modalities to mediate responses to specific stimuli. Transcription factors and their downstream effectors orchestrate this outcome but are incompletely defined. Here, we show that different classes of mechanosensory neurons in C. elegans are distinguished by the combined action of the transcription factors MEC-3, AHR-1, and ZAG-1. Low levels of MEC-3 specify the elaborate branching pattern of PVD nociceptors, whereas high MEC-3 is correlated with the simple morphology of AVM and PVM touch neurons. AHR-1 specifies AVM touch neuron fate by elevating MEC-3 while simultaneously blocking expression of nociceptive genes such as the MEC-3 target, the claudin-like membrane protein HPO-30, that promotes the complex dendritic branching pattern of PVD. ZAG-1 exercises a parallel role to prevent PVM from adopting the PVD fate. The conserved dendritic branching function of the Drosophila AHR-1 homolog, Spineless, argues for similar pathways in mammals. PMID:23889932

  5. Sensory Dissonance Using Memory Model

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer

    2015-01-01

    Music may occur concurrently or in temporal sequences. Current machine-based methods for the estimation of qualities of the music are unable to take into account the influence of temporal context. A method for calculating dissonance from audio, called sensory dissonance is improved by the use...... of a memory model. This approach is validated here by the comparison of the sensory dissonance using memory model to data obtained using human subjects....

  6. Analyzing sensory data with R

    CERN Document Server

    Le, Sebastien

    2014-01-01

    Quantitative Descriptive Approaches When panelists rate products according to one single list of attributes Data, sensory issues, notations In practice For experienced users: Measuring the impact of the experimental design on the perception of the products? When products are rated according to one single list of attributesData, sensory issues, notations In practice For experienced users: Adding supplementary information to the product space When products are rated according to several lists

  7. Anti-inflammatory and anti-nociceptive activities of Sipunculus nudus L. extract.

    Science.gov (United States)

    Zhang, Chen-Xiao; Dai, Zi-Ru; Cai, Qiu-Xing

    2011-10-11

    Sipunculus nudus has long been employed as traditional Chinese medicine in folk remedies for the treatment of carbuncles, tuberculosis and nocturia, regulating the functions of stomach and spleen, as well as for the restoration to health in debilities caused by various pathogens and aging. Decoction of Sipunculus nudus has traditionally been used to remedy sternalgia in folk medicine. This study aimed to assess the anti-inflammatory and anti-nociceptive activity of the water extract from Sipunculus nudus. The water extract from the body wall of Sipunculus nudus was obtained with the yield of 14.1%. The anti-inflammatory effect in six animal models and anti-nociceptive effect in two animal models of the water extract were evaluated by oral for the study. Pretreatment with the extract (at the dose of 50, 100 and 200 mg/kg) produced significant dose-dependent anti-inflammatory and anti-nociceptive effects. At 200 mg/kg dose, the inhibition ratio of the extract on carrageenan-induced rat hind paw oedema, dextran-induced rat paw oedema, cotton pellet granuloma in rats, carrageenan-induced peritonitis and acetic acid-induced vascular permeability were 59.2%, 51.0%, 53.1%, 42.5%, 50.8%, better than that of indomethacin (5 mg/kg) 49.5%, 50%, 44.4%, 37.6%, 46.8%, respectively. The inhibition ratio of the extract (200 mg/kg dose) on xylene-induced mouse ear oedema was 61.5%, lower than 63.7% for indomethacin (5 mg/kg). At 200mg/kg, the extract decreased number of writhing 52.3% in acetic acid-induced writhing model and increased the response latency 25.24% in hot plate test. The water extract from the body wall of Sipunculus nudus possesses excellent anti-inflammatory activity as well as peripheral and central analgesic properties. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Effects of awareness and nociception on heart rate variability during general anaesthesia

    International Nuclear Information System (INIS)

    Huhle, R; Zaunseder, S; Malberg, H; Burghardt, M; Koch, T; Heller, A R; Wessel, N

    2012-01-01

    During anaesthesia awareness and nociception are serious complications that may further lead to haemodynamic instability. Specific monitoring of depth of hypnosis and depth of analgesia based on heart rate variability (HRV) analysis is eligible to improve patient safety and reduce efforts in post-operative care. Consequently, in this analysis we assess the applicability of HRV parameters during surgical interventions with standardized intravenous propofol-remifentanil-anaesthesia. Peri-operative electrocardiograms were recorded from cardiovascular stable patients (ASA Score I/II, N = 32, age: 36.4 ± 11.23 a, BMI: 25.2 ± 3.16) scheduled for trauma and dentofacial surgery. HRV time- and frequency-domain parameters, measures of complexity and nonlinear dynamics were compared by analysing longitudinally distributed 300 s intervals preceding/following induction of anaesthesia (BL–I1), intubation (I1–I2) and extubation (E1–E2). Mean value (meanNN) and standard deviation (sdNN) of the heart rate are influenced in BL–I1 (p < 0.001), I1–I2 (p < 0.05) and E1–E2 (p < 0.001). The number of forbidden words of symbolic dynamics changes significantly for BL–I1 (p < 0.001) and not for I1–I2 and E1–E2 (p > 0.05). Probability of low-variability POLVAR10 is significantly altered in all comparisons (BL–I1: Δ = 0.032, p < 0.01, I1–I2: Δ = 0.12, p < 0.05, E1–E2: Δ = 0.169, p < 0.01) but especially during nociception. While standard time-domain parameters lacked selectivity, parameters of symbolic dynamics appear to be specifically influenced by changes in depth of hypnosis and nociception, respectively. However, the lack of steady-state ventilation/breathing in this study needs to be considered in future research. To be used for clinical anaesthesia monitoring our results have to be prospectively validated in clinical studies. (paper)

  9. Local administration of Δ9-tetrahydrocannabinol attenuates capsaicin-induced thermal nociception in rhesus monkeys: a peripheral cannabinoid action

    Science.gov (United States)

    Ko, Mei-Chuan; Woods, James H.

    2010-01-01

    Rationale Cannabinoids can reduce nociceptive responses by acting on peripheral cannabinoid receptors in rodents. Objectives The study was conducted to evaluate the hypothesis that local administration of Δ9-tetrahydrocannabinol (Δ9-THC) can attenuate capsaicin-induced nociception in rhesus monkeys. Methods Capsaicin (100 µg) was applied locally in the tail of rhesus monkeys to evoke a nociceptive response, thermal allodynia, in normally innocuous 46°C water. Δ9-THC (10–320 µg) was coadministered with capsaicin in the tail to assess local antinociceptive effects. In addition, a local antagonism study was performed to confirm the selectivity of Δ9-THC action. Results Δ9-THC dose-dependently inhibited capsaicin-induced allodynia. This local antinociception was antagonized by small doses (10–100 µg) of the cannabinoid CB1 antagonist, SR141716A, applied in the tail. However, 100 µg SR141716A injected subcutaneously in the back did not antagonize local Δ9-THC. Conclusions These results indicate that the site of action of locally applied Δ9-THC is in the tail. It provides functional evidence that activation of peripheral cannabinoid CB1 receptors can attenuate capsaicin-induced thermal nociception in non-human primates and suggests a new approach for cannabinoids in pain management. PMID:10353438

  10. Pressure pain threshold changes after repeated mechano-nociceptive stimulation of the trapezius muscle: possible influence of previous pain experience

    DEFF Research Database (Denmark)

    Sjölund, Bengt H; Persson, Ann L

    2007-01-01

    We examined the relation between repeated noxious pressure over the trapezius muscle and changes in pressure pain thresholds (PPTs) in a before-after trial design. A conditioning series of 30 mechano-nociceptive stimuli was applied manually with a handheld algometer probe, and PPTs were measured ...

  11. Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain.

    Science.gov (United States)

    Nijs, Jo; Leysen, Laurence; Adriaenssens, Nele; Aguilar Ferrándiz, Maria Encarnación; Devoogdt, Nele; Tassenoy, An; Ickmans, Kelly; Goubert, Dorien; van Wilgen, C Paul; Wijma, Amarins J; Kuppens, Kevin; Hoelen, Wouter; Hoelen, Astrid; Moloney, Niamh; Meeus, Mira

    2016-06-01

    In addition to fatigue, pain is the most frequent persistent symptom in cancer survivors. Clear guidelines for both the diagnosis and treatment of pain in cancer survivors are lacking. Classification of pain is important as it may facilitate more specific targeting of treatment. In this paper we present an overview of nociceptive, neuropathic and central sensitization pain following cancer treatment, as well as the rationale, criteria and process for stratifying pain classification. Recently, a clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain was developed, based on a large body of research evidence and international expert opinion. We, a team of 15 authors from 13 different centers, four countries and two continents have applied this classification algorithm to the cancer survivor population. The classification of pain following cancer treatment entails two steps: (1) examining the presence of neuropathic pain; and (2) using an algorithm for differentiating predominant nociceptive and central sensitization pain. Step 1 builds on the established criteria for neuropathic pain diagnosis, while Step 2 applies a recently developed clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain to the cancer survivor population. The classification criteria allow identifying central sensitization pain following cancer treatment. The recognition of central sensitization pain in practice is an important development in the integration of pain neuroscience into the clinic, and one that is relevant for people undergoing and following cancer treatment.

  12. Modulation of melanocortin- induced changes in spinal nociception by µ-opioid receptor agonist and antagonist in neuropathic rats

    NARCIS (Netherlands)

    Gispen, W.H.; Starowitcz, K.; Przewlocki, R.; Przewlocka, B.

    2002-01-01

    Co-localization of opioid and melanocortin receptor expression, especially at the spinal cord level in the dorsal horn and in the gray matter surrounding the central canal led to the suggestion that melanocortins might play a role in nociceptive processes. In the present studies, we aimed to

  13. THE PARABRACHIAL NUCLEUS IS A CRITICAL LINK IN THE TRANSMISSION OF SHORT LATENCY NOCICEPTIVE INFORMATION TO MIDBRAIN DOPAMINERGIC NEURONS

    NARCIS (Netherlands)

    Coizet, V.; Dommett, E. J.; Klop, E. M.; Redgrave, P.; Overton, P. G.

    2010-01-01

    Many dopaminergic neurons exhibit a short-latency response to noxious stimuli, the source of which is unknown. Here we report that the nociceptive-recipient parabrachial nucleus appears to be a critical link in the transmission of pain related information to dopaminergic neurons. Injections of

  14. Anti-inflammatory and anti-nociceptive activities of methanolic leaf extract of Indigofera cassioides Rottl. Ex. DC.

    Directory of Open Access Journals (Sweden)

    Raju Senthil Kumar

    2013-01-01

    Conclusions: All the results obtained revealed that the extract MEIC showed potent anti-inflammatory and anti-nociceptive activity against all the tested models and the results obtained were comparable with the standards used. The activity of the extract may be due to the presence of terpenoids, flavonoids and other phytochemicals.

  15. Effects of glia metabolism inhibition on nociceptive behavioral testing in rats

    Directory of Open Access Journals (Sweden)

    Yan Lefèvre

    2016-06-01

    Full Text Available Fluoroacetate has been widely used to inhibit glia metabolism in vivo. It has yet to be shown what the effects of chronic intrathecal infusion of fluoroacetate on nociceptive behavioral testing are. The effects of chronic infusion of fluoroacetate (5 nmoles/h for 2 weeks were examined in normal rats. Chronic intrathecal fluoroacetate did not alter mechanical threshold (von Frey filaments, responses to supra-threshold mechanical stimuli (von Frey filaments, responses to hot (hot plate or cool (acetone test stimuli and did not affect motor performance of the animals, which was tested with rotarod. This suggests that fluoroacetate at appropriate dose did not suppress neuronal activity in the spinal cord.

  16. Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

    Science.gov (United States)

    Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

    2011-07-01

    Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.

  17. Involvement of glial cells in the nociceptive behaviors induced by a high-dose of histamine administered intrathecally.

    Science.gov (United States)

    Mizoguchi, Hirokazu; Komatsu, Takaaki; Iwata, Yoko; Watanabe, Chizuko; Watanabe, Hiroyuki; Orito, Tohru; Katsuyama, Soh; Yonezawa, Akihiko; Onodera, Kenji; Sakurada, Tsukasa; Sakurada, Shinobu

    2011-02-25

    The involvement of spinal glial cells in the nociceptive behaviors induced by 1600 pmol of histamine was determined in mice. Histamine injected intrathecally (i.t.) produced nociceptive behaviors, consisting of scratching, biting and licking. The nociceptive behaviors induced by histamine were significantly suppressed by i.t. pretreatment with the glial cell inhibitor DL-fluorocitric acid or minocycline. In Western blot analysis using lumber spinal cords, i.t. treatment with histamine increased the phosphorylation of the NR1 subunit of N-methyl-D-aspartate (NMDA) receptors. The increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was abolished by i.t. pretreatment with DL-fluorocitric acid or minocycline. We have previously reported that the nociceptive behaviors induced by 1600 pmol of histamine were significantly suppressed by the i.t. co-administration of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine (MK-801), an ion channel blocker of NMDA receptors, or agmatine, an antagonist for the polyamine recognition site on the NR1 subunit of NMDA receptors. In the present study, the increased phosphorylation of the NR1 subunit of NMDA receptors by histamine was also abolished by i.t. co-administration of agmatine or MK-801. The present results suggest that histamine at 1600 pmol elicits nociceptive behaviors by stimulating the polyamine recognition site on the NR1 subunit of NMDA receptors on spinal glial cells. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. The Anti-Nociceptive Effect of Aloe. Vera Aqueous Extract in Fructose-Fed Male Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Shahraki

    2010-05-01

    Full Text Available A B S T R A C T Introduction: Aloe Vera extract is used as an anti-inflammatory and anti-bradikinin agent in laboratory animals. The aim of this survey was to evaluate the ant-nociceptive effect of A. Vera aqueous extract in fructose-fed male rats. Methods: Forty-five Wistar-Albino male rats were equally and randomly divided into five groups including sham operated and four test groups. Sham operated group consumed tap water and the test groups consumed fructoseenriched water. Test groups 2, 3 and 4 additionally received, 0, 100, 150 and 200 mg/kg of A. Vera extract, respectively, whereas the other test group received distilled water daily. Tail flick reaction time, serum glucose and oral glucose tolerance test (OGTT were measured. The results were analyzed by SPSS software using ANOVA and Tukey tests. Results were expressed as mean ± SD. Statistical differences were considered significant at p<0.05. Results: The results showed that tail flick reaction time significantly increased in test group 3 which received 200 mg/kg A. Vera extract comparing with that of sham operated group. However, OGTT and serum glucose value were significantly increased in all fructose-fed male rats comparing with those of sham operated group. Discussion: These results indicated that A. Vera aqueous extract can affect tail flick reaction time in fructose-fed male rats. Further studies are required to show the exact mechanism of anti-nociceptive effect of A. Vera extract.

  19. Divergent functions of the left and right central amygdala in visceral nociception.

    Science.gov (United States)

    Sadler, Katelyn E; McQuaid, Neal A; Cox, Abigail C; Behun, Marissa N; Trouten, Allison M; Kolber, Benedict J

    2017-04-01

    The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.

  20. Neurochemical properties of the synapses in the pathways of orofacial nociceptive reflexes.

    Directory of Open Access Journals (Sweden)

    Yu-lin Dong

    Full Text Available The brainstem premotor neurons of the facial nucleus (VII and hypoglossal (XII nucleus can integrate orofacial nociceptive input from the caudal spinal trigeminal nucleus (Vc and coordinate orofacial nociceptive reflex (ONR responses. However, the synaptoarchitectures of the ONR pathways are still unknown. In the current study, we examined the distribution of GABAergic premotor neurons in the brainstem local ONR pathways, their connections with the Vc projections joining the brainstem ONR pathways and the neurochemical properties of these connections. Retrograde tracer fluoro-gold (FG was injected into the VII or XII, and anterograde tracer biotinylated dextran amine (BDA was injected into the Vc. Immunofluorescence histochemical labeling for inhibitory/excitatory neurotransmitters combined with BDA/FG tracing showed that GABAergic premotor neurons were mainly distributed bilaterally in the ponto-medullary reticular formation with an ipsilateral dominance. Some GABAergic premotor neurons made close appositions to the BDA-labeled fibers coming from the Vc, and these appostions were mainly distributed in the parvicellular reticular formation (PCRt, dorsal medullary reticular formation (MdD, and supratrigeminal nucleus (Vsup. We further examined the synaptic relationships between the Vc projecting fibers and premotor neurons in the VII or XII under the confocal laser-scanning microscope and electron microscope, and found that the BDA-labeled axonal terminals that made asymmetric synapses on premotor neurons showed vesicular glutamate transporter 2 (VGluT2 like immunoreactivity. These results indicate that the GABAergic premotor neurons receive excitatory neurotransmission from the Vc and may contribute to modulating the generation of the tonic ONR.

  1. Meal duration as a measure of orofacial nociceptive responses in rodents.

    Science.gov (United States)

    Kramer, Phillip R; Bellinger, Larry L

    2014-01-10

    A lengthening in meal duration can be used to measure an increase in orofacial mechanical hyperalgesia having similarities to the guarding behavior of humans with orofacial pain. To measure meal duration unrestrained rats are continuously kept in sound attenuated, computerized feeding modules for days to weeks to record feeding behavior. These sound-attenuated chambers are equipped with chow pellet dispensers. The dispenser has a pellet trough with a photobeam placed at the bottom of the trough and when a rodent removes a pellet from the feeder trough this beam is no longer blocked, signaling the computer to drop another pellet. The computer records the date and time when the pellets were taken from the trough and from this data the experimenter can calculate the meal parameters. When calculating meal parameters a meal was defined based on previous work and was set at 10 min (in other words when the animal does not eat for 10 min that would be the end of the animal's meal) also the minimum meal size was set at 3 pellets. The meal duration, meal number, food intake, meal size and inter-meal interval can then be calculated by the software for any time period that the operator desires. Of the feeding parameters that can be calculated meal duration has been shown to be a continuous noninvasive biological marker of orofacial nociception in male rats and mice and female rats. Meal duration measurements are quantitative, require no training or animal manipulation, require cortical participation, and do not compete with other experimentally induced behaviors. These factors distinguish this assay from other operant or reflex methods for recording orofacial nociception.

