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Sample records for descending inhibitory pain

  1. The plasticity of descending controls in pain: translational probing.

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    Bannister, Kirsty; Dickenson, A H

    2017-07-01

    Descending controls, comprising pathways that originate in midbrain and brainstem regions and project onto the spinal cord, have long been recognised as key links in the multiple neural networks that interact to produce the overall pain experience. There is clear evidence from preclinical and clinical studies that both peripheral and central sensitisation play important roles in determining the level of pain perceived. Much emphasis has been put on spinal cord mechanisms in central excitability, but it is now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems. One pain can inhibit another. In this respect diffuse noxious inhibitory controls (DNIC) are a unique form of endogenous descending inhibitory pathway since they can be easily evoked and quantified in animals and man. The spinal pharmacology of pathways that subserve DNIC are complicated; in the normal situation these descending controls produce a final inhibitory effect through the actions of noradrenaline at spinal α 2 -adrenoceptors, although serotonin, acting on facilitatory spinal 5-HT 3 receptors, influences the final expression of DNIC also. These descending pathways are altered in neuropathy and the effects of excess serotonin may now become inhibitory through activation of spinal 5-HT 7 receptors. Conditioned pain modulation (CPM) is the human counterpart of DNIC and requires a descending control also. Back and forward translational studies between DNIC and CPM, gauged between bench and bedside, are key for the development of analgesic therapies that exploit descending noradrenergic and serotonergic control pathways. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  2. Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations.

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    Bannister, Kirsty; Patel, Ryan; Goncalves, Leonor; Townson, Louisa; Dickenson, Anthony H

    2015-09-01

    Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control rats but abolished after neuropathy. α2 adrenoceptor mechanisms underlie DNIC because the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist ondansetron or by enhancing norepinephrine modulation through the use of reboxetine (a norepinephrine reuptake inhibitor, NRI) or tapentadol (μ-opioid receptor agonist and NRI). Additionally, ondansetron enhanced DNIC in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of tapentadol and duloxetine (a serotonin, NRI) in patients. We suggest that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.

  3. Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis

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    Xiao-Cui Yuan

    2018-04-01

    Full Text Available Knee osteoarthritis (KOA is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA. EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

  4. The importance of the descending monoamine system for the pain experience and its treatment

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    Dickenson, Anthony H

    2009-01-01

    Brainstem and midbrain areas engage descending facilitatory and inhibitory neurones to potentiate or suppress the passage of sensory inputs from spinal loci to the brain. The balance between descending controls, both excitatory and inhibitory, can be altered in various pain states and can critically determine the efficacy of certain analgesic drugs. There is good evidence for a prominent α2 adrenoceptor-mediated inhibitory system and for 5-HT3 receptor-mediated excitatory control of spinal cord activity that originates in supraspinal areas. Given the multiple roles of these transmitters in pain and functions such as sleep, depression, and anxiety, the link between spinal and supraspinal processing of noxious inputs (via the monoamine transmitters) could be pivotal for linking the sensory and affective components of pain and their common co-morbidities, and also may potentially explain differences in pain scores and treatment outcomes in the patient population. PMID:20948695

  5. Selective deficiencies in descending inhibitory modulation in neuropathic rats: implications for enhancing noradrenergic tone.

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    Patel, Ryan; Qu, Chaoling; Xie, Jennifer Y; Porreca, Frank; Dickenson, Anthony H

    2018-05-31

    Pontine noradrenergic neurones form part of a descending inhibitory system that influences spinal nociceptive processing. Weak or absent descending inhibition is a common feature of chronic pain patients. We examined the extent to which the descending noradrenergic system is tonically active, how control of spinal neuronal excitability is integrated into thalamic relays within sensory-discriminative projection pathways, and how this inhibitory control is altered after nerve injury. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus (VPL). In sham rats, spinal block of α2-adrenoceptors with atipamezole resulted in enhanced stimulus-evoked and spontaneous firing in the VPL, and produced conditioned place avoidance. However, in SNL rats these conditioned avoidance behaviours were absent. Furthermore, inhibitory control of evoked neuronal responses was lost but spinal atipamezole markedly increased spontaneous firing. Augmenting spinal noradrenergic tone in neuropathic rats with reboxetine, a selective noradrenergic reuptake inhibitor, modestly reinstated inhibitory control of evoked responses in the VPL but had no effect on spontaneous firing. In contrast, clonidine, an α2 agonist, inhibited both evoked and spontaneous firing, and exhibited increased potency in SNL rats compared to sham controls. These data suggest descending noradrenergic inhibitory pathways are tonically active in sham rats. Moreover, in neuropathic states descending inhibitory control is diminished, but not completely absent, and distinguishes between spontaneous and evoked neuronal activity. These observations may have implications for how analgesics targeting the noradrenergic system provide relief.

  6. Self-reported Physical Activity Predicts Pain Inhibitory and Facilitatory Function

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    Naugle, Kelly M.; Riley, Joseph L.

    2013-01-01

    Considerable evidence suggests regular physical activity can reduce chronic pain symptoms. Dysfunction of endogenous facilitatory and inhibitory systems has been implicated in multiple chronic pain conditions. However, few studies have investigated the relationship between levels of physical activity and descending pain modulatory function. Purpose This study’s purpose was to determine whether self-reported levels of physical activity in healthy adults predicted 1) pain sensitivity to heat and cold stimuli, 2) pain facilitatory function as tested by temporal summation of pain (TS), and 3) pain inhibitory function as tested by conditioned pain modulation (CPM) and offset analgesia. Methods Forty-eight healthy adults (age range 18–76) completed the International Physical Activity Questionnaire (IPAQ) and the following pain tests: heat pain thresholds (HPT), heat pain suprathresholds, cold pressor pain (CPP), temporal summation of heat pain, conditioned pain modulation, and offset analgesia. The IPAQ measured levels of walking, moderate, vigorous and total physical activity over the past seven days. Hierarchical linear regressions were conducted to determine the relationship between each pain test and self-reported levels of physical activity, while controlling for age, sex and psychological variables. Results Self-reported total and vigorous physical activity predicted TS and CPM (p’s pain and greater CPM. The IPAQ measures did not predict any of the other pain measures. Conclusion Thus, these results suggest that healthy older and younger adults who self-report greater levels of vigorous and total physical activity exhibit enhanced descending pain modulatory function. Improved descending pain modulation may be a mechanism through which exercise reduces or prevents chronic pain symptoms. PMID:23899890

  7. The Role of Cannabinoid Receptors in the Descending Modulation of Pain

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    Francesco Rossi

    2010-08-01

    Full Text Available The endogenous antinociceptive descending pathway represents a circuitry of the supraspinal central nervous system whose task is to counteract pain. It includes the periaqueductal grey (PAG-rostral ventromedial medulla (RVM-dorsal horn (DH axis, which is the best characterized pain modulation system through which pain is endogenously inhibited. Thus, an alternative rational strategy for silencing pain is the activation of this anatomical substrate. Evidence of the involvement of cannabinoid receptors (CB in the supraspinal modulation of pain can be found in several studies in which intra-cerebral microinjections of cannabinoid ligands or positive modulators have proved to be analgesic in different pain models, whereas cannabinoid receptor antagonists or antisense nucleotides towards CB1 receptors have facilitated pain. Like opioids, cannabinoids produce centrally-mediated analgesia by activating a descending pathway which includes PAG and its projection to downstream RVM neurons, which in turn send inhibitory projections to the dorsal horn of the spinal cord. Indeed, several studies underline a supraspinal regulation of cannabinoids on g-aminobutyric acid (GABA and glutamate release which inhibit and enhance the antinociceptive descending pathway, respectively. Cannabinoid receptor activation expressed on presynaptic GABAergic terminals reduces the probability of neurotransmitter release thus dis-inhibiting the PAG-RVM-dorsal horn antinociceptive pathway. Cannabinoids seem to increase glutamate release (maybe as consequence of GABA decrease and to require glutamate receptor activation to induce antinociception. The consequent outcome is behavioral analgesia, which is reproduced in several pain conditions, from acute to chronic pain models such as inflammatory and neuropathic pain. Taken together these findings would suggest that supraspinal cannabinoid receptors have broad applications, from pain control to closely related central nervous system

  8. Effect of ketamine on endogenous pain modulation in healthy volunteers.

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    Niesters, Marieke; Dahan, Albert; Swartjes, Maarten; Noppers, Ingeborg; Fillingim, Roger B; Aarts, Leon; Sarton, Elise Y

    2011-03-01

    Inhibitory and facilitatory descending pathways, originating at higher central nervous system sites, modulate activity of dorsal horn nociceptive neurons, and thereby influence pain perception. Dysfunction of inhibitory pain pathways or a shift in the balance between pain facilitation and pain inhibition has been associated with the development of chronic pain. The N-methyl-d-aspartate receptor antagonist ketamine has a prolonged analgesic effect in chronic pain patients. This effect is due to desensitization of sensitized N-methyl-d-aspartate receptors. Additionally, ketamine may modulate or enhance endogenous inhibitory control of pain perception. Diffuse noxious inhibitory control (DNIC) and offset analgesia (OA) are 2 mechanisms involved in descending inhibition. The present study investigates the effect of a ketamine infusion on subsequent DNIC and OA responses to determine whether ketamine has an influence on descending pain control. Ten healthy subjects (4 men/6 women) received a 1-hour placebo or S(+)-ketamine (40mg per 70kg) infusion on 2 separate occasions in random order. Upon the termination of the infusion, DNIC and OA responses were obtained. After placebo treatment, significant descending inhibition of pain responses was present for DNIC and OA. In contrast, after ketamine infusion, no DNIC was observed, but rather a significant facilitatory pain response (Ppain inhibition and pain facilitation was shifted by ketamine towards pain facilitation. The absence of an effect of ketamine on OA indicates differences in the mechanisms and neurotransmitter influences between OA and DNIC. Diffuse noxious inhibitory control responses following a 1-hour low-dose ketamine treatment displayed facilitation of pain in response to experimental noxious thermal stimulation. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  9. Descending pain modulation in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

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    Chakiath, Rosemary J; Siddall, Philip J; Kellow, John E; Hush, Julia M; Jones, Mike P; Marcuzzi, Anna; Wrigley, Paul J

    2015-12-10

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. While abdominal pain is a dominant symptom of IBS, many sufferers also report widespread hypersensitivity and present with other chronic pain conditions. The presence of widespread hypersensitivity and extra-intestinal pain conditions suggests central nervous dysfunction. While central nervous system dysfunction may involve the spinal cord (central sensitisation) and brain, this review will focus on one brain mechanism, descending pain modulation. We will conduct a comprehensive search for the articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2015, that report on any aspect of descending pain modulation in irritable bowel syndrome. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and, if possible, a meta-analysis will be carried out. The systematic review outlined in this protocol aims to summarise current knowledge regarding descending pain modulation in IBS. PROSPERO CRD42015024284.

  10. What do monoamines do in pain modulation?

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    Bannister, Kirsty; Dickenson, Anthony H

    2016-06-01

    Here, we give a topical overview of the ways in which brain processing can alter spinal pain transmission through descending control pathways, and how these change in pain states. We link preclinical findings on the transmitter systems involved and discuss how the monoamines, noradrenaline, 5-hydroxytryptamine (5-HT), and dopamine, can interact through inhibitory and excitatory pathways. Descending pathways control sensory events and the actions of the neurotransmitters noradrenaline and 5-HT in the dorsal horn of the spinal cord are chiefly implicated in nociception or antinociception according to the receptor that is activated. Abnormalities in descending controls effect central pain processing. Following nerve injury a noradrenaline-mediated control of spinal excitability is lost, whereas its restoration reduces neuropathic hypersensitivity. The story with 5-HT remains more complex because of the myriad of receptors that it can act upon; however the most recent findings support that facilitations may dominate over inhibitions. The monoaminergic system can be manipulated to great effect in the clinic resulting in improved treatment outcomes and is the basis for the actions of the antidepressant drugs in pain. Looking to the future, prediction of treatment responses will possible by monitoring a form of inhibitory descending control for optimized pain relief.

  11. Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia

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    Ge, H-Y; Nie, Hongling; Graven-Nielsen, Thomas

    2012-01-01

    OBJECTIVE: Sustained isometric muscle contraction (fatiguing contraction) recruits segmental and/or extrasegmental descending inhibition in healthy subjects but not in fibromyalgia (FM). We hypothesized that fatiguing contraction may shift descending pain modulation from inhibition towards...

  12. Attenuation of Experimental Pain by Vibro-Tactile Stimulation in Patients with Chronic Local or Widespread Musculoskeletal Pain

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    Staud, Roland; Robinson, Michael E.; Goldman, Casey T.; Price, Donald D.

    2011-01-01

    Patients with chronic pain syndromes, like fibromyalgia (FM) complain of widespread pain and tenderness, as well as non-refreshing sleep, cognitive dysfunction, and negative mood. Several lines of evidence implicate abnormalities of central pain processing as contributors for chronic pain, including dysfunctional descending pain inhibition. One form of endogenous pain inhibition, diffuse noxious inhibitory controls (DNIC), has been found to be abnormal in some chronic pain patients and eviden...

  13. Pain and neuroplasticity

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    Sabine Sator-Katzenschlager, MD.

    2014-07-01

    However, the cerebral processing of hyperalgesia and allodynia is still controversially discussed. In recent years, neuroimaging methods (functional magnetic resonance imaging, fMRI; magnetoencephalography, MEG; positron emission tomography, PET have provided new insightsinto the aberrant cerebral processing of neuropathic pain. Thepresent paper reviews different cerebral mechanisms contributing to chronicity processes in neuropathic pain syndromes. These mechanisms include reorganisation of cortical somatotopic maps in sensory or motor areas (highly relevant for phantom limb pain and CRPS, increased activity in primary nociceptive areas, recruitment of new cortical areas usually not activated by nociceptive stimuli and aberrant activity in brain areas normally involved in descending inhibitory pain networks. Moreover, there is evidence from PET studies for changes of excitatory and inhibitory transmitter systems. Finally, advanced methods of structural brain imaging (voxel-based morphometry, VBM show significant structural changes suggesting that chronic pain syndromes may be associated with neurodegeneration.

  14. Sex Differences in How Erotic and Painful Stimuli Impair Inhibitory Control

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    Yu, Jiaxin; Hung, Daisy L.; Tseng, Philip; Tzeng, Ovid J. L.; Muggleton, Neil G.; Juan, Chi-Hung

    2012-01-01

    Witnessing emotional events such as arousal or pain may impair ongoing cognitive processes such as inhibitory control. We found that this may be true only half of the time. Erotic images and painful video clips were shown to men and women shortly before a stop signal task, which measures cognitive inhibitory control. These stimuli impaired…

  15. Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

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    Asante, Curtis O.; Dickenson, Anthony H.

    2010-01-01

    We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

  16. Descending serotonergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthritic pain

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    Dolphin Annette C

    2009-08-01

    Full Text Available Abstract Background Descending facilitation, from the brainstem, promotes spinal neuronal hyperexcitability and behavioural hypersensitivity in many chronic pain states. We have previously demonstrated enhanced descending facilitation onto dorsal horn neurones in a neuropathic pain model, and shown this to enable the analgesic effectiveness of gabapentin. Here we have tested if this hypothesis applies to other pain states by using a combination of approaches in a rat model of osteoarthritis (OA to ascertain if 1 a role for descending 5HT mediated facilitation exists, and 2 if pregabalin (a newer analogue of gabapentin is an effective antinociceptive agent in this model. Further, quantitative-PCR experiments were undertaken to analyse the α2δ-1 and 5-HT3A subunit mRNA levels in L3–6 DRG in order to assess whether changes in these molecular substrates have a bearing on the pharmacological effects of ondansetron and pregabalin in OA. Results Osteoarthritis was induced via intra-articular injection of monosodium iodoacetate (MIA into the knee joint. Control animals were injected with 0.9% saline. Two weeks later in vivo electrophysiology was performed, comparing the effects of spinal ondansetron (10–100 μg/50 μl or systemic pregabalin (0.3 – 10 mg/kg on evoked responses of dorsal horn neurones to electrical, mechanical and thermal stimuli in MIA or control rats. In MIA rats, ondansetron significantly inhibited the evoked responses to both innocuous and noxious natural evoked neuronal responses, whereas only inhibition of noxious evoked responses was seen in controls. Pregabalin significantly inhibited neuronal responses in the MIA rats only; this effect was blocked by a pre-administration of spinal ondansetron. Analysis of α2δ-1 and 5-HT3A subunit mRNA levels in L3–6 DRG revealed a significant increase in α2δ-1 levels in ipsilateral L3&4 DRG in MIA rats. 5-HT3A subunit mRNA levels were unchanged. Conclusion These data suggest

  17. Electroacupuncture Inhibits the Activation of p38MAPK in the Central Descending Facilitatory Pathway in Rats with Inflammatory Pain

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    Man-Li Hu

    2017-01-01

    Full Text Available The mitogen-activated protein kinases (MAPKs, especially p38MAPK, play a pivotal role in chronic pain. Electroacupuncture (EA relieves inflammatory pain underlying the descending pathway, that is, the periaqueductal gray (PAG, the rostral ventromedial medulla (RVM, and the spinal cord dorsal horn (SCDH. However, whether EA antagonizes inflammatory pain through regulation of p38MAPK in this descending facilitatory pathway is unclear. Complete Freund’s adjuvant (CFA was injected into the hind paw of rats to establish inflammatory pain model. EA was administrated for 30 min at Zusanli and Kunlun acupoints at 0.5, 24.5, 48.5, and 72.5 h, respectively. The paw withdrawal threshold (PWT, paw edema, and Phosphor-p38MAPK-Immunoreactivity (p-p38MAPK-IR cells were measured before (0 h and at 1, 3, 5, 7, 25, and 73 h after CFA or saline injection. EA increased PWT at 1, 3, 25, and 73 h and inhibited paw edema at 25 and 73 h after CFA injection. Moreover, the increasing number of p-p38MAPK-IR cells which was induced by CFA was suppressed by EA stimulation in PAG and RVM at 3 and 5 h and in SCDH at 5, 7, 25, and 73 h. These results suggest that EA suppresses inflammation-induced hyperalgesia probably through inhibiting p38MAPK activation in the descending facilitatory pathway.

  18. Dysregulation of the descending pain system in temporomandibular disorders revealed by low-frequency sensory transcutaneous electrical nerve stimulation: a pupillometric study.

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    Annalisa Monaco

    Full Text Available Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS is dysregulated in patients suffering from temporomandibular disorders (TMDs, suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG is involved in the descending modulation of defensive behavior and pain through μ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of μ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation and long after (recovery period sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired

  19. Perinatal maternal stress and serotonin signaling: effects on pain sensitivity in offspring.

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    Knaepen, Liesbeth; Pawluski, Jodi L; Patijn, Jacob; van Kleef, Maarten; Tibboel, Dick; Joosten, Elbert A

    2014-07-01

    It has been estimated that 20% of pregnant women are facing perinatal stress and depression. Perinatal maternal stress has been shown to increase pain sensitivity in offspring. For the treatment of their depressive symptoms, pregnant women are frequently prescribed selective serotonin reuptake inhibitors (SSRIs). Since the descending pain inhibitory circuit matures perinatally, perinatal SSRI exposure has been shown to affect pain sensitivity in offspring. In the present review, we summarize experimental and clinical evidence for the effect of perinatal maternal stress and SSRI exposure on pain sensitivity in offspring. Both experimental and clinical studies show the effect of perinatal maternal stress on regulation of the hypothalamic-pituitary-adrenal (HPA) system and the serotonin pain inhibitory system. Alterations in these two systems likely underlie long-term alterations in the development of pain sensitivity. This review sheds light on the effect of perinatal maternal stress and treatment with SSRIs on offspring pain sensitivity, in relation to the developing HPA system and 5-HT signaling. © 2013 Wiley Periodicals, Inc.

  20. Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: do conditioning stimulus painfulness, gender and personality variables matter?

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    Granot, Michal; Weissman-Fogel, Irit; Crispel, Yonathan; Pud, Dorit; Granovsky, Yelena; Sprecher, Elliot; Yarnitsky, David

    2008-05-01

    Descending modulation of pain can be demonstrated psychophysically by dual pain stimulation. This study evaluates in 31 healthy subjects the association between parameters of the conditioning stimulus, gender and personality, and the endogenous analgesia (EA) extent assessed by diffuse noxious inhibitory control (DNIC) paradigm. Contact heat pain was applied as the test stimulus to the non-dominant forearm, with stimulation temperature at a psychophysical intensity score of 60 on a 0-100 numerical pain scale. The conditioning stimulus was a 60s immersion of the dominant hand in cold (12, 15, 18 degrees C), hot (44 and 46.5 degrees C), or skin temperature (33 degrees C) water. The test stimulus was repeated on the non-dominant hand during the last 30s of the conditioning immersion. EA extent was calculated as the difference between pain scores of the two test stimuli. State and trait anxiety and pain catastrophizing scores were assessed prior to stimulation. EA was induced only for the pain-generating conditioning stimuli at 46.5 degrees C (p=0.011) and 12 degrees C (p=0.003). EA was independent of conditioning pain modality, or personality, but a significant gender effect was found, with greater EA response in males. Importantly, pain scores of the conditioning stimuli were not correlated with EA extent. The latter is based on both our study population, and on additional 82 patients, who participated in another study, in which EA was induced by immersion at 46.5 degrees C. DNIC testing, thus, seems to be relatively independent of the stimulation conditions, making it an easy to apply tool, suitable for wide range applications in pain psychophysics.

  1. D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

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    Ohtani N

    2016-10-01

    Full Text Available Norimasa Ohtani, Eiji Masaki Division of Dento-oral Anesthesiology, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan Background: Approximately half of all patients who undergo surgery develop postoperative pain, the mechanisms of which are not well understood by anesthesiologists. D2-like receptors in the descending dopaminergic pathway play an important role in regulation of pain transmission in the spinal cord. Impairment of inhibitory neurons in the spinal cord is suggested as part of the mechanism for neuropathic pain, which is one component of postoperative pain. The purpose of this study was to investigate whether impairment of D2-like receptors in the descending dopaminergic pathway in the spinal cord is involved in the decreased postoperative nociceptive threshold in rats.Methods: Male Sprague-Dawley rats (250–300 g were anesthetized with sevoflurane and an intrathecal (IT catheter was implanted. Six days later, a plantar incision was made. On the following day, saline, a D2-like receptor agonist (quinpirole, or a D2-like receptor antagonist (sulpiride was administered intrathecally. Thermal and mechanical nociceptive responses were assessed by exposure to infrared radiant heat and the von Frey filament test before and after plantar incision.Results: Plantar incision decreased both thermal latency and the mechanical nociceptive threshold. IT administration of quinpirole inhibited the nociceptive responses induced by plantar incision, but sulpiride had no effect.Conclusion: A D2-like receptor agonist had antinociceptive effects on the hypersensitivity response triggered by a surgical incision, but a D2-like receptor antagonist had no effect on this response. These results suggest that impairment and/or modification of D2-like receptors in the descending dopaminergic pathway in the spinal cord is not involved in the postoperative decrease in nociceptive threshold. Keywords: postoperative pain, descending pathway

  2. High frequency electrical stimulation concurrently induces central sensitization and ipsilateral inhibitory pain modulation.

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    Vo, L; Drummond, P D

    2013-03-01

    In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high-frequency electrical stimulation (HFS), which triggers signs of central sensitization. Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS-treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB-treated site were similar during both procedures. HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS-treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non-specific effects, as it failed to develop after UVB conditioning. Thus, the supra-spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread. © 2012 European Federation of International Association for the Study of Pain Chapters.

  3. Facilitatory and inhibitory pain mechanisms are altered in patients with carpal tunnel syndrome.

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    Benjamin Soon

    Full Text Available Preliminary evidence from studies using quantitative sensory testing suggests the presence of central mechanisms in patients with carpal tunnel syndrome (CTS as apparent by widespread hyperalgesia. Hallmarks of central mechanisms after nerve injuries include nociceptive facilitation and reduced endogenous pain inhibition. Methods to study nociceptive facilitation in CTS so far have been limited to quantitative sensory testing and the integrity of endogenous inhibition remains unexamined. The aim of this study was therefore to investigate changes in facilitatory and inhibitory processing in patients with CTS by studying hypersensitivity following experimentally induced pain (facilitatory mechanisms and the efficacy of conditioned pain modulation (CPM, inhibitory mechanisms. Twenty-five patients with mild to moderate CTS and 25 age and sex matched control participants without CTS were recruited. Increased pain facilitation was evaluated via injection of hypertonic saline into the upper trapezius. Altered pain inhibition through CPM was investigated through cold water immersion of the foot as the conditioning stimulus and pressure pain threshold over the thenar and hypothenar eminence bilaterally as the test stimulus. The results demonstrated that patients with CTS showed a greater duration (p = 0.047, intensity (p = 0.044 and area (p = 0.012 of pain in response to experimentally induced pain in the upper trapezius and impaired CPM compared to the control participants (p = 0.006. Although typically considered to be driven by peripheral mechanisms, these findings indicate that CTS demonstrates characteristics of altered central processing with increased pain facilitation and reduced endogenous pain inhibition.

  4. Hopes for the Future of Pain Control.

    Science.gov (United States)

    Bannister, Kirsty; Kucharczyk, Mateusz; Dickenson, Anthony H

    2017-12-01

    Here we aim to present an accessible review of the pharmacological targets for pain management, and succinctly discuss the newest trends in pain therapy. A key task for current pain pharmacotherapy is the identification of receptors and channels orchestrating nociception. Notwithstanding peripheral alterations in the receptors and channels following pathophysiological events, the modulatory mechanisms in the central nervous system are also fundamental to the regulation of pain perception. Bridging preclinical and clinical studies of peripheral and central components of pain modulation, we present the different types of pain and relate these to pharmacological interventions. We firstly highlight the roles of several peripheral nociceptors, such as NGF, CGRP, sodium channels, and TRP-family channels that may become novel targets for therapies. In the central nervous system, the roles of calcium channels and gabapentinoids as well as NMDA receptors in generating excitability are covered including ideas on central sensitization. We then turn to central modulatory systems and discuss opioids and monoamines. We aim to explain the importance of central sensitization and the dialogue of the spinal circuits with the brain descending modulatory controls before discussing a mechanism-based effectiveness of antidepressants in pain therapy and their potential to modulate the descending controls. Emphasizing the roles of conditioned pain modulation and its animal's equivalent, diffuse noxious inhibitory controls, we discuss these unique descending modulations as a potential tool for understanding mechanisms in patients suffering from pain. Mechanism-based therapy is the key to picking the correct treatments and recent clinical studies using sensory symptoms of patients as surrogates for underlying mechanisms can be used to subgroup patients and reveal actions of drugs that may be lost when studying heterogenous groups of patients. Key advances in the understanding of basic pain

  5. Suicide awareness of japanese family descendants

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    Carla Tiemi Kawaziri Diogo

    2014-10-01

    Full Text Available This study aimed to comprehend the meaning of suicide for Japanese descendants. This was a qualitative study, based on Grounded Theory, using a structured interview with sixteen questions, digitally recorded. Subjects were ten descendants who were interviewed in 2011. The opinions of the interviewed showed factors of psychological, social and cultural origin involved in suicide, such as: heredity, religion, mental health, personality characteristics and interpersonal relationships, pleasure and pain at work, stigma and consequences of the act on the family. Family without case of suicide showed attitudes of prejudice and judgment, while those with case displayed feelings of pain in their reports. It was concluded that the Japanese rigid culture, personality, interpersonal communication and the way family and work have effects on their behavior are predisposing factors to suicide, as well as the identification of these factors contributes to a better performance of the nurse.

  6. D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats.

    Science.gov (United States)

    Ohtani, Norimasa; Masaki, Eiji

    2016-01-01

    Approximately half of all patients who undergo surgery develop postoperative pain, the mechanisms of which are not well understood by anesthesiologists. D2-like receptors in the descending dopaminergic pathway play an important role in regulation of pain transmission in the spinal cord. Impairment of inhibitory neurons in the spinal cord is suggested as part of the mechanism for neuropathic pain, which is one component of postoperative pain. The purpose of this study was to investigate whether impairment of D2-like receptors in the descending dopaminergic pathway in the spinal cord is involved in the decreased postoperative nociceptive threshold in rats. Male Sprague-Dawley rats (250-300 g) were anesthetized with sevoflurane and an intrathecal (IT) catheter was implanted. Six days later, a plantar incision was made. On the following day, saline, a D2-like receptor agonist (quinpirole), or a D2-like receptor antagonist (sulpiride) was administered intrathecally. Thermal and mechanical nociceptive responses were assessed by exposure to infrared radiant heat and the von Frey filament test before and after plantar incision. Plantar incision decreased both thermal latency and the mechanical nociceptive threshold. IT administration of quinpirole inhibited the nociceptive responses induced by plantar incision, but sulpiride had no effect. A D2-like receptor agonist had antinociceptive effects on the hypersensitivity response triggered by a surgical incision, but a D2-like receptor antagonist had no effect on this response. These results suggest that impairment and/or modification of D2-like receptors in the descending dopaminergic pathway in the spinal cord is not involved in the postoperative decrease in nociceptive threshold.

  7. Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

    Science.gov (United States)

    Rahman, Wahida; Dickenson, Anthony H

    2015-06-01

    Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics. Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy. Somatosensory phenotyping of chronic pain patients, as a surrogate of putative pain generating mechanisms, may predict patient response to treatment. Identification of new targets will inform and guide future research, aiding the development of more effective analgesics. Future clinical trial designs should implement sensory phenotyping of patients, as an inclusion or stratification criterion, in order to establish an individualized, mechanism-based treatment of osteoarthritis pain.

  8. Conditioned pain modulation (CPM) in children and adolescents: Effects of sex and age

    Science.gov (United States)

    Tsao, Jennie C. I.; Seidman, Laura C.; Evans, Subhadra; Lung, Kirsten C.; Zeltzer, Lonnie K.; Naliboff, Bruce D.

    2013-01-01

    Conditioned pain modulation (CPM) refers to the diminution of perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals. Studying CPM in children may inform interventions to enhance central pain inhibition within a developmental framework. We assessed CPM in 133 healthy children (mean age = 13 years; 52.6% girls) and tested the effects of sex and age. Participants were exposed to four trials of a pressure test stimulus before, during, and after the application of a cold water conditioning stimulus. CPM was documented by a reduction in pressure pain ratings during cold water administration. Older children (12–17 years) exhibited greater CPM than younger (8–11 years) children. No sex differences in CPM were found. Lower heart rate variability (HRV) at baseline and after pain induction was associated with less CPM controlling for child age. The findings of greater CPM in the older age cohort suggest a developmental improvement in central pain inhibitory mechanisms. The results highlight the need to examine developmental and contributory factors in central pain inhibitory mechanisms in children to guide effective, age appropriate, pain interventions. PMID:23541066

  9. Interictal dysfunction of a brainstem descending modulatory center in migraine patients.

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    Eric A Moulton

    Full Text Available The brainstem contains descending circuitry that can modulate nociceptive processing (neural signals associated with pain in the dorsal horn of the spinal cord and the medullary dorsal horn. In migraineurs, abnormal brainstem function during attacks suggest that dysfunction of descending modulation may facilitate migraine attacks, either by reducing descending inhibition or increasing facilitation. To determine whether a brainstem dysfunction could play a role in facilitating migraine attacks, we measured brainstem function in migraineurs when they were not having an attack (i.e. the interictal phase.Using fMRI (functional magnetic resonance imaging, we mapped brainstem activity to heat stimuli in 12 episodic migraine patients during the interictal phase. Separate scans were collected to measure responses to 41 degrees C and noxious heat (pain threshold+1 degrees C. Stimuli were either applied to the forehead on the affected side (as reported during an attack or the dorsum of the hand. This was repeated in 12 age-gender-matched control subjects, and the side tested corresponded to that in the matched migraine patients. Nucleus cuneiformis (NCF, a component of brainstem pain modulatory circuits, appears to be hypofunctional in migraineurs. 3 out of the 4 thermal stimulus conditions showed significantly greater NCF activation in control subjects than the migraine patients.Altered descending modulation has been postulated to contribute to migraine, leading to loss of inhibition or enhanced facilitation resulting in hyperexcitability of trigeminovascular neurons. NCF function could potentially serve as a diagnostic measure in migraine patients, even when not experiencing an attack. This has important implications for the evaluation of therapies for migraine.

  10. The Test-Retest Reliability OfTthe Onset Of Core And Vasti Eectromyographic Activity While Ascending And Descending Stairs In Healthy Controls Aand patellofemoral Pain Patients

    Directory of Open Access Journals (Sweden)

    Mohammad-Ali Sanjari

    2011-02-01

    Full Text Available Backgroundentity.It is hypothesized to result from abnormal patellar tracking caused by altered motorcontrol. Deficit in neuromotor control of the core may be a remote contributing factor to thedevelopment of PFP. Application of reliable EMG measures would be helpful to handle thistheory. Therefore, the purpose of this study was to determine the test-retest reliability of thecore and vasti EMG onsets, while ascending/descending stairs.: Patellofemoral pain (PFP is a common affliction and complex clinicalMethodsand Core EMG onsets during stair stepping were assessed two times a day. Intraclass correlationcoefficients (ICCs and standard errors of measurement (SEMs were calculated.: Ten males with PFP and ten healthy controls participated in this study. VastiResultsonsets of control cases (ICC 3,1 ≥ 0.70 except Quadratus Lumborum (QL which showeda moderate reliability (ICC for ascending=0.59 and for descending = 0.61. In controls,Vasti in both tasks showed the highest absolute reliability. During ascending, highreliability (ICC ≥ 0.70 in PFP group was demonstrated for all EMG onsets except Gluteusmaximus (GMAX and QL which showed a moderate reliability (ICC = 0.69 and 0.63 respectively.In this group while descending stairs, all EMG onsets showed high relativereliability (ICC ≥ 0.70. Moderate to high absolute reliability was obtained for onset timeswhile ascending/descending stairs in PFP group.: During both ascending/descending, high reliability was found for all EMGConclusionreliability.: Most EMG onsets during stair scending/descending had moderate to high

  11. Exercise does not produce hypoalgesia when performed immediately after a painful stimulus.

    Science.gov (United States)

    Gajsar, Hannah; Nahrwold, Katharina; Titze, Christina; Hasenbring, Monika I; Vaegter, Henrik B

    2018-04-25

    Exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM) are assumed to reflect descending pain inhibition. Potential interactions between EIH and CPM may be important in the therapy of chronic pain, as reduced CPM and increased pain after exercise are frequently observed. This study compared the EIH response after CPM was activated using a cold pressor task with the EIH response after a control condition. Thirty-one participants (age: 27.7±9.8; 15 female) completed two sessions: a cold pressor task (CPT) session, i.e. testing EIH with preceding CPM activation induced using a 2 min CPT at approximately 2°C, and a control session, i.e. testing EIH after a control condition (2 min of quiet rest). EIH was induced using a 15 min bicycling exercise at a target heart rate corresponding to 75% VO2 max. Repeated measures ANOVAs on pressure pain thresholds (PPTs) at the hand, back and leg were used to determine the effects of exercise after the cold pressor test and control condition. Furthermore, correlations between CPM and EIH, in the CPT session as well as control session, were calculated at each assessment site. A significant time x condition interaction (F(1, 30)=43.61, pCPM at the hand (r=0.37, p=0.043). There was a moderate negative correlation of EIH in the CPT session and CPM at the hand (r=-0.50, p=0.004), and smaller negative correlations at the back (r=-0.37, p=0.036) and at the leg (r=-0.35, p=0.054). Attenuated EIH after the CPM activation in comparison to a control condition suggests that EIH and CPM may share underlying pain inhibitory mechanisms on a systemic level. This assumption is further supported by the finding of small to moderate significant correlations between EIH and CPM at the hand. The attenuated EIH response furthermore suggests that these mechanisms are exhaustible, i.e. that its effects decline after a certain amount of inhibition. In patients with chronic pain, assessing the current capacity of the descending pain

  12. A case of descending colon carcinoma metastasized to left spermatic cord, testis, and epididymis

    Science.gov (United States)

    Augustin, Herbert; Popper, Helmut; Pummer, Karl

    2012-01-01

    We report a case of descending colon carcinoma metastasized to the left spermatic cord, testis, and epididymis. A 77-year old male patient underwent a left hemicolectomy for a descending colon cancer. He was referred to our department because of swelling and pain of the left scrotum two years and six months after surgery. High left orchiectomy was performed. Histological examination revealed a metastasis of the colon carcinoma within the spermatic cord and epididymis approaching the testicle. Reports on metastatic cancer of the testis are scarce, because this metastatic cancer is extremely rare. In general, testicular pain is rare in the elderly. We suggest that any elder presenting with testicular pain deserves a complete clinical and diagnostic evaluation. PMID:24578939

  13. Inhibitory coupling between inhibitory interneurons in the spinal cord dorsal horn

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    Ribeiro-da-Silva Alfredo

    2009-05-01

    Full Text Available Abstract Local inhibitory interneurons in the dorsal horn play an important role in the control of excitability at the segmental level and thus determine how nociceptive information is relayed to higher structures. Regulation of inhibitory interneuron activity may therefore have critical consequences on pain perception. Indeed, disinhibition of dorsal horn neuronal networks disrupts the balance between excitation and inhibition and is believed to be a key mechanism underlying different forms of pain hypersensitivity and chronic pain states. In this context, studying the source and the synaptic properties of the inhibitory inputs that the inhibitory interneurons receive is important in order to predict the impact of drug action at the network level. To address this, we studied inhibitory synaptic transmission in lamina II inhibitory interneurons identified under visual guidance in spinal slices taken from transgenic mice expressing enhanced green fluorescent protein (EGFP under the control of the GAD promoter. The majority of these cells fired tonically to a long depolarizing current pulse. Monosynaptically evoked inhibitory postsynaptic currents (eIPSCs in these cells were mediated by both GABAA and glycine receptors. Consistent with this, both GABAA and glycine receptor-mediated miniature IPSCs were recorded in all of the cells. These inhibitory inputs originated at least in part from local lamina II interneurons as verified by simultaneous recordings from pairs of EGFP+ cells. These synapses appeared to have low release probability and displayed potentiation and asynchronous release upon repeated activation. In summary, we report on a previously unexamined component of the dorsal horn circuitry that likely constitutes an essential element of the fine tuning of nociception.

  14. Modulation of itch by conditioning itch and pain stimulation in healthy humans

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; van Laarhoven, Antoinette I. M.; Elberling, Jesper

    2017-01-01

    Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation (CPM). There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch......-evoked itch, while the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (CPM-effect) by the conditioning pain stimulus (p

  15. Involvement of α2-adrenoceptors in inhibitory and facilitatory pain modulation processes.

    Science.gov (United States)

    Vo, L; Drummond, P D

    2016-03-01

    In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only produces hyperalgesia at the site of stimulation but also reduces sensitivity to pressure-pain on the ipsilateral side of the forehead. In addition, HFS augments the ipsilateral trigeminal nociceptive blink reflex and intensifies the ipsilateral component of conditioned pain modulation. The aim of this study was to determine whether α2-adrenoceptors mediate these ipsilateral nociceptive influences. The α2-adrenoceptor antagonist yohimbine was administered to 22 participants in a double-blind, placebo-controlled crossover study. In each session, thermal and mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, the combined effect of HFS and yohimbine on the nociceptive blink reflex and on conditioned pain modulation was explored. In this paradigm, the conditioning stimulus was cold pain in the ipsilateral or contralateral temple, and the test stimulus was electrically evoked pain in the forearm. Blood pressure and electrodermal activity increased for several hours after yohimbine administration, consistent with blockade of central α2-adrenoceptors. Yohimbine not only augmented the nociceptive blink reflex ipsilateral to HFS but also intensified the inhibitory influence of ipsilateral temple cooling on electrically evoked pain at the HFS-treated site in the forearm. Yohimbine had no consistent effect on primary or secondary hyperalgesia in the forearm or on pressure-pain in the ipsilateral forehead. These findings imply involvement of α2-adrenoceptors both in ipsilateral antinociceptive and pronociceptive pain modulation processes. However, a mechanism not involving α2-adrenoceptors appears to mediate analgesia in the ipsilateral forehead after HFS. © 2015 European Pain Federation - EFIC®

  16. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy.

    Science.gov (United States)

    Yarnitsky, David; Granot, Michal; Nahman-Averbuch, Hadas; Khamaisi, Mogher; Granovsky, Yelena

    2012-06-01

    This study aims to individualize the selection of drugs for neuropathic pain by examining the potential coupling of a given drug's mechanism of action with the patient's pain modulation pattern. The latter is assessed by the conditioned pain modulation (CPM) and temporal summation (TS) protocols. We hypothesized that patients with a malfunctioning pain modulation pattern, such as less efficient CPM, would benefit more from drugs augmenting descending inhibitory pain control than would patients with a normal modulation pattern of efficient CPM. Thirty patients with painful diabetic neuropathy received 1 week of placebo, 1 week of 30 mg/d duloxetine, and 4 weeks of 60 mg/d duloxetine. Pain modulation was assessed psychophysically, both before and at the end of treatment. Patient assessment of drug efficacy, assessed weekly, was the study's primary outcome. Baseline CPM was found to be correlated with duloxetine efficacy (r=0.628, P<.001, efficient CPM is marked negative), such that less efficient CPM predicted efficacious use of duloxetine. Regression analysis (R(2)=0.673; P=.012) showed that drug efficacy was predicted only by CPM (P=.001) and not by pretreatment pain levels, neuropathy severity, depression level, or patient assessment of improvement by placebo. Furthermore, beyond its predictive value, the treatment-induced improvement in CPM was correlated with drug efficacy (r=-0.411, P=.033). However, this improvement occurred only in patients with less efficient CPM (16.8±16.0 to -1.1±15.5, P<.050). No predictive role was found for TS. In conclusion, the coupling of CPM and duloxetine efficacy highlights the importance of pain pathophysiology in the clinical decision-making process. This evaluative approach promotes personalized pain therapy. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  17. Congenital Membrane Causing Duodenal Obstruction and Malpositioning of the Descending Colon

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    Chee-Chee Koh

    2013-08-01

    Full Text Available A congenital membrane without intestinal malrotation is a rare cause of duodenal obstruction. Here we present an 11-year-old girl who had suffered from intermittent abdominal cramping pain and vomiting for more than 5 years. The image studies, including a plain abdomen roentgenogram and sonogram, showed no definite diagnosis. The upper gastrointestinal series and small bowel series showed the contrast was static over the third portion of the duodenum and the descending colon pulled up toward the epigastric area. Laparoscopic exploration revealed a congenital membrane extending from the right-side paraduodenal peritoneum through the third portion of the duodenum to the descending colon, which had caused obstruction of the third portion of the duodenum and malpositioning of the descending colon. To the best of our knowledge, this is the first case report in the literature where a congenital membrane caused both duodenal obstruction and malpositioning of the descending colon.

  18. Using TENS for pain control: the state of the evidence

    Science.gov (United States)

    Vance, Carol GT; Dailey, Dana L; Rakel, Barbara A; Sluka, Kathleen A

    2014-01-01

    Summary Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that activates a complex neuronal network to reduce pain by activating descending inhibitory systems in the central nervous system to reduce hyperalgesia. The evidence for TENS efficacy is conflicting and requires not only description but also critique. Population-specific systemic reviews and meta-analyses are emerging, indicating both HF and LF TENS being shown to provide analgesia, specifically when applied at a strong, nonpainful intensity. The purpose of this article is to provide a critical review of the latest basic science and clinical evidence for TENS. Additional research is necessary to determine if TENS has effects specific to mechanical stimuli and/or beyond reduction of pain and will improve activity levels, function and quality of life. PMID:24953072

  19. Sex differences in the relationship between maternal fear of pain and children's conditioned pain modulation

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    Evans S

    2013-03-01

    Full Text Available Subhadra Evans, Laura C Seidman, Kirsten C Lung, Lonnie K Zeltzer, Jennie C TsaoPediatric Pain Program, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USABackground: Parental behaviors, emotions, and cognitions are known to influence children's response to pain. However, prior work has not tested the association between maternal psychological factors and children's responses to a conditioned pain modulation (CPM task. CPM refers to the reduction in perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals.Methods: The present study examined sex differences in the association between maternal anxiety about pain and children's CPM responses in 133 healthy children aged 8–17 years. Maternal pain anxiety was assessed using the Pain Anxiety Symptoms Scale-20. In addition to the magnitude of CPM, children's anticipatory anxiety and pain-related fear of the CPM task were measured.Results: Sequential multiple linear regression revealed that even after controlling for child age and general maternal psychological distress, greater maternal pain anxiety was significantly related to greater CPM anticipatory anxiety and pain-related fear in girls, and to less CPM (ie, less pain inhibition in boys.Conclusion: The findings indicate sex-specific relationships between maternal pain anxiety and children's responses to a CPM task over and above that accounted for by the age of the child and the mother's general psychological distress.Keywords: diffuse noxious inhibitory controls, pediatric pain, mother-child relationship, cold pressor, pressure pain, laboratory pain

  20. Conditioned pain modulation and situational pain catastrophizing as preoperative predictors of pain following chest wall surgery: a prospective observational cohort study.

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    Kasper Grosen

    Full Text Available Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency.Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2-5. Pain was reevaluated at six months postoperatively.Patients reporting persistent pain at six months follow-up (n = 15 were not significantly different from pain-free patients (n = 16 concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3 or level of catastrophizing (Z = 0.4, P = 1.0. In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007 whereas conditioned pain modulation predicted morphine consumption (β = -0.005, P = 0.001.Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have

  1. Tramadol Extended-Release for the Management of Pain due to Osteoarthritis

    Science.gov (United States)

    Guetti, Cristiana; Paladini, Antonella; Varrassi, Giustino

    2013-01-01

    Current knowledge on pathogenesis of osteoarticular pain, as well as the consequent several, especially on the gastrointestinal, renal, and cardiovascular systems, side effects of NSAIDs, makes it difficult to perform an optimal management of this mixed typology of pain. This is especially observable in elderly patients, the most frequently affected by osteoarthritis (OA). Tramadol is an analgesic drug, the action of which has a twofold action. It has a weak affinity to mu opioid receptors and, at the same time, can result in inhibition of the reuptake of noradrenaline and serotonin in nociceptorial descending inhibitory control system. These two mechanisms, “opioidergic” and “nonopioidergic,” are the grounds for contrasting certain types of pain that are generally less responsive to opioids, such as neuropathic pain or mixed OA pain. The extended-release formulation of tramadol has good efficacy and tolerability and acts through a dosing schedule that allows a high level of patients compliance to therapies with a good recovery outcome for the patients' functional status. PMID:27335872

  2. Conditioned Pain Modulation and Pressure Pain Sensitivity in the Adult Danish General Population: The DanFunD Study

    DEFF Research Database (Denmark)

    Skovbjerg, Sine; Jørgensen, Torben; Arendt-Nielsen, Lars

    2017-01-01

    with cold pressor pain (hand) for 2 minutes. Conditioning pain intensity was assessed using a visual analog scale and questionnaire data were collected. Female sex (P stress......Increased pressure pain sensitivity and impaired descending pain control have been associated with chronic pain, but knowledge on the variability in the adult general population is lacking. Pressure pain thresholds (PPTs) and descending pain control assessed using conditioned pain modulation (CPM...... (P ≤ .02), and high visual analog scale score (P ≤ .02) were associated with a larger CPM response. PERSPECTIVE: Data from this large population-based study provide new insight into the gender and age variation in pain sensitivity and CPM response. Decreased CPM potency and increased pain sensitivity...

  3. Descending thoracic aorta dissection associated with esophageal carcinoma

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    Kaushik Saha

    2013-01-01

    Full Text Available The association of aortic dissection with a malignancy is a rare finding and previous reports are usually those of primary aortic sarcomas. A 45-year-old male presented to us with chest pain and dysphagia for 1 month with a background history of obstructive airway disease and uncontrolled hypertension. In this report we present a case of typical descending aorta dissection with associated esophageal carcinoma.

  4. Neuropathic Pain Medication Use Does Not Alter Outcomes of Spinal Cord Stimulation for Lower Extremity Pain.

    Science.gov (United States)

    Maher, Dermot P; Martins, Yuri Chaves; Doshi, Tina; Bicket, Mark; Zhang, Kui; Hanna, George; Ahmed, Shihab

    2018-01-01

    Spinal cord stimulation (SCS) for the treatment of lower extremity pain is believed to the result of increased activity in the descending inhibitory and decreased activity in the ascending excitatory tracts. Evidence suggests that the analgesia afforded by SCS may be altered using certain neuropathic pain medications that also modulate neurotransmitters in these sensory tracts. We hypothesize that neuropathic pain medications may alter the response to SCS therapy. One hundred and fifteen subjects undergoing SCS therapy for lower extremity pain were retrospectively examined. The pharmacologic profile, including stable use of neuropathic and opioid medications, were recorded. Three separate logistic regression models examined the odds ratio of primary outcomes; a successful SCS trial, a 50% decrease in pain or a 50% reduction in opioid use one year after implant. Neither the use of opioids or neuropathic pain medications were associated with changes in the odds of a successful SCS trial or a 50% pain reduction. A higher dose of chronic opioids use prior to a trial was associated with greater odds of having a 50% reduction in opioid use following implant. OR 1.02, 95% CI 1.01-1.02, p-value neuropathic pain medications did not change the odds of either a successful SCS trial, or of experiencing a 50% reduction in pain at one year. The association between higher opioid doses and greater odds of a 50% reduction in opioid use may be the reflective of SCS's ability to reduce opioid reliance in chronic pain patients. © 2017 International Neuromodulation Society.

  5. Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain.

    Science.gov (United States)

    Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank

    2018-05-01

    The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.

  6. [Management of neuropathic pain].

    Science.gov (United States)

    Lozeron, P; Kubis, N

    2015-07-01

    Neuropathic pain is often underestimated and not adequately treated. The DN4 scale is very useful for its identification since it will benefit from pharmacological and non-pharmacological specific alternative care. The pathophysiological mechanisms involve the hyperexcitability of nociceptive pathways or decreased inhibitory descending controls that will be the target of pharmacological treatments. Frontline molecules are antidepressants (tricyclics and mixed serotonin and norepinephrine reuptake inhibitors) and antiepileptics (α2δ calcium channel inhibitors). However, these drugs will only have a partial efficacy on pain. The therapeutic strategy is based on reasonable goals, starting with a monotherapy adapted to the patient's symptoms and comorbidities and increased step by step. Patient compliance to contract is essential and requires clear and complete information. The impact on profession, social and family integration should rapidly be taken into account. In case of inefficiency, a change of the first-line treatment or an association could be considered. Some indications justify a specific therapy. Patients with resistant chronic pain should be sent to a specialized centre. New drugs are being studied and non-pharmacological support must be evaluated. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  7. Modulation of Itch by Conditioning Itch and Pain Stimulation in Healthy Humans.

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    Andersen, Hjalte H; van Laarhoven, Antoinette I M; Elberling, Jesper; Arendt-Nielsen, Lars

    2017-12-01

    Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation. There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch and pain. This study aimed to investigate whether and the extent to which itch can be modulated by conditioning itch and pain stimuli. Twenty-six healthy volunteers participated. The study consisted of 5 conditions designed to systematically assess endogenous modulation of itch or pain: 1) itch-induced modulation of contralateral itch, 2) pain-induced modulation of contralateral itch, 3) pain-induced modulation of ipsilateral itch, 4) pain-induced modulation of contralateral pain, and 5) itch-induced modulation of contralateral pain. Conditioning stimuli were cold pressor-induced pain and histamine-evoked itch, whereas the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (conditioned pain modulation-effect) by the conditioning pain stimulus (P modulation-effect) by contra- as well as ipsilateral applied conditioning pain (both P modulation of itch as well as pain in humans. Future studies addressing potential aberrations in pain-evoked descending modulation of itch in chronic itch patients are warranted. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  8. Melatonin analgesia is associated with improvement of the descending endogenous pain-modulating system in fibromyalgia: a phase II, randomized, double-dummy, controlled trial

    Science.gov (United States)

    2014-01-01

    Background Central disinhibition is a mechanism involved in the physiopathology of fibromyalgia. Melatonin can improve sleep quality, pain and pain threshold. We hypothesized that treatment with melatonin alone or in combination with amitriptyline would be superior to amitriptyline alone in modifying the endogenous pain-modulating system (PMS) as quantified by conditional pain modulation (CPM), and this change in CPM could be associated with serum brain-derived neurotrophic factor (BDNF). We also tested whether melatonin improves the clinical symptoms of pain, pain threshold and sleep quality. Methods Sixty-three females, aged 18 to 65, were randomized to receive bedtime amitriptyline (25 mg) (n = 21), melatonin (10 mg) (n = 21) or melatonin (10 mg) + amitriptyline (25 mg) (n = 21) for a period of six weeks. The descending PMS was assessed with the CPM-TASK. It was assessed the pain score on the Visual Analog Scale (VAS 0-100 mm), the score on Fibromyalgia Impact Questionnaire (FIQ), heat pain threshold (HPT), sleep quality and BDNF serum. Delta values (post- minus pre-treatment) were used to compare the treatment effect. The outcomes variables were collected before, one and six weeks after initiating treatment. Results Melatonin alone or in combination with amitriptyline reduced significantly pain on the VAS compared with amitriptyline alone (P FIQ and PPT improvement (P FIQ and PPT. Trial registration Current controlled trail is registered at clinical trials.gov upon under number NCT02041455. Registered January 16, 2014. PMID:25052847

  9. Doubling Your Payoff: Winning Pain Relief Engages Endogenous Pain Inhibition

    Science.gov (United States)

    Becker, Susanne; Gandhi, Wiebke; Kwan, Saskia; Ahmed, Alysha-Karima; Schweinhardt, Petra

    2015-01-01

    When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience ("liking") of a reward by the motivation to obtain a reward ("wanting"), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief "won" in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality.

  10. Reduced Pain Sensation and Reduced BOLD Signal in Parietofrontal Networks during Religious Prayer.

    Science.gov (United States)

    Elmholdt, Else-Marie; Skewes, Joshua; Dietz, Martin; Møller, Arne; Jensen, Martin S; Roepstorff, Andreas; Wiech, Katja; Jensen, Troels S

    2017-01-01

    Previous studies suggest that religious prayer can alter the experience of pain via expectation mechanisms. While brain processes related to other types of top-down modulation of pain have been studied extensively, no research has been conducted on the potential effects of active religious coping. Here, we aimed at investigating the neural mechanisms during pain modulation by prayer and their dependency on the opioidergic system. Twenty-eight devout Protestants performed religious prayer and a secular contrast prayer during painful electrical stimulation in two fMRI sessions. Naloxone or saline was administered prior to scanning. Results show that pain intensity was reduced by 11% and pain unpleasantness by 26% during religious prayer compared to secular prayer. Expectancy predicted large amounts (70-89%) of the variance in pain intensity. Neuroimaging results revealed reduced neural activity during religious prayer in a large parietofrontal network relative to the secular condition. Naloxone had no significant effect on ratings or neural activity. Our results thus indicate that, under these conditions, pain modulation by prayer is not opioid-dependent. Further studies should employ an optimized design to explore whether reduced engagement of the frontoparietal system could indicate that prayer may attenuate pain through a reduction in processing of pain stimulus saliency and prefrontal control rather than through known descending pain inhibitory systems.

  11. Pain-related increase of excitatory transmission and decrease of inhibitory transmission in the central nucleus of the amygdala are mediated by mGluR1

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    Neugebauer Volker

    2010-12-01

    Full Text Available Abstract Neuroplasticity in the central nucleus of the amygdala (CeA, particularly its latero-capsular division (CeLC, is an important contributor to the emotional-affective aspects of pain. Previous studies showed synaptic plasticity of excitatory transmission to the CeLC in different pain models, but pain-related changes of inhibitory transmission remain to be determined. The CeLC receives convergent excitatory inputs from the parabrachial nucleus in the brainstem and from the basolateral amygdala (BLA. In addition, feedforward inhibition of CeA neurons is driven by glutamatergic projections from the BLA area to a cluster of GABAergic neurons in the intercalated cell masses (ITC. Using patch-clamp in rat brain slices we measured monosynaptic excitatory postsynaptic currents (EPSCs and polysynaptic inhibitory currents (IPSCs that were evoked by electrical stimulation in the BLA. In brain slices from arthritic rats, input-output functions of excitatory synaptic transmission were enhanced whereas inhibitory synaptic transmission was decreased compared to control slices from normal untreated rats. A non-NMDA receptor antagonist (NBQX blocked the EPSCs and reduced the IPSCs, suggesting that non-NMDA receptors mediate excitatory transmission and also contribute to glutamate-driven feed-forward inhibition of CeLC neurons. IPSCs were blocked by a GABAA receptor antagonist (bicuculline. Bicuculline increased EPSCs under normal conditions but not in slices from arthritic rats, which indicates a loss of GABAergic control of excitatory transmission. A metabotropic glutamate receptor subtype 1 (mGluR1 antagonist (LY367385 reversed both the increase of excitatory transmission and the decrease of inhibitory transmission in the arthritis pain model but had no effect on basal synaptic transmission in control slices from normal rats. The inhibitory effect of LY367385 on excitatory transmission was blocked by bicuculline suggesting the involvement of a GABAergic

  12. The Role of Descending Modulation in Manual Therapy and Its Analgesic Implications: A Narrative Review

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    Andrew D. Vigotsky

    2015-01-01

    Full Text Available Manual therapy has long been a component of physical rehabilitation programs, especially to treat those in pain. The mechanisms of manual therapy, however, are not fully understood, and it has been suggested that its pain modulatory effects are of neurophysiological origin and may be mediated by the descending modulatory circuit. Therefore, the purpose of this review is to examine the neurophysiological response to different types of manual therapy, in order to better understand the neurophysiological mechanisms behind each therapy’s analgesic effects. It is concluded that different forms of manual therapy elicit analgesic effects via different mechanisms, and nearly all therapies appear to be at least partially mediated by descending modulation. Additionally, future avenues of mechanistic research pertaining to manual therapy are discussed.

  13. A Case of Advanced Descending Colon Cancer in an Adult Patient with Intestinal Malrotation

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    Yoshifumi Nakayama

    2016-01-01

    Full Text Available This report presents an operative case of advanced descending colon cancer in an adult patient with intestinal malrotation. A 63-year-old Japanese male was suffering from left side abdominal pain, abdominal distension, and constipation. An endoscopic examination revealed an advanced tumor in the descending colon. Computed tomography (CT of the abdomen revealed the thickening of the descending colon wall and superior mesenteric vein rotation. An opaque enema detected severe stenosis of the descending colon. An abdominal X-ray examination revealed the dilation of the colon and small intestine with niveau. At the insertion of an ileus tube, the C-loop of the duodenum was observed to be absent and the small intestine was located on the right side of the abdomen. After the decompression of the bowel contents, laparotomy was performed. Descending colon cancer was observed to have directly invaded the left side of the transverse colon. Left hemicolectomy, lymph node dissection, and appendectomy were performed. The patient had an uneventful recovery and was discharged from the hospital on the 16th day after surgery. This report presents a rare operative case of descending colon cancer in an adult patient with intestinal malrotation.

  14. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study

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    Ravn P

    2013-01-01

    /heat injury relative to placebo for low-dose morphine was 0.01 (interquartile range: −6.2; 9.9, 0.00 (−2.4; 2.1 for high-dose morphine, 0.03 (−1.8; 2.1 for low-dose buprenorphine, and 0.00 (−3.2; 1.1 for high-dose buprenorphine (P > 0.466. There were no significant differences in opioid responses between high and low pain-sensitive subjects (P > 0.286. High-dose buprenorphine, compared to placebo, was associated with a significantly enhanced action of the descending inhibitory pain control system (P = 0.004.Conclusion: The present study, using multimodal testing technique, could not demonstrate any significant differences between morphine and buprenorphine in the profiles of antihyperalgesia and analgesia. Only high-dose buprenorphine was associated with a significant effect on the descending inhibitory pain control system.Keywords: analgesia, antihyperalgesia, experimental pain, opioid, pain sensitivity, randomized trial

  15. Transmission to interneurons is via slow excitatory synaptic potentials mediated by P2Y(1 receptors during descending inhibition in guinea-pig ileum.

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    Peter D J Thornton

    Full Text Available BACKGROUND: The nature of synaptic transmission at functionally distinct synapses in intestinal reflex pathways has not been fully identified. In this study, we investigated whether transmission between interneurons in the descending inhibitory pathway is mediated by a purine acting at P2Y receptors to produce slow excitatory synaptic potentials (EPSPs. METHODOLOGY/PRINCIPAL FINDINGS: Myenteric neurons from guinea-pig ileum in vitro were impaled with intracellular microelectrodes. Responses to distension 15 mm oral to the recording site, in a separately perfused stimulation chamber and to electrical stimulation of local nerve trunks were recorded. A subset of neurons, previously identified as nitric oxide synthase immunoreactive descending interneurons, responded to both stimuli with slow EPSPs that were reversibly abolished by a high concentration of PPADS (30 μM, P2 receptor antagonist. When added to the central chamber of a three chambered organ bath, PPADS concentration-dependently depressed transmission through that chamber of descending inhibitory reflexes, measured as inhibitory junction potentials in the circular muscle of the anal chamber. Reflexes evoked by distension in the central chamber were unaffected. A similar depression of transmission was seen when the specific P2Y(1 receptor antagonist MRS 2179 (10 μM was in the central chamber. Blocking either nicotinic receptors (hexamethonium 200 μM or 5-HT(3 receptors (granisetron 1 μM together with P2 receptors had no greater effect than blocking P2 receptors alone. CONCLUSIONS/SIGNIFICANCE: Slow EPSPs mediated by P2Y(1 receptors, play a primary role in transmission between descending interneurons of the inhibitory reflexes in the guinea-pig ileum. This is the first demonstration for a primary role of excitatory metabotropic receptors in physiological transmission at a functionally identified synapse.

  16. Learned control over spinal nociception in patients with chronic back pain.

    Science.gov (United States)

    Krafft, S; Göhmann, H-D; Sommer, J; Straube, A; Ruscheweyh, R

    2017-10-01

    Descending pain inhibition suppresses spinal nociception, reducing nociceptive input to the brain. It is modulated by cognitive and emotional processes. In subjects with chronic pain, it is impaired, possibly contributing to pain persistence. A previously developed feedback method trains subjects to activate their descending inhibition. Participants are trained to use cognitive-emotional strategies to reduce their spinal nociception, as quantified by the nociceptive flexor reflex (RIII reflex), under visual feedback about their RIII reflex size. The aim of the present study was to test whether also subjects with chronic back pain can achieve a modulation of their descending pain inhibition under RIII feedback. In total, 33 subjects with chronic back pain received either true (n = 18) or sham RIII feedback (n = 15), 15 healthy control subjects received true RIII feedback. All three groups achieved significant RIII suppression, largest in controls (to 76 ± 26% of baseline), intermediate in chronic back pain subjects receiving true feedback (to 82 ± 13%) and smallest in chronic back pain subjects receiving sham feedback (to 89 ± 14%, all p chronic pain subjects receiving true feedback significantly improved their descending inhibition over the feedback training, quantified by the conditioned pain modulation effect (test pain reduction of baseline before training: to 98 ± 26%, after: to 80 ± 21%, p chronic back pain can achieve a reduction of their spinal nociception and improve their descending pain inhibition under RIII feedback training. Subjects with chronic back pain can learn to control their spinal nociception, quantified by the RIII reflex, when they receive feedback about the RIII reflex. © 2017 European Pain Federation - EFIC®.

  17. Cancer pain and current theory for pain control.

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    Kahan, Brian

    2014-05-01

    This article discusses current trends in managing cancer pain, with specific regard to opioid transmission, descending pathway inhabitation, and ways to facilitate the endogenous antinociceptive chemicals in the human body. Various techniques for opioid and nonopioid control of potential pain situations of patients with cancer are discussed. The benefits of using pharmacogenetics to assess the appropriate medications are addressed. Finally, specific treatment of abdominal cancer pain using radiofrequency lesioning is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

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    Kim, Jinhyung; Ryu, Sang Baek; Lee, Sung Eun; Shin, Jaewoo; Jung, Hyun Ho; Kim, Sung June; Kim, Kyung Hwan; Chang, Jin Woo

    2016-03-01

    Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

  19. Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models.

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    Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria

    2016-09-02

    Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase

  20. Doubling Your Payoff: Winning Pain Relief Engages Endogenous Pain Inhibition1,2,3

    Science.gov (United States)

    Kwan, Saskia; Schweinhardt, Petra

    2015-01-01

    Abstract When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience (“liking”) of a reward by the motivation to obtain a reward (“wanting”), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief “won” in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality. PMID:26464995

  1. Serotonin noradrenaline reuptake inhibitors: New hope for the treatment of chronic pain.

    Science.gov (United States)

    Delgado, Pedro L

    2006-01-01

    Depression and painful symptoms occur frequently together. Over 75% of depressed patients report painful symptoms such as headache, stomach pain, neck and back pain as well as non-specific generalized pain. In addition, World Health Organization data have shown that primary care patients with chronic pain have a four fold greater risk of becoming depressed than pain-free patients. Increasingly, pain is considered as an integral symptom of depression and there evidence to suggest that pain and depression may arise from a common neurobiological dysfunction. Serotonergic cell bodies, in the raphe nucleus, and noradrenergic cell bodies in the locus coeruleus send projections to various parts of the brain, where they are involved in the control of mood, movement, cognitive functioning and emotions. In addition both serotonergic and noradrenergic neurons project to the spinal cord. These descending pathways serve to inhibit input from the intestines, skeletal muscles and other sensory inputs. Usually, these inhibitory effects are modest, but in times of stress, in the interest of the survival of the individual, they can completely inhibit the input from painful stimuli. A dysfunction of the serotonergic and noradrenergic neurons can thus affect both the ascending and descending pathways resulting in the psychological symptoms of depression and somatic pain symptoms such as chronic pain, fibromyalgia, non-cardiac chest pain, or irritable bowel syndrome. In view of this, it is not surprising that tricyclic antidepressants have been a standard treatment of chronic pain for many years. In contrast and in spite of their improved tolerance, selective serotonin reuptake inhibitors do not appear to be particularly effective in the treatment of pain. Recently, a number of open and controlled trials with selective serotonin and noradrenaline reuptake inhibitors such as venlafaxine, milnacipran and duloxetine, suggest that these compounds may be more effective in relieving pain

  2. Contribution of Pro-Inflammatory Cytokine Signaling within Midbrain Periaqueductal Gray to Pain Sensitivity in Parkinson's disease via GABAergic Pathway

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    Xianbo Zhuang

    2016-07-01

    Full Text Available Background/Aims: Hypersensitive pain response is often observed in patients with Parkinson's disease (PD; however, the mechanisms responsible for hyperalgesia are not well understood. Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Since the midbrain periaqueductal gray (PAG is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role for pro-inflammatory cytokines (PICs system of PAG in regulating exaggerated pain evoked by PD. Methods: We used a rat model of PD to perform the experimental protocols. PD was induced by microinjection of 6-hydroxydopamine to lesion the left medial forebrain bundle. Pain responses to mechanical and thermal stimulation were first examined in control rats and PD rats. Then, ELISA and Western Blot analysis were used to determine PIC levels and their receptors expression. Results: Protein expression of IL-1β, IL-6 and TNF-α receptors (namely, IL-1R, IL-6R and TNFR subtype TNFR1 in the plasma membrane PAG of PD rats was upregulated, whereas the total expression of PIC receptors was not significantly altered. The ratio of membrane protein and total protein (IL-1R, IL-6R and TNFR1 was 1.48±0.15, 1.59±0.18 and 1.67±0.16 in PAG of PD rats (P < 0.05 vs. their respective controls. This was accompanied with increases of PICs of PAG, and decreases of GABA (623±21 ng/mg in control rats and 418±18 ng/mg in PD rats; P < 0.05 vs. control rats and withdrawal thresholds to mechanical and thermal stimuli. Our data further showed that the concentrations of GABA and withdrawal thresholds were largely restored by blocking those PIC receptors in PAG of PD rats. Stimulation of GABA receptors in PAG of PD rats also blunted a decrease in withdrawal thresholds. Conclusions: Our data suggest that upregulation of the membrane PIC receptor in the PAG of PD rats is likely to impair the descending inhibitory pathways in regulating pain transmission

  3. Temporomandibular disorders and painful comorbidities: clinical association and underlying mechanisms.

    Science.gov (United States)

    Costa, Yuri Martins; Conti, Paulo César Rodrigues; de Faria, Flavio Augusto Cardoso; Bonjardim, Leonardo Rigoldi

    2017-03-01

    The association between temporomandibular disorders (TMDs) and headaches, cervical spine dysfunction, and fibromyalgia is not artefactual. The aim of this review is to describe the comorbid relationship between TMD and these three major painful conditions and to discuss the clinical implications and the underlying pain mechanisms involved in these relationships. Common neuronal pathways and central sensitization processes are acknowledged as the main factors for the association between TMD and primary headaches, although the establishment of cause-effect mechanisms requires further clarification and characterization. The biomechanical aspects are not the main factors involved in the comorbid relationship between TMD and cervical spine dysfunction, which can be better explained by the neuronal convergence of the trigeminal and cervical spine sensory pathways as well as by central sensitization processes. The association between TMD and fibromyalgia also has supporting evidence in the literature, and the proposed main mechanism underlying this relationship is the impairment of the descending pain inhibitory system. In this particular scenario, a cause-effect relationship is more likely to occur in one direction, that is, fibromyalgia as a risk factor for TMD. Therefore, clinical awareness of the association between TMD and painful comorbidities and the support of multidisciplinary approaches are required to recognize these related conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Lower inhibitory control interacts with greater pain catastrophizing to predict greater pain intensity in women with migraine and overweight/obesity.

    Science.gov (United States)

    Galioto, Rachel; O'Leary, Kevin C; Thomas, J Graham; Demos, Kathryn; Lipton, Richard B; Gunstad, John; Pavlović, Jelena M; Roth, Julie; Rathier, Lucille; Bond, Dale S

    2017-12-01

    Pain catastrophizing (PC) is associated with more severe and disabling migraine attacks. However, factors that moderate this relationship are unknown. Failure of inhibitory control (IC), or the ability to suppress automatic or inappropriate responses, may be one such factor given previous research showing a relationship between higher PC and lower IC in non-migraine samples, and research showing reduced IC in migraine. Therefore, we examined whether lower IC interacts with increased PC to predict greater migraine severity as measured by pain intensity, attack frequency, and duration. Women (n = 105) aged 18-50 years old (M = 38.0 ± 1.2) with overweight/obesity and migraine who were seeking behavioral treatment for weight loss and migraine reduction completed a 28-day smartphone-based headache diary assessing migraine headache severity. Participants then completed a modified computerized Stroop task as a measure of IC and self-report measures of PC (Pain Catastrophizing Scale [PCS]), anxiety, and depression. Linear regression was used to examine independent and joint associations of PC and IC with indices of migraine severity after controlling for age, body mass index (BMI) depression, and anxiety. Participants on average had BMI of 35.1 ± 6.5 kg/m 2 and reported 5.3 ± 2.6 migraine attacks (8.3 ± 4.4 migraine days) over 28 days that produced moderate pain intensity (5.9 ± 1.4 out of 10) with duration of 20.0 ± 14.2 h. After adjusting for covariates, higher PCS total (β = .241, SE = .14, p = .03) and magnification subscale (β = .311, SE = .51, p migraine attacks. Future studies are needed to determine whether interventions to improve IC could lead to less painful migraine attacks via improvements in PC.