  2. Entanglement between thermoregulation and nociception in the rat: the case of morphine.

    Science.gov (United States)

    El Bitar, Nabil; Pollin, Bernard; Karroum, Elias; Pincedé, Ivanne; Le Bars, Daniel

    2016-12-01

    In thermoneutral conditions, rats display cyclic variations of the vasomotion of the tail and paws, the most widely used target organs in current acute or chronic animal models of pain. Systemic morphine elicits their vasoconstriction followed by hyperthermia in a naloxone-reversible and dose-dependent fashion. The dose-response curves were steep with ED 50 in the 0.5-1 mg/kg range. Given the pivotal functional role of the rostral ventromedial medulla (RVM) in nociception and the rostral medullary raphe (rMR) in thermoregulation, two largely overlapping brain regions, the RVM/rMR was blocked by muscimol: it suppressed the effects of morphine. "On-" and "off-" neurons recorded in the RVM/rMR are activated and inhibited by thermal nociceptive stimuli, respectively. They are also implicated in regulating the cyclic variations of the vasomotion of the tail and paws seen in thermoneutral conditions. Morphine elicited abrupt inhibition and activation of the firing of on- and off-cells recorded in the RVM/rMR. By using a model that takes into account the power of the radiant heat source, initial skin temperature, core body temperature, and peripheral nerve conduction distance, one can argue that the morphine-induced increase of reaction time is mainly related to the morphine-induced vasoconstriction. This statement was confirmed by analyzing in psychophysical terms the tail-flick response to random variations of noxious radiant heat. Although the increase of a reaction time to radiant heat is generally interpreted in terms of analgesia, the present data question the validity of using such an approach to build a pain index. Copyright © 2016 the American Physiological Society.

  3. Sensory Transduction in Caenorhabditis elegans

    Science.gov (United States)

    Brown, Austin L.; Ramot, Daniel; Goodman, Miriam B.

    The roundworm Caenorhabditis elegans has a well-defined and comparatively simple repertoire of sensory-guided behaviors, all of which rely on its ability to detect chemical, mechanical or thermal stimuli. In this chapter, we review what is known about the ion channels that mediate sensation in this remarkable model organism. Genetic screens for mutants defective in sensory-guided behaviors have identified genes encoding channel proteins, which are likely transducers of chemical, thermal, and mechanical stimuli. Such classical genetic approaches are now being coupled with molecular genetics and in vivo cellular physiology to elucidate how these channels are activated in specific sensory neurons. The ion channel superfamilies implicated in sensory transduction in C. elegans - CNG, TRP, and DEG/ENaC - are conserved across phyla and also appear to contribute to sensory transduction in other organisms, including vertebrates. What we learn about the role of these ion channels in C. elegans sensation is likely to illuminate analogous processes in other animals, including humans.

  4. Sensory functions in the foot soles in victims of generalized torture, in victims also beaten under the feet (falanga and in healthy controls – A blinded study using quantitative sensory testing

    Directory of Open Access Journals (Sweden)

    Prip Karen

    2012-12-01

    Full Text Available Abstract Background Falanga torture (beatings on the foot soles produces local chronic pain and severe walking difficulties. We have previously reported signs of neuropathic pain in the feet of falanga victims. The objective here was to clarify underlying pain mechanisms by quantifying sensory impairments in the feet of torture victims who had experienced both generalized torture and those who had been exposed to falanga in addition. An ethnically matched control group was available. Methods We employed quantitative sensory testing (QST by investigators blinded to whether the patients, 32 male torture victims from the Middle East, had (n=15, or had not (n=17 been exposed to falanga. Pain intensity, area and stimulus dependence were used to characterize the pain as were interview data on sensory symptoms. QST included thresholds for touch, cold, warmth, cold-pain, heat-pain, deep pressure pain and wind-up to cutaneous noxious stimuli in the foot soles. Clinical data on anxiety and depression were retrieved. Results Almost all falanga victims had moderate or strong pain in their feet and in twice as large an area of their foot soles as other torture victims. One-third of the latter had no pain in their feet and many reported slight pain; in spite of this, there were no differences in foot sole QST data between the tortured groups. A comparison with normal data indicated that both tortured groups had hypoesthesia for all cutaneous sensory fibre groups except those transmitting cold and heat pain, in addition to deep mechano-nociceptive hyperalgesia. Conclusion A comparison of the QST data between victims having been exposed to generalized torture and victims who in addition had been exposed to falanga, showed no differences on the group level. The sensory disturbances in relation to our control group are compatible with central sensitization and de-sensitization, pointing to a core role of central mechanisms. A further analysis to create individual

  5. Sensory functions in the foot soles in victims of generalized torture, in victims also beaten under the feet (falanga) and in healthy controls – A blinded study using quantitative sensory testing

    Science.gov (United States)

    2012-01-01

    Background Falanga torture (beatings on the foot soles) produces local chronic pain and severe walking difficulties. We have previously reported signs of neuropathic pain in the feet of falanga victims. The objective here was to clarify underlying pain mechanisms by quantifying sensory impairments in the feet of torture victims who had experienced both generalized torture and those who had been exposed to falanga in addition. An ethnically matched control group was available. Methods We employed quantitative sensory testing (QST) by investigators blinded to whether the patients, 32 male torture victims from the Middle East, had (n=15), or had not (n=17) been exposed to falanga. Pain intensity, area and stimulus dependence were used to characterize the pain as were interview data on sensory symptoms. QST included thresholds for touch, cold, warmth, cold-pain, heat-pain, deep pressure pain and wind-up to cutaneous noxious stimuli in the foot soles. Clinical data on anxiety and depression were retrieved. Results Almost all falanga victims had moderate or strong pain in their feet and in twice as large an area of their foot soles as other torture victims. One-third of the latter had no pain in their feet and many reported slight pain; in spite of this, there were no differences in foot sole QST data between the tortured groups. A comparison with normal data indicated that both tortured groups had hypoesthesia for all cutaneous sensory fibre groups except those transmitting cold and heat pain, in addition to deep mechano-nociceptive hyperalgesia. Conclusion A comparison of the QST data between victims having been exposed to generalized torture and victims who in addition had been exposed to falanga, showed no differences on the group level. The sensory disturbances in relation to our control group are compatible with central sensitization and de-sensitization, pointing to a core role of central mechanisms. A further analysis to create individual sensory profiles from

  6. Sensory analysis in grapes benitaka

    International Nuclear Information System (INIS)

    Santillo, Amanda G.; Rodrigues, Flavio T.; Arthur, Paula B.; Villavicencio, Ana Lucia C.H.

    2011-01-01

    Abstract Sensory analysis is considered one of the main techniques when you want to know the organoleptic qualities of foods. Marketing strategies, showing that some foods produced organically is more nutritious, flavorful than conventional ones are affecting some consumers. The advantages of using radiation in sensory analysis are not the formation of waste, the less nutritional loss and little change in taste of food. The possibility that the fruit is harvested at more advanced maturity, when all characteristics of flavor and external appearance are fully developed is another advantage. The possibility of fruits being packed irradiated prevents contamination after processing. This type of study, ionizing radiation associated with sensory evaluation scarce, making it necessary for future discoveries. The objective this paper was to evaluate the quality of grapes Benitaka after the irradiation process with doses 0,5; 1; 1,5 e 2 kGy. (author)

  7. Sensory analysis in grapes benitaka

    Energy Technology Data Exchange (ETDEWEB)

    Santillo, Amanda G.; Rodrigues, Flavio T.; Arthur, Paula B.; Villavicencio, Ana Lucia C.H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Abstract Sensory analysis is considered one of the main techniques when you want to know the organoleptic qualities of foods. Marketing strategies, showing that some foods produced organically is more nutritious, flavorful than conventional ones are affecting some consumers. The advantages of using radiation in sensory analysis are not the formation of waste, the less nutritional loss and little change in taste of food. The possibility that the fruit is harvested at more advanced maturity, when all characteristics of flavor and external appearance are fully developed is another advantage. The possibility of fruits being packed irradiated prevents contamination after processing. This type of study, ionizing radiation associated with sensory evaluation scarce, making it necessary for future discoveries. The objective this paper was to evaluate the quality of grapes Benitaka after the irradiation process with doses 0,5; 1; 1,5 e 2 kGy. (author)

  8. Molecular Analysis of Sensory Axon Branching Unraveled a cGMP-Dependent Signaling Cascade

    Directory of Open Access Journals (Sweden)

    Alexandre Dumoulin

    2018-04-01

    Full Text Available Axonal branching is a key process in the establishment of circuit connectivity within the nervous system. Molecular-genetic studies have shown that a specific form of axonal branching—the bifurcation of sensory neurons at the transition zone between the peripheral and the central nervous system—is regulated by a cyclic guanosine monophosphate (cGMP-dependent signaling cascade which is composed of C-type natriuretic peptide (CNP, the receptor guanylyl cyclase Npr2, and cGMP-dependent protein kinase Iα (cGKIα. In the absence of any one of these components, neurons in dorsal root ganglia (DRG and cranial sensory ganglia no longer bifurcate, and instead turn in either an ascending or a descending direction. In contrast, collateral axonal branch formation which represents a second type of axonal branch formation is not affected by inactivation of CNP, Npr2, or cGKI. Whereas axon bifurcation was lost in mouse mutants deficient for components of CNP-induced cGMP formation; the absence of the cGMP-degrading enzyme phosphodiesterase 2A had no effect on axon bifurcation. Adult mice that lack sensory axon bifurcation due to the conditional inactivation of Npr2-mediated cGMP signaling in DRG neurons demonstrated an altered shape of sensory axon terminal fields in the spinal cord, indicating that elaborate compensatory mechanisms reorganize neuronal circuits in the absence of bifurcation. On a functional level, these mice showed impaired heat sensation and nociception induced by chemical irritants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are normal. These data point to a critical role of axon bifurcation for the processing of acute pain perception.

  9. Influence of sensory neuropeptides on human cutaneous wound healing process.

    Science.gov (United States)

    Chéret, J; Lebonvallet, N; Buhé, V; Carre, J L; Misery, L; Le Gall-Ianotto, C

    2014-06-01

    Close interactions exist between primary sensory neurons of the peripheral nervous system (PNS) and skin cells. The PNS may be implicated in the modulation of different skin functions as wound healing. Study the influence of sensory neurons in human cutaneous wound healing. We incubated injured human skin explants either with rat primary sensory neurons from dorsal root ganglia (DRG) or different neuropeptides (vasoactive intestinal peptide or VIP, calcitonin gene-related peptide or CGRP, substance P or SP) at various concentrations. Then we evaluated their effects on the proliferative and extracellular matrix (ECM) remodeling phases, dermal fibroblasts adhesion and differentiation into myofibroblasts. Thus, DRG and all studied neuromediators increased fibroblasts and keratinocytes proliferation and act on the expression ratio between collagen type I and type III in favor of collagen I, particularly between the 3rd and 7th day of culture. Furthermore, the enzymatic activities of matrix metalloprotesases (MMP-2 and MMP-9) were increased in the first days of wound healing process. Finally, the adhesion of human dermal fibroblasts and their differentiation into myofibroblasts were promoted after incubation with neuromediators. Interestingly, the most potent concentrations for each tested molecules, were the lowest concentrations, corresponding to physiological concentrations. Sensory neurons and their derived-neuropeptides are able to promote skin wound healing. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Hydrogen Sulfide Mediating both Excitatory and Inhibitory Effects in a Rat Model of Meningeal Nociception and Headache Generation

    Directory of Open Access Journals (Sweden)

    Christiane Teicher

    2017-07-01

    Full Text Available Background/purposeHydrogen sulfide (H2S is a neuromodulator acting through nitroxyl (HNO when it reacts with nitric oxide (NO. HNO activates transient receptor potential channels of the ankyrin type 1 (TRPA1 causing release of calcitonin gene-related peptide from primary afferents. Activation of meningeal nociceptors projecting to the human spinal trigeminal nucleus (STN may lead to headaches. In a rat model of meningeal nociception, the activity of spinal trigeminal neurons was used as read-out for the interaction between H2S and NO.MethodsIn anesthetized rats extracellular recordings from single neurons in the STN were made. Sodium sulfide (Na2S producing H2S in the tissue and the NO donor diethylamine-NONOate (DEA-NONOate were infused intravenously. H2S was also locally applied onto the exposed cranial dura mater or the medulla. Endogenous production of H2S was inhibited by oxamic acid, and NO production was inhibited by nitro-l-arginine methyl ester hydrochloride (l-NAME to manipulate endogenous HNO formation.Key resultsSystemic administration of Na2S was followed either by increased ongoing activity (in 73% or decreased activity (in 27% of units. Topical application of Na2S onto the cranial dura mater caused a short-lasting activation followed by a long-lasting decrease in activity in the majority of units (70%. Systemic administration of DEA-NONOate increased neuronal activity, subsequent infusion of Na2S added to this effect, whereas DEA-NONOate did not augment the activity after Na2S. The stimulating effect of DEA-NONOate was inhibited by oxamic acid in 75% of units, and l-NAME following Na2S administration returned the activity to baseline.ConclusionIndividual spinal trigeminal neurons may be activated or (less frequently inhibited by the TRPA1 agonist HNO, presumably formed by H2S and NO in the STN, whereby endogenous H2S production seems to be rate-limiting. Activation of meningeal afferents by HNO may induce decreased spinal

  11. Differential roles of galanin on mechanical and cooling responses at the primary afferent nociceptor

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    Hulse Richard P

    2012-06-01

    Full Text Available Abstract Background Galanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naïve animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation. Results Mechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 (a galanin receptor-2/3 agonist confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain (PSNI and the complete Freund’s adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin (Gal-OE after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wildtype (WT mice. 7-days after

  12. Habits of the Sensory System and Mental Health: Understanding Sensory Dissonance.

    Science.gov (United States)

    Bailliard, Antoine L

    2015-01-01

    In occupational therapy, research has studied sensory function predominantly in relation to sensory disorders. There is a gap in the literature exploring how sensory experiences affect mental health. This study sought to provide a phenomenological understanding of how people relate experiences of sensory dissonance to their mental health. Ten immigrants from Latin America participated in semistructured interviews and video observations of their occupational behavior. Participants' experiences of sensory dissonance provoked negative mental states and distress. Participants reported poor mental health following sensory experiences that were incongruent with their habits of sensing. They also intentionally used sensory anchors to induce positive mental states and connect with past occupational experiences. Occupational therapy practitioners should be mindful of how sensory environments can facilitate or impede intervention. Practitioners are encouraged to harness clients' sensory habits and use sensory anchors as a form of sensory scaffolding to facilitate therapeutic gains. Copyright © 2015 by the American Occupational Therapy Association, Inc.

  13. Parasympathetic functions in children with sensory processing disorder.

    Science.gov (United States)

    Schaaf, Roseann C; Benevides, Teal; Blanche, Erna Imperatore; Brett-Green, Barbara A; Burke, Janice P; Cohn, Ellen S; Koomar, Jane; Lane, Shelly J; Miller, Lucy Jane; May-Benson, Teresa A; Parham, Diane; Reynolds, Stacey; Schoen, Sarah A

    2010-01-01

    The overall goal of this study was to determine if parasympathetic nervous system (PsNS) activity is a significant biomarker of sensory processing difficulties in children. Several studies have demonstrated that PsNS activity is an important regulator of reactivity in children, and thus, it is of interest to study whether PsNS activity is related to sensory reactivity in children who have a type of condition associated with sensory processing disorders termed sensory modulation dysfunction (SMD). If so, this will have important implications for understanding the mechanisms underlying sensory processing problems of children and for developing intervention strategies to address them. The primary aims of this project were: (1) to evaluate PsNS activity in children with SMD compared to typically developing (TYP) children, and (2) to determine if PsNS activity is a significant predictor of sensory behaviors and adaptive functions among children with SMD. We examine PsNS activity during the Sensory Challenge Protocol; which includes baseline, the administration of eight sequential stimuli in five sensory domains, recovery, and also evaluate response to a prolonged auditory stimulus. As a secondary aim we examined whether subgroups of children with specific physiological and behavioral sensory reactivity profiles can be identified. Results indicate that as a total group the children with severe SMD demonstrated a trend for low baseline PsNS activity, compared to TYP children, suggesting this may be a biomarker for SMD. In addition, children with SMD as a total group demonstrated significantly poorer adaptive behavior in the communication and daily living subdomains and in the overall Adaptive Behavior Composite of the Vineland than TYP children. Using latent class analysis, the subjects were grouped by severity and the severe SMD group had significantly lower PsNS activity at baseline, tones and prolonged auditory. These results provide preliminary evidence that children

  14. Sensory imagination and narrative perspective

    DEFF Research Database (Denmark)

    Grünbaum, Thor

    2013-01-01

    I argue that we can clarify and explain an important form of focalization or narrative perspective by the structure of perspective in sensory imagination. Understanding focalization in this way enables us to see why one particular form of focalization has to do with the representation of perceptu...

  15. Making Sense of Sensory Systems

    Science.gov (United States)

    Hendrix, Marie

    2010-01-01

    The role of caregivers requires that they continuously assess the needs and performance of children and provide the support necessary for them to achieve their potential. A thorough understanding of child development, including the role and impact of sensory development, is critical for caregivers to properly evaluate and assist these children.…

  16. A review on intelligent sensory modelling

    Science.gov (United States)

    Tham, H. J.; Tang, S. Y.; Teo, K. T. K.; Loh, S. P.

    2016-06-01

    Sensory evaluation plays an important role in the quality control of food productions. Sensory data obtained through sensory evaluation are generally subjective, vague and uncertain. Classically, factorial multivariate methods such as Principle Component Analysis (PCA), Partial Least Square (PLS) method, Multiple Regression (MLR) method and Response Surface Method (RSM) are the common tools used to analyse sensory data. These methods can model some of the sensory data but may not be robust enough to analyse nonlinear data. In these situations, intelligent modelling techniques such as Fuzzy Logic and Artificial neural network (ANNs) emerged to solve the vagueness and uncertainty of sensory data. This paper outlines literature of intelligent sensory modelling on sensory data analysis.

  17. Nerve transfer for sensory reconstruction of C8-T1 dermatomes in tetraplegia.

    Science.gov (United States)

    Bertelli, Jayme A; Ghizoni, Marcos F

    2016-11-01

    Absence of sensation in C8-T1 dermatome is a common finding in midcervical spinal cord injury. The goal was to restore sensation on the C8-T1 dermatomes by transferring sensory nerves with afferents on C5-C6 roots. A mean 10 months post spinal cord injury, we operated on 10 upper limbs from 5 tetraplegics averaging 23 years old. Cutaneous branches of the median nerve were transferred to the palm to the ulnar proper digital nerve of the little finger. In two patients, the lateral antebrachial cutaneous nerve was also transferred to the medial antebrachial cutaneous nerve. At a mean 20 months after surgery, on the ulnar side of the hand and little finger, all patients were able to perceive 19.3 g Semmes-Weinstein monofilament pressure. Nociception was restored on the medial side of the elbow, forearm, and hand. Faulty location was a common finding, but not as a major complaint. Sensory nerve transfers should be incorporated into the reconstruction of the upper limb in tetraplegics. © 2015 Wiley Periodicals, Inc. Microsurgery 36:637-641, 2016. © 2016 Wiley Periodicals, Inc.

  18. Transient receptor potential V2 expressed in sensory neurons is activated by probenecid.

    Science.gov (United States)

    Bang, Sangsu; Kim, Kyung Yoon; Yoo, Sungjae; Lee, Sang-Heon; Hwang, Sun Wook

    2007-09-25

    Temperature-activated transient receptor potential ion channels (thermoTRPs) are known to function as ambient temperature sensors and are also involved in peripheral pain sensation. The thermoTRPs are activated by a variety of chemicals, of which specific activators have been utilized to explore the physiology of particular channels and sensory nerve subtypes. The use of capsaicin for TRPV1 is an exemplary case for nociceptor studies. In contrast, specific agents for another vanilloid subtype channel, TRPV2 have been lacking. Here, we show that probenecid is able to activate TRPV2 using electrophysiological and calcium imaging techniques with TRPV2-expressing HEK293T cells. Five other sensory thermoTRPs-TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1-failed to show a response to this drug in the same heterologous expression system, suggesting that probenecid is a specific activator for TRPV2. Probenecid-evoked responses were also reproduced in a distinct subset of cultured trigeminal neurons that were responsive to 2-aminoethoxydiphenyl borate, a TRPV1-3 activator. The probenecid-sensitive neurons were mainly distributed in a medium to large-diameter population, in agreement with previous observations with TRPV2 immunolocalization. Under inflammation, probenecid elicited nociceptive behaviors in in vivo assays. These results suggest that TRPV2 is specifically activated by probenecid and that this chemical might be useful for investigation of pain-related TRPV2 function.

  19. Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System.

    Science.gov (United States)

    Tillmaand, Emily G; Yang, Ning; Kindt, Callie A C; Romanova, Elena V; Rubakhin, Stanislav S; Sweedler, Jonathan V

    2015-12-01

    The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

  20. Peptidomics and Secretomics of the Mammalian Peripheral Sensory-Motor System

    Science.gov (United States)

    Tillmaand, Emily G.; Yang, Ning; Kindt, Callie A. C.; Romanova, Elena V.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2015-12-01

    The dorsal root ganglion (DRG) and its anatomically and functionally associated spinal nerve and ventral and dorsal roots are important components of the peripheral sensory-motor system in mammals. The cells within these structures use a number of peptides as intercellular signaling molecules. We performed a variety of mass spectrometry (MS)-based characterizations of peptides contained within and secreted from these structures, and from isolated and cultured DRG cells. Liquid chromatography-Fourier transform MS was utilized in DRG and nerve peptidome analysis. In total, 2724 peptides from 296 proteins were identified in tissue extracts. Neuropeptides are among those detected, including calcitonin gene-related peptide I, little SAAS, and known hemoglobin-derived peptides. Solid phase extraction combined with direct matrix-assisted laser desorption/ionization time-of-flight MS was employed to investigate the secretome of these structures. A number of peptides were detected in the releasate from semi-intact preparations of DRGs and associated nerves, including neurofilament- and myelin basic protein-related peptides. A smaller set of analytes was observed in releasates from cultured DRG neurons. The peptide signals observed in the releasates have been mass-matched to those characterized and identified in homogenates of entire DRGs and associated nerves. This data aids our understanding of the chemical composition of the mammalian peripheral sensory-motor system, which is involved in key physiological functions such as nociception, thermoreception, itch sensation, and proprioception.

  1. Sensory TRP Channel Interactions with Endogenous Lipids and Their Biological Outcomes

    Directory of Open Access Journals (Sweden)

    Sungjae Yoo

    2014-04-01

    Full Text Available Lipids have long been studied as constituents of the cellular architecture and energy stores in the body. Evidence is now rapidly growing that particular lipid species are also important for molecular and cellular signaling. Here we review the current information on interactions between lipids and transient receptor potential (TRP ion channels in nociceptive sensory afferents that mediate pain signaling. Sensory neuronal TRP channels play a crucial role in the detection of a variety of external and internal changes, particularly with damaging or pain-eliciting potentials that include noxiously high or low temperatures, stretching, and harmful substances. In addition, recent findings suggest that TRPs also contribute to altering synaptic plasticity that deteriorates chronic pain states. In both of these processes, specific lipids are often generated and have been found to strongly modulate TRP activities, resulting primarily in pain exacerbation. This review summarizes three standpoints viewing those lipid functions for TRP modulations as second messengers, intercellular transmitters, or bilayer building blocks. Based on these hypotheses, we discuss perspectives that account for how the TRP-lipid interaction contributes to the peripheral pain mechanism. Still a number of blurred aspects remain to be examined, which will be answered by future efforts and may help to better control pain states.

  2. Sensory exploitation and sexual conflict.

    Science.gov (United States)

    Arnqvist, Göran

    2006-02-28

    Much of the literature on male-female coevolution concerns the processes by which male traits and female preferences for these can coevolve and be maintained by selection. There has been less explicit focus on the origin of male traits and female preferences. Here, I argue that it is important to distinguish origin from subsequent coevolution and that insights into the origin can help us appreciate the relative roles of various coevolutionary processes for the evolution of diversity in sexual dimorphism. I delineate four distinct scenarios for the origin of male traits and female preferences that build on past contributions, two of which are based on pre-existing variation in quality indicators among males and two on exploitation of pre-existing sensory biases among females. Recent empirical research, and theoretical models, suggest that origin by sensory exploitation has been widespread. I argue that this points to a key, but perhaps transient, role for sexually antagonistic coevolution (SAC) in the subsequent evolutionary elaboration of sexual traits, because (i) sensory exploitation is often likely to be initially costly for individuals of the exploited sex and (ii) the subsequent evolution of resistance to sensory exploitation should often be associated with costs due to selective constraints. A review of a few case studies is used to illustrate these points. Empirical data directly relevant to the costs of being sensory exploited and the costs of evolving resistance is largely lacking, and I stress that such data would help determining the general importance of sexual conflict and SAC for the evolution of sexual dimorphism.

  3. Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

    Directory of Open Access Journals (Sweden)

    L.C.R. Silva

    2012-12-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group. Hyperalgesia was induced by a subcutaneous intraplantar (ipl injection of prostaglandin E2 (PGE2, 2 μg/paw in the rat’s hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE2, which induced hyperalgesia (mean = 83.3 ± 4.505 g. AM-251 (80 μg/paw and AM-630 (100 μg/paw were used as CB1 and CB2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 μg dipyrone (mean = 5.825 ± 2.842 g, 20 μg diclofenac (mean = 4.825 ± 3.850 g and 40 μg indomethacin (mean = 6.650 ± 3.611 g elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g, diclofenac (mean = 2.50 ± 0.8337 g and indomethacin (mean = 6.650 ± 4.069 g or CB2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g, diclofenac (mean = 6.675 ± 1.368 g and indomethacin (mean = 2.85 ± 5.01 g. Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac and

  4. Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

    Energy Technology Data Exchange (ETDEWEB)

    Silva, L.C.R.; Romero, T.R.L.; Guzzo, L.S.; Duarte, I.D.G. [Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-09-21

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E{sub 2} (PGE{sub 2}, 2 µg/paw) in the rat's hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE{sub 2}, which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 µg/paw) and AM-630 (100 µg/paw) were used as CB{sub 1} and CB{sub 2} cannabinoid receptor antagonists, respectively. Ipl injection of 40 µg dipyrone (mean = 5.825 ± 2.842 g), 20 µg diclofenac (mean = 4.825 ± 3.850 g) and 40 µg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB{sub 1} cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB{sub 2} cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of

  5. Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

    International Nuclear Information System (INIS)

    Silva, L.C.R.; Romero, T.R.L.; Guzzo, L.S.; Duarte, I.D.G.

    2012-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E 2 (PGE 2 , 2 µg/paw) in the rat's hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE 2 , which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 µg/paw) and AM-630 (100 µg/paw) were used as CB 1 and CB 2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 µg dipyrone (mean = 5.825 ± 2.842 g), 20 µg diclofenac (mean = 4.825 ± 3.850 g) and 40 µg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB 1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB 2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac

  6. Intrathecal administration of clonidine or yohimbine decreases the nociceptive behavior caused by formalin injection in the marsh terrapin (Pelomedusa subrufa)

    DEFF Research Database (Denmark)

    Makau, Christopher M; Towett, Philemon K; Abelson, Klas S P

    2014-01-01

    BACKGROUND: The role of noradrenergic system in the control of nociception is documented in some vertebrate animals. However, there are no data showing the role of this system on nociception in the marsh terrapins. METHODOLOGY: In this study, the antinociceptive action of intrathecal administration...... of the α 2-adrenoreceptor agonist clonidine and α 2-adrenoreceptor antagonist yohimbine was evaluated in the African marsh terrapin using the formalin test. The interaction of clonidine and yohimbine was also evaluated. RESULTS: Intrathecal administration of clonidine (37.5 or 65 μg/kg) caused...... administration of yohimbine (53 μg/kg) followed immediately by intrathecal injection of the serotonergic methysergide maleate (20 μg/kg) resulted in a significant reversal of the antinociceptive effect of yohimbine. CONCLUSION: The present study documented the intrathecal administration of drugs in the marsh...

  7. Sensory cortex underpinnings of traumatic brain injury deficits.

    Directory of Open Access Journals (Sweden)

    Dasuni S Alwis

    Full Text Available Traumatic brain injury (TBI can result in persistent sensorimotor and cognitive deficits including long-term altered sensory processing. The few animal models of sensory cortical processing effects of TBI have been limited to examination of effects immediately after TBI and only in some layers of cortex. We have now used the rat whisker tactile system and the cortex processing whisker-derived input to provide a highly detailed description of TBI-induced long-term changes in neuronal responses across the entire columnar network in primary sensory cortex. Brain injury (n=19 was induced using an impact acceleration method and sham controls received surgery only (n=15. Animals were tested in a range of sensorimotor behaviour tasks prior to and up to 6 weeks post-injury when there were still significant sensorimotor behaviour deficits. At 8-10 weeks post-trauma, in terminal experiments, extracellular recordings were obtained from barrel cortex neurons in response to whisker motion, including motion that mimicked whisker motion observed in awake animals undertaking different tasks. In cortex, there were lamina-specific neuronal response alterations that appeared to reflect local circuit changes. Hyper-excitation was found only in supragranular layers involved in intra-areal processing and long-range integration, and only for stimulation with complex, naturalistic whisker motion patterns and not for stimulation with simple trapezoidal whisker motion. Thus TBI induces long-term directional changes in integrative sensory cortical layers that depend on the complexity of the incoming sensory information. The nature of these changes allow predictions as to what types of sensory processes may be affected in TBI and contribute to post-trauma sensorimotor deficits.

  8. The evaluation of nociceptive intensity by using free radicals direct measurement by EPR method in the tail of anaesthetized rats

    Czech Academy of Sciences Publication Activity Database

    Rokyta, R.; Stopka, Pavel; Káfuňková, Eva; Křížová, Jana; Fricová, J.; Holeček, V.

    2008-01-01

    Roč. 29, č. 6 (2008), s. 1007-1014 ISSN 0172-780X R&D Projects: GA MŠk(CZ) LC554; GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z40320502 Keywords : EPR - direct measurement in living * rats * nociceptive stimulation Subject RIV: CA - Inorganic Chemistry Impact factor: 1.359, year: 2008

  9. Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT1receptor activation.

    Science.gov (United States)

    Occhieppo, Victoria Belén; Marchese, Natalia Andrea; Rodríguez, Iara Diamela; Basmadjian, Osvaldo Martin; Baiardi, Gustavo; Bregonzio, Claudia

    2017-06-01

    The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes, involving glia and vasculature alterations. Brain Angiotensin II (Ang II), through AT 1 -receptors (AT 1 -R), modulates neurotransmission and plays a crucial role in inflammatory responses in brain vasculature and glia. Our aim for the present work was to evaluate the role of AT 1 -R in long-term alterations induced by repeated exposure to Amph. Astrocyte reactivity, neuronal survival and brain microvascular network were analysed at the somatosensory cortex. Thermal nociception was evaluated as a physiological outcome of this brain area. Male Wistar rats (250-320 g) were administered with AT 1 -R antagonist Candesartan/vehicle (3 mg/kg p.o., days 1-5) and Amph/saline (2.5 mg/kg i.p., days 6-10). The four experimental groups were: Veh-Sal, CV-Sal, Veh-Amph, CV-Amph. On day 17, the animals were sacrificed and their brains were processed for Nissl staining and immunohistochemistry against glial fibrillary acidic protein (GFAP) and von Willebrand factor. In another group of animals, thermal nociception was evaluated using hot plate test, in the four experimental groups, on day 17. Data were analysed with two-way anova followed by Bonferroni test. Our results indicate that Amph exposure induces an increase in: neuronal apoptosis, astrocyte reactivity and microvascular network, evaluated as an augmented occupied area by vessels, branching points and their tortuosity. Moreover, Amph exposure decreased the thermal nociception threshold. Pretreatment with the AT 1 -R blocker prevented the described alterations induced by this psychostimulant. The decreased thermal nociception and the structural changes in somatosensory cortex could be considered as extended neuroadaptative responses to Amph, involving AT 1 -R activation. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. The selective effect of N-feruloylserotonins isolated from Leuzea carthamoides on nociception and anxiety in rats

    Czech Academy of Sciences Publication Activity Database

    Yamamotová, A.; Pometlová, M.; Harmatha, Juraj; Rašková, H.; Rokyta, R.

    2007-01-01

    Roč. 112, č. 2 (2007), s. 368-374 ISSN 0378-8741 R&D Projects: GA MŠk(CZ) 1M0517; GA ČR(CZ) GA203/07/1227 Institutional research plan: CEZ:AV0Z40550506 Keywords : nociception * anxiety * N-feruloylserotonin * Leuzea carthamoides Subject RIV: CC - Organic Chemistry Impact factor: 2.049, year: 2007

  11. Specific features of the planarian Dugesia tigrina regeneration and mollusk Helix albescens nociception under weak electromagnetic shielding

    Science.gov (United States)

    Temur'yants, N. A.; Demtsun, N. A.; Kostyuk, A. S.; Yarmolyuk, N. S.

    2012-12-01

    It has been demonstrated that weak electromagnetic shielding stimulates regeneration in the planarian Dugesia tigrina, the stimulating intensity being dependent on both the initial state of the animals, which is determined by season, and their functional asymmetry. As has been shown, the effect of a weak electromagnetic field induces phasic changes in the nociceptive sensitivity of the mollusk Helix albescens: an increase in the sensitivity to a thermal stimulus is replaced by the development of the hypalgesic effect.

  12. Decreased serotonin level during pregnancy alters morphological and functional characteristics of tonic nociceptive system in juvenile offspring of the rat

    Directory of Open Access Journals (Sweden)

    Mikhailenko Victor A

    2003-11-01

    Full Text Available Abstract Serotonin (5-HT contributes to the prenatal development of the central nervous system, acting as a morphogen in the young embryo and later as a neurotransmitter. This biologically active agent influences both morphological and biochemical differentiation of raphe neurons, which give rise to the descending serotonergic paths that regulate the processing of acutely evoked nociceptive inputs. The involvement of 5-HT in the prenatal development of tonic nociceptive system has not been studied. In the present study we evaluated the effects of a single injection (400 mg/kg, 2 ml, i.p. of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA, given to pregnant rats during the critical period fetal serotonin development. The functional integrity of the tonic nociceptive response was investigated in 25 day old rats using the classic formalin test. Morphological analysis of brain structures involved in formalin-induced pain and 5-HT levels in the heads of 12-day embryos were also evaluated. Embryonic levels of 5-HT were significantly lowered by the treatment. The juvenile rats from pCPA-treated females showed altered brain morphology and cell differentiation in the developing cortex, hippocampus, raphe nuclei, and substantia nigra. In the formalin test, there were significant decreases in the intensity and duration of the second phase of the formalin-induced response, characterizing persistent, tonic pain. The extent of impairments in the brain structures correlated positively with the level of decrease in the behavioral responses. The data demonstrate the involvement of 5-HT in the prenatal development of the tonic nociceptive system. The decreased tonic component of the behavioral response can be explained by lower activity of the descending excitatory serotonergic system originating in the raphe nuclei, resulting in decreased tonic pain processing organized at the level of the dorsal horn of the spinal cord.

  13. Modulation of nociception by medial pre-optic area orexin a receptors and its relation with morphine in male rats.

    Science.gov (United States)

    Emam, Amir Hossein; Hajesfandiari, Naeimeh; Shahidi, Siamak; Komaki, Alireza; Ganji, Maziar; Sarihi, Abdolrahman

    2016-10-01

    Recent studies have shown that medial pre-optic area (MPOA) of hypothalamus are involved in nociception. Orexin A (hypocretin 1) has been found to have numerous applications including pain modulation. However, the role of orexin A receptors in the MPOA on the nociception has not been yet studied. Therefore, the aim of the present study is to investigate the effect of orexin A microinjection on MPOA on the nociception transmission and morphine induced analgesia in adult male rats. Using stereotaxic surgery, a cannula was implanted at a site 1mm above the MPOA in the anesthetized rats. After the recovery period, tail-flick (TF) latency was measured as 0, 15, 30, 45 and 60min following the onset of two experimental protocols. Two experiments were carried out. Experiment 1: The male rats received intra-MPOA of 25, 100, 1000, 10000pmol/0.5μl orexin A or 0.5μl of aCSF (control, just 5min before the TF assay. Experiment 2: The aim of this experiment was to examine the effect of orexin microinjection into MPOA on morphine analgesia (3mg/kg,s.c). Morphine was administered 30min before orexin A intra-MPOA microinjection (four doses similar to experiment 1) or aCSF, then TF latency was measured. The results indicated that microinjection of orexin A into the MPOA showed anti-nociceptive effect in a time-dependent manner. Dose response curve results also revealed that the maximum effective dose of orexin A injection into MPOA for pain inhibition is 1000pmol/0.5μl. Co-administration of systemic morphine and orexin into the MPOA has additive analgesia with different time course compared morphine or orexin alone. It can be concluded that MPOA OrexinA receptors play an important role in the modulation of pain in normal and morphine treated male rats. Copyright © 2016. Published by Elsevier Inc.

  14. Central nociceptive sensitization vs. spinal cord training: opposing forms of plasticity that dictate function after complete spinal cord injury

    OpenAIRE

    Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Grau, James W.

    2012-01-01

    The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive) stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI) field in...

  15. Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

    Science.gov (United States)

    Namer, Barbara; Ørstavik, Kirstin; Schmidt, Roland; Mair, Norbert; Kleggetveit, Inge Petter; Zeidler, Maximillian; Martha, Theresa; Jorum, Ellen; Schmelz, Martin; Kalpachidou, Theodora; Kress, Michaela; Langeslag, Michiel

    2017-01-01

    The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons. PMID:28769867

  16. Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

    Directory of Open Access Journals (Sweden)

    Barbara Namer

    2017-07-01

    Full Text Available The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0. The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons.