  5. Optical inactivation of the anterior cingulate cortex modulate descending pain pathway in a rat model of trigeminal neuropathic pain created via chronic constriction injury of the infraorbital nerve

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    Moon HC

    2017-10-01

    facial cold allodynia scores were significantly improved in the TN lesion group during optical stimulation compared to those in the control group. Thalamic neuronal activity, consisting of the firing rate (spikes/s and burst rate (bursts/s, was also decreased during optical stimulation.Conclusion: Reciprocal optical inhibition of the ACC can alleviate pain-associated behavior and decrease abnormal thalamic sensory neuron activity in the trigeminal neuropathic rat model. The descending pain pathway can modulate thalamic neurons from the ACC following optical stimulation. Keywords: optogenetics, trigeminal neuralgia, anterior cingulate cortex, neuropathic pain

  6. Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.

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    Moont, Ruth; Crispel, Yonatan; Lev, Rina; Pud, Dorit; Yarnitsky, David

    2011-07-01

    For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  7. Contribution of amygdala CRF neurons to chronic pain.

    Science.gov (United States)

    Andreoli, Matthew; Marketkar, Tanvi; Dimitrov, Eugene

    2017-12-01

    We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over

  8. Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy.

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    Up Noh, Sun; Lee, Won-Young; Kim, Won-Serk; Lee, Yong-Taek; Jae Yoon, Kyung

    2018-01-01

    Background Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. Objective of this study was to observe pain syndromes elicited in the footpad of diabetic neuropathy rat model and to assess the contributory role of migration inhibitory factor in the pathogenesis of diabetic neuropathy. Methods Diabetic neuropathy was made in Sprague Dawley rats by streptozotocin. Pain threshold was evaluated using von Frey monofilaments for 24 weeks. On comparable experiment time after streptozotocin injection, all footpads were prepared for following procedures; glutathione assay, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining, immunohistochemistry staining, real-time reverse transcription polymerase chain reaction, and Western blot. Additionally, human HaCaT skin keratinocytes were treated with methylglyoxal, transfected with migration inhibitory factor/control small interfering RNA, and prepared for real-time reverse transcription polymerase chain reaction and Western blot. Results As compared to sham group, pain threshold was significantly reduced in diabetic neuropathy group, and glutathione was decreased in footpad skin, simultaneously, cell death was increased. Over-expression of migration inhibitory factor, accompanied by low expression of glyoxalase-I and intraepidermal nerve fibers, was shown on the footpad skin lesions of diabetic neuropathy. But, there was no significance in expression of neurotransmitters and inflammatory mediators such as transient receptor potential vanilloid 1, mas-related G protein coupled receptor D, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6 between diabetic neuropathy group and sham group. Intriguingly

  9. Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

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    Forkmann, Katarina; Grashorn, Wiebke; Schmidt, Katharina; Fründt, Odette; Buhmann, Carsten; Bingel, Ulrike

    2017-08-01

    Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

  10. Cervical necrotising fasciitis and descending mediastinitis secondary to unilateral tonsillitis: a case report

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    Islam Asad

    2008-12-01

    Full Text Available Abstract Introduction Cervical necrotizing fasciitis is an aggressive infection with high morbidity and mortality. We present a case of cervical necrotizing fasciitis and descending mediastinitis in a healthy young man, caused by unilateral tonsillitis with a successful outcome without aggressive debridement. Case presentation A 41-year-old man was admitted to our unit with a diagnosis of severe acute unilateral tonsillitis. On admission, he had painful neck movements and the skin over his neck was red, hot and tender. Computed tomography scan of his neck and chest showed evidence of cervical necrotizing fasciitis and descending mediastinitis secondary to underlying pharyngeal disease. He was treated with broad-spectrum intravenous antibiotics. His condition improved over the next 3 days but a tender and fluctuant swelling appeared in the suprasternal region. A repeat scan showed the appearance of an abscess extending from the pretracheal region to the upper mediastinum which was drained through a small transverse anterior neck incision. After surgery, the patient's condition quickly improved and he was discharged on the 18th day of admission. Conclusion Less invasive surgical techniques may replace conventional aggressive debridement as the treatment of choice for cervical necrotizing fasciitis and descending necrotizing mediastinitis.

  11. Patellofemoral Pain Syndrome in Iranian Female Athletes

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    Hamid Reza Baradaran

    2011-03-01

    Full Text Available Patellofemoral pain syndrome (PFPS is the most common overuse syndrome in athletes. It is one of the causes of anterior knee pain in athletic population who come to the sports medicine clinic. Patellofemoral pain is more common among female athletes especially adolescents and young adults. Symptoms include: persistent pain behind the patella or peripatella. Pain increases on ascending and descending stairs and squatting and prolonged sitting. The aim of this study was to evaluate the prevalence of PFPS in Iranian female athletes. 418 female athletes aged 15-35 years were examined in five sports: Soccer (190, volleyball (103, running (42, fencing (45 and rock climbing (38. The athletes who had non- traumatic onset anterior knee pain of at least 3 months that increased in descending and ascending stairs and squatting, had no other causes of anterior knee pain such as ligament instability, bursitis, meniscal injury, tendonitis and arthritis and no history of knee surgery during the one past year were diagnosed as PFPS. 26/190 (13.68 % soccer players, 21/103(20.38 % volleyball players, 7/42 (16.66 % runners, 6/45(13.33 % fencers and 10/38 (26.31% rock climbers had patellofemoral pain. Among the 418 female athletes who were evaluated 70 had PFPS. Rock climbers were the most common athletes with PFPS followed by volleyball players and runners.

  12. Mechanisms and management of functional abdominal pain

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    Farmer, Adam D; Aziz, Qasim

    2014-01-01

    Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory sys...

  13. Immediate changes in widespread pressure pain sensitivity, neck pain, and cervical range of motion after cervical or thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain: a randomized clinical trial.

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    Martínez-Segura, Raquel; De-la-Llave-Rincón, Ana I; Ortega-Santiago, Ricardo; Cleland, Joshua A; Fernández-de-Las-Peñas, César

    2012-09-01

    Randomized clinical trial. To compare the effects of cervical versus thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain on pressure pain sensitivity, neck pain, and cervical range of motion (CROM). Evidence suggests that spinal interventions can stimulate descending inhibitory pain pathways. To our knowledge, no study has investigated the neurophysiological effects of thoracic thrust manipulation in individuals with bilateral chronic mechanical neck pain, including widespread changes on pressure sensitivity. Ninety patients (51% female) were randomly assigned to 1 of 3 groups: cervical thrust manipulation on the right, cervical thrust manipulation on the left, or thoracic thrust manipulation. Pressure pain thresholds (PPTs) over the C5-6 zygapophyseal joint, lateral epicondyle, and tibialis anterior muscle, neck pain (11-point numeric pain rating scale), and cervical spine range of motion (CROM) were collected at baseline and 10 minutes after the intervention by an assessor blinded to the treatment allocation of the patients. Mixed-model analyses of covariance were used to examine the effects of the treatment on each outcome variable, with group as the between-subjects variable, time and side as the within-subject variables, and gender as the covariate. The primary analysis was the group-by-time interaction. No significant interactions were found with the mixed-model analyses of covariance for PPT level (C5-6, P>.210; lateral epicondyle, P>.186; tibialis anterior muscle, P>.268), neck pain intensity (P = .923), or CROM (flexion, P = .700; extension, P = .387; lateral flexion, P>.672; rotation, P>.192) as dependent variables. All groups exhibited similar changes in PPT, neck pain, and CROM (all, P.10). The results of the current randomized clinical trial suggest that cervical and thoracic thrust manipulation induce similar changes in PPT, neck pain intensity, and CROM in individuals with bilateral chronic mechanical neck pain

  14. 15. Amygdala pain mechanisms

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    Neugebauer, Volker

    2015-01-01

    A limbic brain area the amygdala plays a key role in emotional responses and affective states and disorders such as learned fear, anxiety and depression. The amygdala has also emerged as an important brain center for the emotional-affective dimension of pain and for pain modulation. Hyperactivity in the laterocapsular division of the central nucleus of the amygdala (CeLC, also termed the “nociceptive amygdala”) accounts for pain-related emotional responses and anxiety-like behavior. Abnormally enhanced output from the CeLC is the consequence of an imbalance between excitatory and inhibitory mechanisms. Impaired inhibitory control mediated by a cluster of GABAergic interneurons in the intercalated cell masses (ITC) allows the development of glutamate- and neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem (parabrachial area) and from the lateral-basolateral amygdala network (LA-BLA, site of integration of polymodal sensory information). BLA hyperactivity also generates abnormally enhanced feedforward inhibition of principal cells in the medial prefrontal cortex (mPFC), a limbic cortical area that is strongly interconnected with the amygdala. Pain-related mPFC deactivation results in cognitive deficits and failure to engage cortically driven ITC-mediated inhibitory control of amygdala processing. Impaired cortical control allows the uncontrolled persistence of amygdala pain mechanisms. PMID:25846623

  15. Dysfunctional pain modulation in somatoform pain disorder patients.

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    Klug, Stefanie; Stefanie, Klug; Anderer, Peter; Peter, Anderer; Saletu-Zyhlarz, Gerda; Gerda, Saletu-Zyhlarz; Freidl, Marion; Marion, Freidl; Saletu, Bernd; Bernd, Saletu; Prause, Wolfgang; Wolfgang, Prause; Aigner, Martin; Martin, Aigner

    2011-06-01

    To date, pain perception is thought to be a creative process of modulation carried out by an interplay of pro- and anti-nociceptive mechanisms. Recent research demonstrates that pain experience constitutes the result of top-down processes represented in cortical descending pain modulation. Cortical, mainly medial and frontal areas, as well as subcortical structures such as the brain stem, medulla and thalamus seem to be key players in pain modulation. An imbalance of pro- and anti-nociceptive mechanisms are assumed to cause chronic pain disorders, which are associated with spontaneous pain perception without physiologic scaffolding or exaggerated cortical activation in response to pain exposure. In contrast to recent investigations, the aim of the present study was to elucidate cortical activation of somatoform pain disorder patients during baseline condition. Scalp EEG, quantitative Fourier-spectral analyses and LORETA were employed to compare patient group (N = 15) to age- and sex-matched controls (N = 15) at rest. SI, SII, ACC, SMA, PFC, PPC, insular, amygdale and hippocampus displayed significant spectral power reductions within the beta band range (12-30 Hz). These results suggest decreased cortical baseline arousal in somatoform pain disorder patients. We finally conclude that obtained results may point to an altered baseline activity, maybe characteristic for chronic somatoform pain disorder.

  16. Subgroups of musculoskeletal pain patients and their psychobiological patterns - the LOGIN study protocol.

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    Gerhardt, Andreas; Hartmann, Mechthild; Tesarz, Jonas; Janke, Susanne; Leisner, Sabine; Seidler, Günter; Eich, Wolfgang

    2012-08-03

    Pain conditions of the musculoskeletal system are very common and have tremendous socioeconomic impact. Despite its high prevalence, musculoskeletal pain remains poorly understood and predominantly non-specifically and insufficiently treated.The group of chronic musculoskeletal pain patients is supposed to be heterogeneous, due to a multitude of mechanisms involved in chronic pain. Psychological variables, psychophysiological processes, and neuroendocrine alterations are expected to be involved. Thus far, studies on musculoskeletal pain have predominantly focused on the general aspects of pain processing, thus neglecting the heterogeneity of patients with musculoskeletal pain. Consequently, there is a need for studies that comprise a multitude of mechanisms that are potentially involved in the chronicity and spread of pain. This need might foster research and facilitate a better pathophysiological understanding of the condition, thereby promoting the development of specific mechanism-based treatments for chronic pain. Therefore, the objectives of this study are as follows: 1) identify and describe subgroups of patients with musculoskeletal pain with regard to clinical manifestations (including mental co-morbidity) and 2) investigate whether distinct sensory profiles or 3) distinct plasma levels of pain-related parameters due to different underlying mechanisms can be distinguished in various subgroups of pain patients. We will examine a population-based chronic pain sample (n = 100), a clinical tertiary care sample (n = 100) and pain-free patients with depression or post-traumatic stress disorder and pain-free healthy controls (each n = 30, respectively). The samples will be pain localisation matched by sex and age to the population-based sample. Patients will undergo physical examination and thorough assessments of mental co-morbidity (including psychological trauma), perceptual and central sensitisation (quantitative sensory testing), descending

  17. Pain management in patients with Parkinson's disease: challenges and solutions.

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    Skogar, Orjan; Lokk, Johan

    2016-01-01

    This review focuses on the diagnosis and management of Parkinson-related pain which is one of the more frequently reported nonmotor symptoms in Parkinson's disease (PD), which is the second most common neurodegenerative disease after Alzheimer's disease. Pain is ranked high by patients as a troublesome symptom in all stages of the disease. In early-stage PD, pain is rated as the most bothersome symptom. Knowledge of the correct diagnosis of pain origin and possible methods of treatments for pain relief in PD is of great importance. The symptoms have a great negative impact on health-related quality of life. Separating PD-related pain from pain of other origins is an important challenge and can be characterized as "many syndromes under the same umbrella". Among the different forms of PD-related pain, musculoskeletal pain is the most common form, accounting for 40%-90% of reported pain in PD patients. Augmentation by pathophysiological pathways other than those secondary to rigidity, tremor, or any of the other motor manifestations of the disease seems most probable. In PD, the basal ganglia process somatosensory information differently, and increased subjective pain sensitivity with lower electrical and heat-pain thresholds has been reported in PD patients. The mechanism is assumed to be diminished activity of the descending inhibitory control system of the basal ganglia. PD pain, like many of the nonmotor symptoms, remains underdiagnosed and, thus, poorly managed. A systematic collection of patient descriptions of type, quality, and duration of pain is, therefore, of utmost importance. Recent studies have validated new and more specific and dedicated pain scales for PD-related symptoms. Symptomatic treatments based on clinical pain classification include not only pharmacological but also nonpharmacological methods and, to some degree, invasive approaches. In the clinic, pharmacological and nonpharmacological interventions can be effective to varying degrees - as

  18. Spinal cord compression injury in lysophosphatidic acid 1 receptor-null mice promotes maladaptive pronociceptive descending control.

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    Suardíaz, M; Galan-Arriero, I; Avila-Martin, G; Estivill-Torrús, G; de Fonseca, F R; Chun, J; Gómez-Soriano, J; Bravo-Esteban, E; Taylor, J

    2016-02-01

    Although activation of the lysophosphatidic acid receptor 1 (LPA1) is known to mediate pronociceptive effects in peripheral pain models, the role of this receptor in the modulation of spinal nociception following spinal cord injury (SCI) is unknown. In this study, LPA1 regulation of spinal excitability mediated by supraspinal descending antinociceptive control systems was assessed following SCI in both wild-type (WT) and maLPA1-null receptor mice. The effect of a T8 spinal compression in WT and maLPA1-null mice was assessed up to 1 month after SCI using histological, immunohistochemical and behavioural techniques analysis including electrophysiological recording of noxious toes-Tibialis Anterior (TA) stimulus-response reflex activity. The effect of a T3 paraspinal transcutaneous electrical conditioning stimulus on TA noxious reflex temporal summation was also assessed. Histological analysis demonstrated greater dorsolateral funiculus damage after SCI in maLPA1-null mice, without a change in the stimulus-response function of the TA noxious reflex when compared to WT mice. While T3 conditioning stimulation in the WT group inhibited noxious TA reflex temporal summation after SCI, this stimulus strongly excited TA reflex temporal summation in maLPA1-null mice. The functional switch from descending inhibition to maladaptive facilitation of central excitability of spinal nociception demonstrated in maLPA1-null mice after SCI was unrelated to a general change in reflex activity. These data suggest that the LPA1 receptor is necessary for inhibition of temporal summation of noxious reflex activity, partly mediated via long-tract descending modulatory systems acting at the spinal level. © 2015 European Pain Federation - EFIC®

  19. [From Descartes to fMRI. Pain theories and pain concepts].

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    Handwerker, H O

    2007-08-01

    In the seventeenth century the philosopher Rene Descartes was the forerunner by establishing a scientific hypothesis on the origin of pain. Much later, in the nineteenth century, pain hypotheses emerged which explained the pain sensation either on the basis of intense stimulation of any kind of nerve fibers (intensity hypothesis) or on the basis of specific nociceptors (specificity hypothesis). The "gate control theory" established by Melzack and Wall (1964) offered an explanation of modulations of pain sensation by the interaction between nociceptive and non-nociceptive nerve fibers and by descending control in the central nervous system. Though this hypothesis is outdated in its original form, it had - in a more common formulation - a great influence on our understanding of pain. For building a bridge to our present knowledge, the molecular structure of the nociceptor membrane is of particular importance. On this basis also new pain therapies have been developed. On the other hand, the methods of functional imaging allow the identification of brain regions related to pain processing at a macroscopic level. This new technology opened up new ways of understanding chronic pain processes and new possibilities for the control of therapeutic effects.

  20. Psychosocial, Physical, and Neurophysiological Risk Factors for Chronic Neck Pain: A Prospective Inception Cohort Study.

    Science.gov (United States)

    Shahidi, Bahar; Curran-Everett, Douglas; Maluf, Katrina S

    2015-12-01

    The purpose of this investigation was to identify modifiable risk factors for the development of first-onset chronic neck pain among an inception cohort of healthy individuals working in a high-risk occupation. Candidate risk factors identified from previous studies were categorized into psychosocial, physical, and neurophysiological domains, which were assessed concurrently in a baseline evaluation of 171 office workers within the first 3 months of hire. Participants completed monthly online surveys over the subsequent year to identify the presence of chronic interfering neck pain, defined as a Neck Disability Index score ≥5 points for 3 or more months. Data were analyzed using backward logistic regression to identify significant predictors within each domain, which were then entered into a multivariate regression model adjusted for age, sex, and body mass index. Development of chronic interfering neck pain was predicted by depressed mood (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 1.10-10.31, P = .03), cervical extensor endurance (OR = .92, 95% CI, .87-.97, P = .001), and diffuse noxious inhibitory control (OR = .90, 95% CI, .83-.98, P = .02) at baseline. These findings provide the first evidence that individuals with preexisting impairments in mood and descending pain modulation may be at greater risk for developing chronic neck pain when exposed to peripheral nociceptive stimuli such as that produced during muscle fatigue. Depressed mood, poor muscle endurance, and impaired endogenous pain inhibition are predisposing factors for the development of new-onset chronic neck pain of nonspecific origin in office workers. These findings may assist with primary prevention by allowing clinicians to screen for individuals at risk of developing chronic neck pain. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  1. The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control.

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    Decker, M W; Meyer, M D; Sullivan, J P

    2001-10-01

    Due to the limitations of currently available analgesics, a number of novel alternatives are currently under investigation, including neuronal nicotinic acetylcholine receptor (nAChR) agonists. During the 1990s, the discovery of the antinociceptive properties of the potent nAChR agonist epibatidine in rodents sparked interest in the analgesic potential of this class of compounds. Although epibatidine also has several mechanism-related toxicities, the identification of considerable nAChR diversity suggested that the toxicities and therapeutic actions of the compound might be mediated by distinct receptor subtypes. Consistent with this view, a number of novel nAChR agonists with antinociceptive activity and improved safety profiles in preclinical models have now been identified, including A-85380, ABT-594, DBO-83, SIB-1663 and RJR-2403. Of these, ABT-594 is the most advanced and is currently in Phase II clinical evaluation. Nicotinically-mediated antinociception has been demonstrated in a variety of rodent pain models and is likely mediated by the activation of descending inhibitory pathways originating in the brainstem with the predominant high-affinity nicotine site in brain, the alpha4beta2 subtype, playing a critical role. Thus, preclinical findings suggest that nAChR agonists have the potential to be highly efficacious treatments in a variety of pain states. However, clinical proof-of-principle studies will be required to determine if nAChR agonists are active in pathological pain.

  2. The effects of elevated pain inhibition on endurance exercise performance

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    Andrew Flood

    2017-03-01

    Full Text Available Background The ergogenic effects of analgesic substances suggest that pain perception is an important regulator of work-rate during fatiguing exercise. Recent research has shown that endogenous inhibitory responses, which act to attenuate nociceptive input and reduce perceived pain, can be increased following transcranial direct current stimulation of the hand motor cortex. Using high-definition transcranial direct current stimulation (HD-tDCS; 2 mA, 20 min, the current study aimed to examine the effects of elevated pain inhibitory capacity on endurance exercise performance. It was hypothesised that HD-tDCS would enhance the efficiency of the endogenous pain inhibitory response and improve endurance exercise performance. Methods Twelve healthy males between 18 and 40 years of age (M = 24.42 ± 3.85 were recruited for participation. Endogenous pain inhibitory capacity and exercise performance were assessed before and after both active and sham (placebo stimulation. The conditioned pain modulation protocol was used for the measurement of pain inhibition. Exercise performance assessment consisted of both maximal voluntary contraction (MVC and submaximal muscular endurance performance trials using isometric contractions of the non-dominant leg extensors. Results Active HD-tDCS (pre-tDCS, −.32 ± 1.33 kg; post-tDCS, −1.23 ± 1.21 kg significantly increased pain inhibitory responses relative to the effects of sham HD-tDCS (pre-tDCS, −.91 ± .92 kg; post-tDCS, −.26 ± .92 kg; p = .046. Irrespective of condition, peak MVC force and muscular endurance was reduced from pre- to post-stimulation. HD-tDCS did not significantly influence this reduction in maximal force (active: pre-tDCS, 264.89 ± 66.87 Nm; post-tDCS, 236.33 ± 66.51 Nm; sham: pre-tDCS, 249.25 ± 88.56 Nm; post-tDCS, 239.63 ± 67.53 Nm or muscular endurance (active: pre-tDCS, 104.65 ± 42.36 s; post-tDCS, 93.07 ± 33.73 s; sham: pre-tDCS, 123.42 ± 72.48 s; post

  3. Surgical treatment of penetrating atherosclerotic ulcer of the descending aorta

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    Kovačević Pavle

    2013-01-01

    Full Text Available Introduction. The term “penetrating atherosclerotic ulcer” (PAU of the aorta describes the condition in which ulceration of an aortic atherosclerotic lesion penetrates the internal elastic lamina into media. PAU is a high-risk lesion due to its deleterious effects on the integrity of aortic wall, with potentially fatal outcome. Case report. A patient with intensive, sharp chest pain irradiating to the back but with no signs of myocardial ischemia on an electrocardiogram was referred to our hospital. Transthoracic echocardiography showed no pathological changes of the ascending aorta. However, multislice computed tomography (CT showed an aortic ulcer with varying degree of the subadventitial hemorrhage in the region of the thoracic aorta at the level of Th 8-9. Due to imminent rupture of the penetrating aortic ulcer, the patient was promptly prepared for surgery. A 15 cm long subadventitial hematoma was found intraoperatively in the right posterolateral aspect of the descending aorta, 5 cm above the diaphragm and 7 cm below the origin of the left subclavial artery. The affected segment of the aorta was resected, followed by an inlay aortic reconstruction with a Dacron tube graft of 24 mm. Control CT revealed satisfactory reconstruction of the descending aorta. Conclusion. PAU is a rare, but potentially fatal disease. Open surgery in patients with PAU is an effective treatment strategy, although endovascular treatment options are emerging.

  4. The effects of transcranial direct current stimulation in patients with neuropathic pain from spinal cord injury.

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    Ngernyam, Niran; Jensen, Mark P; Arayawichanon, Preeda; Auvichayapat, Narong; Tiamkao, Somsak; Janjarasjitt, Suparerk; Punjaruk, Wiyada; Amatachaya, Anuwat; Aree-uea, Benchaporn; Auvichayapat, Paradee

    2015-02-01

    Transcranial direct current stimulation (tDCS) has demonstrated efficacy for reducing neuropathic pain, but the respective mechanisms remain largely unknown. The current study tested the hypothesis that pain reduction with tDCS is associated with an increase in the peak frequency spectrum density in the theta-alpha range. Twenty patients with spinal cord injury and bilateral neuropathic pain received single sessions of both sham and anodal tDCS (2 mA) over the left primary motor area (M1) for 20 min. Treatment order was randomly assigned. Pre- to post-procedure changes in pain intensity and peak frequency of electroencephalogram spectral analysis were compared between treatment conditions. The active treatment condition (anodal tDCS over M1) but not sham treatment resulted in significant decreases in pain intensity. In addition, consistent with the study hypothesis, peak theta-alpha frequency (PTAF) assessed from an electrode placed over the site of stimulation increased more from pre- to post-session among participants in the active tDCS condition, relative to those in the sham tDCS condition. Moreover, we found a significant association between a decrease in pain intensity and an increase in PTAF at the stimulation site. The findings are consistent with the possibility that anodal tDCS over the left M1 may be effective, at least in part, because it results in an increase in M1 cortical excitability, perhaps due to a pain inhibitory effect of motor cortex stimulation that may influence the descending pain modulation system. Future research is needed to determine if there is a causal association between increased left anterior activity and pain reduction. The results provide new findings regarding the effects of tDCS on neuropathic pain and brain oscillation changes. Copyright © 2014 International Federation of Clinical Neurophysiology. All rights reserved.

  5. Methadone for Cancer Pain

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    Eric E. Prommer

    2010-07-01

    Full Text Available Pain is one of the most common and incapacitating symptoms experienced by patients with advanced cancer. Methadone is a potent opioid with strong affinity for the µ opioid receptor. In addition to being a potent µ opioid receptor ligand, methadone blocks the N-methyl-D-aspartic acid receptor and modulates neurotransmitters involved in descending pain modulation. These 3 properties enhance analgesic activity. Methadone’s lack of active metabolites makes it an attractive option when opioid responsiveness declines and renal insufficiency complicates opioid therapy. A lipophilic opioid, methadone can be given by multiple routes. Clinical trial data show equivalence with morphine as an analgesic in moderate to severe cancer pain. Further investigations are needed to define the role of methadone in the management of breakthrough pain and neuropathic pain and to determine whether it is truly superior to morphine, the gold standard of cancer analgesia.

  6. A Review of Select Centralized Pain Syndromes

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    David R. Spiegel

    2015-01-01

    Full Text Available Pain can be broadly divided into 3 classes, including nociceptive or inflammatory pain (protective, neuropathic (pathological, occurring after damage to the nervous system, or centralized (pathological, due to abnormal function but with no damage or inflammation to the nervous system. The latter has been posited to occur when descending analgesic pathways are attenuated and/or glutamatergic transmission is facilitated. Additionally, this “pain prone phenotype” can be associated with early life trauma and a suboptimal response to opiates. This article will review the relationships between centralized pain syndromes (ie, fibromyalgia, chronic low back pain, childhood sexual abuse, and opiate misuse. Finally, treatment implications, potentially effecting primary care physicians, will be discussed.

  7. Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats.

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    Khaled Abdallah

    Full Text Available Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG, into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project. These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.

  8. Bimodal Modulation of Ipsilateral Spinal-Coeruleo-Spinal Pathway in CRPS: A Novel Model for Explaining Different Clinical Features of the Syndrome.

    Science.gov (United States)

    Carcamo, Cesar R

    2015-08-01

    The objective is to present a hypothesis to explain the sensory, autonomic, and motor disturbances associated with complex regional pain syndrome (CRPS) syndrome. The author reviewed the available and relevant literature, which was supplemented with research on experimental animal models, with a focus on how they may translate into humans, particularly in areas about pathophysiologic mechanisms of CRPS. We propose that different CRPS subtypes may result from facilitative or inhibitory influences exerted by the spinal-coeruleo-spinal pathway in three sites at the spinal cord: the dorsal horn (DH), intermediolateral cell column (IML) and ventral horn (VH). A facilitatory influence over DH may have a pronociceptive effect that explains exacerbated pain, sensory disturbances, and spreading sensitization and neuroinflammation. Conversely, a facilitatory influence over preganglionic neurons located in IML cell column may increase sympathetic outflow with peripheral vasoconstriction, which leads to cold skin, ipsilateral limb ischaemia, and sympathetically maintained pain (SMP). For patients presenting with these symptoms, a descending inhibitory influence would be predicted to result in decreased sympathetic outflow and warm skin, as well as impairment of peripheral vasoconstrictor reflexes. Finally, a descending inhibitory influence over VH could explain muscle weakness and decreased active range of motion, while also facilitating motor reflexes, tremor and dystonia. The proposed model provides a mechanistically based diagnostic scheme for classifying and explaining the sensory, autonomic and motor disturbances associated with CRPS syndrome. Wiley Periodicals, Inc.

  9. Subgroups of musculoskeletal pain patients and their psychobiological patterns – The LOGIN study protocol

    Directory of Open Access Journals (Sweden)

    Gerhardt Andreas

    2012-08-01

    (quantitative sensory testing, descending inhibition (conditioned pain modulation, the diffuse noxious inhibitory control-like effect, as well as measurement of the plasma levels of nerve growth factor and endocannabinoids. Discussion The identification of the underlying pathophysiologic mechanisms in different subgroups of chronic musculoskeletal pain patients will contribute to a mechanism-based subgroup classification. This will foster the development of mechanism-based treatments and holds promise to treat patients more sufficient.

  10. Escitalopram in painful polyneuropathy: A randomized, placebo-controlled, cross-over trial

    DEFF Research Database (Denmark)

    Otto, Marit; Bach, Flemming W; Jensen, Troels S

    2008-01-01

    Serotonin (5-HT) is involved in pain modulation via descending pathways in the central nervous system. The aim of this study was to test if escitalopram, a selective serotonin reuptake inhibitor (SSRI), would relieve pain in polyneuropathy. The study design was a randomized, double-blind, placebo......-controlled cross-over trial. The daily dose of escitalopram was 20mg once daily. During the two treatment periods of 5 weeks duration, patients rated pain relief (primary outcome variable) on a 6-point ordered nominal scale. Secondary outcome measures comprised total pain and different pain symptoms (touch...

  11. Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition

    Directory of Open Access Journals (Sweden)

    Bulls HW

    2015-06-01

    Full Text Available Hailey W Bulls,1 Emily L Freeman,1 Austen JB Anderson,2 Meredith T Robbins,3 Timothy J Ness,3 Burel R Goodin1,3 1Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Biology, Samford University, Birmingham, AL, USA; 3Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: It has been suggested that increased pain sensitivity and disruption of endogenous pain inhibitory processes may account, at least in part, for the greater prevalence and severity of chronic pain in women compared to men. However, previous studies addressing this topic have produced mixed findings. This study examined sex differences in pain sensitivity and inhibition using quantitative sensory testing (QST, while also considering the influence of other important factors such as depressive symptoms and sleep quality. Healthy men (n=24 and women (n=24 each completed a QST battery. This battery included an ischemic pain task (IPT that used a submaximal effort tourniquet procedure as well as a conditioned pain modulation (CPM procedure for the assessment of endogenous pain inhibition. Prior to QST, participants completed the Center for Epidemiologic Studies Depression Scale and the Pittsburgh Sleep Quality Index. Analyses revealed significant sex differences for the ischemic pain task and the conditioned pain modulation procedure, such that women tolerated the ischemic pain for a shorter amount of time and demonstrated less pain inhibition compared with men. This remained true even when accounting for sex differences in depressive symptoms and sleep quality. The results of this study suggest that women may be more pain sensitive and possess less-efficient endogenous pain inhibitory capacity compared with men. Whether interventions that decrease pain sensitivity and enhance pain inhibition in women ultimately improve their clinical pain outcomes is an area of research that deserves additional

  12. Preoperative transcranial direct current stimulation: Exploration of a novel strategy to enhance neuroplasticity before surgery to control postoperative pain. A randomized sham-controlled study.

    Directory of Open Access Journals (Sweden)

    Hugo Ribeiro

    Full Text Available An imbalance in the excitatory/inhibitory systems in the pain networks may explain the persistent chronic pain after hallux valgus surgery. Thus, to contra-regulate this dysfunction, the use of transcranial direct current stimulation (tDCS becomes attractive.We tested the hypothesis that two preoperative active(a-tDCS sessions compared with sham(s-tDCS could improve the postoperative pain [as indexed by Visual Analogue Scale (VAS at rest and during walking (primary outcomes]. To assess their effect on the change in the Numerical Pain Scale (NPS0-10 during Conditioned Pain Modulation (CPM-task, disability related to pain (DRP and analgesic consumption (secondary outcomes. Also, we assessed if the brain derived neurotrophic factor (BDNF in the cerebral spinal fluid (CSF after tDCS could predict the intervention's effect on the DRP.It is a prospective, double blind, sham-controlled, randomized single center, 40 women (18-70 years-old who had undergone hallux valgus surgery were randomized to receive two sessions (20 minutes each of anodal a-tDCS or s-tDCS on the primary motor cortex at night and in the morning before the surgery. To assess the DRP was used the Brazilian Profile of Chronic Pain: Screen (B-PCP:S.A-tDCS group showed lower scores on VAS at rest and during walking (P<0.001. At rest, the difference between groups was 2.13cm (95%CI = 1.59 to 2.68 while during walking was 1.67cm (95%CI = 1.05 to 2.28. A-tDCS, when compared to s-tDCS reduced analgesic doses in 73.25% (P<0.001, produced a greater reduction in B-PCP:S (mean difference of 9.41 points, 95%CI = 0.63 to 18.21 and higher function of descending pain modulatory system (DPMS during CPM-task.A-tDCS improves postoperative pain, the DRP and the function of DPMS. Also, the CSF BDNF after a-tDCS predicted the improvement in the DRP. In overall, these findings suggest that a-tDCS effects may be mediated by top-down regulatory mechanisms associated with the inhibitory cortical control

  13. Circuitry and plasticity of the dorsal horn--toward a better understanding of neuropathic pain.

    Science.gov (United States)

    West, S J; Bannister, K; Dickenson, A H; Bennett, D L

    2015-08-06

    Maladaptive plasticity within the dorsal horn (DH) of the spinal cord is a key substrate for development of neuropathic pain following peripheral nerve injury. Advances in genetic engineering, tracing techniques and opto-genetics are leading to a much better understanding of the complex circuitry of the spinal DH and the radical changes evoked in such circuitry by nerve injury. These changes can be viewed at multiple levels including: synaptic remodeling including enhanced excitatory and reduced inhibitory drive, morphological and electrophysiological changes which are observed both to primary afferent inputs as well as DH neurons, and ultimately circuit-level rewiring which leads to altered connectivity and aberrant processing of sensory inputs in the DH. The DH should not be seen in isolation but is subject to important descending modulation from the brainstem, which is further dysregulated by nerve injury. Understanding which changes relate to specific disease-states is essential, and recent work has aimed to stratify patient populations in a mechanistic fashion. In this review we will discuss how such pathophysiological mechanisms may lead to the distressing sensory phenomena experienced by patients suffering neuropathic pain, and the relationship of such mechanisms to current and potential future treatment modalities. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. [Descending ocular myopathy].

    Science.gov (United States)

    de Freitas, M R; Nascimento, O J

    1975-06-01

    The case of a 23 years old female patient, with primary involvement of the extraocular and faringeal muscles without familiar history is reported. Electromyographic and muscular biopsy studies proved the myogenic nature of the process. A clinical comparison between the ocular myopathy and the descending ocular myopathy is made, the authors thinking that both of them would be variants of the same muscle disease.