  17. Phytochemical study and antinociceptive effect of the hexanic extract of leaves from Combretum duarteanum and friedelin, a triterpene isolated from the hexanic extract, in orofacial nociceptive protocols

    Directory of Open Access Journals (Sweden)

    Jullyana S.S. Quintans

    Full Text Available Combretum duarteanum Cambess, Combretaceae, is a plant widely distributed in Northeastern Brazil and, in folk medicine, stems and leaves are used for pain treatment. We investigated the antinociceptive effects of the hexanic extract of leaves from C. duarteanum and of friedelin, its main compound, in formalin-, glutamate- and capsaicin- induced orofacial nociception models. In order to isolate friedelin from the hexanic extract, flash chromatography technique was used. Male mice (n = 8/group were pretreated with hexanic extract, friedelin, morphine or vehicle, before the injection of algogen agents into the right upper lip (perinasal area. The test of formalin-induced orofacial nociception showed that hexanic extract and friedelin significantly reduced nociception (p < 0.001 in both phases of testing. In the glutamate and capsaicin-induced orofacial nociception tests, pre-treatment with hexanic extract produced a significant reduction of orofacial nociception (p < 0.001 at all doses tested.The results suggest the hexanic extract and friedelin possess antinociceptive effects in models of orofacial nociception in rodents.

  18. Multi-Sensory Intervention Observational Research

    Science.gov (United States)

    Thompson, Carla J.

    2011-01-01

    An observational research study based on sensory integration theory was conducted to examine the observed impact of student selected multi-sensory experiences within a multi-sensory intervention center relative to the sustained focus levels of students with special needs. A stratified random sample of 50 students with severe developmental…

  19. Toll-like receptor 4 signaling in neurons of trigeminal ganglion contributes to nociception induced by acute pulpitis in rats.

    Science.gov (United States)

    Lin, Jia-Ji; Du, Yi; Cai, Wen-Ke; Kuang, Rong; Chang, Ting; Zhang, Zhuo; Yang, Yong-Xiang; Sun, Chao; Li, Zhu-Yi; Kuang, Fang

    2015-07-30

    Pain caused by acute pulpitis (AP) is a common symptom in clinical settings. However, its underlying mechanisms have largely remained unknown. Using AP model, we demonstrated that dental injury caused severe pulp inflammation with up-regulated serum IL-1β. Assessment from head-withdrawal reflex thresholds (HWTs) and open-field test demonstrated nociceptive response at 1 day post injury. A consistent up-regulation of Toll-like receptor 4 (TLR4) in the trigeminal ganglion (TG) ipsilateral to the injured pulp was found; and downstream signaling components of TLR4, including MyD88, TRIF and NF-κB, and cytokines such as TNF-α and IL-1β, were also increased. Retrograde labeling indicated that most TLR4 positve neuron in the TG innnervated the pulp and TLR4 immunoreactivity was mainly in the medium and small neurons. Double labeling showed that the TLR4 expressing neurons in the ipsilateral TG were TRPV1 and CGRP positive, but IB4 negative. Furthermore, blocking TLR4 by eritoran (TLR4 antagonist) in TGs of the AP model significantly down-regulated MyD88, TRIF, NF-κB, TNF-α and IL-1β production and behavior of nociceptive response. Our findings suggest that TLR4 signaling in TG cells, particularly the peptidergic TRPV1 neurons, plays a key role in AP-induced nociception, and indicate that TLR4 signaling could be a potential therapeutic target for orofacial pain.

  20. Calcitonin gene-related peptide modulates heat nociception in the human brain - An fMRI study in healthy volunteers

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B.W.

    2016-01-01

    Background: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we record...... cortex. Sumatriptan injection reversed these changes. Conclusion: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli.......Background: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded...... blood-oxygenation-level-dependent (BOLD) signals in the brain by functional MRI after infusion of CGRP in a double-blind placebo-controlled crossover study of 27 healthy volunteers. BOLD-signals were recorded in response to noxious heat stimuli in the V1-area of the trigeminal nerve. In addition, we...

  1. Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Adams, M.L.; Morris, D.L.; Dewey, W.L.

    1986-03-05

    ..beta..-endorphin, (met)enkephalin, and (leu)enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO/sub 4/ or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. ..beta..-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; (met)enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; (leu)-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs.

  2. microRNAs in nociceptive circuits as predictors of future clinical applications

    Directory of Open Access Journals (Sweden)

    Michaela eKress

    2013-10-01

    Full Text Available Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs (ncRNAs – and microRNAs (miRNAs in particular - regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesised as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioural components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome (CRPS. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals.

  3. Prediction of Hemodynamic Reactivity during Sevoflurane Remifentanyl Anesthesia for Laparoscopic Cholecystectomy Using Analgesia Nociception Index

    Directory of Open Access Journals (Sweden)

    Ali Şefik Köprülü

    2016-12-01

    Full Text Available Aim: Pneumoperitoneum may cause serious side effects in high-risk patients during laparoscopic cholecystectomy. Perioperative analgesic sufficiency has been measured by the Analgesia Nociception index (ANI in recent years. We examine the possibility of predicting hemodynamic reactivity by observing sudden changes in ANI during operation. Methods: In this retrospective study, recorded hemodynamic parameters (including heart rate, systolic/ diastolic blood pressure values and ANI values, before and after intubation, nasogastric tube application, intraperitoneal gas insufflation, and surgical incision in 31 patients who were applied laparoscopic cholecystectomy were compared by paired t-test. Additionally, an increment or decrement of 20% in ANI and 15% in hemodynamic parameters with respect to basal observation values were called “sudden changes”. Correlation of these parameters with sudden changes in ANI values was examined either. Results: There was a statistically significant difference in parameters after premedication and intubation. After induction, a statistically significant decrement was detected only in heart rate and systolic/diastolic blood pressure values. There was no significant change after nasogastric tube insertion. During pneumoperitoneum and surgical incision, there was no change in heart rate and systolic/diastolic blood pressure values, but a statistically significant decrement was observed in ANI. No correlation was detected between sudden changes in ANI values and hemodynamic parameters. Conclusion: We assume that use of ANI in analgesia evaluation under general anesthesia at perioperative period is suitable, however, it is not reliable in predicting hemodynamic interaction.

  4. Frontal Lobe Hemodynamic Responses to Painful Stimulation: A Potential Brain Marker of Nociception.

    Science.gov (United States)

    Aasted, Christopher M; Yücel, Meryem A; Steele, Sarah C; Peng, Ke; Boas, David A; Becerra, Lino; Borsook, David

    2016-01-01

    The purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to examine patterns of both activation and deactivation that occur in the frontal lobe in response to noxious stimuli. The frontal lobe was selected because it has been shown to be activated by noxious stimuli in functional magnetic resonance imaging studies. The brain region is located behind the forehead which is devoid of hair, providing a relative ease of placement for fNIRS probes on this area of the head. Based on functional magnetic resonance imaging studies showing blood-oxygenation-level dependent changes in the frontal lobes, we evaluated functional near-infrared spectroscopy measures in response to two levels of electrical pain in awake, healthy human subjects (n = 10; male = 10). Each subject underwent two recording sessions separated by a 30-minute resting period. Data collected from 7 subjects were analyzed, containing a total of 38/36 low/high intensity pain stimuli for the first recording session and 27/31 pain stimuli for the second session. Our results show that there is a robust and significant deactivation in sections of the frontal cortices. Further development and definition of the specificity and sensitivity of the approach may provide an objective measure of nociceptive activity in the brain that can be easily applied in the surgical setting.

  5. Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs

    International Nuclear Information System (INIS)

    Adams, M.L.; Morris, D.L.; Dewey, W.L.

    1986-01-01

    β-endorphin, [met]enkephalin, and [leu]enkephalin were quantitated in canine plasma by radioimmunoassay (RIA) after extraction of the peptides on Sep Pak C18 cartridges. Plasma samples were taken one hour after a 10 mg/kg s.c. injection of (-)-morphine SO 4 or (+)-morphine HBr. Antinociception, measured by a dog tail-flick test, and morphine-induced emesis, salivation, diarrhea, and ataxia were quantitated before sampling. Control levels for each dog were taken one week earlier at the same time of day after saline injections. Antinociception, morphine signs, and opioid peptide levels in plasma were significantly increased by (-)-morphine. Antinociception increased from zero to 83.54 +/- 11.0%. The number of morphine signs increased from zero to 2.9 +/- 0.28 per dog. β-endorphin levels increased from 44.52 +/- 4.25 to 90.6 +/- 7.38 pg/ml; [met]enkephalin levels increased from 253.56 +/- 22.04 to 497.1 +/- 58.12 pg/ml; [leu]-enkephalin increased from 141.65 +/- 12.9 to 313.24 +/- 35.95 pg/ml. None of these effects were observed in the dogs that received (+)-morphine. The conclude that morphine stereospecifically inhibits nociception, induces observable signs, and increases plasma opioid peptide levels in dogs

  6. Mechanical Conflict System: A Novel Operant Method for the Assessment of Nociceptive Behavior.

    Directory of Open Access Journals (Sweden)

    Steven E Harte

    Full Text Available A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS, is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor in rats with neuropathic pain induced by constriction nerve injury (CCI and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg, morphine (2.5 and 5 mg/kg, and the tachykinin NK1 receptor antagonist, RP 67580 (1 and 10 mg/kg. Results indicate that escape latency increased as a function of probe height in both naive and CCI rats. Pregabalin (10 and 30 mg/kg and morphine (5 mg/kg, but not RP 67580, decreased latency to escape in CCI rats suggesting an antinociceptive effect. In contrast, morphine (10 mg/kg but not pregabalin (30 mg/kg increased escape latency in naive rats suggesting a possible anxiolytic action of morphine in response to light-induced fear. No order effects following multiple test sessions were observed. We conclude that the MCS is a valid method to assess behavioral signs of affective pain in rodents.

  7. Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals.

    Science.gov (United States)

    Risberg, Åse I; Spadavecchia, Claudia; Ranheim, Birgit; Hendrickson, Eli H S; Lervik, Andreas; Haga, Henning A

    2015-05-01

    To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. Prospective, experimental cross-over trial. Nine Norwegian Fjord research foals. Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration. We were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p buprenorphine. These findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  8. Synaptic and network consequences of monosynaptic nociceptive inputs of parabrachial nucleus origin in the central amygdala

    Science.gov (United States)

    Sugimura, Yae K.; Takahashi, Yukari; Watabe, Ayako M.

    2016-01-01

    A large majority of neurons in the superficial layer of the dorsal horn projects to the lateral parabrachial nucleus (LPB). LPB neurons then project to the capsular part of the central amygdala (CeA; CeC), a key structure underlying the nociception-emotion link. LPB-CeC synaptic transmission is enhanced in various pain models by using electrical stimulation of putative fibers of LPB origin in brain slices. However, this approach has limitations for examining direct monosynaptic connections devoid of directly stimulating fibers from other structures and local GABAergic neurons. To overcome these limitations, we infected the LPB of rats with an adeno-associated virus vector expressing channelrhodopsin-2 and prepared coronal and horizontal brain slices containing the amygdala. We found that blue light stimulation resulted in monosynaptic excitatory postsynaptic currents (EPSCs), with very small latency fluctuations, followed by a large polysynaptic inhibitory postsynaptic current in CeC neurons, regardless of the firing pattern type. Intraplantar formalin injection at 24 h before slice preparation significantly increased EPSC amplitude in late firing-type CeC neurons. These results indicate that direct monosynaptic glutamatergic inputs from the LPB not only excite CeC neurons but also regulate CeA network signaling through robust feed-forward inhibition, which is under plastic modulation in response to persistent inflammatory pain. PMID:26888105

  9. Sustained nociceptive mechanical stimulation of latent myofascial trigger point induces central sensitization in healthy subjects.

    Science.gov (United States)

    Xu, Yi-Meng; Ge, Hong-You; Arendt-Nielsen, Lars

    2010-12-01

    The aim of the study is to test if sustained nociceptive mechanical stimulation (SNMS) of latent myofascial trigger points (MTrPs) induces widespread mechanical hyperalgesia. SNMS was obtained by inserting and retaining an intramuscular electromyographic (EMG) needle within a latent MTrP or a nonMTrP in the finger extensor muscle for 8 minutes in 12 healthy subjects. Pain intensity (VAS) and referred pain area induced by SNMS were recorded. Pressure pain threshold (PPT) was measured immediately before and after, and 10-, 20-, and 30-minutes after SNMS at the midpoint of the contralateral tibialis anterior muscle. Surface and intramuscular EMG during SNMS were recorded. When compared to nonMTrPs, maximal VAS and the area under VAS curve (VASauc) were significantly higher and larger during SNMS of latent MTrPs (both, P induction of local and referred pain. This study shows that MTrPs are one of the important peripheral pain generators and initiators for central sensitization. Therapeutic methods for decreasing the sensitivity and motor-unit excitability of MTrPs may prevent the development of muscle cramps and thus decrease local and referred pain. Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. In vivo anti-nociceptive and anti-inflammatory activities of Lippia alba

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    Sagnik Haldar

    2012-10-01

    Full Text Available Objective: To evaluate antinociceptive and anti-inflammatory activities of Lippia alba (Mill. N.E. Brown (Verbenaceae leaves. Methods: Soxhlet extraction method was used to obtain extracts using petroleum ether extracts (PELA; chloroform extracts (CELA; ethanol extracts (EELA and aqueous extract (AELA. Antinociceptive activity was assessed on rats by tail flick latency using tail immersion method and anti-inflammatory activity was estimated by carrageenan induced paw edema method. PELA, CELA and AELA at a dose of 500 mg /kg.b.wt. and EELA at a dose of 460 mg /kg.b.wt were administered orally. Result: Competing to control AELA was found to have a higher range of anti-nociceptive activity and showing maximum (79.66% response at 60 min, where as CELA and EELA were found to have a maximum range of anti-inflammatory activity and CELA exhibit maximum (19.5% response at 240 min. Conclusion: The results suggest that the extracts of Lippia alba possess ant-inociceptive and anti-inflammatory activities, and its help to authenticates the use of the plant in the traditional treatment of ailments associated with pain and inflammation.

  11. Mechanical nociception thresholds in lame sows: evidence of hyperalgesia as measured by two different methods.

    Science.gov (United States)

    Nalon, E; Maes, D; Piepers, S; van Riet, M M J; Janssens, G P J; Millet, S; Tuyttens, F A M

    2013-11-01

    Lameness is a frequently occurring, painful condition of breeding sows that may result in hyperalgesia, i.e., an increased sensitivity to pain. In this study a mechanical nociception threshold (MT) test was used (1) to determine if hyperalgesia occurs in sows with naturally-occurring lameness; (2) to compare measurements obtained with a hand-held probe and a limb-mounted actuator connected to a digital algometer; and (3) to investigate the systematic left-to-right and cranial-to-caudal differences in MT. Twenty-eight pregnant sows were investigated, of which 14 were moderately lame and 14 were not lame. Over three testing sessions, repeated measurements were taken at 5 min intervals on the dorsal aspects of the metatarsi and metacarpi of all limbs. The MT was defined as the force in Newtons (N) that elicited an avoidance response, and this parameter was found to be lower in limbs affected by lameness than in normal limbs (Ptesting sessions (P<0.001), as well as between days (P<0.001). The findings provide evidence that lame sows experience hyperalgesia. Systematic differences between forelimb and hindlimb MT must be taken into account when such assessments are performed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Structural studies and nociceptive activity of a native lectin from Platypodium elegans seeds (nPELa).

    Science.gov (United States)

    Cavada, Benildo Sousa; Araripe, David Alencar; Silva, Ivanice Bezerra; Pinto-Junior, Vanir Reis; Osterne, Vinicius Jose Silva; Neco, Antonio Hadson Bastos; Laranjeira, Eva Pollyanna Peixe; Lossio, Claudia Figueiredo; Correia, Jorge Luis Almeida; Pires, Alana Freitas; Assreuy, Ana Maria Sampaio; Nascimento, Kyria Santiago

    2018-02-01

    A native lectin (nPELa), purified from seeds of the species Platypodium elegans, Dalbergieae tribe, was crystallized and structurally characterized by X-ray diffraction crystallography and bioinformatics tools. The obtained crystals diffracted to 1.6Å resolution, and nPELa structure were solved through molecular substitution. In addition, nPELa has a metal binding site and a conserved carbohydrate recognition domain (CRD) similar to other Dalbergieae tribe lectins, such as PAL (Pterocarpus angolensis) and CTL (Centrolobium tomentosum). Molecular docking analysis indicated high affinity of this lectin for different mannosides, mainly trimannosides, formed by α-1,3 or α-1,6 glycosidic bond, as evidenced by the obtained scores. In addition, molecular dynamics simulations were performed to demonstrate the structural behavior of nPELa in aqueous solution. In solution, nPELa was highly stable, and structural modifications in its carbohydrate recognition site allowed interaction between the lectin and the different ligands. Different modifications were observed during simulations for each one of the glycans, which included different hydrogen bonds and hydrophobic interactions through changes in the relevant residues. In addition, nPELa was evaluated for its nociceptive activity in mice and was reported to be the first lectin of the Dalbergieae tribe to show CRD-dependent hypernociceptive activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field.

    Science.gov (United States)

    Moran, Magdalene M; Szallasi, Arpad

    2017-09-19

    Control of chronic pain is frequently inadequate and/or associated with intolerable adverse effects, prompting a frantic search for new therapeutics and new therapeutic targets. Nearly two decades of preclinical and clinical research supports the involvement of transient receptor potential (TRP) channels in temperature perception, nociception and sensitization. Although there has been considerable excitement around the therapeutic potential of this channel family since the cloning and identification of TRPV1 cation channels as the capsaicin receptor more than 20 years ago, only modulators of a few channels have been tested clinically. TRPV1 channel antagonists have suffered from side effects related to the channel's role in temperature sensation; however, high dose formulations of capsaicin have reached the market and shown therapeutic utility. A number of potent, small molecule antagonists of TRPA1 channels have recently advanced into clinical trials for the treatment of inflammatory and neuropathic pain, and TRPM8 antagonists are following closely behind for cold allodynia. TRPV3, TRPV4, TRPM2 and TRPM3 channels have also been of significant interest. This review discusses the preclinical promise and status of novel analgesic agents that target TRP channels and the challenges that these compounds may face in development and clinical practice. © 2017 The British Pharmacological Society.

  14. Tramadol effects on clinical variables and the mechanical nociceptive threshold in horses

    Directory of Open Access Journals (Sweden)

    Leandro Guimarães Franco

    2014-03-01

    Full Text Available This study assessed the clinical effects and the mechanical antinociceptive potential of intravenous (IV tramadol in horses.A blinded and randomized study was designed with 7 horses treated with 1 (Tr1, 2 (Tr2 or 3 (Tr3 mg kg-1 of tramadol IV. The heart rate, respiratory rate (fR, arterial pressure, degree of sedation, gastrointestinal motility (GI, behavior changes and the mechanical nociceptive threshold (MNT were evaluated. The MNT was determined with von Frey device method.Tr3 had a significant increase in their fR and more pronounced behavioral changes than other treatments.The Tr1 showed a significant increase in arterial pressure. The GI reduced significantly, mainly in Tr2. The tramadol did not change the MNT of the horses.The clinical alterations observed with the different treatments were considered mild and transitory, being most evident in Tr2. However the tramadol did not have any analgesic effect with any of the doses evaluated.

  15. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

    Directory of Open Access Journals (Sweden)

    Liu Xian-Guo

    2011-03-01

    Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

  16. Specific alpha- and beta-tubulin isotypes optimize the functions of sensory Cilia in Caenorhabditis elegans.

    Science.gov (United States)

    Hurd, Daryl D; Miller, Renee M; Núñez, Lizbeth; Portman, Douglas S

    2010-07-01

    Primary cilia have essential roles in transducing signals in eukaryotes. At their core is the ciliary axoneme, a microtubule-based structure that defines cilium morphology and provides a substrate for intraflagellar transport. However, the extent to which axonemal microtubules are specialized for sensory cilium function is unknown. In the nematode Caenorhabditis elegans, primary cilia are present at the dendritic ends of most sensory neurons, where they provide a specialized environment for the transduction of particular stimuli. Here, we find that three tubulin isotypes--the alpha-tubulins TBA-6 and TBA-9 and the beta-tubulin TBB-4--are specifically expressed in overlapping sets of C. elegans sensory neurons and localize to the sensory cilia of these cells. Although cilia still form in mutants lacking tba-6, tba-9, and tbb-4, ciliary function is often compromised: these mutants exhibit a variety of sensory deficits as well as the mislocalization of signaling components. In at least one case, that of the CEM cephalic sensory neurons, cilium architecture is disrupted in mutants lacking specific ciliary tubulins. While there is likely to be some functional redundancy among C. elegans tubulin genes, our results indicate that specific tubulins optimize the functional properties of C. elegans sensory cilia.

  17. THE EFFECT OF THE C-LEG KNEE PROSTHESIS ON SENSORY DEPENDENCY AND FALLS DURING SENSORY ORGANIZATION TESTING

    OpenAIRE

    Highsmith, M. Jason; Kahle, Jason T.; Shepard, Neil T.; Kaufman, Kenton R.

    2014-01-01

    A mechanistic explanation for previously observed safety improvements with microprocessor-controlled prosthetic knees is needed. A repeated measures design of 15 subjects with unilateral transfemoral amputation was used to assess changes between baseline use of their standard of care, mechanical pros-theses, and a C-Leg microprocessor-controlled prosthetic knee. The primary outcome measures were sensory dependency scores for somatosensory, visual, vestibular, and visual preference, which were...

  18. Sensory modulation disorders in childhood epilepsy.

    Science.gov (United States)

    van Campen, Jolien S; Jansen, Floor E; Kleinrensink, Nienke J; Joëls, Marian; Braun, Kees Pj; Bruining, Hilgo

    2015-01-01

    Altered sensory sensitivity is generally linked to seizure-susceptibility in childhood epilepsy but may also be associated to the highly prevalent problems in behavioral adaptation. This association is further suggested by the frequent overlap of childhood epilepsy with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), conditions in which altered behavioral responses to sensory stimuli have been firmly established. A continuum of sensory processing defects due to imbalanced neuronal inhibition and excitation across these disorders has been hypothesizedthat may lead to common symptoms of inadequate modulation of behavioral responses to sensory stimuli. Here, we investigated the prevalence of sensory modulation disorders among children with epilepsy and their relation with symptomatology of neurodevelopmental disorders. We used the Sensory Profile questionnaire to assess behavioral responses to sensory stimuli and categorize sensory modulation disorders in children with active epilepsy (aged 4-17 years). We related these outcomes to epilepsy characteristics and tested their association with comorbid symptoms of ASD (Social Responsiveness Scale) and ADHD (Strengths and Difficulties Questionnaire). Sensory modulation disorders were reported in 49 % of the 158 children. Children with epilepsy reported increased behavioral responses associated with sensory "sensitivity," "sensory avoidance," and "poor registration" but not "sensory seeking." Comorbidity of ASD and ADHD was associated with more severe sensory modulation problems, although 27 % of typically developing children with epilepsy also reported a sensory modulation disorder. Sensory modulation disorders are an under-recognized problem in children with epilepsy. The extent of the modulation difficulties indicates a substantial burden on daily functioning and may explain an important part of the behavioral distress associated with childhood epilepsy.

  19. Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat.

    Science.gov (United States)

    Due, Michael R; Park, Jonghyuck; Zheng, Lingxing; Walls, Michael; Allette, Yohance M; White, Fletcher A; Shi, Riyi

    2014-03-01

    Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here, we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound's pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggest that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. Following spinal cord injury (SCI), acrolein involvement in neuropathic pain is likely through direct activation and elevated levels of pro-nociceptive channel TRPA1. While acrolein elevation correlates with neuropathic pain, suppression of this aldehyde by hydralazine leads to an analgesic effect. Acrolein may serve as a novel therapeutic target for preclinical and clinical SCI to relieve both acute and chronic post-SCI neuropathic pain. © 2013 International Society for Neurochemistry.

  20. The mechanism of functional up-regulation of P2X3 receptors of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine type 1 (FHM-1.

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    Swathi K Hullugundi

    Full Text Available A knock-in (KI mouse model of FHM-1 expressing the R192Q missense mutation of the Cacna1a gene coding for the α1 subunit of CaV2.1 channels shows, at the level of the trigeminal ganglion, selective functional up-regulation of ATP -gated P2X3 receptors of sensory neurons that convey nociceptive signals to the brainstem. Why P2X3 receptors are constitutively more responsive, however, remains unclear as their membrane expression and TRPV1 nociceptor activity are the same as in wildtype (WT neurons. Using primary cultures of WT or KI trigeminal ganglia, we investigated whether soluble compounds that may contribute to initiating (or maintaining migraine attacks, such as TNFα, CGRP, and BDNF, might be responsible for increasing P2X3 receptor responses. Exogenous application of TNFα potentiated P2X3 receptor-mediated currents of WT but not of KI neurons, most of which expressed both the P2X3 receptor and the TNFα receptor TNFR2. However, sustained TNFα neutralization failed to change WT or KI P2X3 receptor currents. This suggests that endogenous TNFα does not regulate P2X3 receptor responses. Nonetheless, on cultures made from both genotypes, exogenous TNFα enhanced TRPV1 receptor-mediated currents expressed by a few neurons, suggesting transient amplification of TRPV1 nociceptor responses. CGRP increased P2X3 receptor currents only in WT cultures, although prolonged CGRP receptor antagonism or BDNF neutralization reduced KI currents to WT levels. Our data suggest that, in KI trigeminal ganglion cultures, constitutive up-regulation of P2X3 receptors probably is already maximal and is apparently contributed by basal CGRP and BDNF levels, thereby rendering these neurons more responsive to extracellular ATP.

  1. Sensory augmentation for the blind

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    Silke Manuela Kärcher

    2012-03-01

    Full Text Available Enacted theories of consciousness conjecture that perception and cognition arise from an active experience of the regular relations that are tying together the sensory stimulation of different modalities and associated motor actions. Previous experiments investigated this concept by employing the technique of sensory substitution. Building on these studies, here we test a set of hypotheses derived from this framework and investigate the utility of sensory augmentation in handicapped people. We provide a late blind subject with a new set of sensorimotor laws: A vibro-tactile belt continually signals the direction of magnetic north. The subject completed a set of behavioral tests before and after an extended training period. The tests were complemented by questionnaires and interviews. This newly supplied information improved performance on different time scales. In a pointing task we demonstrate an instant improvement of performance based on the signal provided by the device. Furthermore, the signal was helpful in relevant daily tasks, often complicated for the blind, such as keeping a direction over longer distances or taking shortcuts in familiar environments. A homing task with an additional attentional load demonstrated a significant improvement after training. The subject found the directional information highly expedient for the adjustment of his inner maps of familiar environments and describes an increase in his feeling of security when exploring unfamiliar environments with the belt. The results give evidence for a firm integration of the newly supplied signals into the behavior of this late blind subject with better navigational performance and more courageous behavior in unfamiliar environments. Most importantly, the complementary information provided by the belt lead to a positive emotional impact with enhanced feeling of security. This experimental approach demonstrates the potential of sensory augmentation devices for the help of

  2. Sensory properties of irradiated foods

    International Nuclear Information System (INIS)

    Plestenjak, A.

    1997-01-01

    Food irradiation is a simple and effective preservation technique. The changes caused by irradiation depend on composition of food, on the absorbed dose, the water content and temperature during and after irradiation. In this paper the changes of food components caused by irradiation, doses for various food irradiation treatments, foods and countries where the irradiation is allowed, and sensory properties of irradiated food are reviewed

  3. Sensory Coordination of Insect Flight

    Science.gov (United States)

    2009-12-29

    strains at the base of antennae, similar to halteres in Diptera . We are investigating various aspects of these phenomena in greater detail to understand...coordination in the soldier fly, Hermetia illucens (Tanvi Deora): One of the key sensory inputs for flight stability in Diptera comes from the haltere...as they land on visual objects that we provide them. This assay relies on the fact that houseflies are attracted to strong contrast visual cues when

  4. Sensory Systems and Environmental Change on Behavior during Social Interactions

    Directory of Open Access Journals (Sweden)

    S. M. Bierbower

    2013-01-01

    Full Text Available The impact of environmental conditions for transmitting sensory cues and the ability of crayfish to utilize olfaction and vision were examined in regards to social interactive behavior. The duration and intensity of interactions were examined for conspecific crayfish with different sensory abilities. Normally, vision and chemosensory have roles in agonistic communication of Procambarus clarkii; however, for the blind cave crayfish (Orconectes australis packardi, that lack visual capabilities, olfaction is assumed to be the primary sensory modality. To test this, we paired conspecifics in water and out of water in the presence and absence of white light to examine interactive behaviors when these various sensory modalities are altered. For sighted crayfish, in white light, interactions occurred and escalated; however, when the water was removed, interactions and aggressiveness decreased, but, there was an increase in visual displays out of the water. The loss of olfaction abilities for blind cave and sighted crayfish produced fewer social interactions. The importance of environmental conditions is illustrated for social interactions among sighted and blind crayfish. Importantly, this study shows the relevance in the ecological arena in nature for species survival and how environmental changes disrupt innate behaviors.

  5. Ultrastructural description of rabies virus infection in cultured sensory neurons

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    Myriam L Velandia

    2007-06-01

    Full Text Available Primary cultures were made from adult mouse spinal ganglia for depicting an ultrastructural description of rabies virus (RABV infection in adult mouse sensory neuron cultures; they were infected with rabies virus for 24, 36, and 48 h. The monolayers were processed for transmission electron microscopy and immunochemistry studies at the end of each period. As previously reported, sensory neurons showed great susceptibility to infection by RABV; however, in none of the periods evaluated were assembled virions observed in the cytoplasm or seen to be associated with the cytoplasmic membrane. Instead, fibril matrices of aggregated ribonucleoprotein were detected in the cytoplasm. When infected culture lysate were inoculated into normal animals via intra-cerebral route it was observed that these animals developed clinical symptoms characteristic of infection and transmission electron microscopy revealed assembled virions in the cerebral cortex and other areas of the brain. Sensory neurons infected in vitro by RABV produced a large amount of unassembled viral ribonucleoprotein. However, this intracellular material was able to produce infection and virions on being intra-cerebrally inoculated. It can thus be suggested that the lack of intracellular assembly in sensory neurons forms part of an efficient dissemination strategy.

  6. Tactile sensory system: encoding from the periphery to the cortex.

    Science.gov (United States)

    Jones, Lynette A; Smith, Allan M

    2014-01-01

    Specialized mechanoreceptors in the skin respond to mechanical deformation and provide the primary input to the tactile sensory system. Although the morphology of these receptors has been documented, there is still considerable uncertainty as to the relation between cutaneous receptor morphology and the associated physiological responses to stimulation. Labelled-line models of somatosensory processes in which specific mechanoreceptors are associated with particular sensory qualities fail to account for the evidence showing that all types of tactile afferent units respond to a varying extent to most types of natural stimuli. Neurophysiological and psychophysical experiments have provided the framework for determining the relation between peripheral afferent or cortical activity and tactile perception. Neural codes derived from these afferent signals are evaluated in terms of their capacity to predict human perceptual performance. One particular challenge in developing models of the tactile sensory system is the dual use of sensory signals from the skin. In addition to their perceptual function they serve as inputs to the sensorimotor control system involved in manipulation. Perceptions generated through active touch differ from those resulting from passive stimulation of the skin because they are the product of self-generated exploratory processes. Recent research in this area has highlighted the importance of shear forces in these exploratory movements and has shown that fingertip skin is particularly sensitive to shear generated during both object manipulation and tactile exploration. © 2014 Wiley Periodicals, Inc.

  7. Hyperactivation balances sensory processing deficits during mood induction in schizophrenia.

    Science.gov (United States)

    Dyck, Miriam; Loughead, James; Gur, Ruben C; Schneider, Frank; Mathiak, Klaus

    2014-02-01

    While impairments in emotion recognition are consistently reported in schizophrenia, there is some debate on the experience of emotion. Only few studies investigated neural correlates of emotional experience in schizophrenia. The present functional magnetic resonance imaging study compared a standard visual mood induction paradigm with an audiovisual method aimed at eliciting emotions more automatically. To investigate the interplay of sensory, cognitive and emotional mechanisms during emotion experience, we examined connectivity patterns between brain areas. Sixteen schizophrenia patients and sixteen healthy subjects participated in two different mood inductions (visual and audiovisual) that were administered for different emotions (happiness, sadness and neutral). Confirming the dissociation of behavioral and neural correlates of emotion experience, patients rated their mood similarly to healthy subjects but showed differences in neural activations. Sensory brain areas were activated less, increased activity emerged in higher cortical areas, particularly during audiovisual stimulation. Connectivity was increased between primary and secondary sensory processing areas in schizophrenia. These findings support the hypothesis of a deficit in filtering and processing sensory information alongside increased higher-order cognitive effort compensating for perception deficits in the affective domain. This may suffice to recover emotion experience in ratings of clinically stable patients but may fail during acute psychosis.

  8. Measurement of pharyngeal sensory cortical processing: technique and physiologic implications

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    Ringelstein E Bernd

    2009-07-01

    Full Text Available Abstract Background Dysphagia is a major complication of different diseases affecting both the central and peripheral nervous system. Pharyngeal sensory impairment is one of the main features of neurogenic dysphagia. Therefore an objective technique to examine the cortical processing of pharyngeal sensory input would be a helpful diagnostic tool in this context. We developed a simple paradigm to perform pneumatic stimulation to both sides of the pharyngeal wall. Whole-head MEG was employed to study changes in cortical activation during this pharyngeal stimulation in nine healthy subjects. Data were analyzed by means of synthetic aperture magnetometry (SAM and the group analysis of individual SAM data was performed using a permutation test. Results Our results revealed bilateral activation of the caudolateral primary somatosensory cortex following sensory pharyngeal stimulation with a slight lateralization to the side of stimulation. Conclusion The method introduced here is simple and easy to perform and might be applicable in the clinical setting. The results are in keeping with previous findings showing bihemispheric involvement in the complex task of sensory pharyngeal processing. They might also explain changes in deglutition after hemispheric strokes. The ipsilaterally lateralized processing is surprising and needs further investigation.

  9. Omnidirectional sensory and motor volumes in electric fish.

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    James B Snyder

    2007-11-01

    Full Text Available Active sensing organisms, such as bats, dolphins, and weakly electric fish, generate a 3-D space for active sensation by emitting self-generated energy into the environment. For a weakly electric fish, we demonstrate that the electrosensory space for prey detection has an unusual, omnidirectional shape. We compare this sensory volume with the animal's motor volume--the volume swept out by the body over selected time intervals and over the time it takes to come to a stop from typical hunting velocities. We find that the motor volume has a similar omnidirectional shape, which can be attributed to the fish's backward-swimming capabilities and body dynamics. We assessed the electrosensory space for prey detection by analyzing simulated changes in spiking activity of primary electrosensory afferents during empirically measured and synthetic prey capture trials. The animal's motor volume was reconstructed from video recordings of body motion during prey capture behavior. Our results suggest that in weakly electric fish, there is a close connection between the shape of the sensory and motor volumes. We consider three general spatial relationships between 3-D sensory and motor volumes in active and passive-sensing animals, and we examine hypotheses about these relationships in the context of the volumes we quantify for weakly electric fish. We propose that the ratio of the sensory volume to the motor volume provides insight into behavioral control strategies across all animals.

  10. Development of Metallic Sensory Alloys

    Science.gov (United States)

    Wallace Terryl A.; Newman, John A.; Horne, Michael R.; Messick, Peter L.

    2010-01-01

    Existing nondestructive evaluation (NDE) technologies are inherently limited by the physical response of the structural material being inspected and are therefore not generally effective at the identification of small discontinuities, making the detection of incipient damage extremely difficult. One innovative solution to this problem is to enhance or complement the NDE signature of structural materials to dramatically improve the ability of existing NDE tools to detect damage. To address this need, a multifunctional metallic material has been developed that can be used in structural applications. The material is processed to contain second phase sensory particles that significantly improve the NDE response, enhancing the ability of conventional NDE techniques to detect incipient damage both during and after flight. Ferromagnetic shape-memory alloys (FSMAs) are an ideal material for these sensory particles as they undergo a uniform and repeatable change in both magnetic properties and crystallographic structure (martensitic transformation) when subjected to strain and/or temperature changes which can be detected using conventional NDE techniques. In this study, the use of a ferromagnetic shape memory alloy (FSMA) as the sensory particles was investigated.

  11. Sensory evaluation of buffalo butter

    Directory of Open Access Journals (Sweden)

    J.C.S. Carneiro

    2010-02-01

    Full Text Available Butter obtained from buffalo milk was compared with commercial products obtained from cow milk. One buffalo butter and two cow butters were subjected to sensory analysis using non-trained panelists. The acceptance related to sensorial characteristics (color, flavor, and firmness was evaluated through a 9 point structured hedonic scale varying from “I displeased extremely” to “I liked extremely”. Analysis of variance (ANOVA was performed to evaluate the sensory characteristics and the means were compared by Tukey’s Test at 5% of significance. The buffalo butter received lower scores than the others for all attributes. The greatest difference was observed for color, as the buffalo butter exhibited a white color contrasting with the yellow color of commercial butters, which is the pattern expected by the consumers. For flavor and firmness attributes, the buffalo butter received scores similar to the commercial products. These results show. These results shows that the buffalo’s butter has a good acceptance on local market, and this could be improved through the correction of product’s color, what can be obtained by adding a dye.