  15. Pain management in patients with Parkinson's disease: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Skogar O

    2016-09-01

    Full Text Available Orjan Skogar,1,2 Johan Lokk2 1Academy for Health and Care (FUTURUM, Region Jönköping County, Jönköping, 2Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Stockholm, Sweden Abstract: This review focuses on the diagnosis and management of Parkinson-related pain which is one of the more frequently reported nonmotor symptoms in Parkinson’s disease (PD, which is the second most common neurodegenerative disease after Alzheimer’s disease. Pain is ranked high by patients as a troublesome symptom in all stages of the disease. In early-stage PD, pain is rated as the most bothersome symptom. Knowledge of the correct diagnosis of pain origin and possible methods of treatments for pain relief in PD is of great importance. The symptoms have a great negative impact on health-related quality of life. Separating PD-related pain from pain of other origins is an important challenge and can be characterized as “many syndromes under the same umbrella”. Among the different forms of PD-related pain, musculoskeletal pain is the most common form, accounting for 40%–90% of reported pain in PD patients. Augmentation by pathophysiological pathways other than those secondary to rigidity, tremor, or any of the other motor manifestations of the disease seems most probable. In PD, the basal ganglia process somatosensory information differently, and increased subjective pain sensitivity with lower electrical and heat-pain thresholds has been reported in PD patients. The mechanism is assumed to be diminished activity of the descending inhibitory control system of the basal ganglia. PD pain, like many of the nonmotor symptoms, remains underdiagnosed and, thus, poorly managed. A systematic collection of patient descriptions of type, quality, and duration of pain is, therefore, of utmost importance. Recent studies have validated new and more specific and dedicated pain scales for PD-related symptoms. Symptomatic treatments based

  16. Torsed pulmonary sequestration presenting as a painful chest mass

    International Nuclear Information System (INIS)

    Shah, Ricki; Carver, Terrence W.; Rivard, Douglas C.

    2010-01-01

    Pulmonary sequestration is a congenital abnormality that can be divided into intralobar or extralobar types. Both types are characterized by pulmonary tissue that does not communicate with the bronchial tree or pulmonary arteries and typically has its arterial supply arising from the descending aorta. We report a case of an 11-year-old girl with extralobar sequestration who presented with torsion causing abdominal pain and pleuritic chest pain. (orig.)

  17. Chronic Widespread Back Pain is Distinct From Chronic Local Back Pain: Evidence From Quantitative Sensory Testing, Pain Drawings, and Psychometrics.

    Science.gov (United States)

    Gerhardt, Andreas; Eich, Wolfgang; Janke, Susanne; Leisner, Sabine; Treede, Rolf-Detlef; Tesarz, Jonas

    2016-07-01

    Whether chronic localized pain (CLP) and chronic widespread pain (CWP) have different mechanisms or to what extent they overlap in their pathophysiology is controversial. The study compared quantitative sensory testing profiles of nonspecific chronic back pain patients with CLP (n=48) and CWP (n=29) with and fibromyalgia syndrome (FMS) patients (n=90) and pain-free controls (n = 40). The quantitative sensory testing protocol of the "German-Research-Network-on-Neuropathic-Pain" was used to measure evoked pain on the painful area in the lower back and the pain-free hand (thermal and mechanical detection and pain thresholds, vibration threshold, pain sensitivity to sharp and blunt mechanical stimuli). Ongoing pain and psychometrics were captured with pain drawings and questionnaires. CLP patients did not differ from pain-free controls, except for lower pressure pain threshold (PPT) on the back. CWP and FMS patients showed lower heat pain threshold and higher wind-up ratio on the back and lower heat pain threshold and cold pain threshold on the hand. FMS showed lower PPT on back and hand, and higher comorbidity of anxiety and depression and more functional impairment than all other groups. Even after long duration CLP presents with a local hypersensitivity for PPT, suggesting a somatotopically specific sensitization of nociceptive processing. However, CWP patients show widespread ongoing pain and hyperalgesia for different stimuli that is generalized in space, suggesting the involvement of descending control systems, as also suggested for FMS patients. Because mechanisms in nonspecific chronic back pain with CLP and CWP differ, these patients should be distinguished in future research and allocated to different treatments.

  18. 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.

  19. Modern pain neuroscience in clinical practice: applied to post-cancer, paediatric and sports-related pain.

    Science.gov (United States)

    Malfliet, Anneleen; Leysen, Laurence; Pas, Roselien; Kuppens, Kevin; Nijs, Jo; Van Wilgen, Paul; Huysmans, Eva; Goudman, Lisa; Ickmans, Kelly

    In the last decade, evidence regarding chronic pain has developed exponentially. Numerous studies show that many chronic pain populations show specific neuroplastic changes in the peripheral and central nervous system. These changes are reflected in clinical manifestations, like a generalized hypersensitivity of the somatosensory system. Besides a hypersensitivity of bottom-up nociceptive transmission, there is also evidence for top-down facilitation of pain due to malfunctioning of the endogenous descending nociceptive modulatory systems. These and other aspects of modern pain neuroscience are starting to be applied within daily clinical practice. However, currently the application of this knowledge is mostly limited to the general adult population with musculoskeletal problems, while evidence is getting stronger that also in other chronic pain populations these neuroplastic processes may contribute to the occurrence and persistence of the pain problem. Therefore, this masterclass article aims at giving an overview of the current modern pain neuroscience knowledge and its potential application in post-cancer, paediatric and sports-related pain problems. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

  20. Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain

    NARCIS (Netherlands)

    Lefaucheur, Jean-Pascal; Holsheimer, J.; Goujon, Colette; Keravel, Yves; Nguyen, Jean-Paul

    Epidural motor cortex stimulation (EMCS) is a therapeutic option for chronic, drug-resistant neuropathic pain, but its mechanisms of action remain poorly understood. In two patients with refractory hand pain successfully treated by EMCS, the presence of implanted epidural cervical electrodes for

  1. A Randomized Controlled Trial on the Effect of Tapentadol and Morphine on Conditioned Pain Modulation in Healthy Volunteers.

    Directory of Open Access Journals (Sweden)

    Chris Martini

    Full Text Available Modulatory descending pathways, originating at supraspinal sites that converge at dorsal horn neurons, influence pain perception in humans. Defects in descending pain control are linked to chronic pain states and its restoration may be a valuable analgesic tool. Conditioned pain modulation (CPM is a surrogate marker of descending inhibition that reduces the perception of pain from a primary test stimulus during application of a conditioning stimulus. Here the effects of the analgesics tapentadol, a combined mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and morphine, a strong mu-opioid receptor agonist, were tested on CPM in a randomized, double-blind, placebo-controlled crossover trial in 12 healthy pain-free volunteers, to understand possible differences in mechanism of action between these opioids.On three occasions CPM responses were obtained 60-90 and 120-150 min following intake of tapentadol (100 mg immediate release tablet, morphine (40 mg immediate release tablet or placebo. At both time points, CPM was detectable after treatment with placebo and tapentadol (peak pain ratings reduced by 20-30% after application of the conditioning stimulus but not after morphine. Compared to placebo morphine displayed significantly less CPM: mean treatment difference 18.2% (95% CI 3.4 to 32.9% at 60-90 min after drug intake and 19.5% (95% CI 5.7 to 33.2% at 120-150 min after drug intake (p = 0.001. No difference in CPM between placebo and tapentadol was detected: mean treatment difference 1.5% (95% CI -11.6 to 14.6% at 60-90 min after drug intake and 1.5% (95% CI -16.0 to 18.9% at 120-150 min after drug intake (p = 0.60.Our data show that in volunteers morphine affects CPM, while tapentadol was without effect despite identical experimental conditions. These data confirm that tapentadol's main mechanism of action is distinct from that of morphine and likely related to the effect of adrenergic stimulation on descending controls

  2. Descendants of the Chiral Anomaly

    OpenAIRE

    Jackiw, R.

    2000-01-01

    Chern-Simons terms are well-known descendants of chiral anomalies, when the latter are presented as total derivatives. Here I explain that also Chern-Simons terms, when defined on a 3-manifold, may be expressed as total derivatives.

  3. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model

    DEFF Research Database (Denmark)

    Ravn, Pernille; Secher, EL; Skram, U

    2013-01-01

    Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than μ-opioid receptor agonists. The primary outcome of this study was therefore...... to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending...... pain modulation....

  4. Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Annett Eitner

    2017-11-01

    Full Text Available Pain due to osteoarthritis (OA is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate

  5. An investigation into the inhibitory function of serotonin in diffuse noxious inhibitory controls in the neuropathic rat.

    Science.gov (United States)

    Bannister, K; Lockwood, S; Goncalves, L; Patel, R; Dickenson, A H

    2017-04-01

    Following neuropathy α2-adrenoceptor-mediated diffuse noxious inhibitory controls (DNIC), whereby a noxious conditioning stimulus inhibits the activity of spinal wide dynamic range (WDR) neurons, are abolished, and spinal 5-HT7 receptor densities are increased. Here, we manipulate spinal 5-HT content in spinal nerve ligated (SNL) animals and investigate which 5-HT receptor mediated actions predominate. Using in vivo electrophysiology we recorded WDR neuronal responses to von frey filaments applied to the hind paw before, and concurrent to, a noxious ear pinch (the conditioning stimulus) in isoflurane-anaesthetised rats. The expression of DNIC was quantified as a reduction in WDR neuronal firing in the presence of conditioning stimulus and was investigated in SNL rats following spinal application of (1) selective serotonin reuptake inhibitors (SSRIs) citalopram or fluoxetine, or dual application of (2) SSRI plus 5-HT7 receptor antagonist SB269970, or (3) SSRI plus α2 adrenoceptor antagonist atipamezole. DNIC were revealed in SNL animals following spinal application of SSRI, but this effect was abolished upon joint application of SSRI plus SB269970 or atipamezole. We propose that in SNL animals the inhibitory actions (quantified as the presence of DNIC) of excess spinal 5-HT (presumed present following application of SSRI) were mediated via 5-HT7 receptors. The anti-nociception depends upon an underlying tonic noradrenergic inhibitory tone via the α2-adrenoceptor. Following neuropathy enhanced spinal serotonin availability switches the predominant spinal 5-HT receptor-mediated actions but also alters noradrenergic signalling. We highlight the therapeutic complexity of SSRIs and monoamine modulators for the treatment of neuropathic pain. © 2016 European Pain Federation - EFIC®.

  6. Descending with Angels

    DEFF Research Database (Denmark)

    Suhr, Christian

    2014-01-01

    Islamic exorcism or psychotropic medication? “Descending with Angels” explores two highly different solutions to the same problem: namely Danish Muslims who are possessed by invisible spirits, called jinn. A Palestinian refugee living in the city of Aarhus has been committed to psychiatric......, and directed by Christian Suhr Produced by Persona Film, November 2013 Distribution: Documentary Educational Resources (DER, Watertown) Screening format: DCP / Blu-ray / ProRes / Mpeg4 / DVD / DV SP. Original format: XDCAM 1080p Languages: Arabic, Danish, English Subtitles: English...

  7. The role of Omega-3 and Omega-9 fatty acids for the treatment of neuropathic pain after neurotrauma.

    Science.gov (United States)

    Galán-Arriero, Iriana; Serrano-Muñoz, Diego; Gómez-Soriano, Julio; Goicoechea, Carlos; Taylor, Julian; Velasco, Ana; Ávila-Martín, Gerardo

    2017-09-01

    Omega-3 polyunsaturated fatty acids (PUFAs), such as docosaexaenoic acid (DHA) and eicosapentaenoic acid (EPA), mediate neuroactive effects in experimental models of traumatic peripheral nerve and spinal cord injury. Cellular mechanisms of PUFAs include reduced neuroinflammation and oxidative stress, enhanced neurotrophic support, and activation of cell survival pathways. Bioactive Omega-9 monounsaturated fatty acids, such as oleic acid (OA) and 2-hydroxy oleic acid (2-OHOA), also show therapeutic effects in neurotrauma models. These FAs reduces noxious hyperreflexia and pain-related anxiety behavior following peripheral nerve injury and improves sensorimotor function following spinal cord injury (SCI), including facilitation of descending inhibitory antinociception. The relative safe profile of neuroactive fatty acids (FAs) holds promise for the future clinical development of these molecules as analgesic agents. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

    Science.gov (United States)

    Gonçalves, Leonor; Friend, Lauren V.; Dickenson, Anthony H.

    2015-01-01

    Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain. PMID:25576174

  9. Buspirone before prenatal stress protects against adverse effects of stress on emotional and inflammatory pain-related behaviors in infant rats: age and sex differences.

    Science.gov (United States)

    Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Otellin, Vladimir A; Aloisi, Anna Maria

    2011-10-24

    Prenatal stress strengthens tonic pain and provokes depression. The serotoninergic system is involved in these processes. We recently showed that maternal buspirone, a 5-HT1A receptor agonist, protects against the adverse effects of in utero stress on depression and pain in adult rat offspring. Using a similar maternal treatment with buspirone, we focus here on the infant stage, which is important for the correction of prenatal abnormalities. Maternal buspirone before restraint stress during the last week of pregnancy decreased the time of immobility in the forced swim test in the infant offspring. Prenatal stress increased formalin-induced pain in the second part of the time-course of the response to formalin in males of middle infancy but in the first part of the response in males of late infancy. The effect was reversed by maternal buspirone. Pain dominated in males of both middle and late infancy but the time-course of formalin pain in infant females revealed a slower development of the processes. The results show that the time-course of formalin-induced pain in infant rats reacts to prenatal stress in an age-dependent and sexually dimorphic manner. Our finding of opposite influences of prenatal stress and buspirone before prenatal stress on formalin-induced pain during the interphase indicates that functional maturity of the descending serotonergic inhibitory system occurs in late infancy males (11-day-olds), and 5-HT1A receptors participate in this process. The data provide evidence that maternal treatment with buspirone prior to stress during pregnancy alleviates depression-like and tonic pain-related behaviors in the infant offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Diversity of Cortico-descending Projections

    DEFF Research Database (Denmark)

    Innocenti, Giorgio M; Caminiti, Roberto; Rouiller, Eric M

    2018-01-01

    The axonal composition of cortical projections originating in premotor, supplementary motor (SMA), primary motor (a4), somatosensory and parietal areas and descending towards the brain stem and spinal cord was characterized in the monkey with histological tract tracing, electron microscopy (EM) a...

  11. Similar alteration of motor unit recruitment strategies during the anticipation and experience of pain.

    Science.gov (United States)

    Tucker, Kylie; Larsson, Anna-Karin; Oknelid, Stina; Hodges, Paul

    2012-03-01

    A motor unit consists of a motoneurone and the multiple muscle fibres that it innervates, and forms the final neural pathway that influences movement. Discharge of motor units is altered (decreased discharge rate and/or cessation of firing; and increased discharge rate and/or recruitment of new units) during matched-force contractions with pain. This is thought to be mediated by nociceptive (pain) input on motoneurones, as demonstrated in animal studies. It is also possible that motoneurone excitability is altered by pain related descending inputs, that these changes persist after noxious stimuli cease, and that direct nociceptive input is not necessary to induce pain related changes in movement. We aimed to determine whether anticipation of pain (descending pain related inputs without nociceptor discharge) alters motor unit discharge, and to observe motor unit discharge recovery after pain has ceased. Motor unit discharge was recorded with fine-wire electrodes in the quadriceps of 9 volunteers. Subjects matched isometric knee-extension force during anticipation of pain (anticipation: electrical shocks randomly applied over the infrapatellar fat-pad); pain (hypertonic saline injected into the fat-pad); and 3 intervening control conditions. Discharge rate of motor units decreased during pain (Precruitment of 1 population of units and new recruitment of another population were observed during both anticipation and pain; some changes in motor unit recruitment persisted after pain ceased. This challenges the fundamental theory that pain-related changes in muscle activity result from direct nociceptor discharge, and provides a mechanism that may underlie long-term changes in movement/chronicity in some musculoskeletal conditions. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

    Science.gov (United States)

    Lin, C-R; Cheng, J-K; Wu, C-H; Chen, K-H; Liu, C-K

    2017-02-01

    Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 μg per 10 μL per rat) or HDAC inhibitor (10 μg per 10 μL per rat) was injected once daily for 3 days before CFA injection. Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of

  13. ENDOGENOUS ANALGESIA, DEPENDENCE, AND LATENT PAIN SENSITIZATION

    Science.gov (United States)

    Taylor, Bradley K; Corder, Gregory

    2015-01-01

    Endogenous activation of μ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) that is masked by spinal MOR signaling for months, even after complete recovery from injury and re-establishment of normal pain thresholds. Disruption with MOR inverse agonists reinstates pain and precipitates cellular, somatic and aversive signs of physical withdrawal; this phenomenon requires N-methyl-D-aspartate receptor-mediated activation of calcium-sensitive adenylyl cyclase type 1 (AC1). In this review, we present a new conceptual model of the transition from acute to chronic pain, based on the delicate balance between LS and endogenous analgesia that develops after painful tissue injury. First, injury activates pain pathways. Second, the spinal cord establishes MOR constitutive activity (MORCA) as it attempts to control pain. Third, over time, the body becomes dependent on MORCA, which paradoxically sensitizes pain pathways. Stress or injury escalates opposing inhibitory and excitatory influences on nociceptive processing as a pathological consequence of increased endogenous opioid tone. Pain begets MORCA begets pain vulnerability in a vicious cycle. The final result is a silent insidious state characterized by the escalation of two opposing excitatory and inhibitory influences on pain transmission: LS mediated by AC1 (which maintains accelerator), and pain inhibition mediated by MORCA (which maintains the brake). This raises the prospect that opposing homeostatic interactions between MORCA analgesia and latent NMDAR–AC1-mediated pain sensitization create a lasting vulnerability to develop chronic pain. Thus, chronic pain syndromes may result from a failure in constitutive signaling of spinal MORs and a loss of endogenous analgesic control. An overarching long-term therapeutic goal of future research is to alleviate chronic pain by either: a) facilitating endogenous opioid

  14. Descending colon endometriosis misdiagnosis as diverticulitis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyun; Kim, Min Jeong; Ha, Hong Il; Lee, Kwan Seop; Min, Soo Kee [Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang (Korea, Republic of)

    2016-09-15

    Endometriosis is defined as the presence of ectopic endometrial tissue outside the uterus. It is a common disease in menstruating females and intestinal involvement is not uncommon. Intestinal endometriosis most commonly involves the sigmoid colon, rectum, ileum, appendix, and cecum. However, the descending colon is a rare site of intestinal endometriosis. Although computed tomography (CT) findings of bowel endometriosis have been presented in several articles, there has been no report describing the CT findings of descending colon endometriosis above the pelvic cavity. Here, we report a rare case of descending colon endometriosis located in the retroperitoneal space, in which the initial impression was acute colonic diverticulitis with a small abscess on preoperative multidetector CT.

  15. Descending colon endometriosis misdiagnosis as diverticulitis: A case report

    International Nuclear Information System (INIS)

    Kim, Ji Hyun; Kim, Min Jeong; Ha, Hong Il; Lee, Kwan Seop; Min, Soo Kee

    2016-01-01

    Endometriosis is defined as the presence of ectopic endometrial tissue outside the uterus. It is a common disease in menstruating females and intestinal involvement is not uncommon. Intestinal endometriosis most commonly involves the sigmoid colon, rectum, ileum, appendix, and cecum. However, the descending colon is a rare site of intestinal endometriosis. Although computed tomography (CT) findings of bowel endometriosis have been presented in several articles, there has been no report describing the CT findings of descending colon endometriosis above the pelvic cavity. Here, we report a rare case of descending colon endometriosis located in the retroperitoneal space, in which the initial impression was acute colonic diverticulitis with a small abscess on preoperative multidetector CT

  16. A combinatorial approach for analyzing the number of descendants ...

    African Journals Online (AJOL)

    This work is devoted to a study of the number of descendants of node j in random increasing trees, previously treated in [5, 8, 10, 15], and also to a study of the number of descendants of node j in pairs of random trees generated by a certain growth process generalizing the corresponding analysis of various classes of ...

  17. Sex differences in the stability of conditioned pain modulation (CPM) among patients with chronic pain.

    Science.gov (United States)

    Martel, Marc O; Wasan, Ajay D; Edwards, Robert R

    2013-11-01

    To examine the temporal stability of conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory controls, among a sample of patients with chronic pain. The study also examined the factors that might be responsible for the stability of CPM. In this test-retest study, patients underwent a series of standardized psychophysical pain-testing procedures designed to assess CPM on two separate occasions (i.e., baseline and follow up). Patients also completed self-report measures of catastrophizing (Pain Catastrophizing Scale [PCS] and negative affect [NA]). Overall, results provided evidence for the stability of CPM among patients with chronic pain. Results, however, revealed considerable sex differences in the stability of CPM. For women, results revealed a significant test-retest correlation between baseline and follow-up CPM scores. For men, however, the test-retest correlation between baseline and follow-up CPM scores was not significant. Results of a Fisher's Z-test revealed that the stability of CPM was significantly greater for women than for men. Follow-up analyses revealed that the difference between men and women in the stability of CPM could not be accounted for by any demographic (e.g., age) and/or psychological factors (PCS and NA). Our findings suggest that CPM paradigms possess sufficient reliability to be incorporated into bedside clinical evaluation of patients with chronic pain, but only among women. The lack of CPM reproducibility/stability observed among men places limits on the potential use of CPM paradigms in clinical settings for the assessment of men's endogenous pain-inhibitory function. Wiley Periodicals, Inc.

  18. Influence of transcranial direct current stimulation of the dorsolateral prefrontal cortex on pain related emotions: a study using electroencephalographic power spectrum analysis.

    Science.gov (United States)

    Maeoka, Hiroshi; Matsuo, Atsushi; Hiyamizu, Makoto; Morioka, Shu; Ando, Hiroshi

    2012-03-14

    Pain is a multidimensional experience with sensory-discriminative, cognitive-evaluative and affective-motivational components. Emotional factors such as unpleasantness or anxiety are known to have influence on pain in humans. The aim of this single-blinded, cross over study was to evaluate the effects of transcranial direct current stimulation (tDCS) on emotional aspects of pain in pain alleviation. Fifteen subjects (5 females, 10 males) volunteered to participate in this study. In an oddball paradigm, three categories of 20 pictures (unpleasant, neutral, and pleasant) served as rare target pictures from the International Affective Picture System (IAPS). The power of the delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-25 Hz), and gamma (30-40 Hz) frequency bands in the three categories were measured using electroencephalography during an oddball paradigm at pre- and post-anodal or sham tDCS above the left dorsolateral prefrontal cortex (DLPFC). Results showed that the beta band power was significantly increased, and the alpha band power was significantly decreased during unpleasant pictures after anodal tDCS compared with sham tDCS. Furthermore, regarding unpleasant pictures, subjective reports of Self Assessment Manikin (SAM) for emotional valence after anodal tDCS showed a significant decrease of unpleasantness. Therefore, emotional aspects of pain may be effectively alleviated by tDCS of the left DLPFC as was shown not only by subjective evaluation, but also by objective observation of cerebral neural activity. This processing may be mediated by facilitation of the descending pain inhibitory system through enhancing neural activity of the left DLPFC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Descending perineum syndrome: new perspectives.

    Science.gov (United States)

    Pucciani, F

    2015-08-01

    The classical clinical profile of descending perineum syndrome (DPS) has been replaced by new pathophysiological, diagnostic, and therapeutic acquisitions. This paper will focus on trigger factors ranging from dyssynergic defecation to excessive straining, fecal incontinence against the backdrop of obstructed defecation, attendant rectal diseases, and therapy tailored to evolving stages of DPS.

  20. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    Directory of Open Access Journals (Sweden)

    Bouwense SA

    2015-07-01

    Full Text Available Stefan AW Bouwense,1 Søren S Olesen,2 Asbjørn M Drewes,2 Harry van Goor,1 Oliver HG Wilder-Smith31Pain and Nociception Neuroscience Research Group, Department of Surgery, Radboud university medical center, Nijmegen, The Netherlands; 2Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 3Pain and Nociception Neuroscience Research Group, Department of Anaesthesiology, Pain and Palliative Medicine, Radboud university medical center, Nijmegen, The NetherlandsBackground: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders to placebo or pregabalin treatment. Methods: This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15 or placebo (n=12; n=17 treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT in dermatomes C5 (generalized effects and Ventral T10 (segmental effects. Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM paradigm. Results: Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA vs placebo responders (−0.1 mA; P=0.015. This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9% vs placebo responders (−17%; P<0.001. CPM changed significantly vs baseline only for pregabalin responders (P=0.006. Conclusion: This hypothesis

  1. Pronociceptive pain modulation in patients with painful chemotherapy-induced polyneuropathy.

    Science.gov (United States)

    Nahman-Averbuch, Hadas; Yarnitsky, David; Granovsky, Yelena; Sprecher, Elliot; Steiner, Mariana; Tzuk-Shina, Tzahala; Pud, Dorit

    2011-08-01

    Several chemotherapy agents induce polyneuropathy that is painful for some patients, but not for others. We assumed that these differences might be attributable to varying patterns of pain modulation. The aim of the present study was to evaluate pain modulation in such patients. Twenty-seven patients with chemotherapy-induced polyneuropathy were tested for detection thresholds (cold, warm, and mechanical) in both the forearm and foot, as well as for heat pain threshold, mechanical temporal summation (TS), and conditioned pain modulation (CPM; also known as the diffuse noxious inhibitory control-like effect), which were tested in the upper limbs. Positive correlations were found between clinical pain levels and both TS (r=0.52, P=0.005) and CPM (r=0.40, P=0.050) for all patients. In addition, higher TS was associated with less efficient CPM (r=0.56, P=0.004). The group of patients with painful polyneuropathy (n=12) showed a significantly higher warm detection threshold in the foot (P=0.03), higher TS (P<0.01), and less efficient CPM (P=0.03) in comparison to the group with nonpainful polyneuropathy. The painfulness of polyneuropathy is associated with a "pronociceptive" modulation pattern, which may be primary to the development of pain. The higher warm sensory thresholds in the painful polyneuropathy group suggest that the severity of polyneuropathy may be another factor in determining its painfulness. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  2. Measuring empathy for human and robot hand pain using electroencephalography.

    Science.gov (United States)

    Suzuki, Yutaka; Galli, Lisa; Ikeda, Ayaka; Itakura, Shoji; Kitazaki, Michiteru

    2015-11-03

    This study provides the first physiological evidence of humans' ability to empathize with robot pain and highlights the difference in empathy for humans and robots. We performed electroencephalography in 15 healthy adults who observed either human- or robot-hand pictures in painful or non-painful situations such as a finger cut by a knife. We found that the descending phase of the P3 component was larger for the painful stimuli than the non-painful stimuli, regardless of whether the hand belonged to a human or robot. In contrast, the ascending phase of the P3 component at the frontal-central electrodes was increased by painful human stimuli but not painful robot stimuli, though the interaction of ANOVA was not significant, but marginal. These results suggest that we empathize with humanoid robots in late top-down processing similarly to human others. However, the beginning of the top-down process of empathy is weaker for robots than for humans.

  3. Descending necrotising mediastinitis: Case report

    Directory of Open Access Journals (Sweden)

    Canan Eren

    2010-12-01

    Full Text Available Descending necrotising mediastinitis is a rare but usually fatal infection. It commonly results of oropharyngeal and odontogenic infections. Complete recovery may be achieved by early diagnosis, prompt medical and surgical approach. We are reporting our desending necrotizing mediastinitis case secondary to tooth abscess, and it’s successfull surgical treatment.A-48-year-old man admitted with fever, exhaustion neck distendion for a week. He had a tooth abscess one week ago. Chest tomography showed neck and mediastinal air and fluid collections. Antibiothreapy was started and urgent surgical management applied. Neck drainage was performed via transcervical approach. Mediastinal drainage was performed via right thoracotomy. Continue mediastinal washing feasibility was done by drainage tubes. Drainage was ended after nonextra drainage and cultural growthless. Vital signs became stable and control tomography showed complete recovery. He was healthfull at the 6th month’s follow-up.Broad antibiothreapy, surgical management are the main approaches for descending necrotising mediastinitis. The most common surgical procedure is the combination of transcervical approach and thoracotomy. We suggest early and agressive surgical management for the complete recovery. J Clin Exp Invest 2010; 1(3: 228-231

  4. Effect of two contrasting types of physical exercise on chronic neck muscle pain

    DEFF Research Database (Denmark)

    Andersen, Lars L; Kjaer, Michael; Søgaard, Karen

    2008-01-01

    trial and recruited subjects from 7 workplaces characterized by monotonous jobs (e.g., computer-intensive work). Forty-eight employed women with chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia) were randomly assigned to 10 weeks of specific strength training locally......OBJECTIVE: The prevalence of neck muscle pain has steadily increased and especially pain from the descending part of the trapezius muscle has been associated with monotonous work tasks such as computer work. Physical exercise is generally recommended as treatment, but it is unclear which type...... of training is most effective. Our objective was to determine the effectiveness of specific strength training of the painful muscle versus general fitness training without direct involvement of the painful muscle (leg bicycling) on work-related neck muscle pain. METHODS: We conducted a randomized controlled...

  5. Effect of two contrasting types of physical exercise on chronic neck muscle pain

    DEFF Research Database (Denmark)

    Andersen, L.L.; Kjær, Michael; Søgaard, Kirsten

    2008-01-01

    trial and recruited subjects from 7 workplaces characterized by monotonous jobs (e.g., computer-intensive work). Forty-eight employed women with chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia) were randomly assigned to 10 weeks of specific strength training locally......Objective. The prevalence of neck muscle pain has steadily increased and especially pain from the descending part of the trapezius muscle has been associated with monotonous work tasks such as computer work. Physical exercise is generally recommended as treatment, but it is unclear which type...... of training is most effective. Our objective was to determine the effectiveness of specific strength training of the painful muscle versus general fitness training without direct involvement of the painful muscle (leg bicycling) on work-related neck muscle pain. Methods. We conducted a randomized controlled...

  6. Effects of ascending and descending climbers on space elevator cable dynamics

    Science.gov (United States)

    Ishikawa, Yoji; Otsuka, Kiyotoshi; Yamagiwa, Yoshiki; Doi, Hinata

    2018-04-01

    Based on a mass-point model, the cable dynamics of a space elevator during a climber's travel motion are examined. The cable response during a single operation of one ascending or descending climber is analyzed first, and then, based on the results, the cable dynamics for simultaneous operation of an ascending and a descending climber are evaluated. For the single operation, bending is significant when the climber is traveling near the Earth's surface. The cable also inclines with periodic oscillation as a result of a Coriolis force corresponding to the climber velocity. However, simultaneous operation of ascending and descending climbers can suppress the inclination of the cable by almost a factor of ten. In simultaneous operation, compared to single operation, a descending climber has a smaller amplitude of libration angle and less cable bending, while an ascending climber has a smaller amplitude when the climber is traveling at a higher altitude with climber velocities of 200 km/h and 400 km/h. The phase of the oscillation of the overall cable is found to be close to that of the descending climber. Cable bending is suppressed for any examined climber velocity, but the dependency of this suppression of displacement on climber velocity is not found. In summary, simultaneous operation can surely suppress the inclination of the cable via the cancellation of Coriolis forces by the two climbers.

  7. Successful outcome of descending necrotizing mediastinitis due to neck trauma

    International Nuclear Information System (INIS)

    Kurowski, K.; Matuszek, I.; Nunez, C. F. M.

    2011-01-01

    Descending necrotizing mediastinitis (DNM) is an uncommon form of mediastinitis that can rapidly progress to septicemia. The optimal surgical approach still remains controversial. In this paper we would like to present a case of descending necrotizing mediastinitis that was treated successfully by means of thoracic drainage through trans-thoracic approach. In our case DNM occurred as a complication of oropharyngeal abscesses and a complication of cervical spine trauma. (authors)

  8. Mechanisms and management of functional abdominal pain.

    Science.gov (United States)

    Farmer, Adam D; Aziz, Qasim

    2014-09-01

    Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory systems may have an important role. The management of patients with functional abdominal pain requires a tailored multidisciplinary approach in a supportive and empathetic environment in order to develop an effective therapeutic relationship. Patient education directed towards an explanation of the pathophysiology of functional abdominal pain is in our opinion a prerequisite step and provides the rationale for the introduction of interventions. Interventions can usefully be categorised into general measures, pharmacotherapy, psychological interventions and 'step-up' treatments. Pharmacotherapeutic/step-up options include tricyclic antidepressants, serotonin noradrenergic reuptake inhibitors and the gabapentinoids. Psychological treatments include cognitive behavioural therapy and hypnotherapy. However, the objective evidence base for these interventions is largely derived from other chronic pain syndrome, and further research is warranted in adult patients with functional abdominal pain. © The Royal Society of Medicine.

  9. Pain perception studies in tension-type headache

    DEFF Research Database (Denmark)

    Bezov, David; Ashina, Sait; Jensen, Rigmor

    2011-01-01

    Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies...... of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC...... to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti-depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has...

  10. Management of chronic ankle pain using joint mobilization and ASTYM® treatment: a case report.

    Science.gov (United States)

    Slaven, Emily J; Mathers, Jessie

    2011-05-01

    Treatment of ankle sprains predominately focuses on the acute management of this condition; less emphasis is placed on the treatment of ankle sprains in the chronic phase of recovery. Manual therapy, in the form of joint mobilization and manipulation, has been shown to be effective in the management of this condition, but the combination of joint mobilization and manipulation in tandem with ASTYM® treatment has not been explored. The purpose of this case report is to chronicle the management of a patient with chronic ankle pain who was treated with manual therapy including manipulation and ASTYM treatment. As a result of a fall down stairs 6 months previously, the patient sustained a severe ankle sprain. The soft tissue damage was accompanied by bony disruptions which warranted the patient spending 3 weeks in a walking boot. At the initial evaluation, the patient reported difficulty with descending stairs reciprocally and not being able to run more than 4 minutes on the treadmill before the pain escalated to the level that she had to stop running. After five sessions of therapy consisting of joint mobilization, manipulation and ASTYM, the patient was able to descend stairs and run 40 minutes without pain.

  11. The descendants of the first quasars in the BlueTides simulation

    Science.gov (United States)

    Tenneti, Ananth; Di Matteo, Tiziana; Croft, Rupert; Garcia, ThomasJae; Feng, Yu

    2018-02-01

    Supermassive blackholes with masses of a billion solar masses or more are known to exist up to z = 7. However, the present-day environments of the descendants of first quasars are not well understood and it is not known if they live in massive galaxy clusters or more isolated galaxies at z = 0. We use a dark matter-only realization (BTMassTracer) of the BlueTides cosmological hydrodynamic simulation to study the halo properties of the descendants of the most massive black holes at z = 8. We find that the descendants of the quasars with most massive black holes are not amongst the most massive haloes. They reside in haloes of with group-like (˜1014 M⊙) masses, while the most massive haloes in the simulations are rich clusters with masses ˜1015 M⊙. At z = 0, the distribution of halo masses of these quasar descendants is similar to that of the descendants of least massive black holes, which indicates that they are likely to exist in similar environments. By tracing back to the z = 8 progenitors of the most massive (cluster sized) haloes at z = 0; we find that their most likely black hole mass is less than 107 M⊙; they are clearly not amongst the most massive black holes. For haloes above 1015 M⊙, there is only 20 per cent probability that their z = 8 progenitors hosted a black hole with mass above 107 M⊙.

  12. Performance and physiological effects of different descending strategies for cross-country mountain biking.

    Science.gov (United States)

    Miller, Matthew C; Macdermid, Paul W; Fink, Phil W; Stannard, Stephen R

    2017-04-01

    This study investigated the performance-related feasibility and physiological benefits of purposefully eliminating propulsive work while descending in mountain biking and compared values to those measured during road descending. Participants cycled uphill on a road at race pace before descending over three conditions (off-road pedalling; off-road coasting; road coasting). Relatively low power output during off-road pedalling was associated with a greater oxygen uptake (p  .05). Importantly, pedalling did not invoke a performance benefit (p > .05) on the descent used in this study. Significantly greater heart rate and oxygen uptake (both p bike athletes focus on skills to increase descending speed without the addition of pedalling, and that equipment be used to decrease vibrations nearer to those seen on the road.