  12. Timing flickers across sensory modalities.

    Science.gov (United States)

    Vicario, Carmelo Mario; Rappo, Gaetano; Pepi, Anna Maria; Oliveri, Massimiliano

    2009-01-01

    In tasks requiring a comparison of the duration of a reference and a test visual cue, the spatial position of test cue is likely to be implicitly coded, providing a form of a congruency effect or introducing a response bias according to the environmental scale or its vectorial reference. The precise mechanism generating these perceptual shifts in subjective duration is not understood, although several studies suggest that spatial attentional factors may play a critical role. Here we use a duration comparison task within and across sensory modalities to examine if temporal performance is also modulated when people are exposed to spatial distractors involving different sensory modalities. Different groups of healthy participants performed duration comparison tasks in separate sessions: a time comparison task of visual stimuli during exposure to spatially presented auditory distractors; and a time comparison task of auditory stimuli during exposure to spatially presented visual distractors. We found the duration of visual stimuli biased depending on the spatial position of auditory distractors. Observers underestimated the duration of stimuli presented in the left spatial field, while there was an overestimation trend in estimating the duration of stimuli presented in the right spatial field. In contrast, timing of auditory stimuli was unaffected by exposure to visual distractors. These results support the existence of multisensory interactions between space and time showing that, in cross-modal paradigms, the presence of auditory distractors can modify visuo-temporal perception but not vice versa. This asymmetry is discussed in terms of sensory perceptual differences between the two systems.

  13. Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex.

    Science.gov (United States)

    Sreenivasan, Varun; Kyriakatos, Alexandros; Mateo, Celine; Jaeger, Dieter; Petersen, Carl C H

    2017-07-01

    The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs.

  14. Somatosensory nociceptive characteristics differentiate subgroups in people with chronic low back pain: a cluster analysis.

    Science.gov (United States)

    Rabey, Martin; Slater, Helen; OʼSullivan, Peter; Beales, Darren; Smith, Anne

    2015-10-01

    The objectives of this study were to explore the existence of subgroups in a cohort with chronic low back pain (n = 294) based on the results of multimodal sensory testing and profile subgroups on demographic, psychological, lifestyle, and general health factors. Bedside (2-point discrimination, brush, vibration and pinprick perception, temporal summation on repeated monofilament stimulation) and laboratory (mechanical detection threshold, pressure, heat and cold pain thresholds, conditioned pain modulation) sensory testing were examined at wrist and lumbar sites. Data were entered into principal component analysis, and 5 component scores were entered into latent class analysis. Three clusters, with different sensory characteristics, were derived. Cluster 1 (31.9%) was characterised by average to high temperature and pressure pain sensitivity. Cluster 2 (52.0%) was characterised by average to high pressure pain sensitivity. Cluster 3 (16.0%) was characterised by low temperature and pressure pain sensitivity. Temporal summation occurred significantly more frequently in cluster 1. Subgroups were profiled on pain intensity, disability, depression, anxiety, stress, life events, fear avoidance, catastrophizing, perception of the low back region, comorbidities, body mass index, multiple pain sites, sleep, and activity levels. Clusters 1 and 2 had a significantly greater proportion of female participants and higher depression and sleep disturbance scores than cluster 3. The proportion of participants undertaking Low back pain, therefore, does not appear to be homogeneous. Pain mechanisms relating to presentations of each subgroup were postulated. Future research may investigate prognoses and interventions tailored towards these subgroups.

  15. Increased expression of Trpv1 in peripheral terminals mediates thermal nociception in Fabry disease mouse model.

    Science.gov (United States)

    Lakomá, Jarmila; Rimondini, Roberto; Ferrer Montiel, Antonio; Donadio, Vincenzo; Liguori, Rocco; Caprini, Marco

    2016-01-01

    Fabry disease is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (α-GalA) enzyme. α-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3) in the endothelium and vascular smooth muscles. A hallmark symptom of Fabry disease patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. The α-GalA gene null mouse model (α-GalA(-/0)) has provided molecular evidence for the molecular alterations in small type-C nociceptors in Fabry disease that may underlie their hyperexcitability, although the specific mechanism remains elusive. Here, we have addressed this question and report that small type-C nociceptors from α-GalA(-/0) mice exhibit a significant increase in the expression and function of the TRPV1 channel, a thermoTRP channel implicated in painful heat sensation. Notably, male α-GalA(-/0) mice displayed a ≈2-fold higher heat sensitivity than wild-type animals, consistent with the augmented expression levels and activity of TRPV1 in α-GalA(-/0) nociceptors. Intriguingly, blockade of neuronal exocytosis with peptide DD04107, a process that inhibits among others the algesic membrane recruitment of TRPV1 channels in peptidergic nociceptors, virtually eliminated the enhanced heat nociception of α-GalA(-/0) mice. Together, these findings suggest that the augmented expression of TRPV1 in α-GalA(-/0) nociceptors may underly at least in part their increased heat sensitivity, and imply that blockade of peripheral neuronal exocytosis may be a valuable pharmacological strategy to reduce pain in Fabry disease patients, increasing their quality of life. © The Author(s) 2016.

  16. Dynamic Changes in Nociception and Pain Perception After Spinal Cord Stimulation in Chronic Neuropathic Pain Patients.

    Science.gov (United States)

    Biurrun Manresa, José A; Sörensen, Jan; Andersen, Ole K; Arendt-Nielsen, Lars; Gerdle, Björn

    2015-12-01

    Patients with an implanted spinal cord stimulation (SCS) system for pain management present an opportunity to study dynamic changes in the pain system in a situation where patients are not stimulated (ie, experiencing severe pain) compared with a situation in which patients have just been stimulated (ie, pain free or greatly reduced pain). The aims of this study were (1) to determine if there are differences in nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) before and after SCS; and (2) to establish if these differences are related to psychological factors associated with chronic pain. Seventeen volunteers with chronic neuropathic pain participated in the experiment. Electrical stimuli were applied to assess the NWR-T and the EP-T. In addition, psychological factors (ie, pain characteristics, depression, anxiety, and disability indexes) were also recorded. The NWR-T and EP-T were assessed with the SCS system off (at least 8 h before the experiment), and then reassessed 1 hour after the SCS system was turned on. Ongoing pain intensity ratings decreased (P=0.018), whereas the NWR-T increased (P=0.028) after the SCS was turned on, whereas no significant difference was found for EP-T (P=0.324). Psychological factors were significant predictors for EP-T but not for NWR-T. The results of this study suggest that pain relief after SCS is partially mediated by a decrease in the excitability of dorsal horn neurons in the spinal cord.

  17. Neonatal paracetamol treatment reduces long-term nociceptive behaviour after neonatal procedural pain in rats.

    Science.gov (United States)

    van den Hoogen, N J; Tibboel, D; Honig, W M M; Hermes, D; Patijn, J; Joosten, E A

    2016-09-01

    Pain from skin penetrating procedures (procedural pain) during infancy in the neonatal intensive care unit (NICU) may result in changes of nociceptive sensitivity in later life. This supports the need for pain management during such vulnerable periods in life. This study, therefore, analyses the short- and long-term consequences of neonatal paracetamol (acetaminophen) treatment on pain behaviour in an experimental rat model of neonatal procedural pain. A repetitive needle-prick model was used, in which neonatal rats received four needle pricks into the left hind paw per day from postnatal day 0 to day 7 (P0-P7). Paracetamol (50 mg/kg/day s.c.) was administered daily (P0-P7), and sensitivity to mechanical stimuli was compared with a needle-prick/saline-treated group and to a tactile control group. At 8 weeks of age, all animals underwent an ipsilateral paw-incision, modelling postoperative pain, and the duration of hypersensitivity was assessed. Neonatal paracetamol administration had no effect upon short-term mechanical hypersensitivity during the first postnatal week or upon long-term baseline sensitivity from 3 to 8 weeks. However, neonatal paracetamol administration significantly reduced the postoperative mechanical hypersensitivity in young adults, caused by repetitive needle pricking. Paracetamol administration during neonatal procedural pain does not alter short-term or long-term effects on mechanical sensitivity, but does reduce the duration of increased postoperative mechanical hypersensitivity in a clinically relevant neonatal procedural pain model. Paracetamol can be used safely in neonatal rats. Neonatal paracetamol treatment had no effect upon short-term mechanical hypersensitivity during the first postnatal week, nor upon long-term baseline sensitivity from 3 to 8 weeks. Paracetamol treatment during the first postnatal week significantly reduced the postoperative mechanical hypersensitivity in young adult rats. © 2016 European Pain Federation

  18. Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses.

    Science.gov (United States)

    Love, E J; Taylor, P M; Murrell, J; Whay, H R

    2012-03-01

    To investigate the antinociceptive effects of buprenorphine administered in combination with acepromazine in horses and to establish an effective dose for use in a clinical environment. To evaluate the responses to thermal and mechanical stimulation following administration of 3 doses of buprenorphine compared to positive (butorphanol) and negative (glucose) controls. Observer blinded, randomised, crossover design using 6 Thoroughbred geldings (3-10 years, 500-560 kg). Thermal and mechanical nociceptive thresholds were measured 3 times at 15 min intervals. Horses then received acepromazine 0.05 mg/kg bwt with one of 5 treatments i.v.: 5% glucose (Glu), butorphanol 100 µg/kg bwt (But) buprenorphine 5 µg/kg bwt (Bup5), buprenorphine 7.5 µg/kg bwt (Bup7.5) and buprenorphine 10 µg/kg bwt (Bup10). Thresholds were measured 15, 30, 45, 60, 90, 120, 150, 180, 230 min, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 24 h post treatment administration. The 95% confidence intervals for threshold temperature (ΔT) for each horse were calculated and an antinociceptive effect defined as ΔT, which was higher than the upper limit of the confidence interval. Duration of thermal antinociception was analysed using a within-subjects ANOVA and peak mechanical thresholds with a general linear model with post hoc Tukey tests. Significance was set at Pbuprenorphine produced antinociception to a thermal stimulus for significantly longer than acepromazine and either butorphanol or glucose. This study suggests that buprenorphine has considerable potential as an analgesic in horses and should be examined further under clinical conditions and by investigation of the pharmacokinetic/pharmacodynamic profile. © 2011 EVJ Ltd.

  19. Brain potentials evoked by intraepidermal electrical stimuli reflect the central sensitization of nociceptive pathways.

    Science.gov (United States)

    Liang, M; Lee, M C; O'Neill, J; Dickenson, A H; Iannetti, G D

    2016-08-01

    Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS. Copyright © 2016 the American Physiological Society.

  20. Inward-rectifying potassium (Kir) channels regulate pacemaker activity in spinal nociceptive circuits during early life

    Science.gov (United States)

    Li, Jie; Blankenship, Meredith L.; Baccei, Mark L.

    2013-01-01

    Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst-firing and are distinguished by a lower “leak” membrane conductance compared to adjacent, non-bursting neurons. However, little is known about which subtypes of leak channels regulate the level of pacemaker activity within the developing rat superficial dorsal horn (SDH). Here we demonstrate that a hallmark feature of lamina I pacemaker neurons is a reduced conductance through inward-rectifying potassium (Kir) channels at physiological membrane potentials. Differences in the strength of inward rectification between pacemakers and non-pacemakers indicate the presence of functionally distinct Kir currents in these two populations at room temperature. However, Kir currents in both groups showed high sensitivity to block by extracellular Ba2+ (IC50 ~ 10 µM), which suggests the presence of ‘classical’ Kir (Kir2.x) channels in the neonatal SDH. The reduced Kir conductance within pacemakers is unlikely to be explained by an absence of particular Kir2.x isoforms, as immunohistochemical analysis revealed the expression of Kir2.1, Kir2.2 and Kir2.3 within spontaneously bursting neurons. Importantly, Ba2+ application unmasked rhythmic burst-firing in ~42% of non-bursting lamina I neurons, suggesting that pacemaker activity is a latent property of a sizeable population of SDH cells during early life. In addition, the prevalence of spontaneous burst-firing within lamina I was enhanced in the presence of high internal concentrations of free Mg2+, consistent with its documented ability to block Kir channels from the intracellular side. Collectively, the results indicate that Kir channels are key modulators of pacemaker activity in newborn central pain networks. PMID:23426663

  1. Fast non-genomic effects of progesterone-derived neurosteroids on nociceptive thresholds and pain symptoms.

    Science.gov (United States)

    Charlet, Alexandre; Lasbennes, François; Darbon, Pascal; Poisbeau, Pierrick

    2008-10-31

    Fast Inhibitory controls mediated by glycine (GlyRs) and GABAA receptors (GABAARs) play an important role to prevent the apparition of pathological pain symptoms of allodynia and hyperalgesia. The use of positive allosteric modulators of these receptors, specifically expressed in the spinal cord, may represent an interesting strategy to limit or block pain expression. In this study, we have used stereoisomers of progesterone metabolites, acting only via non-genomic effects, in order to evaluate the contribution of GlyRs and GABAARs for the reduction of mechanical and thermal heat hypernociception. We show that 3alpha neurosteroids were particularly efficient to elevate nociceptive thresholds in naive animal. It also reduced mechanical allodynia and thermal heat hyperalgesia in the carrageenan model of inflammatory pain. This effect is likely to be mediated by GABAA receptors since 3beta isomer was inefficient. More interestingly, 3alpha5beta neurosteroid was only efficient on mechanical allodynia while having no effect on thermal heat hyperalgesia. We characterized these paradoxical effects of 3alpha5beta neurosteroid using the strychnine and bicuculline models of allodynia. We clearly show that 3alpha5beta neurosteroid exerts an antinociceptive effect via a positive allosteric modulation of GABAARs but, at the same time, is pronociceptive by reducing GlyR function. This illustrates the importance of the inhibitory amino acid receptor channels and their allosteric modulators in spinal pain processing. Moreover, our results indicate that neurosteroids, which are synthesized in the dorsal horn of the spinal cord and have limited side effects, may be of significant interest in order to treat pathological pain symptoms.

  2. Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Yanmei Qi

    2018-02-01

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in numerous physiological and pathophysiological processes. We have previously reported a S1P-induced nocifensive response in mice by excitation of sensory neurons via activation of an excitatory chloride current. The underlying molecular mechanism for the S1P-induced chloride conductance remains elusive. In the present study, we identified two CLCN voltage-gated chloride channels, CLCN3 and CLCN5, which mediated a S1P-induced excitatory Cl− current in sensory neurons by combining RNA-seq, adenovirus-based gene silencing and whole-cell electrophysiological voltage-clamp recordings. Downregulation of CLCN3 and CLCN5 channels by adenovirus-mediated delivery of shRNA dramatically reduced S1P-induced Cl− current and membrane depolarization in sensory neurons. The mechanism of S1P-induced activation of the chloride current involved Rho GTPase but not Rho-associated protein kinase. Although S1P-induced potentiation of TRPV1-mediated ionic currents also involved Rho-dependent process, the lack of correlation of the S1P-activated Cl− current and the potentiation of TRPV1 by S1P suggests that CLCN3 and CLCN5 are necessary components for S1P-induced excitatory Cl− currents but not for the amplification of TRPV1-mediated currents in sensory neurons. This study provides a novel mechanistic insight into the importance of bioactive sphingolipids in nociception.

  3. Hereditary sensory neuropathy type I

    Directory of Open Access Journals (Sweden)

    Auer-Grumbach Michaela

    2008-03-01

    Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

  4. Sensory Motor Coordination in Robonaut

    Science.gov (United States)

    Peters, Richard Alan, II

    2003-01-01

    As a participant of the year 2000 NASA Summer Faculty Fellowship Program, I worked with the engineers of the Dexterous Robotics Laboratory at NASA Johnson Space Center on the Robonaut project. The Robonaut is an articulated torso with two dexterous arms, left and right five-fingered hands, and a head with cameras mounted on an articulated neck. This advanced space robot, now driven only teleoperatively using VR gloves, sensors and helmets, is to be upgraded to a thinking system that can find, interact with and assist humans autonomously, allowing the Crew to work with Robonaut as a (junior) member of their team. Thus, the work performed this summer was toward the goal of enabling Robonaut to operate autonomously as an intelligent assistant to astronauts. Our underlying hypothesis is that a robot can develop intelligence if it learns a set of basic behaviors (i.e., reflexes - actions tightly coupled to sensing) and through experience learns how to sequence these to solve problems or to accomplish higher-level tasks. We describe our approach to the automatic acquisition of basic behaviors as learning sensory-motor coordination (SMC). Although research in the ontogenesis of animals development from the time of conception) supports the approach of learning SMC as the foundation for intelligent, autonomous behavior, we do not know whether it will prove viable for the development of autonomy in robots. The first step in testing the hypothesis is to determine if SMC can be learned by the robot. To do this, we have taken advantage of Robonaut's teleoperated control system. When a person teleoperates Robonaut, the person's own SMC causes the robot to act purposefully. If the sensory signals that the robot detects during teleoperation are recorded over several repetitions of the same task, it should be possible through signal analysis to identify the sensory-motor couplings that accompany purposeful motion. In this report, reasons for suspecting SMC as the basis for

  5. Cognitive mechanisms associated with auditory sensory gating

    Science.gov (United States)

    Jones, L.A.; Hills, P.J.; Dick, K.M.; Jones, S.P.; Bright, P.

    2016-01-01

    Sensory gating is a neurophysiological measure of inhibition that is characterised by a reduction in the P50 event-related potential to a repeated identical stimulus. The objective of this work was to determine the cognitive mechanisms that relate to the neurological phenomenon of auditory sensory gating. Sixty participants underwent a battery of 10 cognitive tasks, including qualitatively different measures of attentional inhibition, working memory, and fluid intelligence. Participants additionally completed a paired-stimulus paradigm as a measure of auditory sensory gating. A correlational analysis revealed that several tasks correlated significantly with sensory gating. However once fluid intelligence and working memory were accounted for, only a measure of latent inhibition and accuracy scores on the continuous performance task showed significant sensitivity to sensory gating. We conclude that sensory gating reflects the identification of goal-irrelevant information at the encoding (input) stage and the subsequent ability to selectively attend to goal-relevant information based on that previous identification. PMID:26716891

  6. Food Intake Is Influenced by Sensory Sensitivity

    Science.gov (United States)

    Naish, Katherine R.; Harris, Gillian

    2012-01-01

    Wide availability of highly palatable foods is often blamed for the rising incidence of obesity. As palatability is largely determined by the sensory properties of food, this study investigated how sensitivity to these properties affects how much we eat. Forty females were classified as either high or low in sensory sensitivity based on their scores on a self-report measure of sensory processing (the Adult Sensory Profile), and their intake of chocolate during the experiment was measured. Food intake was significantly higher for high-sensitivity compared to low-sensitivity individuals. Furthermore, individual scores of sensory sensitivity were positively correlated with self-reported emotional eating. These data could indicate that individuals who are more sensitive to the sensory properties of food have a heightened perception of palatability, which, in turn, leads to a greater food intake. PMID:22916284

  7. Sensory characteristics of different cod products

    DEFF Research Database (Denmark)

    Sveinsdottir, K.; Martinsdottir, E.; Hyldig, Grethe

    2010-01-01

    Sensory characteristics of cod products available to consumers were analyzed, and different ways to analyze sensory results were viewed. Ten cod samples of different origin (wild and farmed cod), storage time (short and extended) and storage method (stored fresh, frozen or packed in modified...... atmosphere) were evaluated with quantitative descriptive analysis by a trained sensory panel. Signal-to-noise analysis, p*MSE (discrimination and repeatability) and line plots proved to be very useful in studying panelists' performance. Most sensory attributes described significant differences between...... the products, and principal component analysis provided an overview of the differences and similarities between the products with regard to sensory characteristics. Farmed cod had different sensory characteristics compared with wild cod, such as more meat flavor, and rubbery and meaty texture. Different...