  13. Entanglement entropy for descendent local operators in 2D CFTs

    International Nuclear Information System (INIS)

    Chen, Bin; Guo, Wu-Zhong; He, Song; Wu, Jie-qiang

    2015-01-01

    We mainly study the Rényi entropy and entanglement entropy of the states locally excited by the descendent operators in two dimensional conformal field theories (CFTs). In rational CFTs, we prove that the increase of entanglement entropy and Rényi entropy for a class of descendent operators, which are generated by L"("−")L̄"("−") onto the primary operator, always coincide with the logarithmic of quantum dimension of the corresponding primary operator. That means the Rényi entropy and entanglement entropy for these descendent operators are the same as the ones of their corresponding primary operator. For 2D rational CFTs with a boundary, we confirm that the Rényi entropy always coincides with the logarithmic of quantum dimension of the primary operator during some periods of the evolution. Furthermore, we consider more general descendent operators generated by ∑d_{_n__i_}_{_n__j_}(∏_iL_−_n__i∏_jL̄_−_n__j) on the primary operator. For these operators, the entanglement entropy and Rényi entropy get additional corrections, as the mixing of holomorphic and anti-holomorphic Virasoro generators enhance the entanglement. Finally, we employ perturbative CFT techniques to evaluate the Rényi entropy of the excited operators in deformed CFT. The Rényi and entanglement entropies are increased, and get contributions not only from local excited operators but also from global deformation of the theory.

  14. Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

    Science.gov (United States)

    Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

    2016-03-01

    Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest

  15. Glia and pain: is chronic pain a gliopathy?

    Science.gov (United States)

    Ji, Ru-Rong; Berta, Temugin; Nedergaard, Maiken

    2013-12-01

    Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. Although widely detected in chronic pain resulting from nerve trauma, inflammation, cancer, and chemotherapy in rodents, and more recently, human immunodeficiency virus-associated neuropathy in human beings, glial reaction (activation state 1) is not thought to mediate pain sensitivity directly. Instead, activation states 2 to 4 have been demonstrated to enhance pain sensitivity via a number of synergistic neuro-glial interactions. Glial mediators have been shown to powerfully modulate excitatory and inhibitory synaptic transmission at presynaptic, postsynaptic, and extrasynaptic sites. Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of "gliopathy," that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions. Copyright © 2013 International Association for the

  16. Hybrid Approach of Aortic Diseases: Zone 1 Delivery and Volumetric Analysis on the Descending Aorta

    Directory of Open Access Journals (Sweden)

    José Augusto Duncan

    Full Text Available Abstract Introduction: Conventional techniques of surgical correction of arch and descending aortic diseases remains as high-risk procedures. Endovascular treatments of abdominal and descending thoracic aorta have lower surgical risk. Evolution of both techniques - open debranching of the arch and endovascular approach of the descending aorta - may extend a less invasive endovascular treatment for a more extensive disease with necessity of proximal landing zone in the arch. Objective: To evaluate descending thoracic aortic remodeling by means of volumetric analysis after hybrid approach of aortic arch debranching and stenting the descending aorta. Methods: Retrospective review of seven consecutive patients treated between September 2014 and August 2016 for diseases of proximal descending aorta (aneurysms and dissections by hybrid approach to deliver the endograft at zone 1. Computed tomography angiography were analyzed using a specific software to calculate descending thoracic aorta volumes pre- and postoperatively. Results: Follow-up was done in 100% of patients with a median time of 321 days (range, 41-625 days. No deaths or permanent neurological complications were observed. There were no endoleaks or stent migrations. Freedom from reintervention was 100% at 300 days and 66% at 600 days. Median volume reduction was of 45.5 cm3, representing a median volume shrinkage by 9.3%. Conclusion: Hybrid approach of arch and descending thoracic aorta diseases is feasible and leads to a favorable aortic remodeling with significant volume reduction.

  17. Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2018-01-01

    Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.

  18. Therapeutic Basis of Clinical Pain Modulation

    Science.gov (United States)

    Kirkpatrick, Daniel R.; McEntire, Dan M.; Hambsch, Zakary J.; Kerfeld, Mitchell J.; Smith, Tyler A.; Reisbig, Mark D.; Youngblood, Charles F.

    2015-01-01

    Abstract Pain is a hallmark of almost all bodily ailments and can be modulated by agents, including analgesics and anesthetics that suppress pain signals in the central nervous system. Defects in the modulatory systems, including the endogenous pain‐inhibitory pathways, are a major factor in the initiation and chronicity of pain. Thus, pain modulation is particularly applicable to the practice of medicine. This review summarizes the existing literature on pain modulation. Here, we critically reviewed the literature from PubMed on pain modulation published primarily within the past 5 years in high impact journals. Specifically, we have discussed important anatomical landmarks of pain modulation and outlined the endogenous networks and underlying mechanisms of clinically relevant pain modulatory methods. The Gate Control Theory is briefly presented with discussion on the capacity of pain modulation to cause both hyper‐ and hypoalgesia. An emphasis has been given to highlight key areas in pain research that, because of unanswered questions or therapeutic potential, merit additional scientific scrutiny. The information presented in this paper would be helpful in developing novel therapies, metrics, and interventions for improved patient management. PMID:25962969

  19. Pain physiology education improves health status and endogenous pain inhibition in fibromyalgia: a double-blind randomized controlled trial.

    Science.gov (United States)

    Van Oosterwijck, Jessica; Meeus, Mira; Paul, Lorna; De Schryver, Mieke; Pascal, Aurelie; Lambrecht, Luc; Nijs, Jo

    2013-10-01

    There is evidence that education on pain physiology can have positive effects on pain, disability, and catastrophization in patients with chronic musculoskeletal pain disorders. A double-blind randomized controlled trial (RCT) was performed to examine whether intensive pain physiology education is also effective in fibromyalgia (FM) patients, and whether it is able to influence the impaired endogenous pain inhibition of these patients. Thirty FM patients were randomly allocated to either the experimental (receiving pain physiology education) or the control group (receiving pacing self-management education). The primary outcome was the efficacy of the pain inhibitory mechanisms, which was evaluated by spatially accumulating thermal nociceptive stimuli. Secondary outcome measures included pressure pain threshold measurements and questionnaires assessing pain cognitions, behavior, and health status. Assessments were performed at baseline, 2 weeks, and 3 months follow-up. Repeated measures ANOVAS were used to reveal possible therapy effects and effect sizes were calculated. After the intervention the experimental group had improved knowledge of pain neurophysiology (Pphysiology. Pain physiology education seems to be a useful component in the treatment of FM patients as it improves health status and endogenous pain inhibition in the long term.

  20. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

    Science.gov (United States)

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help

  1. Investigating Circadian Rhythmicity in Pain Sensitivity Using a Neural Circuit Model for Spinal Cord Processing of Pain

    DEFF Research Database (Denmark)

    Crodelle, Jennifer; Piltz, Sofia Helena; Booth, Victoria

    2017-01-01

    Primary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating the resu......Primary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating...... the resultant pain signal. The differential equation models describe the average firing rates of excitatory and inhibitory interneuron populations, as well as the wide dynamic range (WDR) neurons whose output correlates with the pain signal. The temporal profile of inputs on the different afferent nerve fibers...

  2. Resection and anastomosis of the descending colon in 43 horses.

    Science.gov (United States)

    Prange, Timo; Holcombe, Susan J; Brown, Jennifer A; Dechant, Julie E; Fubini, Susan L; Embertson, Rolf M; Peroni, John; Rakestraw, Peter C; Hauptman, Joe G

    2010-08-01

    To determine (1) the short- (to hospital discharge) and long- (>6 months) term survival, (2) factors associated with short-term survival, and (3) the perioperative course for horses with resection and anastomosis of the descending colon. Multicentered case series. Horses (n=43) that had descending colon resection and anastomosis. Medical records (January 1995-June 2009) of 7 equine referral hospitals were reviewed for horses that had descending colon resection and anastomosis and were recovered from anesthesia. Retrieved data included history, results of clinical and clinicopathologic examinations, surgical findings, postsurgical treatment and complications, and short-term survival (hospital discharge). Long-term survival was defined as survival > or =6 months after hospital discharge. Of 43 horses, 36 (84%) were discharged from the hospital. Twenty-eight of 30 horses with follow-up information survived > or =6 months. No significant associations between perioperative factors and short-term survival were identified. Lesions included strangulating lipoma (n=27), postfoaling trauma (4), infarction (4), intraluminal obstruction (2), and other (6). Common postoperative complications included fever and diarrhea. During hospitalization 7 horses were euthanatized or died because of septic peritonitis (3), endotoxemia (3), and colic and ileus (1). Descending colon resection and anastomosis has a favorable prognosis for hospital discharge and survival > or =6 months. The most common cause of small colon incarceration was strangulating lipoma. Complications include postoperative fever and diarrhea but the prognosis is good after small colon resection and anastomosis.

  3. Cartographies of the Political Camp of Afro-Descendents in Latin America

    Directory of Open Access Journals (Sweden)

    Agustín Lao-Montes

    2009-07-01

    Full Text Available This article lays out, in general terms, what it calls the political camp of Afro-descendents in Latin America. After establishing a series of theoretical and methodological criteria for the historical analysis of black movements in modernity and the Afro-American movements in particular, the article focuses on the emergence of afro-descendant movements in Latin America during the last part of the 1980s. One of the principal arguments is that in the 1990s a political camp of afro-descendents starts to emerge in the region of Latin America based on a series of developments, including the emergence of new social movements that included ethno-racial movements of Afros and indigenous people, events of regional importance like the contra-celebration of 1492 in 1992, the World Conference against Racism 2001 in Durban, South Africa, and the effects of the neoliberal pattern of globalization. The political camp of Afro-descendents is composed not only of social movements, but also of state actors and transnational actors (such as the World Bank and the Ford Foundation. The article concludes with an analysis of the challenges and perspectives of Afro-American politics in general and of Afro-Latin movements in particular considering the current crisis of the modern/colonial world-system.

  4. Mural Thrombus in the Normal-Appearing Descending Thoracic Aorta of a Chronic Smoker

    Science.gov (United States)

    Habib, Habib; Hsu, Judy; Winchell, Patricia Jo; Daoko, Joseph

    2013-01-01

    Thrombus formation in an atherosclerotic or aneurysmal descending thoracic aorta is a well-described, frequently encountered vascular condition. In comparison, thrombus formation in a normal-appearing descending thoracic aorta is reported far less often. We describe the case of a 46-year-old woman who had splenic and renal infarctions secondary to embolic showers from a large, mobile thrombus in a morphologically normal proximal descending thoracic aorta. After the patient underwent anticoagulation, stent-grafting, and surgical bypass to correct an arterial blockage caused by the stent-graft, she resumed a relatively normal life. In contrast with other cases of a thrombotic but normal-appearing descending thoracic aorta, this patient had no known malignancy or systemic coagulative disorders; her sole risk factor was chronic smoking. We discuss our patient's case and review the relevant medical literature, focusing on the effect of smoking on coagulation physiology. PMID:24391341

  5. Descending brain neurons in larval lamprey: Spinal projection patterns and initiation of locomotion

    Science.gov (United States)

    Shaw, Albert C.; Jackson, Adam W.; Holmes, Tamra; Thurman, Suzie; Davis, G.R.; McClellan, Andrew D.

    2010-01-01

    In larval lamprey, partial lesions were made in the rostral spinal cord to determine which spinal tracts are important for descending activation of locomotion and to identify descending brain neurons that project in these tracts. In whole animals and in vitro brain/spinal cord preparations, brain-initiated spinal locomotor activity was present when the lateral or intermediate spinal tracts were spared but usually was abolished when the medial tracts were spared. We previously showed that descending brain neurons are located in eleven cell groups, including reticulospinal (RS) neurons in the mesenecephalic reticular nucleus (MRN) as well as the anterior (ARRN), middle (MRRN), and posterior (PRRN) rhombencephalic reticular nuclei. Other descending brain neurons are located in the diencephalic (Di) as well as the anterolateral (ALV), dorsolateral (DLV), and posterolateral (PLV) vagal groups. In the present study, the Mauthner and auxillary Mauthner cells, most neurons in the Di, ALV, DLV, and PLV cell groups, and some neurons in the ARRN and PRRN had crossed descending axons. The majority of neurons projecting in medial spinal tracts included large identified Müller cells and neurons in the Di, MRN, ALV, and DLV. Axons of individual descending brain neurons usually did not switch spinal tracts, have branches in multiple tracts, or cross the midline within the rostral cord. Most neurons that projected in the lateral/intermediate spinal tracts were in the ARRN, MRRN, and PRRN. Thus, output neurons of the locomotor command system are distributed in several reticular nuclei, whose neurons project in relatively wide areas of the cord. PMID:20510243

  6. Catastrophizing Interferes with Cognitive Modulation of Pain in Women with Fibromyalgia.

    Science.gov (United States)

    Ellingson, Laura D; Stegner, Aaron J; Schwabacher, Isaac J; Lindheimer, Jacob B; Cook, Dane B

    2018-02-21

    Pain modulation is a critical function of the nociceptive system that includes the ability to engage descending pain control systems to maintain a functional balance between facilitation and inhibition of incoming sensory stimuli. Dysfunctional pain modulation is associated with increased risk for chronic pain and is characteristic of fibromyalgia (FM). Catastrophizing is also common in FM. However, its influence on pain modulation is poorly understood. To determine the role of catastrophizing on central nervous system processing during pain modulation in FM via examining brain responses and pain sensitivity during an attention-distraction paradigm. Twenty FM patients and 18 healthy controls (CO) underwent functional magnetic resonance imaging while receiving pain stimuli, administered alone and during distracting cognitive tasks. Pain ratings were assessed after each stimulus. Catastrophizing was assessed with the Pain Catastrophizing Scale (PCS). The ability to modulate pain during distraction varied among FM patients and was associated with catastrophizing. This was demonstrated by significant positive relationships between PCS scores and pain ratings (P modulation did not differ between FM and CO (P > 0.05). FM patients with higher levels of catastrophizing were less able to distract themselves from pain, indicative of catastrophizing-related impairments in pain modulation. These results suggest that the tendency to catastrophize interacts with attention-resource allocation and may represent a mechanism of chronic pain exacerbation and/or maintenance. Reducing catastrophizing may improve FM symptoms via improving central nervous system regulation of pain.

  7. Role of microglia in neuropathic pain, postoperative pain, and morphine tolerance

    Science.gov (United States)

    Wen, Yeong-Ray; Tan, Ping-Heng; Cheng, Jen-Kun; Liu, Yen-Chin; Ji, Ru-Rong

    2011-01-01

    Management of chronic pain such as nerve injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer is a real clinical challenge. Major surgeries such as breast and thoracic surgery, leg amputation, and coronary artery bypass surgery also lead to chronic pain in 10–50% of individuals after acute postoperative pain, in part due to surgery-induced nerve injury. Current treatments mainly focus on blocking neurotransmission in the pain pathway and have only resulted in limited success. Ironically, chronic opioid exposure may lead to paradoxical pain. Development of effective therapeutic strategies requires a better understanding of cellular mechanisms underlying the pathogenesis of neuropathic pain. An important progress in pain research points to important role of microglial cells in the development of chronic pain. Spinal cord microglia are strongly activated after nerve injury, surgical incision, and chronic opioid exposure. Increasing evidence suggests that under all these conditions the activated microglia not only exhibit increased expression of microglial markers CD11b and Iba1 but also display elevated phosphorylation of p38 MAP kinase. Inhibition of spinal cord p38 has been shown to attenuate neuropathic pain and postoperative pain, as well as morphine-induced antinociceptive tolerance. Activation of p38 in spinal microglia results in increased synthesis and release of the neurotrophin BDNF and the proinflammatory cytokines IL-1β, IL-6, and TNF-α. These microglia-released mediators can powerfully modulate spinal cord synaptic transmission, leading to increased excitability of dorsal horn neurons, i.e. central sensitization, in part via suppressing inhibitory synaptic transmission. We review the studies that support the pronociceptive role of microglia in conditions of neuropathic pain, post-surgical pain, and opioid tolerance. Some of these studies have been accomplished by four Taiwanese anesthesiologists who are also

  8. 5-HT modulation of pain perception in humans.

    Science.gov (United States)

    Martin, Sarah L; Power, Andrea; Boyle, Yvonne; Anderson, Ian M; Silverdale, Monty A; Jones, Anthony K P

    2017-10-01

    Although there is clear evidence for the serotonergic regulation of descending control of pain in animals, little direct evidence exists in humans. The majority of our knowledge comes from the use of serotonin (5-HT)-modulating antidepressants as analgesics in the clinical management of chronic pain. Here, we have used an acute tryptophan depletion (ATD) to manipulate 5-HT function and examine its effects of ATD on heat pain threshold and tolerance, attentional manipulation of nociceptive processing and mood in human volunteers. Fifteen healthy participants received both ATD and balanced amino acid (BAL) drinks on two separate sessions in a double-blind cross-over design. Pain threshold and tolerance were determined 4 h post-drink via a heat thermode. Additional attention, distraction and temperature discrimination paradigms were completed using a laser-induced heat pain stimulus. Mood was assessed prior and throughout each session. Our investigation reported that the ATD lowered plasma TRP levels by 65.05 ± 7.29% and significantly reduced pain threshold and tolerance in response to the heat thermode. There was a direct correlation between the reduction in total plasma TRP levels and reduction in thermode temperature. In contrast, ATD showed no effect on laser-induced pain nor significant impact of the distraction-induced analgesia on pain perception but did reduce performance of the painful temperature discrimination task. Importantly, all findings were independent of any effects of ATD on mood. As far as we are aware, it is the first demonstration of 5-HT effects on pain perception which are not confounded by mood changes.

  9. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vranken, J. H.; Hollmann, M. W.; van der Vegt, M. H.; Kruis, M. R.; Heesen, M.; Vos, K.; Pijl, A. J.; Dijkgraaf, M. G. W.

    2011-01-01

    The mechanisms underlying central neuropathic pain are poorly understood. Pain inhibitory mechanisms including sertononergic and norepinephrine systems may be dysfunctional. In this randomized, double-blinded, placebo-controlled trial we evaluated the effects of duloxetine on pain relief

  10. Exercise does not produce hypoalgesia when performed immediately after a painful stimulus

    DEFF Research Database (Denmark)

    Gajsar, Hannah; Nahrwold, Katharina; Titze, Christina

    2018-01-01

    Exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM) are assumed to reflect descending pain inhibition. Potential interactions between EIH and CPM may be important in the therapy of chronic pain, as reduced CPM and increased pain after exercise are frequently observed....... This study compared the EIH response after CPM was activated using a cold pressor task with the EIH response after a control condition. Thirty-one participants (age: 27.7±9.8; 15 female) completed two sessions: a cold pressor task (CPT) session, i.e. testing EIH with preceding CPM activation induced using......, back and leg were used to determine the effects of exercise after the cold pressor test and control condition. Furthermore, correlations between CPM and EIH, in the CPT session as well as control session, were calculated at each assessment site. A significant time x condition interaction (F(1, 30...

  11. A combined electrophysiological and morphological study of neuropeptide Y?expressing inhibitory interneurons in the spinal dorsal horn of the mouse

    OpenAIRE

    Iwagaki, Noboru; Ganley, Robert P.; Dickie, Allen C.; Polg?r, Erika; Hughes, David I.; Del Rio, Patricia; Revina, Yulia; Watanabe, Masahiko; Todd, Andrew J.; Riddell, John S.

    2015-01-01

    Abstract The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still have limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty in assigning them to functional populations. Around 15% of inhibitory interneurons in laminae I-III express neuropeptide Y (NPY), but little is known about this population. We th...

  12. Degree of synchronization modulated by inhibitory neurons in clustered excitatory-inhibitory recurrent networks

    Science.gov (United States)

    Li, Huiyan; Sun, Xiaojuan; Xiao, Jinghua

    2018-01-01

    An excitatory-inhibitory recurrent neuronal network is established to numerically study the effect of inhibitory neurons on the synchronization degree of neuronal systems. The obtained results show that, with the number of inhibitory neurons and the coupling strength from an inhibitory neuron to an excitatory neuron increasing, inhibitory neurons can not only reduce the synchronization degree when the synchronization degree of the excitatory population is initially higher, but also enhance it when it is initially lower. Meanwhile, inhibitory neurons could also help the neuronal networks to maintain moderate synchronized states. In this paper, we call this effect as modulation effect of inhibitory neurons. With the obtained results, it is further revealed that the ratio of excitatory neurons to inhibitory neurons being nearly 4 : 1 is an economic and affordable choice for inhibitory neurons to realize this modulation effect.

  13. Factors influencing the mechanical behaviour of healthy human descending thoracic aorta

    International Nuclear Information System (INIS)

    Guinea, Gustavo V; Atienza, José M; Rojo, Francisco J; Yiqun, Li; Claes, Els; Elices, Manuel; García-Herrera, Claudio M; Goicolea, José M; García-Montero, Carlos; Burgos, Raúl L; Goicolea, Francisco J

    2010-01-01

    In recent times, significant effort has been made to understand the mechanical behaviour of the arterial wall and how it is affected by the different vascular pathologies. However, to be able to interpret the results correctly, it is essential that the influence of other factors, such as aging or anisotropy, be understood. Knowledge of mechanical behaviour of the aorta has been customarily constrained by lack of data on fresh aortic tissue, especially from healthy young individuals. In addition, information regarding the point of rupture is also very limited. In this study, the mechanical behaviour of the descending thoracic aorta of 28 organ donors with no apparent disease, whose ages vary from 17 to 60 years, is evaluated. Tensile tests up to rupture are carried out to evaluate the influence of age and wall anisotropy. Results reveal that the tensile strength and stretch at failure of healthy descending aortas show a significant reduction with age, falling abruptly beyond the age of 30. This fact places age as a key factor when mechanical properties of descending aorta are considered

  14. Schwannoma of the descending loop of the hypoglossal nerve: Case report.

    Science.gov (United States)

    Illuminati, Giulio; Pizzardi, Giulia; Pasqua, Rocco; Palumbo, Piergaspare; Vietri, Francesco

    2017-01-01

    Schwannomas of the descending loop of the hypoglossal nerve are very rare. They are slow-growing tumors that may masquerade a carotid body tumor. A 60-year-old female was referred for a latero-cervical mass appearing as a chemodectoma at CT-scan. At operation, a 2cm mass arising from the descending loop of the hypoglossal nerve was resected en bloc with the loop itself and a functional lymphadenectomy was associated. Post-operative course was uneventful and the patient is free from disease recurrence at one year follow-up. En bloc resection remains the real curative treatment of Schwannomas, ensuring unlimited freedom from disease, although causing functional impairment which may be significant. Nonetheless recurrence should be prevented as, beside requiring reintervention, it may harbor a malignant evolution towards sarcoma. Schwannomas of the descending lop of the hypoglossal nerve may masquerade a chemodectoma of the carotid bifurcation and can be curatively resected without any functional impairment. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. The Last Descendant of Tycho Brahe Lives in Romania

    Science.gov (United States)

    Stavinschi, M.

    On 24 October 1601 passed away, in the 55th year of his life, the great astronomer Tycho Brahe. Now, four centuries since his death, his last descendant is living in Romania: Lydia Baroness Løvendal-Papae. An encyclopedic culture and training as hers can rarely be found today; she also is an excellent specialist in genealogy and heraldry. She has not only the merit of studying the cosmic symbols in heraldry, but especially that of establishing the genealogical tree of the famous Danish astronomer. She also holds a genealogical record: as the last descendant of the old Danish dynasty, she descends from all European dynasties, including the founders of the Romanian countries. We shall dwell here neither upon the great personality of Tycho Brahe, nor on his role in the modern astronomy. We shall not refer to the Tycho catalogue resulted from the space mission Hipparcos. We shall dwell upon the ancient aristocratic family Brahe. The oldest firm mention goes as far back as in 1364, but there are data enough on the existence of some members of this family in the 13th century. The Brahe family was related to a no less famous family, that of the Barons Løvendal. One of the ancestors of Lydia Baroness Løvendal is the renowned Ulrik Frederik Voldemar, Baron, then Count Lovendal, marshal of France (1700-1755), whose name was assigned to one of the most important boulevards of Paris.

  16. Pain increases during sympathetic arousal in patients with complex regional pain syndrome.

    Science.gov (United States)

    Drummond, P D; Finch, P M; Skipworth, S; Blockey, P

    2001-10-09

    To investigate the effect of sympathetic arousal on pain and vasomotor responses in healthy control subjects and patients with complex regional pain syndrome (CRPS), and to determine whether pain increases in patients with particular symptoms. In experiments 1 and 2, capsaicin was applied to the forearm of 24 healthy subjects to induce thermal hyperalgesia. Vascular responses were monitored and subjects rated thermal hyperalgesia before and after being startled (experiment 1), and before, during, and after mental arithmetic, breath holding, forehead cooling, the Valsalva maneuver, and a cold pressor test in experiment 2. In a third experiment, sensitivity to heat, cold, and mechanical stimulation was investigated in 61 patients with CRPS. Pain ratings and vascular and electrodermal responses were recorded after patients were startled and during forehead cooling. In experiment 1, thermal hyperalgesia decreased in healthy control subjects after they were startled, and digital blood vessels constricted symmetrically. In experiment 2, thermal hyperalgesia decreased during and after other forms of sympathetic arousal. However, in experiment 3, ratings of clinical pain increased during forehead cooling or after being startled in over 70% of patients with CRPS. Pain increased most consistently during forehead cooling in patients with cold allodynia or punctate allodynia. Digital blood vessels constricted more intensely on the symptomatic than the nonsymptomatic side in patients with CRPS during sympathetic arousal. Normal inhibitory influences on pain during sympathetic arousal are compromised in the majority of patients with CRPS. The augmented vasoconstrictor response in the symptomatic limb during sympathetic arousal is consistent with adrenergic supersensitivity. An adrenergic sensitivity in nociceptive afferents might contribute to pain and hyperalgesia during sympathetic arousal in certain patients with CRPS.

  17. Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.

    Science.gov (United States)

    Long, Caela C; Sadler, Katelyn E; Kolber, Benedict J

    2016-10-15

    The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180min after stress and noxious stimulation. Copyright

  18. Inhibitory noise

    Directory of Open Access Journals (Sweden)

    Alain Destexhe

    2010-03-01

    Full Text Available Cortical neurons in vivo may operate in high-conductance states, in which the major part of the neuron's input conductance is due to synaptic activity, sometimes several-fold larger than the resting conductance. We examine here the contribution of inhibition in such high-conductance states. At the level of the absolute conductance values, several studies have shown that cortical neurons in vivo are characterized by strong inhibitory conductances. However, conductances are balanced and spiking activity is mostly determined by fluctuations, but not much is known about excitatory and inhibitory contributions to these fluctuations. Models and dynamic-clamp experiments show that, during high-conductance states, spikes are mainly determined by fluctuations of inhibition, or by inhibitory noise. This stands in contrast to low-conductance states, in which excitatory conductances determine spiking activity. To determine these contributions from experimental data, maximum likelihood methods can be designed and applied to intracellular recordings in vivo. Such methods indicate that action potentials are indeed mostly correlated with inhibitory fluctuations in awake animals. These results argue for a determinant role for inhibitory fluctuations in evoking spikes, and do not support feed-forward modes of processing, for which opposite patterns are predicted.

  19. Nonpainful remote electrical stimulation alleviates episodic migraine pain.

    Science.gov (United States)

    Yarnitsky, David; Volokh, Lana; Ironi, Alon; Weller, Boaz; Shor, Merav; Shifrin, Alla; Granovsky, Yelena

    2017-03-28

    To evaluate the efficacy of remote nonpainful electrical upper arm skin stimulation in reducing migraine attack pain. This is a prospective, double-blinded, randomized, crossover, sham-controlled trial. Migraineurs applied skin electrodes to the upper arm soon after attack onset for 20 minutes, at various pulse widths, and refrained from medications for 2 hours. Patients were asked to use the device for up to 20 attacks. In 71 patients (299 treatments) with evaluable data, 50% pain reduction was obtained for 64% of participants based on best of 200-μs, 150-μs, and 100-μs pulse width stimuli per individual vs 26% for sham stimuli. Greater pain reduction was found for active stimulation vs placebo; for those starting at severe or moderate pain, reduction (1) to mild or no pain occurred in 58% (25/43) of participants (66/134 treatments) for the 200-μs stimulation protocol and 24% (4/17; 8/29 treatments) for placebo ( p = 0.02), and (2) to no pain occurred in 30% (13/43) of participants (37/134 treatments) and 6% (1/17; 5/29 treatments), respectively ( p = 0.004). Earlier application of the treatment, within 20 minutes of attack onset, yielded better results: 46.7% pain reduction as opposed to 24.9% reduction when started later ( p = 0.02). Nonpainful remote skin stimulation can significantly reduce migraine pain, especially when applied early in an attack. This is presumably by activating descending inhibition pathways via the conditioned pain modulation effect. This treatment may be proposed as an attractive nonpharmacologic, easy to use, adverse event free, and inexpensive tool to reduce migraine pain. NCT02453399. This study provides Class III evidence that for patients with an acute migraine headache, remote nonpainful electrical stimulation on the upper arm skin reduces migraine pain. © 2017 American Academy of Neurology.

  20. Conditioned pain modulation dampens the thermal grill illusion.

    Science.gov (United States)

    Harper, D E; Hollins, M

    2017-10-01

    The thermal grill illusion (TGI) refers to the perception of burning heat and often pain that arises from simultaneous cutaneous application of innocuous warm and cool stimuli. This study utilized conditioned pain modulation (CPM) to help elucidate the TGI's underlying neural mechanisms, including the debated role of ascending nociceptive signals in generating the illusion. To trigger CPM, subjects placed the left hand in noxious cold (6 °C) water before placing the right volar forearm onto a thermal grill. Lower pain and unpleasantness ratings of the grill in this CPM run compared to those in a control run (i.e. 33 °C water) were taken as evidence of CPM. To determine whether CPM reduces noxious heat pain and illusory heat pain equally, an experimental group of subjects rated pain and unpleasantness of a grill consisting of innocuous alternating warm (42 °C) and cool (18 °C) bars, while a control group rated a grill with all bars controlled to a noxious temperature (45 °C). CPM produced significant and comparable reductions in pain, unpleasantness and perceived heat of both noxious heat and the TGI. This result suggests that the TGI results from signals in nociceptive dorsal horn convergent neurons, since CPM involves descending inhibition with high selectivity for this neuronal population. More broadly, CPM's ability to produce a shift in perceived thermal sensation of both noxious heat and the TGI from 'hot' to 'warm' implies that nociceptive signals generated by a cutaneous stimulus can contribute to its perceived thermal intensity. Conditioned pain modulation reduces the perceived painfulness, unpleasantness and heat of the thermal grill illusion and noxious heat similarly. The results have important theoretical implications for both types of pain. © 2017 European Pain Federation - EFIC®.

  1. Hypnotic analgesia reduces brain responses to pain seen in others.

    Science.gov (United States)

    Braboszcz, Claire; Brandao-Farinelli, Edith; Vuilleumier, Patrik

    2017-08-29

    Brain responses to pain experienced by oneself or seen in other people show consistent overlap in the pain processing network, particularly anterior insula, supporting the view that pain empathy partly relies on neural processes engaged by self-nociception. However, it remains unresolved whether changes in one's own pain sensation may affect empathic responding to others' pain. Here we show that inducing analgesia through hypnosis leads to decreased responses to both self and vicarious experience of pain. Activations in the right anterior insula and amygdala were markedly reduced when participants received painful thermal stimuli following hypnotic analgesia on their own hand, but also when they viewed pictures of others' hand in pain. Functional connectivity analysis indicated that this hypnotic modulation of pain responses was associated with differential recruitment of right prefrontal regions implicated in selective attention and inhibitory control. Our results provide novel support to the view that self-nociception is involved during empathy for pain, and demonstrate the possibility to use hypnotic procedures to modulate higher-level emotional and social processes.

  2. Inhibition of Pain and Pain-Related Brain Activity by Heterotopic Noxious Counter-Stimulation and Selective Attention in Chronic Non-Specific Low Back Pain.

    Science.gov (United States)

    Ladouceur, Alexandra; Rustamov, Nabi; Dubois, Jean-Daniel; Tessier, Jessica; Lehmann, Alexandre; Descarreaux, Martin; Rainville, Pierre; Piché, Mathieu

    2017-10-10

    The aim of the present study was to assess inhibition of pain and somatosensory-evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by selective attention in patients with chronic non-specific LBP. Seventeen patients and age/sex-matched controls were recruited (10 men, 7 women; mean age ± SD: 43.3 ± 10.4 and 42.7 ± 11.1, respectively). On average, patients with LBP reported pain duration of 7.6 ± 6.5 years, light to moderate disability (19.3 ± 5.7/100) and low clinical pain intensity (21.8 ± 1.5/100), while pain catastrophizing, state and trait anxiety and depressive symptoms were not significantly different between groups (all p's >0.05). HNCS and selective attention had differential inhibitory effects on pain and SEP, but no difference was observed between groups. Across both groups, HNCS decreased pain (p = 0.06) as well as the N100 and the N150 components of SEP (p's selective attention only decreased pain (p attention was directed toward the HNCS stimulus (pselective attention. Importantly, this experiment was carefully designed to control for non-specific effects associated with the repetition of the test stimulus and the effect of an innocuous counter-stimulation. It remains to be determined if these results hold for patients with severe LBP and psychological symptoms or whether symptom severity may be associated with pain inhibition deficits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Managing neuropathic pain in dogs

    Directory of Open Access Journals (Sweden)

    Sarah A Moore

    2016-02-01

    Full Text Available Disorders of the somatosensory system such as neuropathic pain are common in people with chronic neurologic and musculoskeletal diseases, yet these conditions remain an underappreciated morbidity in our veterinary patients. This is likely because assessment of neuropathic pain in people relies heavily on self-reporting, something our veterinary patients are not able to do. The development of neuropathic pain is a complex phenomenon, and concepts related to it are frequently not addressed in the standard veterinary medical curriculum such that veterinarians may not recognize this as a potential problem in patients. The goals of this review are to discuss basic concepts in the pathophysiology of neuropathic pain, provide definitions for common clinical terms used in association with the condition, and discuss available medical treatment options for dogs with neuropathic pain. The development of neuropathic pain involves key mechanisms such as ectopic afferent nerve activity, peripheral sensitization, central sensitization, impaired inhibitory modulation, and activation of microglia. Treatments aimed at reducing neuropathic pain are targeted at one or more of these mechanisms. Several drugs are commonly used in the veterinary clinical setting to treat neuropathic pain. These include gabapentin, pregabalin, amantadine, and amitriptyline. Proposed mechanisms of action for each drug, and known pharmacokinetic profiles in dogs are discussed. Strong evidence exists in the human literature for the utility of most of these treatments, but clinical veterinary-specific literature is currently limited. Future studies should focus on objective methods to document neuropathic pain and monitor response to therapy in our veterinary patients.

  4. Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury

    Science.gov (United States)

    Benthall, Katelyn N.; Hough, Ryan A.

    2016-01-01

    Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3–5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. NEW & NOTEWORTHY In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the

  5. Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury.

    Science.gov (United States)

    Benthall, Katelyn N; Hough, Ryan A; McClellan, Andrew D

    2017-01-01

    Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3-5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results

  6. The importance of context: When relative relief renders pain pleasant

    Science.gov (United States)

    Leknes, Siri; Berna, Chantal; Lee, Michael C.; Snyder, Gregory D.; Biele, Guido; Tracey, Irene

    2013-01-01

    Context can influence the experience of any event. For instance, the thought that “it could be worse” can improve feelings towards a present misfortune. In this study we measured hedonic feelings, skin conductance, and brain activation patterns in 16 healthy volunteers who experienced moderate pain in two different contexts. In the “relative relief context,” moderate pain represented the best outcome, since the alternative outcome was intense pain. However, in the control context, moderate pain represented the worst outcome and elicited negative hedonic feelings. The context manipulation resulted in a “hedonic flip,” such that moderate pain elicited positive hedonics in the relative relief context. Somewhat surprisingly, moderate pain was even rated as pleasant in this context, despite being reported as painful in the control context. This “hedonic flip” was corroborated by physiological and functional neuroimaging data. When moderate pain was perceived as pleasant, skin conductance and activity in insula and dorsal anterior cingulate were significantly attenuated relative to the control moderate stimulus. “Pleasant pain” also increased activity in reward and valuation circuitry, including the medial orbitofrontal and ventromedial prefrontal cortices. Furthermore, the change in outcome hedonics correlated with activity in the periacqueductal grey (PAG) of the descending pain modulatory system (DPMS). The context manipulation also significantly increased functional connectivity between reward circuitry and the PAG, consistent with a functional change of the DPMS due to the altered motivational state. The findings of this study point to a role for brainstem and reward circuitry in a context-induced “hedonic flip” of pain. PMID:23352758

  7. Analgesic effect of clobazam in chronic low-back pain but not in experimentally induced pain.

    Science.gov (United States)

    Schliessbach, J; Vuilleumier, P H; Siegenthaler, A; Bütikofer, L; Limacher, A; Juni, P; Zeilhofer, H U; Arendt-Nielsen, L; Curatolo, M

    2017-09-01

    Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests. In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake. Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed. This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds. Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target. © 2017 European Pain Federation - EFIC®.

  8. Effect of TENS on pain in relation to central sensitization in patients with osteoarthritis of the knee: study protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Beckwée David

    2012-02-01

    Full Text Available Abstract Background Central sensitization has recently been documented in patients with knee osteoarthritis (OAk. So far, the presence of central sensitization has not been considered as a confounding factor in studies assessing the pain inhibitory effect of tens on osteoarthritis of the knee. The purpose of this study is to explore the pain inhibitory effect of burst tens in OAk patients and to explore the prognostic value of central sensitization on the pain inhibitory effect of tens in OAk patients. Methods Patients with knee pain due to OAk will be recruited through advertisements in local media. Temporal summation, before and after a heterotopic noxious conditioning stimulation, will be measured. In addition, pain on a numeric rating score, WOMAC subscores for pain and function and global perceived effect will be assessed. Patients will be randomly allocated to one of two treatment groups (tens, sham tens. Follow-up measurements will be scheduled after a period of 6 and 12 weeks. Discussion Tens influences pain through the electrical stimulation of low-threshold A-beta cutaneous fibers. The responsiveness of central pain-signaling neurons of centrally sensitized OAk patients may be augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens. To increase treatment effectiveness it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens. Trial Registration ClinicalTrials.gov: NCT01390285

  9. Assessment and manifestation of central sensitisation across different chronic pain conditions.

    Science.gov (United States)

    Arendt-Nielsen, L; Morlion, B; Perrot, S; Dahan, A; Dickenson, A; Kress, H G; Wells, C; Bouhassira, D; Mohr Drewes, A

    2018-02-01

    Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation. Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based

  10. Seawifs Technical Report Series. Volume 2: Analysis of Orbit Selection for Seawifs: Ascending Versus Descending Node

    Science.gov (United States)

    Hooker, Stanford B. (Editor); Firestone, Elaine R. (Editor); Gregg, Watson W.

    1992-01-01

    Due to range safety considerations, the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) ocean color instrument may be required to be launched into a near-noon descending node, as opposed to the ascending node used by the predecessor sensor, the Coastal Zone Color Scanner (CZCS). The relative importance of ascending versus descending near-noon orbits was assessed here to determine if descending node will meet the scientific requirements of SeaWiFS. Analyses focused on ground coverage, local times of coverage, solar and viewing geometries (zenith and azimuth angles), and sun glint. Differences were found in the areas covered by individual orbits, but were not important when taken over a 16 day repeat time. Local time of coverage was also different: for ascending node orbits the Northern Hemisphere was observed in the morning and the Southern Hemisphere in the afternoon, while for descending node orbits the Northern Hemisphere was observed in the afternoon and the Southern in the morning. There were substantial differences in solar azimuth and spacecraft azimuth angles both at equinox and at the Northern Hemisphere summer solstice. Negligible differences in solar and spacecraft zenith angles, relative azimuth angles, and sun glint were obtained at the equinox. However, large differences were found in solar zenith angles, relative azimuths, and sun glint for the solstice. These differences appeared to compensate across the scan, however, an increase in sun glint in descending node over that in ascending node on the western part of the scan was compensated by a decrease on the eastern part of the scan. Thus, no advantage or disadvantage could be conferred upon either ascending node or descending node for noon orbits. Analyses were also performed for ascending and descending node orbits that deviated from a noon equator crossing time. For ascending node, afternoon orbits produced the lowest mean solar zenith angles in the Northern Hemisphere, and morning orbits produced

  11. Union formation and dissolution among immigrants and their descendants in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Tina Hannemann

    2015-08-01

    Full Text Available Background: There is a growing literature on the dynamics of immigrant fertility and mixed marriages, but partnership transitions among immigrants and ethnic minorities are little studied. Objective: This study investigates union formation and dissolution among immigrants and their descendants in the UK. Methods: We use data from the Understanding Society study and apply the techniques of event history analysis. We contrast partnership trajectories of various immigrant groups and compare these with those of the 'native' British population. Results: The analysis shows significant differences in partnership formation and dissolution among immigrants and ethnic minorities. Women of Caribbean origin have the highest cohabitation and the lowest marriage rates, whereas cohabitation remains rare among immigrants from South Asia and their descendants, as most of them marry directly. Immigrants from the Caribbean region and their descendants also show higher divorce rates than 'native' British women, whereas women of South Asian origin have a low divorce risk.

  12. DESCENDING PATHWAYS AND THE HOPPING RESPONSE IN THE RABBIT

    NARCIS (Netherlands)

    HOBBELEN, JF; GRAMSBERGEN, A; VANHOF, MW

    1992-01-01

    Descending pathways were studied in 5 adult rabbits by means of HRP, injected in the cervical spinal cord (in C2 and C3) at the right side. Results indicate the existence of pathways from the contralateral motor cortex, bilateral projections from the red nuclei, from the vestibular nuclei and from

  13. Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks.

    Science.gov (United States)

    Kucyi, Aaron; Salomons, Tim V; Davis, Karen D

    2013-11-12

    Human minds often wander away from their immediate sensory environment. It remains unknown whether such mind wandering is unsystematic or whether it lawfully relates to an individual's tendency to attend to salient stimuli such as pain and their associated brain structure/function. Studies of pain-cognition interactions typically examine explicit manipulation of attention rather than spontaneous mind wandering. Here we sought to better represent natural fluctuations in pain in daily life, so we assessed behavioral and neural aspects of spontaneous disengagement of attention from pain. We found that an individual's tendency to attend to pain related to the disruptive effect of pain on his or her cognitive task performance. Next, we linked behavioral findings to neural networks with strikingly convergent evidence from functional magnetic resonance imaging during pain coupled with thought probes of mind wandering, dynamic resting state activity fluctuations, and diffusion MRI. We found that (i) pain-induced default mode network (DMN) deactivations were attenuated during mind wandering away from pain; (ii) functional connectivity fluctuations between the DMN and periaqueductal gray (PAG) dynamically tracked spontaneous attention away from pain; and (iii) across individuals, stronger PAG-DMN structural connectivity and more dynamic resting state PAG-DMN functional connectivity were associated with the tendency to mind wander away from pain. These data demonstrate that individual tendencies to mind wander away from pain, in the absence of explicit manipulation, are subserved by functional and structural connectivity within and between default mode and antinociceptive descending modulation networks.

  14. Enhanced pain expectation in migraine: EEG-based evidence for impaired prefrontal function.

    Science.gov (United States)

    Lev, Rina; Granovsky, Yelena; Yarnitsky, David

    2013-01-01

    Dysexcitability characterizes the interictal migraineous brain. The main central expressions of this dysexcitability are decreased habituation and enhanced anticipation and attention to pain and other external sensory stimuli. This study evaluates the effects of anticipation on pain modulation and their neural correlates in migraine. In 39 migraineurs (20 migraine with aura [MWA] and 19 migraine without aura [MOA]) and 22 healthy controls, cortical responses to 2 successive trains of noxious contact-heat stimuli, presented in either predicted or unpredicted manner, were analyzed using standardized low-resolution electromagnetic tomography key. A lack of habituation to repeated predicted pain was associated with significantly increased pain-evoked potential amplitudes in MWAs (increase of 3.9 μV) and unchanged ones in MOAs (1.1 μV) but not in controls (decrease of 5 μV). Repeated unpredicted pain resulted in enhanced pain-evoked potential amplitudes in both MWA and MOA groups (increase of 5.5 μV and 4.4 μV, respectively) compared with controls (decrease of 0.2 μV). Source localization revealed reduced activations in the anterior-medial prefrontal cortices and subsequent increased somatosensory activity in migraineurs (P < .05). The prefrontal-somatosensory dysfunction positively correlated with lifetime headache duration (P < .05) and concern of upcoming migraine attacks (P < .05) in MWAs, and with frequency of migraine attacks in MOAs (P < .05). Our findings of impaired modulation of anticipated pain in migraine suggest a heightened state of anticipatory readiness combined with ineffective recruitment of prefrontal inhibitory pathways during experience of pain; the latter might account for the former, at least partially. In line, less efficient inhibitory capability is a plausible mechanistic explanation for patients' high concern about their upcoming migraine attacks. © 2012 American Headache Society.

  15. Prediction of persistent post-surgery pain by preoperative cold pain sensitivity: biomarker development with machine-learning-derived analysis.

    Science.gov (United States)

    Lötsch, J; Ultsch, A; Kalso, E

    2017-10-01

    To prevent persistent post-surgery pain, early identification of patients at high risk is a clinical need. Supervised machine-learning techniques were used to test how accurately the patients' performance in a preoperatively performed tonic cold pain test could predict persistent post-surgery pain. We analysed 763 patients from a cohort of 900 women who were treated for breast cancer, of whom 61 patients had developed signs of persistent pain during three yr of follow-up. Preoperatively, all patients underwent a cold pain test (immersion of the hand into a water bath at 2-4 °C). The patients rated the pain intensity using a numerical ratings scale (NRS) from 0 to 10. Supervised machine-learning techniques were used to construct a classifier that could predict patients at risk of persistent pain. Whether or not a patient rated the pain intensity at NRS=10 within less than 45 s during the cold water immersion test provided a negative predictive value of 94.4% to assign a patient to the "persistent pain" group. If NRS=10 was never reached during the cold test, the predictive value for not developing persistent pain was almost 97%. However, a low negative predictive value of 10% implied a high false positive rate. Results provide a robust exclusion of persistent pain in women with an accuracy of 94.4%. Moreover, results provide further support for the hypothesis that the endogenous pain inhibitory system may play an important role in the process of pain becoming persistent. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.

  16. Effect of Transcutaneous Electrical Nerve Stimulation on Sensation Thresholds in Patients with Painful Diabetic Neuropathy: An Observational Study

    Science.gov (United States)

    Moharic, Metka

    2010-01-01

    Transcutaneous electrical nerve stimulation (TENS) is one of the therapies for painful neuropathy. Its analgesic mechanisms probably involve the gate control theory, the physiological block and the endogenous pain inhibitory system. The aim of the study was to determine whether TENS improves small fibre function diminished because of painful…

  17. Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders

    Directory of Open Access Journals (Sweden)

    Bountra Chas

    2006-12-01

    Full Text Available Abstract Background The Bladder cooling reflex (BCR i.e. uninhibited detrusor contractions evoked by intravesical instillation of cold saline, is a segmental reflex believed to be triggered by menthol sensitive cold receptors in the bladder wall, with the afferent signals transmitted by C fibres. The BCR is a neonatal reflex that becomes suppressed by descending signals from higher centres at approximately the time when the child gains full voluntary control of voiding. It re-emerges in adults with neurogenic detrusor overactivity as a consequence of loss of central descending inhibition, resulting from conditions such as spinal cord injury or multiple sclerosis. We have recently shown an increase of nerve fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO and painful bladder syndrome (PBS, but its functional significance is unknown. We have therefore studied the bladder cooling reflex and associated sensory symptoms in patients with PBS and overactivity disorders. Methods The BCR, elicited by ice water test (IWT was performed in patients with painful bladder syndrome (PBS, n = 17, idiopathic detrusor overactivity (IDO, n = 22, neurogenic detrusor overactivity (NDO, n = 4 and stress urinary incontinence (as controls, n = 21. The IWT was performed by intravesical instillation of cold saline (0 – 4°C. A positive IWT was defined as presence of uninhibited detrusor contraction evoked by cold saline, associated with urgency or with fluid expulsion. Patients were asked to report and rate any pain and cold sensation during the test. Results A positive IWT was observed in IDO (6/22, 27.3% and NDO (4/4, 100% patients, but was negative in all control and PBS patients. Thirteen (76.5% PBS patients reported pain during the IWT, with significantly higher pain scores during ice water instillation compared to the baseline (P = 0.0002, or equivalent amount of bladder filling (100 mls with saline at room temperature (P = 0.015. None

  18. Is there Equity in Use of Healthcare Services among immigrants, their descendents, and ethnic Danes?

    DEFF Research Database (Denmark)

    Nielsen, Signe Smith; Hempler, Nana Folmann; Waldorff, Frans Boch

    2012-01-01

    Background: Legislation in Denmark explicitly states the right to equal access to healthcare. Nevertheless, inequities may exist; accordingly evidence is needed. Our objective was to investigate whether differences in healthcare utilization in immigrants, their descendents, and ethnic Danes could...... were linked to registries on healthcare utilization. Using Poisson regression models, contacts to hospital, emergency room (ER), general practitioner (GP), specialist in private practice, and dentist were estimated. Analyses were adjusted for health symptoms, sociodemographic factors, and proxies...... of integration. Results: In adjusted analyses, immigrants and their descendents had increased use of ER (multiplicative effect=1.19–5.02 dependent on immigrant and descendent group) and less frequent contact to dentist (multiplicative effect=0.04–0.80 dependent on the group). For hospitalization, GP...

  19. Inhibitory effect of Sphagnum palustre extract and its bioactive compounds on aromatase activity

    Directory of Open Access Journals (Sweden)

    Hee Jeong Eom

    2016-09-01

    Full Text Available Sphagnum palustre (a moss has been traditionally used in Korea for the cure of several diseases such as cardiac pain and stroke. In this research, the inhibitory effect of S. palustre on aromatase (cytochrome P450 19, CYP19 activity was studied. [1β-3H] androstenedione was used as a substrate and incubated with S. palustre extract and recombinant human CYP19 in the presence of NADPH. S. palustre extract inhibited aromatase in a concentration-dependent manner (IC50 value: 36.4 ± 8.1 µg/mL. To elucidate the major compounds responsible for the aromatase inhibitory effects of S. palustre extract, nine compounds were isolated from the extract and tested for their inhibition of aromatase activity. Compounds 1, 6, and 7 displayed aromatase inhibition, while the inhibition by the other compounds was negligible.

  20. Integration of Descending Command Systems for the Generation of Context-Specific Locomotor Behaviors

    Directory of Open Access Journals (Sweden)

    Linda H. Kim

    2017-10-01

    Full Text Available Over the past decade there has been a renaissance in our understanding of spinal cord circuits; new technologies are beginning to provide key insights into descending circuits which project onto spinal cord central pattern generators. By integrating work from both the locomotor and animal behavioral fields, we can now examine context-specific control of locomotion, with an emphasis on descending modulation arising from various regions of the brainstem. Here we examine approach and avoidance behaviors and the circuits that lead to the production and arrest of locomotion.

  1. CASE REPORT Dual (type IV) left anterior descending artery

    African Journals Online (AJOL)

    about 1.38%. [1,3] This anomaly is seen relatively often with congenital malformations such as complete transposition of the great arteries and tetralogy of Fallot.[2]. When a short or hypoplastic LAD is detected, a differential diagnosis should be sought. There may be a long dominant posterior descending branch of the RCA, ...

  2. Pain perception studies in tension-type headache.

    Science.gov (United States)

    Bezov, David; Ashina, Sait; Jensen, Rigmor; Bendtsen, Lars

    2011-02-01

    Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC) have played a central role in elucidating the pathophysiology of TTH. It has been demonstrated that continuous nociceptive input from peripheral myofascial structures may induce central sensitization and thereby chronification of the headache. Measurements of pain tolerance thresholds and suprathreshold stimulation have shown presence of generalized hyperalgesia in chronic tension-type headache (CTTH) patients, while DNIC function has been shown to be reduced in CTTH. One imaging study showed loss of gray matter structures involved in pain processing in CTTH patients. Future studies should aim to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti-depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has been shown to rapidly reverse central sensitization and may be a new modality in treatment of CTTH and other chronic pain disorders. © 2010 American Headache Society.

  3. Bilateral anterior thalamic low densities in descending transtentorial herniation

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, Chikao; Watanabe, Takao

    1985-02-01

    Round, well-demarcated, symmetrical low densities in a bilateral thalamus in a case of descending transtentorial herniation due secondarily to acute traumatic left subdural hematoma are reported. An 8-year-old boy, on whom emergency surgery was refused by his parents, showed a marked shift due to the hematoma on admission; this was followed by a low density in the left PCA territory and round, equivocal hypodensities in the anterior thalamus 44 hours post-trauma. The equivocal hypodensities became definite, well-demarcated, round low densities situated symmetrically in the anterior thalamus on the 39th day post-trauma. Akinetic mutism was noted at this time. The symmetrical low densities and the PCA-territory low density persisted as late as the 39th day post-trauma, suggesting infarcts. The downward stretch of the bilateral thalamoperforators, which was effected by a narrowing of the interpeduncular fossa with an approximation of the bilateral perforators, plus a downward shift of the PCA due to descending transtentorial herniation, was assumed to be the mechanism involved. (author).

  4. Preschool Inhibitory Control Predicts ADHD Group Status and Inhibitory Weakness in School.

    Science.gov (United States)

    Jacobson, Lisa A; Schneider, Heather; Mahone, E Mark

    2017-12-26

    Discriminative utility of performance measures of inhibitory control was examined in preschool children with and without ADHD to determine whether performance measures added to diagnostic prediction and to prediction of informant-rated day-to-day executive function. Children ages 4-5 years (N = 105, 61% boys; 54 ADHD, medication-naïve) were assessed using performance measures (Auditory Continuous Performance Test for Preschoolers-Commission errors, Conflicting Motor Response Test, NEPSY Statue) and caregiver (parent, teacher) ratings of inhibition (Behavior Rating Inventory of Executive Function-Preschool version). Performance measures and parent and teacher reports of inhibitory control significantly and uniquely predicted ADHD group status; however, performance measures did not add to prediction of group status beyond parent reports. Performance measures did significantly predict classroom inhibitory control (teacher ratings), over and above parent reports of inhibitory control. Performance measures of inhibitory control may be adequate predictors of ADHD status and good predictors of young children's classroom inhibitory control, demonstrating utility as components of clinical assessments. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Neurotransmitter implications in descending motility of longitudinal and circular muscles in rat colon

    Directory of Open Access Journals (Sweden)

    Zornitsa V. Gorcheva

    2018-03-01

    Full Text Available Introduction. The role of neurotransmitter systems in the motor activity of longitudinal or circular muscles in autonomic regulation of the motility of the colon by the nervous system is unclear. The aim of the study was to investigate the neurotransmitter implications in descending motility of longitudinal and circular muscles in rat colon. Methods. Electrically-induced (2, 5 or 10 Hz, 0.8 ms, 40 V, 20 s local or descending motor responses of longitudinal and circular muscles in isolated preparations and drugs were used to define the neurotransmitters’ role in colonic motility. Results. The spontaneous activity of the distal part of preparations manifested as high-amplitude irregular contractions more expressed in the longitudinal muscles. The electrically-induced local responses differed considerably in the two muscles: in longitudinal muscle there were frequency-dependent contractions, while initial relaxation followed by contraction was observed in circular muscle. The descending motor response resembled the pattern of the local responses, but the amplitudes were significantly less expressed, as compared to the respective local responses.

  6. Semi-automated segmentation of the sigmoid and descending colon for radiotherapy planning using the fast marching method

    International Nuclear Information System (INIS)

    Losnegaard, Are; Hodneland, Erlend; Lundervold, Arvid; Hysing, Liv Bolstad; Muren, Ludvig Paul

    2010-01-01

    A fast and accurate segmentation of organs at risk, such as the healthy colon, would be of benefit for planning of radiotherapy, in particular in an adaptive scenario. For the treatment of pelvic tumours, a great challenge is the segmentation of the most adjacent and sensitive parts of the gastrointestinal tract, the sigmoid and descending colon. We propose a semi-automated method to segment these bowel parts using the fast marching (FM) method. Standard 3D computed tomography (CT) image data obtained from routine radiotherapy planning were used. Our pre-processing steps distinguish the intestine, muscles and air from connective tissue. The core part of our method separates the sigmoid and descending colon from the muscles and other segments of the intestine. This is done by utilizing the ability of the FM method to compute a specified minimal energy functional integrated along a path, and thereby extracting the colon centre line between user-defined control points in the sigmoid and descending colon. Further, we reconstruct the tube-shaped geometry of the sigmoid and descending colon by fitting ellipsoids to points on the path and by adding adjacent voxels that are likely voxels belonging to these bowel parts. Our results were compared to manually outlined sigmoid and descending colon, and evaluated using the Dice coefficient (DC). Tests on 11 patients gave an average DC of 0.83 (±0.07) with little user interaction. We conclude that the proposed method makes it possible to fast and accurately segment the sigmoid and descending colon from routine CT image data.

  7. [Distribution of the male lineages of Genghis Khan's descendants in northern Eurasian populations].

    Science.gov (United States)

    Derenko, M V; Maliarchuk, B A; Wozniak, M; Denisova, G A; Dambueva, I K; Dorzhu, C M; Grzybowski, T; Zakharov, I A

    2007-03-01

    Data on the variation of 12 microsatellite loci of Y-chromosome haplogroup C3 were used to screen lineages included in the cluster of Genghis Khan's descendants in 18 northern Eurasian populations (Altaian Kazakhs, Altaians-Kizhi, Teleuts, Khakassians, Shorians, Tyvans, Todjins, Tofalars, Sojots, Buryats, Khamnigans, Evenks, Mongols, Kalmyks, Tajiks, Kurds, Persians, and Russians; the total sample size was 1437 people). The highest frequency of haplotypes from the cluster of the Genghis Khan's descendants was found in Mongols (34.8%). In Russia, this cluster was found in Altaian Kazakhs (8.3%), Altaians (3.4%), Buryats (2.3%), Tyvans (1.9%), and Kalmyks (1.7%).

  8. Asymmetric pain processing in Parkinson's disease.

    Science.gov (United States)

    Granovsky, Y; Schlesinger, I; Fadel, S; Erikh, I; Sprecher, E; Yarnitsky, D

    2013-10-01

    Reduced endogenous pain inhibition, as part of the degenerative process, is presumed to be the mechanism underlying the common presence of pain in patients with Parkinson's disease (PD). The present study aimed to assess an endogenous pain inhibitory system in PD using the conditioned pain modulation paradigm. Twenty-six predominantly unilateral PD patients and 19 controls underwent psychophysical pain assessment before and after patients' morning dopaminergic medication. An unexpected increase in several parameters of pain perception for PD patients was found after dopaminergic medication (e.g. for 49°C noxious heat stimulation an increase from 70.6 ± 4.0 to 77.6 ± 4.0 on the numerical pain scale, P < 0.001). This increase was seen in patients with predominantly left-sided PD, regardless of the stimulated side (for 49°C noxious heat stimulation, predominantly left-sided PD patients, pain perception increased from 73.5 ± 6.8 to 85.0 ± 6.8, P < 0.001, whereas predominantly right-sided PD patients did not show a significant increase, 68.3 ± 6.8 to 70.4 ± 6.5, P = 0.777). Baseline efficiency of conditioned pain modulation inversely correlated with age at disease onset (r = -0.522; P = 0.009) and disease severity (Unified PD Rating Scale, r = 0.447; P = 0.032) but did not differ between patients and controls. Increased sensory response causing hyperalgesia occurs after dopaminergic medication in patients with predominantly left-sided PD. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

  9. Nonpainful wide-area compression inhibits experimental pain.

    Science.gov (United States)

    Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

    2016-09-01

    Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM.

  10. [Descending control of quiet standing and walking: a plausible neurophysiological basis of falls in elderly people].

    Science.gov (United States)

    Nakajima, Masashi

    2011-03-01

    Quiet standing and walking are generally considered to be an automatic process regulated by sensory feedback. In our report "Astasia without abasia due to peripheral neuropathy," which was published in 1994, we proposed that forced stepping in patients lacking the ankle torque is a compensatory motor control in order to maintain an upright posture. A statistical-biomechanics approach to the human postural control system has revealed open-loop (descending) control as well as closed-loop (feedback) control in quiet standing, and fractal dynamics in stride-to-stride fluctuations of walking. The descending control system of bipedal upright posture and gait may have a functional link to cognitive domains. Increasing dependence on the descending control system with aging may play a role in falls in elderly people.

  11. Responsibility of parents for misdemeanors committed by their descendants

    Directory of Open Access Journals (Sweden)

    Ristivojević Branislav R.

    2016-01-01

    Full Text Available The subject of the authors' attention are certain questions concerning the responsibility for the acts of other persons in the misdemeanor law of the Republic of Serbia. Under certain conditions, if a child or a minor (descendants commits a misdemeanor, instead of him or together with him, other persons can be held responsible as well, foremost his parents who had not exercised due supervision. There is a difference between the responsibility of a parent whose children have committed a misdemeanor and are under 14, and that of a parent whose children are between 14 and 18 years old. Therefore, there is a difference in terms of responsibility of the parent depending on if the person who committed the misdemeanor is, from the perspective of the Misdemeanor Law, a child or a minor. The authors critically analyze the articles of the Misdemeanor Law that concern the responsibility of the parent for the misdemeanors committed by their descendants. In the end, they conclude that the Misdemeanor Law undermines one of the essential legal principle that the 'scope of rights has to correspond to the scope of obligations and responsibility'.

  12. Adrenergic factors involved in the control of crypt cell proliferation in jejunum and descending colon of mouse.

    Science.gov (United States)

    Kennedy, M F; Tutton, P J; Barkla, D H

    1983-01-01

    The mitotic rates in the crypts of Lieberkühn of the proximal jejunum and descending colon of mouse, following different treatments, were measured using a stathmokinetic technique. Regression coefficients, representing mitotic rates, were then calculated by the method of least squares. Treatment with adrenaline, isoprenaline, phenylephrine, phentolamine, and yohimbine all resulted in decreased mitotic rate of jejunal and colonic crypt cells. Chemical sympathectomy and cryosympathectomy had a similar effect, and chemical sympathectomy was followed by a supersensitivity to clonidine. Intraperitoneal injection of metaraminol, clonidine, propranolol, prazosin, labetolol and simultaneous injection of propranolol and adrenaline all resulted in an increased rate of crypt cell proliferation in both jejunum and colon. A significant increase in mitotic rate was observed in both tissues at night. The amplitude of this diurnal variation was decreased in both jejunum and colon following chemical sympathectomy. In addition, the amplitude of this variation in jejunum was decreased after treatment with yohimbine or phentolamine. The results of the study suggest that the sympathetic nervous system stimulates epithelial cell proliferation in both the small and large intestine and that this effect is mediated by an alpha 2-adrenoceptor. By contrast, stimulation of alpha 1- and beta-adrenoceptors is inhibitory to cell proliferation in these tissues.

  13. Mitochondrial DNA mapping of social-biological interactions in Brazilian Amazonian African-descendant populations

    Directory of Open Access Journals (Sweden)

    Bruno Maia Carvalho

    2008-01-01

    Full Text Available The formation of the Brazilian Amazonian population has historically involved three main ethnic groups, Amerindian, African and European. This has resulted in genetic investigations having been carried out using classical polymorphisms and molecular markers. To better understand the genetic variability and the micro-evolutionary processes acting in human groups in the Brazilian Amazon region we used mitochondrial DNA to investigate 159 maternally unrelated individuals from five Amazonian African-descendant communities. The mitochondrial lineage distribution indicated a contribution of 50.2% from Africans (L0, L1, L2, and L3, 46.6% from Amerindians (haplogroups A, B, C and D and a small European contribution of 1.3%. These results indicated high genetic diversity in the Amerindian and African lineage groups, suggesting that the Brazilian Amazonian African-descendant populations reflect a possible population amalgamation of Amerindian women from different Amazonian indigenous tribes and African women from different geographic regions of Africa who had been brought to Brazil as slaves. The present study partially mapped the historical biological and social interactions that had occurred during the formation and expansion of Amazonian African-descendant communities.

  14. Descending necrotizing mediastinitis following dental extraction. Radiological features and surgical treatment considerations.

    Science.gov (United States)

    González-García, Raúl; Risco-Rojas, Roberto; Román-Romero, Leticia; Moreno-García, Carlos; López García, Cipriano

    2011-07-01

    Descending necrotizing mediastinitis (DNM) following dental extraction is an extremely serious infection with a high mortality rate. Oral infection may rapidly descend into the mediastinum across the retropharyngeal and retrovisceral spaces. Once established, mediastinitis is rapidly followed by sepsis and death. If DNM is suspected cervical and thoracic CT must be carried out urgently. After this, prompt control of the upper airway with tracheostomy, aggressive surgical debridement of the deep cervical spaces and mediastinum, and intravenous broad spectrum antibiotic therapy are mandatory. The present paper reports two new cases of DNM following dental extraction, and focuses on radiological features of abscess progression through the cervical spaces down into the mediastinum. 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  15. The oligosaccharidic content of the glycoconjugates of the prepubertal descended and undescended testis: lectin histochemical study.

    Science.gov (United States)

    Gheri, Gherardo; Sgambati, Eleonora; Thyrion, Giorgia D Zappoli; Vichi, Debora; Orlandini, Giovanni E

    2004-01-01

    The saccharidic content of the glycoconjugates has been studied in the descended the undescended testes of a 8 years old boy. For this purpose, a battery of seven HRP-conjugated lectins (SBA, DBA,PNA,WGA,UEAI, LTA and ConA) was used. D-galactose-N-acetyl-D-galactosamine and alpha-L-fucose sugar residues, which were present in the cytoplasm of the Sertoli cells of the normally positioned prepubertal testis, were not detected in the same cells of the undescended testis. The Leydig's cells of the descended testis appeared characterized by N-acetyl-D-glucosamine which was absent in the rare and atrophic Leydig's cells of the cryptorchid testis. Differences in sugar residues distribution between the descended and the undescended testis were also detected in the lamina propria of the seminiferous tubules. Peritubular myoid cells in the undescended testis only reacted with PNA, after neuraminidase digestion, thus revealing the presence of D-galactose (beta1-->3)-N-acetyl-D-galactosamine and sialic acid. In this study a complete distributional map of the sugar residues of the glycoconjugates in the descended and undescended prepubertal testis is reported.

  16. Cognitive Impairment in Patients with Chronic Neuropathic or Radicular Pain: An Interaction of Pain and Age

    Directory of Open Access Journals (Sweden)

    Orla Moriarty

    2017-06-01

    Full Text Available A growing body of empirical research has confirmed an association between chronic pain and cognitive dysfunction. The aim of the present study was to determine whether cognitive function is affected in patients with a diagnosis of chronic neuropathic or radicular pain relative to healthy control participants matched by age, gender, and years of education. We also examined the interaction of pain with age in terms of cognitive performance. Some limitations of previous clinical research investigating the effects of chronic pain on cognitive function include differences in the pain and cognitive scale materials used, and the heterogeneity of patient participants, both in terms of their demographics and pathological conditions. To address these potential confounds, we have used a relatively homogenous patient group and included both experimental and statistical controls. We have also specifically investigated the interaction effect of pain and age on cognitive performance. Patients (n = 38 and controls (n = 38 were administered a battery of cognitive tests measuring IQ, spatial and verbal memory, attention, and executive function. Educational level, depressive symptoms, and state anxiety were assessed as were medication usage, caffeine, and nicotine consumption to control for possible confounding effects. Both the level of depressive symptoms and the state anxiety score were higher in chronic pain patients than in matched control participants. Chronic pain patients had a lower estimated IQ than controls, and showed impairments on measures of spatial and verbal memory. Attentional responding was altered in the patient group, possibly indicative of impaired inhibitory control. There were significant interactions between chronic pain condition and age on a number of cognitive outcome variables, such that older patients with chronic pain were more impaired than both age-matched controls and younger patients with chronic pain. Chronic pain did not appear

  17. Does Acupuncture Needling Induce Analgesic Effects Comparable to Diffuse Noxious Inhibitory Controls?

    Directory of Open Access Journals (Sweden)

    Juerg Schliessbach

    2012-01-01

    Full Text Available Diffuse noxious inhibitory control (DNIC is described as one possible mechanism of acupuncture analgesia. This study investigated the analgesic effect of acupuncture without stimulation compared to nonpenetrating sham acupuncture (NPSA and cold-pressor-induced DNIC. Forty-five subjects received each of the three interventions in a randomized order. The analgesic effect was measured using pressure algometry at the second toe before and after each of the interventions. Pressure pain detection threshold (PPDT rose from 299 kPa (SD 112 kPa to 364 kPa (SD 144, 353 kPa (SD 135, and 467 kPa (SD 168 after acupuncture, NPSA, and DNIC test, respectively. There was no statistically significant difference between acupuncture and NPSA at any time, but a significantly higher increase of PPDT in the DNIC test compared to acupuncture and NPSA. PPDT decreased after the DNIC test, whereas it remained stable after acupuncture and NPSA. Acupuncture needling at low pain stimulus intensity showed a small analgesic effect which did not significantly differ from placebo response and was significantly less than a DNIC-like effect of a painful noninvasive stimulus.

  18. Measuring and Comparing Descend in Elite Race Cycling with a Perspective on Real-Time Feedback for Improving Individual Performance

    OpenAIRE

    Reijne, M.M.; Bregman, D.J.J.; Schwab, A.L.; Espinosa, Hugo G.; Rowlands, David R.; Shepherd, Jonathan; Thiel, David V.

    2018-01-01

    Descend technique and performance vary among elite racing cyclists and it is not clear what slower riders should do to improve their performance. An observation study was performed of the descending technique of members of a World Tour cycling team and the technique of each member was compared with the fastest descender amongst them. The obtained data gives us guidelines for rider specific feedback in order to improve his performance. The bicycles were equipped with a system that could measur...

  19. ranching pattern of the left anterior descending coronary artery in a ...

    African Journals Online (AJOL)

    Branching pattern of the left anterior descending coronary artery is important in explaining variations in occurrence of coronary atherosclerosis, informing management strategies for coronary heart disease and interventional cardiology. Data on African populations are, however, scarce. Since coronary heart disease is ...

  20. Nitric oxide inhibitory substances from Curcuma mangga rhizomes

    Directory of Open Access Journals (Sweden)

    Kanidta Kaewkroek

    2009-08-01

    Full Text Available Curcuma mangga Val. & Zijp. is a member of the Zingiberaceae family commonly grown in Thailand. It is locally known as mango tumeric because of its mango-like smell when the fresh rhizomes are cut. C. mangga is a popular vegetable, the tips of the young rhizomes and shoots are consumed raw with rice. Medicinally, the rhizomes are used as a stomachic and for chest pains, fever, and general debility. It is also used in postpartum care. In the present study, we investigated the anti-inflammatory effect of the extract and compounds from C. mangga rhizomes against lipopolysaccharide (LPS-induced nitric oxide (NO production in RAW 264.7 cell line. From bioassay-guided fractionation, the chloroform fraction exhibited the most potent inhibitory activity with an IC50 value of 2.1 g/ml, followed by the hexane fraction (IC50 = 3.8 g/ml and the ethyl acetate fraction (IC50 = 23.5 g/ml, respectively. Demethoxycurcumin (1 and 3-buten-2-one, 4-[(1R, 4aR, 8aR-decahydro-5, 5, 8a-trimethyl-2-methylene-1-naphthalenyl]-, (3E-rel- (2 were isolated from the chloroform- and hexane fractions, respectively. Bisdemethoxycurcumin (3 whose structure is similar to that of 1 was also tested for NO inhibitory activity. Of the tested compounds, compound 1 exhibited the highest activity with an IC50 value of 12.1 μM, followed by 3(IC50 = 16.9 M and 2 (IC50 = 30.3 M. These results suggest that C. mangga and its compounds exert NO inhibitory activity and have a potential to be developed as a pharmaceutical preparation for treatment of inflammatory-related diseases. Moreover, this is the first report of compound 2 that was isolated from C. mangga rhizomes.