  8. Multivariate analysis of data in sensory science

    CERN Document Server

    Naes, T; Risvik, E

    1996-01-01

    The state-of-the-art of multivariate analysis in sensory science is described in this volume. Both methods for aggregated and individual sensory profiles are discussed. Processes and results are presented in such a way that they can be understood not only by statisticians but also by experienced sensory panel leaders and users of sensory analysis. The techniques presented are focused on examples and interpretation rather than on the technical aspects, with an emphasis on new and important methods which are possibly not so well known to scientists in the field. Important features of the book are discussions on the relationship among the methods with a strong accent on the connection between problems and methods. All procedures presented are described in relation to sensory data and not as completely general statistical techniques. Sensory scientists, applied statisticians, chemometricians, those working in consumer science, food scientists and agronomers will find this book of value.

  9. Food intake is influenced by sensory sensitivity.

    Directory of Open Access Journals (Sweden)

    Katherine R Naish

    Full Text Available Wide availability of highly palatable foods is often blamed for the rising incidence of obesity. As palatability is largely determined by the sensory properties of food, this study investigated how sensitivity to these properties affects how much we eat. Forty females were classified as either high or low in sensory sensitivity based on their scores on a self-report measure of sensory processing (the Adult Sensory Profile, and their intake of chocolate during the experiment was measured. Food intake was significantly higher for high-sensitivity compared to low-sensitivity individuals. Furthermore, individual scores of sensory sensitivity were positively correlated with self-reported emotional eating. These data could indicate that individuals who are more sensitive to the sensory properties of food have a heightened perception of palatability, which, in turn, leads to a greater food intake.

  10. Anti-nociceptive and anti-hyperprolactinemia activities of Fructus Viticis and its effective fractions and chemical constituents.

    Science.gov (United States)

    Hu, Y; Xin, H-L; Zhang, Q-Y; Zheng, H-C; Rahman, K; Qin, L-P

    2007-10-01

    Vitex rotundifolia L. is widely distributed along the sea coast of China. The aim of this study was to investigate the anti-nociceptive and anti-hyperprolactinemia activities of substances isolated from Fructus Viticis (the fruit of Vitex rotundifolia), which may be effective in the treatment of pre-menstrual symptoms, using acetic-acid-induced writhing and metoclopramide-dihydrochloride-induced hyperprolactinemia in mice. The fractions effective in terms of anti-nociceptive and anti-hyperprolactinemia activities were obtained from Fructus Viticis by elution through macro-porous resin, and polyamide and silica gel column chromatography. The standardization of the fractions obtained from the separation procedures was carried out by means of high-performance liquid chromatography (HPLC)-fingerprint. In this study, the flavone-enriched fraction (Fraction 6) showed a higher inhibitory rate than indomethacin (69.4% vs. 56.4%) at a dose of 50 mg/kg body wt., and significantly reduced the prolactin level as compared to HPRL-treated mice (8.2 ng/ml vs. 25.5 ng/ml). Furthermore, this fraction showed anti-nociceptive activity in a dose-dependent manner (10-50 mg/kg body wt., i.g.). On further purification with silica gel, Casticin was isolated from this fraction and it decreased abnormal serum levels of prolactin by approximately 50% (p screening methods, our results indicate that the presence of flavonoids such as Casticin in this plant may be responsible for the activity effects. Casticin has potent analgesic and anti-hyperprolactinaemia properties, is likely to be one of the active components of Fructus Viticis, and may have a role in treating PMS (premenstrual syndrom).

  11. Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors.

    Science.gov (United States)

    Itoh, K; Chiang, C-Y; Li, Z; Lee, J-C; Dostrovsky, J O; Sessle, B J

    2011-09-29

    Central sensitization is a crucial process underlying the increased neuronal excitability of nociceptive pathways following peripheral tissue injury and inflammation. Our previous findings have suggested that extracellular adenosine 5'-triphosphate (ATP) molecules acting at purinergic receptors located on presynaptic terminals (e.g., P2X2/3, P2X3 subunits) and glial cells are involved in the glutamatergic-dependent central sensitization induced in medullary dorsal horn (MDH) nociceptive neurons by application to the tooth pulp of the inflammatory irritant mustard oil (MO). Since growing evidence indicates that activation of P2X7 receptors located on glia is involved in chronic inflammatory and neuropathic pain, the aim of the present study was to test in vivo for P2X7 receptor involvement in this acute inflammatory pain model. Experiments were carried out in anesthetized Sprague-Dawley male rats. Single unit recordings were made in MDH functionally identified nociceptive neurons for which mechanoreceptive field, mechanical activation threshold and responses to noxious stimuli were tested. We found that continuous intrathecal (i.t.) superfusion over MDH of the potent P2X7 receptor antagonists brilliant blue G and periodated oxidized ATP could each significantly attenuate the MO-induced MDH central sensitization. MDH central sensitization could also be produced by i.t. superfusion of ATP and even more effectively by the P2X7 receptor agonist benzoylbenzoyl ATP. Superfusion of the microglial blocker minocycline abolished the MO-induced MDH central sensitization, consistent with reports that dorsal horn P2X7 receptors are mostly expressed on microglia. In control experiments, superfusion over MDH of vehicle did not produce any significant changes. These novel findings suggest that activation of P2X7 receptors in vivo may be involved in the development of central sensitization in an acute inflammatory pain model. Copyright © 2011 IBRO. All rights reserved.

  12. Neuronal nitric oxide synthase is involved in the induction of nerve growth factor-induced neck muscle nociception.

    Science.gov (United States)

    Isaak, Andreas; Ellrich, Jens

    2011-05-01

    Neck muscle nociception mediated by nitric oxide may play a role in the pathophysiology of tension-type headache. The present study addresses the involvement of neuronal nitric oxide synthase (nNOS) in the facilitation of neck muscle nociception after local application of nerve growth factor (NGF). After administration of NGF into semispinal neck muscles, the impact of neck muscle noxious input on brainstem processing was monitored by the jaw-opening reflex in anesthetized mice. The modulatory effect of preceding and subsequent administration of an inhibitor of neuronal nitric oxide synthase on central facilitation was addressed in a controlled study. With preceding i.p. application of saline or 0.096 mg/kg of the specific nNOS inhibitor Nω-propyl-L-arginine (NPLA), NGF induced a sustained reflex facilitation within 60 minutes. Preceding injection of 0.96 mg/kg or 1.92 mg/kg NPLA completely prevented the potentially facilitatory effect of NGF. Subsequent administration of 0.96 mg/kg NPLA did not affect established NGF-evoked reflex facilitation. Thus, NPLA prevents facilitation of brainstem processing by noxious myofascial input from neck muscles in a dose-dependent manner. These findings suggest that nNOS is involved in the induction but not the maintenance of NGF-evoked facilitation of nociception in the brainstem. These results from an experimental animal model may support the idea of NOS and nNOS as potential targets for pharmacological treatment of tension-type headache. © 2011 American Headache Society.

  13. The Discriminative validity of "nociceptive," "peripheral neuropathic," and "central sensitization" as mechanisms-based classifications of musculoskeletal pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-02-01

    OBJECTIVES: Empirical evidence of discriminative validity is required to justify the use of mechanisms-based classifications of musculoskeletal pain in clinical practice. The purpose of this study was to evaluate the discriminative validity of mechanisms-based classifications of pain by identifying discriminatory clusters of clinical criteria predictive of "nociceptive," "peripheral neuropathic," and "central sensitization" pain in patients with low back (+\\/- leg) pain disorders. METHODS: This study was a cross-sectional, between-patients design using the extreme-groups method. Four hundred sixty-four patients with low back (+\\/- leg) pain were assessed using a standardized assessment protocol. After each assessment, patients\\' pain was assigned a mechanisms-based classification. Clinicians then completed a clinical criteria checklist indicating the presence\\/absence of various clinical criteria. RESULTS: Multivariate analyses using binary logistic regression with Bayesian model averaging identified a discriminative cluster of 7, 3, and 4 symptoms and signs predictive of a dominance of "nociceptive," "peripheral neuropathic," and "central sensitization" pain, respectively. Each cluster was found to have high levels of classification accuracy (sensitivity, specificity, positive\\/negative predictive values, positive\\/negative likelihood ratios). DISCUSSION: By identifying a discriminatory cluster of symptoms and signs predictive of "nociceptive," "peripheral neuropathic," and "central" pain, this study provides some preliminary discriminative validity evidence for mechanisms-based classifications of musculoskeletal pain. Classification system validation requires the accumulation of validity evidence before their use in clinical practice can be recommended. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.

  14. Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice.

    Science.gov (United States)

    Munoz, Frances M; Gao, Ruby; Tian, Yuzhen; Henstenburg, Brian A; Barrett, James E; Hu, Huijuan

    2017-06-14

    ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R-induced pain remains unexplored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079. A similar effect was observed with a P2X7R agonist, BzATP, and was attenuated by a NADPH oxidase inhibitor apocynin. Intrathecal administration of BzATP resulted in ROS production in the spinal cord and oxidative DNA damage in dorsal horn neurons. BzATP also induced robust biphasic spontaneous nociceptive behavior. Pre-treatment with A438079 abolished all BzATP-induced nociceptive behaviors, while ROS scavengers dose-dependently attenuated the secondary response. Here, we provide evidence that neuronal P2X7R activation leads to ROS production and subsequent nociceptive pain in mice. Together, the data indicate that P2X7R-induced ROS play a critical role in the P2X7R signaling pathway of the CNS.

  15. Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process.

    Science.gov (United States)

    Le Roy, Chloé; Laboureyras, Emilie; Gavello-Baudy, Stéphanie; Chateauraynaud, Jérémy; Laulin, Jean-Paul; Simonnet, Guy

    2011-10-01

    Although stress induces analgesia, there is evidence that stressful events may exacerbate pain syndromes. Here, we studied the effects of 1 to 3 prestressful events (days 0, 2, and 7), such as non-nociceptive environmental stress, on inflammatory hyperalgesia induced by a carrageenan injection (day 14) in 1 rat hind paw. Changes in nociceptive threshold were evaluated by the paw pressure vocalization test. The higher the number of stress sessions presented to the rats, the greater was the inflammatory hyperalgesia. Blockade of opioid receptors by naltrexone before each stress inhibited stress-induced analgesia and suppressed the exaggerated inflammatory hyperalgesia. Stressed versus nonstressed animals could be discriminated by their response to a fentanyl ultra-low dose (fULD), that produced hyperalgesia or analgesia, respectively. This pharmacological test permitted the prediction of the pain vulnerability level of prestressed rats because fULD analgesic or hyperalgesic indices were positively correlated with inflammatory hyperalgesic indices (r(2) = .84). In prestressed rats, fULD-induced hyperalgesia and the exaggerated inflammatory hyperalgesia were prevented NMDA receptor antagonists. This study provides some preclinical evidence that pain intensity is not only the result of nociceptive input level but is also dependent on the individual history, especially prior life stress events associated with endogenous opioid release. Based on these preclinical data, it would be of clinical interest to evaluate whether prior stressful events may also affect further pain sensation in humans. Moreover, this preclinical model could be a good tool for evaluating new therapeutic strategies for relieving pain hypersensitivity. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  16. Expression of TRPV4 in the stimulated rat oral mucous membrane--nociceptive mechanisms of lingual conical papillae.

    Science.gov (United States)

    Nakatsuka, Michiko; Iwai, Yasutomo

    2009-08-01

    The study was supported by 2006-2007 Aid Program for Overseas Training of the Promotion and Mutual Aid Corporation for Private School of Japan and International Exchange Grant, Osaka Dental University. We studied the function of TRPV4 expression and its neuronal activation in response to noxious stimulation of oral mucosa. The intermolar region of dorsal lingual eminence (IDLE) of rats was stimulated with 10 microl of either normal saline or 5% formalin. Immunohistological studies of the TRPV4, pERK and serotonin (5HT) expression in designated regions of tongues and brainstems were performed for studying the descending pain modulatory system in response to nociception. Specimens of the experimental IDLE demonstrated a significant increase of TRPV4 activity in particular in stratum basale of conical papillae (p < 0.01). pERK-IR positive neurons were significantly increased in the RMg (p < 0.05), Sp5C (p < 0.05) and Md (p < 0.01); TRPV4-IR neurons were found to show a similar distribution with pERK-IR cells in the peripheral Sp5C (p < 0.05). A significant increase of 5HT expression was observed in the RMg (p < 0.01), RPa (p < 0.01) and ROb (p < 0.05). The results suggest that TRPV4 in the oral mucosa is nociceptor of peripheral hyperalgesia, and pERK expression in the Sp5C is closely related with central hyperalgesia of the nociception. Furthermore, pERK-IR cells of the central 5HT nervous system are activated to accelerate 5HT release for neuronal modulation of the descending pain modulatory system in response to nociception.

  17. Antinociceptive action of diphenyl diselenide in the nociception induced by neonatal administration of monosodium glutamate in rats.

    Science.gov (United States)

    Rosa, Suzan G; Quines, Caroline B; da Rocha, Juliana T; Bortolatto, Cristiani F; Duarte, Thiago; Nogueira, Cristina W

    2015-07-05

    Monosodium glutamate (MSG) is a neuroexcitatory amino acid commonly used as flavoring of foods. MSG neonatal administration to animals leads to behavioral and physiological disorders in adulthood, including increased pain sensitivity. This study aimed to investigate the effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, on nociception induced by MSG. Newborn Wistar rats received 10 subcutaneous injections of MSG at a dose of 4.0g/kg or saline (once daily). At the 60th day of life, the rats were daily treated with (PhSe)2 (1mg/kg) or vehicle (canola oil) by the intragastric route for 7 days. The behavioral tests (locomotor activity, hot plate, tail-immersion and mechanical allodynia) were carried out. Ex vivo assays were performed in samples of hippocampus to determine Na(+), K(+)-ATPase and Ca(2+)-ATPase activities, cytokine levels and [(3)H]glutamate uptake. The results demonstrated that MSG increased nociception in the hot plate test and in the mechanical allodynia stimulated by Von-Frey hair but did not alter the tail immersion test. (PhSe)2 reversed all nociceptive behaviors altered by MSG. MSG caused an increase in Na(+),K(+)-ATPase and Ca(2+)-ATPase activities and in pro-inflammatory cytokine levels and a decrease in the anti-inflammatory cytokine and in the [(3)H]glutamate uptake. (PhSe)2 was effective in reversing all alterations caused by MSG. The results indicate that (PhSe)2 had a potential antinociceptive and anti-inflammatory action in the MSG model. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Anti-nociceptive and anti-inflammatory activities of ethanolic flower extract of Newbouldia laevis in mice and rats

    OpenAIRE

    Y Tanko; B Kamba; MI Saleh; K Y Musa; A Mohammed

    2008-01-01

    Summary: The ethanolic flower extract of Newbouldia laevis was investigated for possible anti-nociceptive and anti-inflammatory effects in rodents. Acetic acid induced writhing (in mice) and formalin tests (in rats) were used to study. The extract caused a significant decrease (P< 0.05), which was not dose a dependent inhibition on acetic acid-induced writhing and the neurogenic pain induced by formalin. The extract at the doses (25, 50 and 100mg/kg) tested showed 59, 71 and 47% inhibition...

  19. Central nociceptive sensitization vs. spinal cord training: opposing forms of plasticity that dictate function after complete spinal cord injury.

    Science.gov (United States)

    Ferguson, Adam R; Huie, J Russell; Crown, Eric D; Grau, James W

    2012-01-01

    The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive) stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI) field indicates that the lumbar spinal cord demonstrates several other forms of plasticity, including formal learning and memory. After complete thoracic SCI, the lumbar spinal cord can be trained by delivering stimulation to the hindleg when the leg is extended. In the presence of this response-contingent stimulation the spinal cord rapidly learns to hold the leg in a flexed position, a centrally mediated effect that meets the formal criteria for instrumental (response-outcome) learning. Instrumental flexion training produces a central change in spinal plasticity that enables future spinal learning on both the ipsilateral and contralateral leg. However, if stimulation is given in a response-independent manner, the spinal cord develops central maladaptive plasticity that undermines future spinal learning on both legs. The present paper tests for interactions between spinal cord training and central nociceptive sensitization after complete spinal cord transection. We found that spinal training alters future central sensitization by intradermal formalin (24 h post-training). Conversely intradermal formalin impaired future spinal learning (24 h post-injection). Because formalin-induced central sensitization has been shown to involve NMDA receptor activation, we tested whether pre-treatment with NMDA would also affect spinal learning in manner similar to formalin. We found intrathecal NMDA impaired learning in a dose-dependent fashion, and that this effect endures for at least 24 h. These

  20. Sensory processing abilities of children with ADHD

    Directory of Open Access Journals (Sweden)

    Vitoria T. Shimizu

    2014-08-01

    Full Text Available OBJECTIVE: To assess and compare the sensory processing abilities of children with Attention Deficit/Hyperactivity Disorder (ADHD and children without disabilities, and to analyze the relationship between sensory processing difficulties and behavioural symptoms presented by children with ADHD. METHOD : Thirty-seven children with ADHD were compared with thirty-seven controls using a translated and adapted version of the "Sensory Profile" answered by the parents/caregivers. For the ADHD group, Sensory Profile scores were correlated to behavioural symptoms assessed using the Child Behaviour Check List (CBCL and the Behavioural Teacher Rating Scale (EACI-P. The statistical analyses were conducted using the Mann Whitney test and Pearson correlation coefficients. RESULTS : Children with ADHD showed significant impairments compared to the control group in sensory processing and modulation, as well as in behavioural and emotional responses as observed in 11 out of 14 sections and 6 out of 9 factors. Differences in all Sensory Profile response patterns were also observed between the two groups of children. Sensory Profile scores showed a moderately negative correlation with CBCL and EACI-P scores in the ADHD group. CONCLUSION : These results indicate that children with ADHD may present sensory processing impairments, which may contribute to the inappropriate behavioural and learning responses displayed by children with ADHD. It also suggests the importance of understanding the sensory processing difficulties and its possible contribution to the ADHD symptomatology.