  1. Papillary Adenocarcinoma of the descending colon in a dog: case report

    Directory of Open Access Journals (Sweden)

    M.G.P.A. Ferreira

    Full Text Available ABSTRACT The aim of this report was to describe the clinical findings and therapeutic management of a case of papillary adenocarcinoma of the descending colon in a Beagle. The patient presented soft stools, haematochezia, tenesmus, and dyschezia. Clinical examination revealed alterations on the ultrasonographic features of the descending colon suggestive of colitis and neoplasia. Following local mass resection, histopathology analysis revealed mild lymphoplasmocytic enteritis and papillary adenocarcinoma of the colon. Enterectomy for tumoral resection and biopsy of locoregional lymph nodes were carried out. Subsequent to the surgical procedure, it was possible to confirm the previous diagnosis and the tumor was classified as intestinal intraluminal papillary adenocarcinoma, with incomplete surgical margins. Adjuvant chemotherapy was performed using carboplatin, cyclophosphamide, and piroxicam, leading to remission of clinical signs and absence of any clinical or imaging alterations compatible with the patient’s previous clinical condition.

  2. Discrete torsion in non-geometric orbifolds and their open-string descendants

    International Nuclear Information System (INIS)

    Bianchi, Massimo; Morales, Jose F.; Pradisi, Gianfranco

    2000-01-01

    We discuss some Z N L xZ N R orbifold compactifications of the type IIB superstring to D=4,6 dimensions and their type I descendants. Although the Z N L xZ N R generators act asymmetrically on the chiral string modes, they result into left-right symmetric models that admit sensible unorientable reductions. We carefully work out the phases that appear in the modular transformations of the chiral amplitudes and identify the possibility of introducing discrete torsion. We propose a simplifying ansatz for the construction of the open-string descendants in which the transverse-channel Klein-bottle, annulus and Moebius-strip amplitudes are numerically identical in the proper parametrization of the world-sheet. A simple variant of the ansatz for the Z 2 L xZ 2 R orbifold gives rise to models with supersymmetry breaking in the open-string sector

  3. Participation: A Descending Road of the Metaphysical Cognition of Being

    Directory of Open Access Journals (Sweden)

    Andrzej Maryniarczyk

    2016-12-01

    Full Text Available When we see in the world the fact that there are many beings, and we indicate that the particular beings exist in a compositional way, we face the task of learning about a new problem: how can we define and determine the relations between beings and between the elements within a being? Although the theory of participation has roots that go back to Plato, and so to a philosophy in which the pluralism of being was rejected and which accepted an identity-based conception of being, participation finds its ontological rational justification only (and ultimately in the pluralistic and compositional conception of being. With the description of participation as a “descending road” in the cognition of being, we are restricting ourselves to the presentation of how participation is understood in realistic metaphysics (while we shall leave aside the history of the question. We will show the aspects of participation that provide a foundation for wisdom-oriented cognition, and we will show the specific character of participation-oriented cognition as a “descending road.”

  4. Descending projections from the nucleus accumbens shell excite activity of taste-responsive neurons in the nucleus of the solitary tract in the hamster.

    Science.gov (United States)

    Li, Cheng-Shu; Lu, Da-Peng; Cho, Young K

    2015-06-01

    The nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN) are the first and second relays in the rodent central taste pathway. A series of electrophysiological experiments revealed that spontaneous and taste-evoked activities of brain stem gustatory neurons are altered by descending input from multiple forebrain nuclei in the central taste pathway. The nucleus accumbens shell (NAcSh) is a key neural substrate of reward circuitry, but it has not been verified as a classical gustatory nucleus. A recent in vivo electrophysiological study demonstrated that the NAcSh modulates the spontaneous and gustatory activities of hamster pontine taste neurons. In the present study, we investigated whether activation of the NAcSh modulates gustatory responses of the NST neurons. Extracellular single-unit activity was recorded from medullary neurons in urethane-anesthetized hamsters. After taste response was confirmed by delivery of sucrose, NaCl, citric acid, and quinine hydrochloride to the anterior tongue, the NAcSh was stimulated bilaterally with concentric bipolar stimulating electrodes. Stimulation of the ipsilateral and contralateral NAcSh induced firings from 54 and 37 of 90 medullary taste neurons, respectively. Thirty cells were affected bilaterally. No inhibitory responses or antidromic invasion was observed after NAcSh activation. In the subset of taste cells tested, high-frequency electrical stimulation of the NAcSh during taste delivery enhanced taste-evoked neuronal firing. These results demonstrate that two-thirds of the medullary gustatory neurons are under excitatory descending influence from the NAcSh, which is a strong indication of communication between the gustatory pathway and the mesolimbic reward pathway. Copyright © 2015 the American Physiological Society.

  5. A Computational Model of a Descending Mechanosensory Pathway Involved in Active Tactile Sensing.

    Directory of Open Access Journals (Sweden)

    Jan M Ache

    2015-07-01

    Full Text Available Many animals, including humans, rely on active tactile sensing to explore the environment and negotiate obstacles, especially in the dark. Here, we model a descending neural pathway that mediates short-latency proprioceptive information from a tactile sensor on the head to thoracic neural networks. We studied the nocturnal stick insect Carausius morosus, a model organism for the study of adaptive locomotion, including tactually mediated reaching movements. Like mammals, insects need to move their tactile sensors for probing the environment. Cues about sensor position and motion are therefore crucial for the spatial localization of tactile contacts and the coordination of fast, adaptive motor responses. Our model explains how proprioceptive information about motion and position of the antennae, the main tactile sensors in insects, can be encoded by a single type of mechanosensory afferents. Moreover, it explains how this information is integrated and mediated to thoracic neural networks by a diverse population of descending interneurons (DINs. First, we quantified responses of a DIN population to changes in antennal position, motion and direction of movement. Using principal component (PC analysis, we find that only two PCs account for a large fraction of the variance in the DIN response properties. We call the two-dimensional space spanned by these PCs 'coding-space' because it captures essential features of the entire DIN population. Second, we model the mechanoreceptive input elements of this descending pathway, a population of proprioceptive mechanosensory hairs monitoring deflection of the antennal joints. Finally, we propose a computational framework that can model the response properties of all important DIN types, using the hair field model as its only input. This DIN model is validated by comparison of tuning characteristics, and by mapping the modelled neurons into the two-dimensional coding-space of the real DIN population. This

  6. Implications and mechanism of action of gabapentin in neuropathic pain.

    Science.gov (United States)

    Kukkar, Ankesh; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2013-03-01

    Gabapentin is an anti-epileptic agent but now it is also recommended as first line agent in neuropathic pain, particularly in diabetic neuropathy and post herpetic neuralgia. α2δ-1, an auxillary subunit of voltage gated calcium channels, has been documented as its main target and its specific binding to this subunit is described to produce different actions responsible for pain attenuation. The binding to α2δ-1 subunits inhibits nerve injury-induced trafficking of α1 pore forming units of calcium channels (particularly N-type) from cytoplasm to plasma membrane (membrane trafficking) of pre-synaptic terminals of dorsal root ganglion (DRG) neurons and dorsal horn neurons. Furthermore, the axoplasmic transport of α2δ-1 subunits from DRG to dorsal horns neurons in the form of anterograde trafficking is also inhibited in response to gabapentin administration. Gabapentin has also been shown to induce modulate other targets including transient receptor potential channels, NMDA receptors, protein kinase C and inflammatory cytokines. It may also act on supra-spinal region to stimulate noradrenaline mediated descending inhibition, which contributes to its anti-hypersensitivity action in neuropathic pain.

  7. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    Science.gov (United States)

    Farmer, A D; Aziz, Q

    2009-01-01

    Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.

  8. Are immigrants and descendants with ill health more prone to unemployment? Evidence from 18 European countries.

    Science.gov (United States)

    Heggebø, Kristian

    2017-08-01

    Previous research has established that both ill health and minority status are associated with unemployment. Less is known, however, about the interplay between having ill health and being from minority background. The present study examines whether immigrants and descendants with ill health are particularly prone to unemployment during an economic downturn in Europe. The European Union Statistics on Income and Living Conditions (EU-SILC) cross-sectional data material is utilized, and linear probability models are estimated. The analysis is run for countries in which the two minority samples are acceptably large (N ≥ 100), resulting in 18 included European countries. The year 2011 is chosen because it is possible to identify both immigrants and descendants in EU-SILC due to a module on intergenerational transfer of disadvantages. The results indicate - as expected - that both ill health and minority status are independently related to higher unemployment likelihood. Immigrants and descendants with ill health, however, are not particularly likely to be unemployed. This finding is robust to a number of sensitivity tests, and the empirical pattern is very similar across the 18 included countries. Both minority status and ill health are associated with high unemployment probability in Europe. However, there does not seem to exist a 'double disadvantage' for immigrants and descendants with ill health, which is in line with a human capital perspective on how employers evaluate potential employees. Both a non-native-sounding name and bad health status are interpreted as a risk factor, but there is no reason to expect ill health to lower the productivity level more if the applicant is a descendant or immigrant.

  9. Whiplash evokes descending muscle recruitment and sympathetic responses characteristic of startle

    Science.gov (United States)

    Mang, Daniel WH; Siegmund, Gunter P; Blouin, Jean-Sébastien

    2014-01-01

    Whiplash injuries are the most common injuries following rear-end collisions. During a rear-end collision, the human muscle response consists of both a postural and a startle response that may exacerbate injury. However, most previous studies only assessed the presence of startle using data collected from the neck muscles and head/neck kinematics. The startle response also evokes a descending pattern of muscle recruitment and changes in autonomic activity. Here we examined the recruitment of axial and appendicular muscles along with autonomic responses to confirm whether these other features of a startle response were present during the first exposure to a whiplash perturbation. Ten subjects experienced a single whiplash perturbation while recording electromyography, electrocardiogram, and electrodermal responses. All subjects exhibited a descending pattern of muscle recruitment, and increasing heart rate and electrodermal responses following the collision. Our results provide further support that the startle response is a component of the response to whiplash collisions. PMID:24932015

  10. the priests and the descendants of levi in the book of malachi

    African Journals Online (AJOL)

    Fanie Snyman for his hospitality and for all his generous efforts to make my stay ... This interpretation of the descendants of Levi has long since found many ...... 1998. Malachi. A New Translation with Introduction and Commentary. New.

  11. Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter

    Science.gov (United States)

    Dantzler, William H.; Pannabecker, Thomas L.

    2012-01-01

    We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na+ or urea-Cl− cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na+ or urea- Cl− cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data. PMID:22088433

  12. Fixed or adapted conditioning intensity for repeated conditioned pain modulation.

    Science.gov (United States)

    Hoegh, M; Petersen, K K; Graven-Nielsen, T

    2017-12-29

    Aims Conditioned pain modulation (CPM) is used to assess descending pain modulation through a test stimulation (TS) and a conditioning stimulation (CS). Due to potential carry-over effects, sequential CPM paradigms might alter the intensity of the CS, which potentially can alter the CPM-effect. This study aimed to investigate the difference between a fixed and adaptive CS intensity on CPM-effect. Methods On the dominant leg of 20 healthy subjects the cuff pressure detection threshold (PDT) was recorded as TS and the pain tolerance threshold (PTT) was assessed on the non-dominant leg for estimating the CS. The difference in PDT before and during CS defined the CPM-effect. The CPM-effect was assessed four times using a CS with intensities of 70% of baseline PTT (fixed) or 70% of PTT measured throughout the session (adaptive). Pain intensity of the conditioning stimulus was assessed on a numeric rating scale (NRS). Data were analyzed with repeated-measures ANOVA. Results No difference was found comparing the four PDTs assessed before CSs for the fixed and the adaptive paradigms. The CS pressure intensity for the adaptive paradigm was increasing during the four repeated assessments (P CPM-effect was higher using the fixed condition compared with the adaptive condition (P CPM paradigms using a fixed conditioning stimulus produced an increased CPM-effect compared with adaptive and increasing conditioning intensities.

  13. [Coarctation of the descending aorta. A rare form of connatal aortic stenosis].

    Science.gov (United States)

    Stammwitz, E; Schöttler, M; Brix, F; Poser, H L; Langkau, G; Yükseltan, I

    1983-07-01

    A clinical diagnosis of a coarctation of the aorta was made in a 17-year-old female hypertensive patient. Angiography revealed an atypical stenosis of the descending aorta which was surgically corrected. The causes of aortic stenoses are discussed.

  14. The Diversity of Cortical Inhibitory Synapses

    Directory of Open Access Journals (Sweden)

    Yoshiyuki eKubota

    2016-04-01

    Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

  15. Genome-wide Ancestry and Demographic History of African-Descendant Maroon Communities from French Guiana and Suriname.

    Science.gov (United States)

    Fortes-Lima, Cesar; Gessain, Antoine; Ruiz-Linares, Andres; Bortolini, Maria-Cátira; Migot-Nabias, Florence; Bellis, Gil; Moreno-Mayar, J Víctor; Restrepo, Berta Nelly; Rojas, Winston; Avendaño-Tamayo, Efren; Bedoya, Gabriel; Orlando, Ludovic; Salas, Antonio; Helgason, Agnar; Gilbert, M Thomas P; Sikora, Martin; Schroeder, Hannes; Dugoujon, Jean-Michel

    2017-11-02

    The transatlantic slave trade was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the demographic history of African-descendant Marron populations, we generated genome-wide data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations. Throughout the Americas, thousands of enslaved Africans managed to escape captivity and establish lasting communities, such as the Noir Marron. We find that this population has the highest proportion of African ancestry (∼98%) of any African-descendant population analyzed to date, presumably because of centuries of genetic isolation. By contrast, African-descendant populations in Brazil and Colombia harbor substantially more European and Native American ancestry as a result of their complex admixture histories. Using ancestry tract-length analysis, we detect different dates for the European admixture events in the African-Colombian (1749 CE; confidence interval [CI]: 1737-1764) and African-Brazilian (1796 CE; CI: 1789-1804) populations in our dataset, consistent with the historically attested earlier influx of Africans into Colombia. Furthermore, we find evidence for sex-specific admixture patterns, resulting from predominantly European paternal gene flow. Finally, we detect strong genetic links between the African-descendant populations and specific source populations in Africa on the basis of haplotype sharing patterns. Although the Noir Marron and African-Colombians show stronger affinities with African populations from the Bight of Benin and the Gold Coast, the African-Brazilian population from Rio de Janeiro has greater genetic affinity with Bantu-speaking populations from the Bight of Biafra and west central Africa. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. Torsion and volvulus of the transverse and descending colon in a German shepherd dog.

    Science.gov (United States)

    Halfacree, Z J; Beck, A L; Lee, K C L; Lipscomb, V J

    2006-08-01

    A German shepherd dog was presented two months after surgery for correction of acute gastric dilatation volvulus. The dog had been diagnosed with exocrine pancreatic insufficiency. Radiographs revealed marked gaseous distension of one loop of intestine with a generalised increase in intestinal gas content. A 360 degrees anticlockwise rotation of the descending and transverse colon, around the longitudinal axis of the mesocolon, was diagnosed at exploratory coeliotomy. The transverse and descending colon appeared uniformly necrotic and an end-to-end colo-colic resection and anastomosis was performed. The dog initially made satisfactory postoperative progress but was euthanased on the third postoperative day after it developed an intestinal intussusception.

  17. [Descending necrotizing mediastinitis: the need for early diagnosis and aggressive treatment

    NARCIS (Netherlands)

    Schoenmakers, M.C.J.; Marres, H.A.M.; Merkx, M.A.W.; Verhagen, A.F.T.M.; Swieten, H.A. van

    2009-01-01

    Three patients developed descending necrotizing mediastinitis (DNM): a 44-year-old man due to poor dental status; a 54-year-old women due to a throat infection, 6 weeks after a tooth extraction; and a 30-year-old man a few days after a tooth extraction. Presenting symptoms were dyspnoea, fever,

  18. Clinical outcomes of laparoscopic surgery for advanced transverse and descending colon cancer: a single-center experience.

    Science.gov (United States)

    Yamamoto, Masashi; Okuda, Junji; Tanaka, Keitaro; Kondo, Keisaku; Tanigawa, Nobuhiko; Uchiyama, Kazuhisa

    2012-06-01

    The role of laparoscopic surgery in management of transverse and descending colon cancer remains controversial. The aim of the present study is to investigate the short-term and oncologic long-term outcomes associated with laparoscopic surgery for transverse and descending colon cancer. This cohort study analyzed 245 patients (stage II disease, n = 70; stage III disease, n = 63) who underwent resection of transverse and descending colon cancers, including 200 laparoscopic surgeries (LAC) and 45 conventional open surgeries (OC) from December 1996 to December 2010. Short-term and oncologic long-term outcomes were recorded. The operative time was longer in the LAC group than in the OC group. However, intraoperative blood loss was significantly lower and postoperative recovery time was significantly shorter in the LAC group than in the OC group. The 5-year overall and disease-free survival rates for patients with stage II were 84.9% and 84.9% in the OC group and 93.7% and 90.0% in the LAC group, respectively. The 5-year overall and disease-free survival rates for patients with stage III disease were 63.4% and 54.6% in the OC group and 66.7% and 56.9% in the LAC group, respectively. Use of laparoscopic surgery resulted in acceptable short-term and oncologic outcomes in patients with advanced transverse and descending colon cancer.

  19. A novel paradigm to evaluate conditioned pain modulation in fibromyalgia

    Directory of Open Access Journals (Sweden)

    Schoen CJ

    2016-09-01

    Full Text Available Cynthia J Schoen,1,* Jacob N Ablin,2,* Eric Ichesco,1 Rupal J Bhavsar,3 Laura Kochlefl,1 Richard E Harris,1 Daniel J Clauw,1 Richard H Gracely,4 Steven E Harte1 1Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI, USA; 2Institute of Rheumatology, Tel Aviv Suorasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Neurology, University of Pennsylvania, Philadelphia, PA, 4Department of Endodontics, University of North Carolina – Chapel Hill, Chapel Hill, NC, USA *These authors contributed equally to this work Introduction: Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM. The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM patients using thumb pressure as both a test and conditioning stimulus.Methods: Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus.Results: In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively. In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect P-values >0

  20. Measuring and Comparing Descend in Elite Race Cycling with a Perspective on Real-Time Feedback for Improving Individual Performance

    Directory of Open Access Journals (Sweden)

    M. M. Reijne

    2018-02-01

    Full Text Available Descend technique and performance vary among elite racing cyclists and it is not clear what slower riders should do to improve their performance. An observation study was performed of the descending technique of members of a World Tour cycling team and the technique of each member was compared with the fastest descender amongst them. The obtained data gives us guidelines for rider specific feedback in order to improve his performance. The bicycles were equipped with a system that could measure: velocity, cadence, pedal power, position, steer angle, 3D orientation, rotational speeds and linear accelerations of the rear frame and brake force front and rear. From our observation study, the brake point and apex position turned out to be distinctive indicators of a fast cornering technique in a descent for a tight, hairpin corner. These two indicators can be used as feedback for a slower rider to improve his descend performance.

  1. [Descending hypoglossal branch-facial nerve anastomosis in treating unilateral facial palsy after acoustic neuroma resection].

    Science.gov (United States)

    Liang, Jiantao; Li, Mingchu; Chen, Ge; Guo, Hongchuan; Zhang, Qiuhang; Bao, Yuhai

    2015-12-15

    To evaluate the efficiency of the descending hypoglossal branch-facial nerve anastomosis for the severe facial palsy after acoustic neuroma resection. The clinical data of 14 patients (6 males, 8 females, average age 45. 6 years old) underwent descending hypoglossal branch-facial nerve anastomosis for treatment of unilateral facial palsy was analyzed retrospectively. All patients previously had undergone resection of a large acoustic neuroma. House-Brackmann (H-B) grading system was used to evaluate the pre-, post-operative and follow up facial nerve function status. 12 cases (85.7%) had long follow up, with an average follow-up period of 24. 6 months. 6 patients had good outcome (H-B 2 - 3 grade); 5 patients had fair outcome (H-B 3 - 4 grade) and 1 patient had poor outcome (H-B 5 grade) Only 1 patient suffered hemitongue myoparalysis owing to the operation. Descending hypoglossal branch-facial nerve anastomosis is effective for facial reanimation, and it has little impact on the function of chewing, swallowing and pronunciation of the patients compared with the traditional hypoglossal-facial nerve anastomosis.

  2. Measuring and Comparing Descend in Elite Race Cycling with a Perspective on Real-Time Feedback for Improving Individual Performance

    NARCIS (Netherlands)

    Reijne, M.M.; Bregman, D.J.J.; Schwab, A.L.; Espinosa, Hugo G.; Rowlands, David R.; Shepherd, Jonathan; Thiel, David V.

    2018-01-01

    Descend technique and performance vary among elite racing cyclists and it is not clear what slower riders should do to improve their performance. An observation study was performed of the descending technique of members of a World Tour cycling team and the technique of each member was compared with

  3. Ascending and Descending in Virtual Reality: Simple and Safe System Using Passive Haptics.

    Science.gov (United States)

    Nagao, Ryohei; Matsumoto, Keigo; Narumi, Takuji; Tanikawa, Tomohiro; Hirose, Michitaka

    2018-04-01

    This paper presents a novel interactive system that provides users with virtual reality (VR) experiences, wherein users feel as if they are ascending/descending stairs through passive haptic feedback. The passive haptic stimuli are provided by small bumps under the feet of users; these stimuli are provided to represent the edges of the stairs in the virtual environment. The visual stimuli of the stairs and shoes, provided by head-mounted displays, evoke a visuo-haptic interaction that modifies a user's perception of the floor shape. Our system enables users to experience all types of stairs, such as half-turn and spiral stairs, in a VR setting. We conducted a preliminary user study and two experiments to evaluate the proposed technique. The preliminary user study investigated the effectiveness of the basic idea associated with the proposed technique for the case of a user ascending stairs. The results demonstrated that the passive haptic feedback produced by the small bumps enhanced the user's feeling of presence and sense of ascending. We subsequently performed an experiment to investigate an improved viewpoint manipulation method and the interaction of the manipulation and haptics for both the ascending and descending cases. The experimental results demonstrated that the participants had a feeling of presence and felt a steep stair gradient under the condition of haptic feedback and viewpoint manipulation based on the characteristics of actual stair walking data. However, these results also indicated that the proposed system may not be as effective in providing a sense of descending stairs without an optimization of the haptic stimuli. We then redesigned the shape of the small bumps, and evaluated the design in a second experiment. The results indicated that the best shape to present haptic stimuli is a right triangle cross section in both the ascending and descending cases. Although it is necessary to install small protrusions in the determined direction, by

  4. Learning to predict and control harmful events: chronic pain and conditioning.

    Science.gov (United States)

    Vlaeyen, Johan W S

    2015-04-01

    Pain is a biologically relevant signal and response to bodily threat, associated with the urge to restore the integrity of the body. Immediate protective responses include increased arousal, selective attention, escape, and facial expressions, followed by recuperative avoidance and safety-seeking behaviors. To facilitate early and effective protection against future bodily threat or injury, learning takes place rapidly. Learning is the observable change in behavior due to events in the internal and external environmental and includes nonassociative (habituation and sensitization) and associative learning (Pavlovian and operant conditioning). Once acquired, these knowledge representations remain stored in memory and may generalize to perceptually or functionally similar events. Moreover, these processes are not just a consequence of pain; they may directly influence pain perception. In contrast to the rapid acquisition of learned responses, their extinction is slow, fragile, context dependent and only occurs through inhibitory processes. Here, we review features of associative forms of learning in humans that contribute to pain, pain-related distress, and disability and discuss promising future directions. Although conditioning has a long and honorable history, a conditioning perspective still might open new windows on novel treatment modalities that facilitate the well-being of individuals with chronic pain.

  5. The Impact of the Organism on Its Descendants

    Directory of Open Access Journals (Sweden)

    Patrick Bateson

    2012-01-01

    Full Text Available Historically, evolutionary biologists have taken the view that an understanding of development is irrelevant to theories of evolution. However, the integration of several disciplines in recent years suggests that this position is wrong. The capacity of the organism to adapt to challenges from the environment can set up conditions that affect the subsequent evolution of its descendants. Moreover, molecular events arising from epigenetic processes can be transmitted from one generation to the next and influence genetic mutation. This in turn can facilitate evolution in the conditions in which epigenetic change was first initiated.

  6. Physical Activity May Be Associated with Conditioned Pain Modulation in Women but Not Men among Healthy Individuals

    OpenAIRE

    Shiro, Yukiko; Ikemoto, Tatsunori; Terasawa, Yuta; Arai, Young-Chang P.; Hayashi, Kazuhiro; Ushida, Takahiro; Matsubara, Takako

    2017-01-01

    Background. Conditioned pain modulation (CPM), a phenomenon also known as diffuse noxious inhibitory control, is thought to be affected by various factors, including sex and level of physical activity. However, the involvement of these factors in CPM remains unclear. Methods. Eighty-six healthy young subjects (M/F, 43/43) participated in this study. Participants were assessed on the basis of their mechanical pressure pain threshold (PPT), CPM response, body mass index (BMI), basal metabolic r...

  7. Minocycline enhances inhibitory transmission to substantia gelatinosa neurons of the rat spinal dorsal horn.

    Science.gov (United States)

    Peng, H-Z; Ma, L-X; Lv, M-H; Hu, T; Liu, T

    2016-04-05

    Minocycline, a second-generation tetracycline, is well known for its antibiotic, anti-inflammatory, and antinociceptive effects. Modulation of synaptic transmission is one of the analgesic mechanisms of minocycline. Although it has been reported that minocycline may suppress excitatory glutamatergic synaptic transmission, it remains unclear whether it could affect inhibitory synaptic transmission, which also plays a key role in modulating pain signaling. To examine the effect of minocycline on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons, we recorded spontaneous inhibitory postsynaptic currents (sIPSCs) using whole-cell patch-clamp recording at a holding potential of 0 mV. Bath application of minocycline significantly increased the frequency but not the amplitude of sIPSCs in a reversible and concentration-dependent manner with an EC50 of 85. The enhancement of inhibitory synaptic transmission produced by minocycline was not affected by the glutamate receptor antagonists CNQX and D-APV or by the voltage-gated sodium channel blocker tetrodotoxin (TTX). Moreover, the potency of minocycline for facilitating sIPSC frequency was the same in both glycinergic and GABAergic sIPSCs without changing their decay phases. However, the facilitatory effect of minocycline on sIPSCs was eliminated in a Ca(2+)-free Krebs solution or by co-administration with calcium channel blockers. In summary, our data demonstrate that baseline inhibitory synaptic transmission in SG neurons is markedly enhanced by minocycline. This may function to decrease the excitability of SG neurons, thus leading to a modulation of nociceptive transmission. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Hao Zhao

    2015-01-01

    Full Text Available Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells (OECs remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L 4-5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L 4-5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.

  9. Fertility among descendants of immigrants in Belgium: The role of the partner

    NARCIS (Netherlands)

    Van Landschoot, L.; de Valk, H.A.G.; Van Bavel, J.

    2017-01-01

    BACKGROUND Research on the fertility behavior of descendants of immigrants has focused on female characteristics and has largely neglected those of the male partner. One key aspect is whether the partner is of same (endogamous) or of different (exogamous) ethnic origin. Moreover, the male partner

  10. Follow-up of pain processing recovery after ketamine in hyperalgesic fibromyalgia patients using brain perfusion ECD-SPECT

    International Nuclear Information System (INIS)

    Guedj, Eric; Cammilleri, Serge; Colavolpe, Cecile; Laforte, Catherine de; Mundler, Olivier; Niboyet, Jean

    2007-01-01

    The aim of this study was to determine whether the follow-up of pain processing recovery in hyperalgesic fibromyalgia (FM) could be objectively evaluated with brain perfusion ethyl cysteinate dimer single photon computerized tomography (ECD-SPECT) after administration of ketamine. We enrolled 17 hyperalgesic FM women patients (48.5 ± 11 years, range 25-63). After treatment with subcutaneous ketamine, 11 patients were considered as ''good responders'', with a decrease in pain intensity, evaluated by visual analog scale (VAS), greater than 50%. On the other hand, six patients were considered as ''poor responders''. A voxel-based analysis of regional cerebral blood flow (rCBF) was conducted (p voxel cluster = 0.016c). In agreement with the clinical response, the change in midbrain rCBF after ketamine was highly correlated with the reduction of VAS pain score (r = 0.7182; p = 0.0041). This prospective study suggests that blockade of facilitatory descending modulation of pain with ketamine can be evaluated in the periaqueductal grey with brain perfusion SPECT. (orig.)

  11. The effects of laser radiation on the descendants of irradiated rats

    International Nuclear Information System (INIS)

    Hernandez, J.W.R.; Barbosa, C.A.A.; Moderno, L.A.O.; Parizzotto, N.A.

    1991-01-01

    The effects of low energy laser radiation on the descendants of irradiated rats were investigated by comparing natimortality and the frequency of congenital malformations in three experimental and a control group. Natimortality was not significantly different among the groups. However, cardiomegaly, anophtalmia, dilated abdominal viscera, and premature closures of cranial sutures were recorded only in the experimental groups. (author)

  12. Acute Type II Aortic Dissection with Severe Aortic Regurgitation and Chronic Descending Aortic Dissection in Pregnant Patient with Marfan Syndrome.

    Science.gov (United States)

    Lee, Seok-Soo; Jung, Tae-Eun; Lee, Dong Hyup

    2012-12-01

    Aortic dilatation and dissection are severe complications during pregnancy that can be fatal to both the mother and the fetus. The risks of these complications are especially high in pregnant patients with Marfan syndrome; however, incidents of descending aortic dissection are very rare. This case report involves a successful Bentall procedure for and recovery from a rare aortic dissection in a pregnant Marfan patient who developed acute type II aortic dissection with severe aortic regurgitation and chronic descending aortic dissection immediately after Cesarean section. Regular follow-up will be needed to monitor the descending aortic dissection.

  13. Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

    Science.gov (United States)

    Byrne, N. G.; Muir, T. C.

    1985-01-01

    The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is

  14. Stress and visceral pain: from animal models to clinical therapies

    Science.gov (United States)

    Larauche, Muriel; Mulak, Agata; Taché, Yvette

    2011-01-01

    Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain. PMID:21575632

  15. Short-term test-retest-reliability of conditioned pain modulation using the cold-heat-pain method in healthy subjects and its correlation to parameters of standardized quantitative sensory testing.

    Science.gov (United States)

    Gehling, Julia; Mainka, Tina; Vollert, Jan; Pogatzki-Zahn, Esther M; Maier, Christoph; Enax-Krumova, Elena K

    2016-08-05

    Conditioned Pain Modulation (CPM) is often used to assess human descending pain inhibition. Nine different studies on the test-retest-reliability of different CPM paradigms have been published, but none of them has investigated the commonly used heat-cold-pain method. The results vary widely and therefore, reliability measures cannot be extrapolated from one CPM paradigm to another. Aim of the present study was to analyse the test-retest-reliability of the common heat-cold-pain method and its correlation to pain thresholds. We tested the short-term test-retest-reliability within 40 ± 19.9 h using a cold-water immersion (10 °C, left hand) as conditioning stimulus (CS) and heat pain (43-49 °C, pain intensity 60 ± 5 on the 101-point numeric rating scale, right forearm) as test stimulus (TS) in 25 healthy right-handed subjects (12females, 31.6 ± 14.1 years). The TS was applied 30s before (TSbefore), during (TSduring) and after (TSafter) the 60s CS. The difference between the pain ratings for TSbefore and TSduring represents the early CPM-effect, between TSbefore and TSafter the late CPM-effect. Quantitative sensory testing (QST, DFNS protocol) was performed on both sessions before the CPM assessment. paired t-tests, Intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Pearson's correlation, Bland-Altman analysis, significance level p Pain ratings during CPM correlated significantly (ICC: 0.411…0.962) between both days, though ratings for TSafter were lower on day 2 (p pain thresholds. The short-term test-retest-reliability of the early CPM-effect using the heat-cold-pain method in healthy subjects achieved satisfying results in terms of the ICC. The SRD of the early CPM effect showed that an individual change of > 20 NRS can be attributed to a real change rather than chance. The late CPM-effect was weaker and not reliable.

  16. Clinical features and imaging of central poststroke pain

    Directory of Open Access Journals (Sweden)

    Ramesh Bhattacharyya

    2016-01-01

    Full Text Available Introduction: Central post stroke pain is a variety of neuropathic pain that occurs after stroke as a result of dysfunction of either spino-thalamic tract or thalamo-cortical sensory pathway. Hyperirritability in surviving cells along the affected pain pathways found with changes in inhibitory pathways, spinal and cortical reorganization and central sensitization. Aim: Clinical features like character of pain and other sensory features with neuroimaging findings of central post stroke pain for a part of Indian population were analyzed in this study. Materials and Method including analysis: 120 numbers of patients, who developed new onset pain symptoms after stroke, attending outpatient and inpatient department of a neurology department during a whole year were examined with history including extensive sensory symptoms analysis; sensory examinations including assessment of pain score and other neurological examinations were done and rechecked by neurologists. All were investigated by neuroimaging with either MRI or CT scan or both. Neuro imaging was interpreted by experienced neuroradiologist and corroborated by neurologists and pain physician. Results: 45% of the lesions were in Thalamus when 75% of the lesions were detected as infarction. 57.5% symptoms started within 3 months. Ataxia found with 60%, increased threshold to warm and cold were seen in 40% of patients, burning sensation was seen in 40% followed by numbness with 20%, dysesthesia found with 60%, reduced sensation to temperature changes found with 40% patients. Conclusion: CPSP patients may presents with various sensory symptoms beside pain. Distribution of sensory symptoms may be with any part of the body as well as over one half of the body. Most common trigger factor was mechanical; while thalamic lesions found in 45%, extra thalamic lesions werefound with 55% of patients.

  17. Do Children with Better Inhibitory Control Donate More? Differentiating between Early and Middle Childhood and Cool and Hot Inhibitory Control

    Directory of Open Access Journals (Sweden)

    Jian Hao

    2017-12-01

    Full Text Available Inhibitory control may play an important part in prosocial behavior, such as donating behavior. However, it is not clear at what developmental stage inhibitory control becomes associated with donating behavior and which aspects of inhibitory control are related to donating behavior during development in early to middle childhood. The present study aimed to clarify these issues with two experiments. In Experiment 1, 103 3- to 5-year-old preschoolers completed cool (Stroop-like and hot (delay of gratification inhibitory control tasks and a donating task. The results indicated that there were no relationships between cool or hot inhibitory control and donating behavior in the whole group and each age group of the preschoolers. In Experiment 2, 140 elementary school children in Grades 2, 4, and 6 completed cool (Stroop-like and hot (delay of gratification inhibitory control tasks and a donating task. The results showed that inhibitory control was positively associated with donating behavior in the whole group. Cool and hot inhibitory control respectively predicted donating behavior in the second and sixth graders. Therefore, the present study reveals that donating behavior increasingly relies on specific inhibitory control, i.e., hot inhibitory control as children grow in middle childhood.