  1. Sensory processing abilities of children with ADHD.

    Science.gov (United States)

    Shimizu, Vitoria T; Bueno, Orlando F A; Miranda, Mônica C

    2014-01-01

    To assess and compare the sensory processing abilities of children with Attention Deficit/Hyperactivity Disorder (ADHD) and children without disabilities, and to analyze the relationship between sensory processing difficulties and behavioural symptoms presented by children with ADHD. Thirty-seven children with ADHD were compared with thirty-seven controls using a translated and adapted version of the "Sensory Profile" answered by the parents/caregivers. For the ADHD group, Sensory Profile scores were correlated to behavioural symptoms assessed using the Child Behaviour Check List (CBCL) and the Behavioural Teacher Rating Scale (EACI-P). The statistical analyses were conducted using the Mann Whitney test and Pearson correlation coefficients. Children with ADHD showed significant impairments compared to the control group in sensory processing and modulation, as well as in behavioural and emotional responses as observed in 11 out of 14 sections and 6 out of 9 factors. Differences in all Sensory Profile response patterns were also observed between the two groups of children. Sensory Profile scores showed a moderately negative correlation with CBCL and EACI-P scores in the ADHD group. These results indicate that children with ADHD may present sensory processing impairments, which may contribute to the inappropriate behavioural and learning responses displayed by children with ADHD. It also suggests the importance of understanding the sensory processing difficulties and its possible contribution to the ADHD symptomatology.

  2. Sensorial evaluation of irradiated mangoes

    International Nuclear Information System (INIS)

    Broisler, Paula Olhe; Cruz, Juliana Nunes da; Sabato, Susy Frey

    2007-01-01

    Mango (Mangifera indica L.) is a tropical fruit of great economical relevance in the world, mainly for tropical countries like Brazil. It consists in the second tropical fruit more important grown in the world. On the other hand it is a very perishable fruit and its delivery to distant points is restricted due to short shelf life at environmental temperature. Food irradiation process is applied to fruits for their preservation, once it promotes disinfestation and even maturation retard, among other mechanisms. The Brazilian legislation permits the food irradiation and does not restrict the doses to be delivered. In order to verify eventual changes, sensorial evaluation is very important to study how irradiation affects the quality of the fruit and its acceptability. Mangoes were irradiated in a Cobalto-60 source, from the Radiation Technology Center, CTR, of IPEN/CNEN-SP at doses 0,5 kGy e 0,75 kGy. The sensorial evaluation was measured through Acceptance Test where irradiated samples were offered together with control sample to the tasters who answered their perception through hedonic scale. The parameters Color, Odor, Flavor and Texture were analyzed. Statistical analysis showed that only Odor parameter was different from control (sample irradiated at 0.5 kGy). Few tasters indicated that irradiated mangoes had fewer odors in relation to non-irradiated samples. (author)

  3. Do Birds Experience Sensory Pleasure?

    Directory of Open Access Journals (Sweden)

    Michel Cabanac

    2009-01-01

    Full Text Available To answer the question of whether sensory pleasure exists in birds, I trained an African-gray parrot (Psittacus erythacus named Aristote to speak. Stage 1 of the study consisted in gaining Aristote's affection. In Stage 2 Aristote was taught to speak, following Irene Pepperberg's triangular method: another person and I would talk together and look at Aristote only when it used understandable French words. Thus Aristote learned to say a few words for obtaining toys or getting my attention; e.g. “donne bouchon” (give cork or “donne gratte” (give scratch/tickle, with the appropriate reward. In Stage 3, the word bon (good was added to the short list of words used by Aristote. I said “bon” when giving Aristote the stimuli it requested and which would, presumably, be pleasurable; e.g. gratte bon. Aristote started to use short sentences such as “yaourt bon” (good yogurt. Eventually, Aristote transferred the word bon to new stimuli such as raisin (grape, an association I myself had never made. Such a use of vocabulary, and moreover its transfer, likely shows that this bird experienced sensory pleasure.

  4. SPECIFIC LONG-TERM MEMORY TRACES IN PRIMARY AUDITORY CORTEX

    Science.gov (United States)

    Weinberger, Norman M.

    2013-01-01

    Learning and memory involve the storage of specific sensory experiences. However, until recently the idea that the primary sensory cortices could store specific memory traces had received little attention. Converging evidence obtained using techniques from sensory physiology and the neurobiology of learning and memory supports the idea that the primary auditory cortex acquires and retains specific memory traces about the behavioural significance of selected sounds. The cholinergic system of the nucleus basalis, when properly engaged, is sufficient to induce both specific memory traces and specific behavioural memory. A contemporary view of the primary auditory cortex should incorporate its mnemonic and other cognitive functions. PMID:15034553

  5. The sensory timecourses associated with conscious visual item memory and source memory.

    Science.gov (United States)

    Thakral, Preston P; Slotnick, Scott D

    2015-09-01

    Previous event-related potential (ERP) findings have suggested that during visual item and source memory, nonconscious and conscious sensory (occipital-temporal) activity onsets may be restricted to early (0-800 ms) and late (800-1600 ms) temporal epochs, respectively. In an ERP experiment, we tested this hypothesis by separately assessing whether the onset of conscious sensory activity was restricted to the late epoch during source (location) memory and item (shape) memory. We found that conscious sensory activity had a late (>800 ms) onset during source memory and an early (memory. In a follow-up fMRI experiment, conscious sensory activity was localized to BA17, BA18, and BA19. Of primary importance, the distinct source memory and item memory ERP onsets contradict the hypothesis that there is a fixed temporal boundary separating nonconscious and conscious processing during all forms of visual conscious retrieval. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans.

    Science.gov (United States)

    Mukhopadhyay, Saikat; Lu, Yun; Shaham, Shai; Sengupta, Piali

    2008-05-01

    Nonmotile primary cilia are sensory organelles composed of a microtubular axoneme and a surrounding membrane sheath that houses signaling molecules. Optimal cellular function requires the precise regulation of axoneme assembly, membrane biogenesis, and signaling protein targeting and localization via as yet poorly understood mechanisms. Here, we show that sensory signaling is required to maintain the architecture of the specialized AWB olfactory neuron cilia in C. elegans. Decreased sensory signaling results in alteration of axoneme length and expansion of a membraneous structure, thereby altering the topological distribution of a subset of ciliary transmembrane signaling molecules. Signaling-regulated alteration of ciliary structures can be bypassed by modulation of intracellular cGMP or calcium levels and requires kinesin-II-driven intraflagellar transport (IFT), as well as BBS- and RAB8-related proteins. Our results suggest that compensatory mechanisms in response to altered levels of sensory activity modulate AWB cilia architecture, revealing remarkable plasticity in the regulation of cilia structure.

  7. Sensory-evoked perturbations of locomotor activity by sparse sensory input: a computational study

    OpenAIRE

    Bui, Tuan V.; Brownstone, Robert M.

    2015-01-01

    Sensory inputs from muscle, cutaneous, and joint afferents project to the spinal cord, where they are able to affect ongoing locomotor activity. Activation of sensory input can initiate or prolong bouts of locomotor activity depending on the identity of the sensory afferent activated and the timing of the activation within the locomotor cycle. However, the mechanisms by which afferent activity modifies locomotor rhythm and the distribution of sensory afferents to the spinal locomotor networks...

  8. Sensory Sensitivities and Performance on Sensory Perceptual Tasks in High-Functioning Individuals with Autism

    Science.gov (United States)

    Minshew, Nancy J.; Hobson, Jessica A.

    2008-01-01

    Most reports of sensory symptoms in autism are second hand or observational, and there is little evidence of a neurological basis. Sixty individuals with high-functioning autism and 61 matched typical participants were administered a sensory questionnaire and neuropsychological tests of elementary and higher cortical sensory perception. Thirty-two…

  9. Sensory-evoked perturbations of locomotor activity by sparse sensory input: a computational study.

    Science.gov (United States)

    Bui, Tuan V; Brownstone, Robert M

    2015-04-01

    Sensory inputs from muscle, cutaneous, and joint afferents project to the spinal cord, where they are able to affect ongoing locomotor activity. Activation of sensory input can initiate or prolong bouts of locomotor activity depending on the identity of the sensory afferent activated and the timing of the activation within the locomotor cycle. However, the mechanisms by which afferent activity modifies locomotor rhythm and the distribution of sensory afferents to the spinal locomotor networks have not been determined. Considering the many sources of sensory inputs to the spinal cord, determining this distribution would provide insights into how sensory inputs are integrated to adjust ongoing locomotor activity. We asked whether a sparsely distributed set of sensory inputs could modify ongoing locomotor activity. To address this question, several computational models of locomotor central pattern generators (CPGs) that were mechanistically diverse and generated locomotor-like rhythmic activity were developed. We show that sensory inputs restricted to a small subset of the network neurons can perturb locomotor activity in the same manner as seen experimentally. Furthermore, we show that an architecture with sparse sensory input improves the capacity to gate sensory information by selectively modulating sensory channels. These data demonstrate that sensory input to rhythm-generating networks need not be extensively distributed. Copyright © 2015 the American Physiological Society.

  10. [Effects of morphine, butorphanol and levomethadone in different doses on thermal nociceptive thresholds in horses].

    Science.gov (United States)

    Dönselmann Im Sande, Paula; Hopster, Klaus; Kästner, Sabine

    2017-04-19

    Various opioids are available for use in equine medicine. Studies directly comparing their analgesic effects and side effects are rare. Therefore, the aim of this study was to compare the antinociceptive effect and the duration of analgesia of two different doses of morphine, butorphanol and levomethadone in horses. Eight adult, healthy horses were used for this randomized, placebo-controlled, blinded cross-over trail. Each horse received placebo (P = 0.9% saline) and morphine (M 0.1  = 0.1 mg/kg; M 0.2  = 0.2 mg/kg), butorphanol (B 0.1  = 0.1 mg/kg; B 0.2  = 0.2 mg/kg) and levomethadone (L 0.1  = 0.1 mg/kg; L 0.2  = 0.2 mg/kg) in a low and a high dose and with a wash-out period of 14 days. Thermal thresholds were determined by incremental contact heat applied to the skin at the withers. Single stimulations were performed 15 minutes prior and 10, 30, 60, 90, 120, 180, 240, 300, 360, 420, 540 and 1350 minutes after treatment. Threshold values, gastrointestinal auscultation score and horses' behavior were recorded. Data were analyzed with analysis of variance for repeated measurements (p thermal thresholds did not reach significance. Thermal threshold increased significantly in the groups M 0.2 , B 0.1 , B 0.2 , L 0.1 and L 0.2 for 240, 90, 90, 60 and 300 minutes, respectively. Behavioural changes, increased locomotion and decreased bowel sounds as well as delayed time until defecation were noticed in all groups. Levomethadone induced a dose-dependent increase and prolongation of analgesia, whereas with butorphanol there was no difference between dosages regarding duration and intensity of analgesia. Morphine provided detectable analgesia only in the high dose of 0.2 mg/kg. Levomethadone and morphine in the low dose (0.1 mg/kg) produced only minor and short lived anti-nociception and further studies are necessary to give a profound dose recommendation for the use of these drugs in horses.

  11. Cross-modal plasticity in sensory deprived animal models: From the thalamocortical development point of view.

    Science.gov (United States)

    Mezzera, Cecilia; López-Bendito, Guillermina

    2016-09-01

    Over recent decades, our understanding of the plasticity of the central nervous system has expanded enormously. Accordingly, it is now widely accepted that the brain can adapt to changes by reorganizing its circuitry, both in response to external stimuli and experience, as well as through intrinsic mechanisms. A clear example of this is the activation of a deprived sensory area and the expansion of spared sensory cortical regions in individuals who suffered peripheral sensory loss. Despite the efforts to understand these neuroplastic changes, the mechanisms underlying such adaptive remodeling remains poorly understood. Progress in understanding these events may be hindered by the highly varied data obtained from the distinct experimental paradigms analyzed, which include different animal models and neuronal systems, as well as studies into the onset of sensory loss. Here, we will establish the current state-of-the-art describing the principal observations made according to the time of sensory deprivation with respect to the development of the thalamocortical connectivity. We will review the experimental data obtained from animal models where sensory deprivation has been induced either before or after thalamocortical axons reach and invade their target cortical areas. The anatomical and functional effects of sensory loss on the primary sensory areas of the cortex will be presented. Indeed, we consider that the comparative approach of this review is a necessary step in order to help deciphering the processes that underlie sensory neuroplasticity, for which studies in animal models have been indispensable. Understanding these mechanisms will then help to develop restorative strategies and prostheses that will overcome the functional loss. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Cilia - The sensory antennae in the eye.

    Science.gov (United States)

    May-Simera, Helen; Nagel-Wolfrum, Kerstin; Wolfrum, Uwe

    2017-09-01

    Cilia are hair-like projections found on almost all cells in the human body. Originally believed to function merely in motility, the function of solitary non-motile (primary) cilia was long overlooked. Recent research has demonstrated that primary cilia function as signalling hubs that sense environmental cues and are pivotal for organ development and function, tissue hoemoestasis, and maintenance of human health. Cilia share a common anatomy and their diverse functional features are achieved by evolutionarily conserved functional modules, organized into sub-compartments. Defects in these functional modules are responsible for a rapidly growing list of human diseases collectively termed ciliopathies. Ocular pathogenesis is common in virtually all classes of syndromic ciliopathies, and disruptions in cilia genes have been found to be causative in a growing number of non-syndromic retinal dystrophies. This review will address what is currently known about cilia contribution to visual function. We will focus on the molecular and cellular functions of ciliary proteins and their role in the photoreceptor sensory cilia and their visual phenotypes. We also highlight other ciliated cell types in tissues of the eye (e.g. lens, RPE and Müller glia cells) discussing their possible contribution to disease progression. Progress in basic research on the cilia function in the eye is paving the way for therapeutic options for retinal ciliopathies. In the final section we describe the latest advancements in gene therapy, read-through of non-sense mutations and stem cell therapy, all being adopted to treat cilia dysfunction in the retina. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Sensory feedback for upper limb prostheses.

    Science.gov (United States)

    Hsiao, Steven S; Fettiplace, Michael; Darbandi, Bejan

    2011-01-01

    In this chapter, we discuss the neurophysiological basis of how to provide sensory feedback to users with an upper limb prosthesis and discuss some of the theoretical issues that need to be considered when directly stimulating neurons in the somatosensory system. We focus on technologies that are currently available and discuss approaches that are most likely to succeed in providing natural perception from the artificial hand to the user. First, we discuss the advantages and disadvantages of providing feedback by stimulating directly the remaining afferents that originally innervated the arm and hand. In particular, we pay close attention to the normal functional roles that the peripheral afferents play in perception. What are the consequences and implications of stimulating these afferents? We then discuss whether it is reasonable to stimulate neurons in the ascending pathways that carry the information from the afferents to the cortex or directly in neurons in the primary somatosensory cortex. We show that for some modalities there are advantages for stimulating in the spinal cord, while for others it is advantageous to stimulate directly in the somatosensory cortex. Finally, we discuss results from a current experiment in which we used electrical stimuli in primary somatosensory cortex to restore the percept of the intensity of a mechanical probe indented into the hand. The results suggest that the simple percept of stimulus intensity can be provided to the animal from a single finger using four electrodes. We propose that significantly more electrodes will be needed to reproduce more complex aspects of tactile perception. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Anti-nociceptive effect of patchouli alcohol: Involving attenuation of cyclooxygenase 2 and modulation of mu-opioid receptor.

    Science.gov (United States)

    Yu, Xuan; Wang, Xin-Pei; Yan, Xiao-Jin; Jiang, Jing-Fei; Lei, Fan; Xing, Dong-Ming; Guo, Yue-Ying; Du, Li-Jun

    2017-08-09

    To explore the anti-nociceptive effect of patchouli alcohol (PA), the essential oil isolated from Pogostemon cablin (Blanco) Bent, and determine the mechanism in molecular levels. The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to confifirm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor (MOR). Cyclooxygenase 2 (COX2) and MOR of mouse brain were expressed for determination of PA's target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA. PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution (Peffect of PA. A decrease in the intracellular calcium level (Peffect. PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect. Both COX2 and MOR are involved in the mechanism of PA's anti-nociceptive effect, and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA's effect on MOR.

  15. Central Sensitization of Mechanical Nociceptive Pathways Is Associated with a Long-Lasting Increase of Pinprick-Evoked Brain Potentials.

    Science.gov (United States)

    van den Broeke, Emanuel N; Lambert, Julien; Huang, Gan; Mouraux, André

    2016-01-01

    Intense or sustained nociceptor activation, occurring, for example, after skin injury, can induce "central sensitization," i.e., an increased responsiveness of nociceptive neurons in the central nervous system. A hallmark of central sensitization is increased mechanical pinprick sensitivity in the area surrounding the injured skin. The aim of the present study was to identify changes in brain activity related to this increased pinprick sensitivity. In 20 healthy volunteers, increased pinprick sensitivity was induced using high frequency electrical stimulation of the forearm skin (HFS). Mechanical pinprick stimulation (64 and 90 mN) was used to elicit event-related brain potentials (ERPs). The recordings were performed before, 20 min after and 45 min after applying HFS. The contralateral non-sensitized arm served as control. Pinprick stimulation of 64 mN, but not 90 mN, applied in the area of increased pinprick sensitivity elicited a significant increase of a late-latency positive wave, between 300 and 1100 ms after stimulus onset and was maximal at midline posterior electrodes. Most importantly, this increase in EEG activity followed the time course of the increase in pinprick perception, both being present 20 and 45 min after applying HFS. Our results show that the central sensitization of mechanical nociceptive pathways, manifested behaviorally as increased pinprick sensitivity, is associated with a long-lasting increase in pinprick-evoked brain potentials provided that a 64 mN stimulation intensity is used.

  16. Automated single-trial assessment of laser-evoked potentials as an objective functional diagnostic tool for the nociceptive system.

    Science.gov (United States)

    Hatem, S M; Hu, L; Ragé, M; Gierasimowicz, A; Plaghki, L; Bouhassira, D; Attal, N; Iannetti, G D; Mouraux, A

    2012-12-01

    To assess the clinical usefulness of an automated analysis of event-related potentials (ERPs). Nociceptive laser-evoked potentials (LEPs) and non-nociceptive somatosensory electrically-evoked potentials (SEPs) were recorded in 37 patients with syringomyelia and 21 controls. LEP and SEP peak amplitudes and latencies were estimated using a single-trial automated approach based on time-frequency wavelet filtering and multiple linear regression, as well as a conventional approach based on visual inspection. The amplitudes and latencies of normal and abnormal LEP and SEP peaks were identified reliably using both approaches, with similar sensitivity and specificity. Because the automated approach provided an unbiased solution to account for average waveforms where no ERP could be identified visually, it revealed significant differences between patients and controls that were not revealed using the visual approach. The automated analysis of ERPs characterized reliably and objectively LEP and SEP waveforms in patients. The automated single-trial analysis can be used to characterize normal and abnormal ERPs with a similar sensitivity and specificity as visual inspection. While this does not justify its use in a routine clinical setting, the technique could be useful to avoid observer-dependent biases in clinical research. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Effect of plantar subcutaneous administration of bergamot essential oil and linalool on formalin-induced nociceptive behavior in mice.

    Science.gov (United States)

    Katsuyama, Soh; Otowa, Akira; Kamio, Satomi; Sato, Kazuma; Yagi, To