  18. Wandering spleen, gastric and pancreatic volvulus and right-sided descending and sigmoid colon.

    Science.gov (United States)

    Flores-Ríos, Enrique; Méndez-Díaz, Cristina; Rodríguez-García, Esther; Pérez-Ramos, Tania

    2015-10-01

    Wandering spleen is a rare condition, characterized by a mobile spleen that is attached only by an elongated vascular pedicle, allowing it to migrate to any part of the abdomen or pelvis. Mesenteroaxial gastric volvulus usually occurs in children and may be associated with wandering spleen. Both entities result from abnormal laxity or absence of the peritoneal attachments due to abnormal fusion of the peritoneal mesenteries. Pancreatic volvulus is a very rare anomaly, with only a few isolated case reports described in association with wandering spleen. Anomalous right sided descending and sigmoid colon is a very rare entity and its association with wandering spleen has not been previously reported. We report a case of wandering spleen associated with mesenteroaxial gastric volvulus, pancreatic volvulus and rightward shift of the splenic flexure of the colon and right sided descending and sigmoid colon in a young female.

  19. Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy.

    Science.gov (United States)

    Chattopadhyay, Munmun; Zhou, Zhigang; Hao, Shuanglin; Mata, Marina; Fink, David J

    2012-03-22

    Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms Na(V)1.7 and Na(V)1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer-mediated release of the inhibitory neurotransmitters enkephalin or gamma amino butyric acid (GABA) from DRG neurons in diabetic animals reduced pain-related behaviors coincident with a reduction in Na(V)1.7 protein levels in DRG in vivo. To further evaluate the role of Na(V)α subunit levels in DRG in the pathogenesis of pain in diabetic neuropathy, we constructed a non-replicating herpes simplex virus (HSV)-based vector expressing a microRNA (miRNA) against Na(V)α subunits. Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in Na(V)α subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia. These data support the role of increased Na(V)α protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy.

  20. Testicular Descend, How and Why: A Review Article

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    Sujan Narayan Agrawal

    2017-08-01

    Full Text Available Background: The testis develops in the dorsal abdominal wall, and then descends to scrotum. The development begins as early as 6th week of intrauterine life and is completed by fifth month of intrauterine life. The testis may get arrested during its descent from dorsal abdominal wall to scrotum. The anomalies of descent includes cryptorchism (and its variant like anarchism, monarchism or partially descended testis, ectopic testis, persistent processus vaginalis and encysted hydrocoel of spermatic cord etc. Cryptorchism is usually diagnosed during the new born examination. The recognition of this condition, identification of associated syndromes, proper diagnostic evaluation and timely treatment by surgical urologist is important to prevent adverse consequences like sterility, congenital hernia & hydrocoel, testicular carcinoma etc. Objectives: the objective of this review is to study the role of gubernaculum in the testicular migration process. Material & Method: We performed a descriptive review of the literature about the role of the gubernaculum in testicular migration during the human fetal life. This article provides an overview of role of gubernaculum and other factors responsible for gonadal migration. Results: In the first phase of testicular migration the gubernaculum enlarges to hold the testis near groin and in the second phase the gubernaculum migrates across the pubic region to reach the scrotum. The proximal end of gubernaculum is attached to the testis and epididymis. The lower end reaches to bottom of scrotum. A failure in the proper functioning of gubernaculum causes cryptorchism. Rarely male gonads may deviate from main pathway due to presence of many tails of distal gubernaculum, and it may give rise to ectopic testis. The processus vaginalis usually closes by birth. If it remains patent, it leads to congenital hernia, hydrocoel, encysted hydrocoel etc. Conclusion: the gubernaculum presents a significant structure during

  1. Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief

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    Tozaki-Saitoh Hidetoshi

    2009-04-01

    Full Text Available Abstract Background Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain. Results Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 μM and 1.87 μM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine. Conclusion These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part

  2. Contingency Awareness Shapes Acquisition and Extinction of Emotional Responses in a Conditioning Model of Pain-Related Fear.

    Science.gov (United States)

    Labrenz, Franziska; Icenhour, Adriane; Benson, Sven; Elsenbruch, Sigrid

    2015-01-01

    As a fundamental learning process, fear conditioning promotes the formation of associations between predictive cues and biologically significant signals. In its application to pain, conditioning may provide important insight into mechanisms underlying pain-related fear, although knowledge especially in interoceptive pain paradigms remains scarce. Furthermore, while the influence of contingency awareness on excitatory learning is subject of ongoing debate, its role in pain-related acquisition is poorly understood and essentially unknown regarding extinction as inhibitory learning. Therefore, we addressed the impact of contingency awareness on learned emotional responses to pain- and safety-predictive cues in a combined dataset of two pain-related conditioning studies. In total, 75 healthy participants underwent differential fear acquisition, during which rectal distensions as interoceptive unconditioned stimuli (US) were repeatedly paired with a predictive visual cue (conditioned stimulus; CS(+)) while another cue (CS(-)) was presented unpaired. During extinction, both CS were presented without US. CS valence, indicating learned emotional responses, and CS-US contingencies were assessed on visual analog scales (VAS). Based on an integrative measure of contingency accuracy, a median-split was performed to compare groups with low vs. high contingency accuracy regarding learned emotional responses. To investigate predictive value of contingency accuracy, regression analyses were conducted. Highly accurate individuals revealed more pronounced negative emotional responses to CS(+) and increased positive responses to CS(-) when compared to participants with low contingency accuracy. Following extinction, highly accurate individuals had fully extinguished pain-predictive cue properties, while exhibiting persistent positive emotional responses to safety signals. In contrast, individuals with low accuracy revealed equally positive emotional responses to both, CS(+) and CS

  3. Contingency awareness shapes acquisition and extinction of emotional responses in a conditioning model of pain-related fear

    Directory of Open Access Journals (Sweden)

    Franziska eLabrenz

    2015-11-01

    Full Text Available As a fundamental learning process, fear conditioning promotes the formation of associations between predictive cues and biologically-significant signals. In its application to pain, conditioning may provide important insight into mechanisms underlying pain-related fear, although knowledge especially in interoceptive pain paradigms remains scarce. Furthermore, while the influence of contingency awareness on excitatory learning is subject of ongoing debate, its role in pain-related acquisition is poorly understood and essentially unknown regarding extinction as inhibitory learning. Therefore, we addressed the impact of contingency awareness on learned emotional responses to pain- and safety-predictive cues in a combined dataset of two pain-related conditioning studies.In total, 75 healthy participants underwent differential fear acquisition, during which rectal distensions as interoceptive unconditioned stimuli (US were repeatedly paired with a predictive visual cue (conditioned stimulus; CS+ while another cue (CS- was presented unpaired. During extinction, both CS were presented without US. CS valence, indicating learned emotional responses, and CS-US contingencies were assessed on visual analogue scales. Based on an integrative measure of contingency accuracy, a median-split was performed to compare groups with low versus high contingency accuracy regarding learned emotional responses. To investigate predictive value of contingency accuracy, regression analyses were conducted. Highly accurate individuals revealed more pronounced negative emotional responses to CS+ and increased positive responses to CS- when compared to participants with low contingency accuracy. Following extinction, highly accurate individuals had fully extinguished pain-predictive cue properties, while exhibiting persistent positive emotional responses to safety signals. In contrast, individuals with low accuracy revealed equally positive emotional responses to both, CS+ and

  4. Ketamine for chronic pain: risks and benefits

    Science.gov (United States)

    Niesters, Marieke; Martini, Christian; Dahan, Albert

    2014-01-01

    The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4–14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. PMID:23432384

  5. Orbitofrontal disinhibition of pain in migraine with aura: an interictal EEG-mapping study.

    Science.gov (United States)

    Lev, Rina; Granovsky, Yelena; Yarnitsky, David

    2010-08-01

    This study aimed to identify the cortical mechanisms underlying the processes of interictal dishabituation to experimental pain in subjects suffering from migraine with aura (MWA). In 21 subjects with MWA and 22 healthy controls, cortical responses to two successive trials of noxious contact-heat stimuli were analyzed using EEG-tomography software. When compared with controls, MWA patients showed significantly increased pain-evoked potential amplitudes accompanied by reduced activity in the orbitofrontal cortex (OFC) and increased activity in the pain matrix regions, including the primary somatosensory cortex (SI) (p < .05). Similarly to controls, MWA subjects displayed an inverse correlation between the OFC and SI activities, and positive interrelations between other pain-specific regions. The activity changes in the OFC negatively correlated with lifetime headache duration and longevity (p < .05). Reduced inhibitory functioning of the prefrontal cortex is a possible cause for disinhibition of the pain-related sensory cortices in migraine. The finding of OFC hypofunction over the disease course is in keeping with current concepts of migraine as a progressive brain disorder.

  6. Isometric Back Exercise Has Different Effect on Pressure Pain Thresholds in Healthy Men and Women

    DEFF Research Database (Denmark)

    Gajsar, Hannah; Titze, Christina; Hasenbring, Monika Ilona

    2017-01-01

    .07). CONCLUSIONS: The results of this pilot study indicate that isometric back exercise produces local and remote hypoalgesia. Remote EIH was only demonstrated in women, supporting the influence of sex in the hypoalgesic response after exercise. The effect of isometric back exercise on pain sensitivity in patients......OBJECTIVE: Isometric exercises produce an acute decrease in the pain sensitivity, known as exercise-induced hypoalgesia (EIH). Existing EIH paradigms use exercises at the extremities with more pronounced EIH at local compared to remote body sites, indicating local inhibition in addition to central...... inhibitory mechanisms. So far the results on EIH in patients with low back pain (LBP) are equivocal and no studies have investigated an EIH paradigm targeting the lower back in order to assess EIH in patients with LBP. Thus, the aim of this pilot study was to assess pressure pain sensitivity at local...

  7. Sodium-hydrogen exchanger inhibitory potential of Malus domestica, Musa × paradisiaca, Daucus carota, and Symphytum officinale.

    Science.gov (United States)

    Verma, Vivek; Singh, Nirmal; Jaggi, Amteshwar Singh

    2014-02-01

    The involvement of sodium-hydrogen exchangers (NHE) has been described in the pathophysiology of diseases including ischemic heart and brain diseases, cardiomyopathy, congestive heart failure, epilepsy, dementia, and neuropathic pain. Synthetic NHE inhibitors have not achieved much clinical success; therefore, plant-derived phytoconstituents may be explored as NHE inhibitors. In the present study, the NHE inhibitory potential of hydroalcoholic and alkaloidal fractions of Malus domestica, Musa × paradisiaca, Daucus carota, and Symphytum officinale was evaluated. The different concentrations of hydroalcoholic and alkaloidal extracts of the selected plants were evaluated for their NHE inhibitory activity in the platelets using the optical swelling assay. Among the hydroalcoholic extracts, the highest NHE inhibitory activity was shown by M. domestica (IC50=2.350 ± 0.132 μg/mL) followed by Musa × paradisiaca (IC50=7.967 ± 0.451 μg/mL), D. carota (IC50=37.667 ± 2.517 μg/mL), and S. officinale (IC50=249.330 ± 1.155 μg/mL). Among the alkaloidal fractions, the highest NHE inhibitory activity was shown by the alkaloidal fraction of Musa × paradisiacal (IC50=0.010 ± 0.001 μg/mL) followed by D. carota (IC50=0.024 ± 0.002 μg/mL), M. domestica (IC50=0.031 ± 0.005 μg/mL), and S. officinale (IC50=4.233 ± 0.379 μg/mL). The IC50 of alkaloidal fractions was comparable to the IC50 of synthetic NHE inhibitor, EIPA [5-(N-ethyl-N-isopropyl)amiloride] (IC50=0.033 ± 0.004 μg/mL). It may be concluded that the alkaloidal fractions of these plants possess potent NHE inhibitory activity and may be exploited for their therapeutic potential in NHE activation-related pathological complications.

  8. Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism

    Science.gov (United States)

    Lei, Tianluo; Zhou, Lei; Layton, Anita T.; Zhou, Hong; Zhao, Xuejian; Bankir, Lise

    2011-01-01

    Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending limb of Henle's loop and in descending vasa recta, respectively. To study their role and possible interaction in the context of the urine concentration mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B transcripts and proteins and showed normal survival and growth. Daily urine output was significantly higher in UT-A2/B knockout mice than that in wild-type mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B knockout mice was intermediate between that in UT-B knockout and wild-type mice. The changes in urine osmolality and flow rate, plasma and urine urea concentration, as well as non-urea solute concentration after an acute urea load or chronic changes in protein intake suggested that UT-A2 plays a role in the progressive accumulation of urea in the inner medulla. These results suggest that in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B knockout mice partially remedies the urine concentrating defect caused by UT-B deletion, by reducing urea loss from the descending limbs to the peripheral circulation; instead, urea is returned to the inner medulla through the loops of Henle and the collecting ducts. PMID:21849488

  9. Plasticity of cortical excitatory-inhibitory balance.

    Science.gov (United States)

    Froemke, Robert C

    2015-07-08

    Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.

  10. Descending motor pathways and the spinal motor system. Limbic and non-limbic components

    NARCIS (Netherlands)

    G. Holstege (Gert)

    1990-01-01

    textabstractFor a thorough understanding of the descending pathways of the motor system originating in the forebrain, knowledge about the anatomy and function of the structures in the more caudally located parts of the central nervous system is indispensable. In this paper an overview will be

  11. Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by Transforming Growth Factor β and Angiotensin II.

    Directory of Open Access Journals (Sweden)

    Pedley Kevin C

    2002-02-01

    Full Text Available Abstract Background Absorption of water and Na+ in descending colonic crypts is dependent on the barrier function of the surrounding myofibroblastic pericryptal sheath. Here the effects of high and low Na+ diets and exposure to whole body ionising radiation on the growth and activation of the descending colonic pericryptal myofibroblasts are evaluated. In addition the effect of a post-irradiation treatment with the angiotensin converting enzyme inhibitor Captopril was investigated. Methods The levels of Angiotensin II type 1 receptor (AT1, ACE, collagen type IV, transforming growth factor-β type 1 receptor (TGF-βR1, OB cadherin and α-smooth muscle actin in both descending colon and caecum were evaluated, using immunocytochemistry and confocal microscopy, in rats fed on high and low Na+ diets (LS. These parameters were also determined during 3 months post-irradiation with 8Gy from a 60Co source in the presence and absence of the angiotensin converting enzyme inhibitor, Captopril. Results Increases in AT1 receptor (135.6% ± 18.3, P Conclusions These results demonstrate an activation of descending colonic myofibroblasts to trophic stimuli, or irradiation, which can be attenuated by Captopril, indicative of local trophic control by angiotensin II and TGF-β release.

  12. Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.

    Science.gov (United States)

    Touj, Sara; Houle, Sébastien; Ramla, Djamel; Jeffrey-Gauthier, Renaud; Hotta, Harumi; Bronchti, Gilles; Martinoli, Maria-Grazia; Piché, Mathieu

    2017-06-03

    Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation. The aim of this study was to determine whether sympathetic regulation and ACC surface and volume are affected in a rat model of chronic back pain, in which complete Freund Adjuvant (CFA) is injected in back muscles. Sympathetic regulation was assessed with renal blood flow (RBF) changes induced by electrical stimulation of a hind paw, while ACC structure was examined by measuring cortical surface and volume. RBF changes and ACC volume were compared between control rats and rats injected with CFA in back muscles segmental (T10) to renal sympathetic innervation or not (T2). In rats with CFA, chronic inflammation was observed in the affected muscles in addition to increased nuclear factor-kappa B (NF-kB) protein expression in corresponding spinal cord segments (p=0.01) as well as decreased ACC volume (pchronic pain at T2 (p'schronic back pain alters sympathetic functions through non-segmental mechanisms, possibly by altering descending regulatory pathways from ACC. Yet, segmental somato-sympathetic reflexes may compete with non-segmental processes depending on the back region affected by pain and according to the segmental organization of the sympathetic nervous system. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Descending motor pathways and the spinal motor system. Limbic and non-limbic components

    NARCIS (Netherlands)

    Holstege, G.

    1991-01-01

    For a thorough understanding of the descending pathways of the motor system originating in the forebrain, knowledge about the anatomy and function of the structures in the more caudally located parts of the central nervous system is indispensable. In this paper an overview will be presented of these

  14. Inverted Lymphoglandular Polyp in Descending Colon

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    Shengmei Zhou

    2015-01-01

    Full Text Available A 47-year-old male with a history of left colon cancer, status post left colon resection for 12 years, presented with rectal bleeding. Colonoscopic examination revealed an 8 mm sessile polyp in the proximal descending colon. Microscopic examination showed that the surface of this polyp was covered with a layer of normal colonic mucosa with focal surface erosion. In the submucosal layer, an intimate admixture of multiple cystically dilated glands and prominent lymphoid aggregates with germinal centers was seen. The glands were lined by columnar epithelium. Immunohistochemical staining showed the glands were positive for CK20 and CDX2 and negative for CK7, with a low proliferative index, mostly consistent with reactive colonic glands. The patient remained asymptomatic after one-year follow-up. A review of the literature shows very rare descriptions of similar lesions, but none fits exactly this pattern. We would designate this inverted lymphoglandular polyp and present this case to raise the awareness of recognizing this unusual histological entity.

  15. Clinical outcomes of laparoscopic surgery for transverse and descending colon cancers in a community setting.

    Science.gov (United States)

    Matsuda, Takeru; Fujita, Hirofumi; Kunimoto, Yukihiro; Kimura, Taisei; Hayashi, Tomomi; Maeda, Toshiyuki; Yamakawa, Junichi; Mizumoto, Takuya; Ogino, Kazunori

    2013-08-01

    The feasibility, safety and oncological outcomes of laparoscopic surgery for transverse and descending colon cancers in a community hospital setting were evaluated. Twenty-six patients with transverse or descending colon cancers who underwent laparoscopic surgery at our hospital were included in this retrospective analysis (group A). Their outcomes were compared with those of 71 patients who underwent laparoscopic surgery for colon cancer at other tumor sites (group B). There were no significant differences between the two groups in terms of operative time, estimated blood loss, postoperative hospital stay and morbidity rate. Extended lymphadenectomy was performed more frequently and the number of harvested lymph nodes was significantly higher in group B than in group A. However, no recurrence developed in group A, while recurrence occurred in four patients from group B. The 3-year disease-free survival rates were 100% for group A and 93.5% for group B. The 3-year overall survival rates were 100% for group A and 91.6% for group B. Laparoscopic surgery for transverse and descending colon cancers can be performed safely with oncological validity in a community hospital setting, provided there is careful selection of the patients and adequate lymphadenectomy considering the clinical stage of their disease. © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

  16. Detection of genomic instability in descendants of male mice exposed to chronic low-level gamma-radiation using the test 'adaptive response'

    International Nuclear Information System (INIS)

    Rozanova, O.M.; Zaichkina, S.I.; Akhmadieva, A.; Aptikaeva, G.F.; Klokov, D.J.

    2003-01-01

    Full text: The goal of the present study was to examine whether the genomic instability can be revealed in vivo using the test 'adaptive response' (AR). Two-month-old BALB/C male mice were subjected to chronic irradiation in the gamma-field with a dose of 0.1 Gy (0.01 Gy/day) and a dose of 0.5 Gy (0.01 and 0.05 Gy/day). Control animals were kept under similar conditions but without irradiation. Fifteen days after the irradiation, males from the irradiated and control groups were mated in separate cages with unirradiated females for 2 weeks. The males, descendants from irradiated and unirradiated parents, at an age of two months were subjected to additional irradiation with a dose of 1.5 Gy. To reveal the genetic instability using the AR test, another group of males, the descendants from irradiated and unirradiated parents, were exposed to acute irradiation by the scheme of AR: with an adapting dose (D1) of 0.1 Gy (0.125 Gy/min) followed after a day by a challenging dose (D2) of 1.5 Gy (0.47 Gy/min). After 28 h, the animals of all groups were killed. Bone marrow specimens for calculating micronuclei (MN) in polychromatophyl erythrocytes (PCE) were prepared. It was found that in descendants that resulted from unirradiated parents and the parents irradiated with a dose of 0.1 Gy, the percentages of PCE with injuries were nearly equal. Upon irradiation of parents with a dose of 0.5 Gy, the percentage of PCE with MN in descendants increased. The examination of radiosensitivity of descendants from irradiated parents showed that the percentage of PCE with MN decreased three-to-fourfold (depending on the dose of irradiation of the parents) compared to descendants from unirradiated parents. If the descendants from exposed parents were irradiated by the scheme of AR, no AR was observed. Thus, the experimental data indicated that, it is possible to detect the transition of gamma-radiation-induced genomic instability in sex cells of male parents into somatic cells of mice (F1

  17. Determining the anatomy of the descending palatine artery and pterygoid plates with computed tomography in Class III patients.

    Science.gov (United States)

    Ueki, Koichiro; Hashiba, Yukari; Marukawa, Kohei; Nakagawa, Kiyomasa; Okabe, Katsuhiko; Yamamoto, Etsuhide

    2009-12-01

    Understanding the anatomy of the pterygomaxillary junction region helps prevent blood loss in Le Fort I osteotomy. Here, we determined the location of the descending palatine artery and the structure of the pterygomaxillary region. The study group consisted of 82 Japanese patients with mandibular prognathism and asymmetry, with and without maxillary retrognathism or asymmetry. A total of 164 sides were measured and divided into right versus left, men versus women, and bimaxillary osteotomy (B) versus mandibular osteotomy (S). Lateral and frontal cephalograms and computed tomography (CT) were analysed for all patients. The relationship between the cephalometric measurements and the measurements of the descending palatine artery and pterygoid plate (PP) were assessed. There were no significant correlations between measurements of cephalograms and those of the descending palatine artery and PPs. There were significant differences between right and left in lateral plate length (p=0.0014) and thickness of PP (p=0.0047). There were significant differences between men and women in right width of PP (p=0.0034), right thickness of PP (p=0.0063), left posterior length (p=0.0196), and left thickness of PP (p=0.0279). The B group had a shorter anterior length than the S group (right: ppalatine artery and the morphology of the PPs were not significantly associated with any cephalometric measurements. CT examination is necessary to recognize the anatomy of pterygomaxillary region and the exact positions of descending palatine artery before Le Fort I osteotomy.

  18. NON INVASIVE PAIN MANAGEMENT IN POST PARTUM MOTHER WITHEVIDENCE BASED PRACTICE APPROACH

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    Nikmatur Rohmah

    2017-04-01

    Full Text Available Introduction: Pain is a sensation of discomfort that most post-partum mothers complain about, in the case of prolonged pain, the risk of post-partum blues is higher. The usage of evidence based practice method gives a bigger opportunity for nurse and medical attendants to think more critically in making decisions and in performing the appropriate treatment in accordance with the patient's problem and uniqueness. This research aimed to applicate management of non-invasive pain on post partum mother through the approach of evidence based practice. Method: This was a case-study, performed to client Mrs. A P1-1 A0 post sectio caesarea day 1 as there is an indication of suspect cepalo pelvis disproportion secondary arrest. Data were collected at maternity room, dr. Soebandi Regional General Hospital. Using interview, observation, and physical examination. Data analysis was conducted through a descriptive analysis. Result: Through a careful nursing, it is found out that pain location and spreading that generally spotted at the patient’s back during the contraction in the uterus, occurred around the shoulders when evidence-base practice is applied. The basic principle of applying an intervention to non invasive pain based on evidence–base practice are: cutaneous stimulation and distraction, while massaging area was set on the face, while the distraction media was interaction with the baby. Evaluation on evidence –based practice showed that pain is reduced to scale 2, while face and mobilitation become more relaxed. Discussion: Massage was intended to stimulated the production of endorphine and dinorphine that play an important roke to block the pain transmission through the descendent control system. Interaction with the baby was intended to function as a distraction media to dominate the incoming impuls into the ascendant control system,which further may close the gate of the pain transmitter. Both of the interventions were axpected to work

  19. Alterations in the Anandamide Metabolism in the Development of Neuropathic Pain

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    Natalia Malek

    2014-01-01

    Full Text Available Endocannabinoids (EC, particularly anandamide (AEA, released constitutively in pain pathways might be accountable for the inhibitory effect on nociceptors. Pathogenesis of neuropathic pain may reflect complex remodeling of the dorsal root ganglia (DRGs and spinal cord EC system. Multiple pathways involved both in the biosynthesis and degradation of AEA have been suggested. We investigated the local synthesis and degradation features of AEA in DRGs and spinal cord during the development and maintenance of pain in a model of chronic constriction injury (CCI. All AEA synthesis and degradation enzymes are present on the mRNA level in DRGs and lumbar spinal cord of intact as well as CCI-treated animals. Deregulation of EC system components was consistent with development of pain phenotype at days 3, 7, and 14 after CCI. The expression levels of enzymes involved in AEA degradation was significantly upregulated ipsilateral in DRGs and spinal cord at different time points. Expression of enzymes of the alternative, sPLA2-dependent and PLC-dependent, AEA synthesis pathways was elevated in both of the analyzed structures at all time points. Our data have shown an alteration of alternative AEA synthesis and degradation pathways, which might contribute to the variation of AEA levels and neuropathic pain development.

  20. The Effect of Step Frequency Training on a Male Runner with Patellofemoral Pain

    Directory of Open Access Journals (Sweden)

    Shelley Payne

    2016-10-01

    Full Text Available Running is a very popular form of exercise. The most common site of injury for runners is the knee with patellofemoral pain being the most common complaint. Patellofemoral pain is described as pain around the patella that is worse with activities such as running, squatting, ascending or descending stairs, or sitting for long periods. Much of the recent work with the treatment of patellofemoral pain has involved strengthening of the hip musculature to reduce pain about the knee. However, the ability of these strengthening programs to change lower extremity mechanics or sustain long-term pain reduction has been unproven. More recently, researchers have started to examine the impact of step frequency modification on the forces encountered in the lower extremity, and specifically about the patellofemoral joint. The purpose of this study was to examine the short term effects of step frequency training in a recreational runner with PFP. Methods: This was a single-subject case study design. The subject completed a pre- and post-training assessment to determine the preferred step frequency. The subject also completed a Visual Analog Scale (VAS and a Lower Extremity Functional Scale (LEFS. Results: After the initial evaluation, the subject completed training 2 times per week for 4 weeks using auditory feedback to increase their step frequency by 5% above their preferred step frequency. The subject experienced a decrease in pain as measured by the VAS and an increase in function as measured by the LEFS across the 4 week training. Discussion: Although the results of this case study may not be generalized, the positive findings support additional research to determine both the short and long-term effects of step frequency training on PFP.

  1. Changes in Pain Modulation Occur Soon After Whiplash Trauma but are not Related to Altered Perception of Distorted Visual Feedback.

    Science.gov (United States)

    Daenen, Liesbeth; Nijs, Jo; Cras, Patrick; Wouters, Kristien; Roussel, Nathalie

    2014-09-01

    Widespread sensory hypersensitivity has been observed in acute whiplash associated disorders (WAD). Changes in descending pain modulation take part in central sensitization. However, endogenous pain modulation has never been investigated in acute WAD. Altered perception of distorted visual feedback has been observed in WAD. Both mechanisms (ie, pain modulation and perception of distorted visual feedback) may be different components of one integrated system orchestrated by the brain. This study evaluated conditioned pain modulation (CPM) in acute WAD. Secondly, we investigated whether changes in CPM are associated with altered perception of distorted visual feedback. Thirty patients with acute WAD, 35 patients with chronic WAD and 31 controls were subjected to an experiment evaluating CPM and a coordination task inducing visual mediated changes between sensory feedback and motor output. A significant CPM effect was observed in acute WAD (P = 0.012 and P = 0.006), which was significantly lower compared to controls (P = 0.004 and P = 0.020). No obvious differences in CPM were found between acute and chronic WAD (P = 0.098 and P = 0.041). Changes in CPM were unrelated to altered perception of distorted visual feedback (P > 0.01). Changes in CPM were observed in acute WAD, suggesting less efficient pain modulation. The results suggest that central pain and sensorimotor processing underlie distinctive mechanisms. © 2013 World Institute of Pain.

  2. Left anterior descending coronary artery dissection during ventricular tachycardia ablation – case report

    Directory of Open Access Journals (Sweden)

    Kordic Kresimir

    2018-03-01

    Full Text Available Fascicular left ventricular tachycardia (VT is the second most frequent idiopathic left VT in the setting of a structurally normal heart. Catheter ablation is curative in most patients with low complication rates. We report a case of ostial left anterior descending coronary artery (LAD occlusion during fascicular ventricular tachycardia ablation.

  3. Opportunities for mourning when grief is disenfranchised: descendants of Nazi perpetrators in dialogue with Holocaust survivors.

    Science.gov (United States)

    Livingston, Kathy

    2010-01-01

    This article explores the concepts of unmourned and disenfranchised grief as a way to understand the experiences of adult children of Nazi perpetrators, who grew up with cultural norms of grieving alone or in silence. The scholarly literature on descendants of Nazis reflects a group unlikely to warrant empathy or support from others because of the stigma surrounding their family's possible involvement in the Holocaust atrocities. This article uses, as a case study approach, the testimony given by Monika Hertwig, the adult daughter of a high ranking Nazi, who appears in the documentary film, Inheritance. From the perspective of disenfranchised grief, defined as grief that is not socially recognized or supported, the article links Monika's testimony with existing research from in-depth interviews with other descendants of Nazis to suggest that, as a group, they lacked permission to grieve their deceased parents, acknowledgment of their grief, and opportunities to mourn. Based on the theory that the effects of grief can be transgenerational, the disenfranchisement experienced by the "children of the Third Reich" does not have to pass to subsequent generations if opportunities for mourning are made possible and some resolution of grief occurs. Studies have shown that ongoing dialogue groups between Holocaust survivors and descendants of Nazis provide opportunities for mourning to both groups.

  4. Impulsivity: A deficiency of inhibitory control?

    NARCIS (Netherlands)

    Lansbergen, M.M.

    2007-01-01

    Impulsivity has been defined as acting without thinking. Impulsivity can be quantified by impulsivity questionnaires, but also by behavioral paradigms which tax inhibitory control. Previous research has repeatedly demonstrated deficient inhibitory control in psychopathological samples characterized

  5. A "novel" association to treat pain: tramadol/dexketoprofen. The first drug of a "new pharmacological class".

    Science.gov (United States)

    Fornasari, D; Allegri, M; Gerboni, S; Fanelli, Guido

    2017-04-28

     Acute and chronic pain have an important socio-economical impact. In order to help physicians to choose the appropriate drug, especially for cancer pain, in 1986 WHO has developed a three-step analgesic "ladder" for cancer pain relief in adults. Later it has also been used for acute pain and chronic non-cancer pain. In step I nonsteroidal anti-inflammatory drugs (NSAIDs) are considered with or without adjuvants, in step II the use of weak opioids for mild-moderate pain, with or without NSAIDs and adjuvant, is suggested, while the step III is reserved to strong opioids for moderate-severe pain with or without non-opioids or adjuvants. In the last two decades, a better pathophysiology knowledge has improved pain management shifting our view from the pain ladder to a modern pain pyramid, in which drugs are selected not only on the basis of pain intensity, but mainly according to mechanisms underlying pain, including peripheral and spinal sensitization which is the main trigger of chronic pain. The best pharmacological approach has become multimodal, in which drugs belonging to different steps should be combined, matching the mechanisms of action with the type of pain. An important corollary of combining analgesic drugs with different mechanism of action is that proper matching achieves the same effect with lower doses, better outcome and fewer adverse effects. In this new perspective, fixed-dose pharmaceutical combinations of different drugs are very useful to fulfil pharmacodynamics, pharmacokinetics and adherence criteria, enriching the pain pyramid of half-steps between the first and second step and between the second and third step. Hence, a new fixed combination of a NSAID with peripheral and central anti-infilammatory activities, such as dexketoprofen, and a weak opioid, such as tramadol, with double analgesic activity in the spinal cord as an opioid and, at the same time, on the descending modulatory pathways, is expected to cover a wide range of acute and

  6. Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.

    Science.gov (United States)

    Yarnitsky, David; Crispel, Yonathan; Eisenberg, Elon; Granovsky, Yelena; Ben-Nun, Alon; Sprecher, Elliot; Best, Lael-Anson; Granot, Michal

    2008-08-15

    Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.

  7. Supracardiac total anomalous pulmonary venous connection with a descending vertical vein.

    Science.gov (United States)

    Shah, Sejal; Singh, Mukesh; John, Colin; Maheshwari, Sunita

    2009-10-01

    The commonly used Darling classification for total anomalous pulmonary venous connection (TAPVC) consists of supracardiac, cardiac, infracardiac, and mixed types (Craig et al., Lab Invest 6:44-64, 1967). In supracardiac TAPVC, the common pulmonary vein drains superiorly into the left innominate vein, the superior vena cava, or the azygos vein by way of an ascending vertical vein. We describe a case of supracardiac TAPVC draining into the azygos vein atypically by way of a descending vertical vein.

  8. Ketamine for chronic pain: risks and benefits.

    Science.gov (United States)

    Niesters, Marieke; Martini, Christian; Dahan, Albert

    2014-02-01

    The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4-14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

  9. Length and coverage of inhibitory decision rules

    KAUST Repository

    Alsolami, Fawaz

    2012-01-01

    Authors present algorithms for optimization of inhibitory rules relative to the length and coverage. Inhibitory rules have a relation "attribute ≠ value" on the right-hand side. The considered algorithms are based on extensions of dynamic programming. Paper contains also comparison of length and coverage of inhibitory rules constructed by a greedy algorithm and by the dynamic programming algorithm. © 2012 Springer-Verlag.

  10. Myocardial bridging causing ischemia and recurrent chest pain: a case report

    Directory of Open Access Journals (Sweden)

    Abdou Mohamed

    2011-07-01

    Full Text Available Abstract Background Myocardial bridging is present when a segment of a major epicardial coronary artery runs intramurally through the myocardium. It usually has a benign prognosis, but in some cases myocardial ischemia, infarction and sudden cardiac death have been reported. We are here reporting a case of myocardial bridging which was complicated with recurrent chest pain and transient ST-segment elevation during exercise treadmill test. Case presentation A 40 year-old-man presented with recurrent retrosternal chest pain of 2 months duration. He had history of smoking and was obese, otherwise no physical abnormalities were detected by examination. Electrocardiogram and blood tests were normal apart from impaired glucose tolerance with elevated triglycerides and decreased level of high density lipoprotein cholesterol. While doing exercise treadmill test, the patient developed chest pain and significant ST-segment elevation in almost all precordial leads that persisted for about 15 minutes through recovery. We decided to admit the patient to the coronary care unit for further management and to perform coronary angiogram. Myocardial bridging was observed in the mid segment of the left anterior descending coronary artery. Medical treatment was decided. At one year follow up, our patient was healthy and had no cardiac complaints. In conclusion, myocardial bridging may predispose to coronary vasospasm that may leads to ischemic complications.

  11. The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.

    Science.gov (United States)

    Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam

    2016-04-01

    It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

    Science.gov (United States)

    Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

    2012-12-01

    Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. The frontal lobes and inhibitory function

    International Nuclear Information System (INIS)

    Konishi, Seiki

    2011-01-01

    Neuropsychological studies using traditional tasks of inhibitory functions, such as the Wisconsin card sorting test (WCST) and the Go/No-Go Task have revealed that the frontal lobe is responsible for several types of inhibitory functions. However, the detailed psychological nature of the inhibitory functions and the precise location of their critical foci within the frontal lobe remain to be investigated. Functional magnetic resonance imaging provides spatial and temporal resolution that allowed us to illuminate at least 4 frontal regions involved in inhibitory functions: the dorsolateral, ventrolateral, and rostral parts of the frontal lobe and the presupplementary motor area (preSMA). The ventrolateral part of the frontal lobe in the right hemisphere was activated during response inhibition. The preSMA in the left hemisphere was activated during inhibition of proactive interference immediately after the dimension changes of the WCST. The rostral part of the frontal lobe in the left hemisphere was activated during inhibition long after the dimension changes. The dorsolateral part of the frontal lobe in the left hemisphere was activated at the dimension changes in the first time, but not in the second time. These findings provide clues to our understanding of functional differentiation of inhibitory functions and their localization in the frontal lobe. (author)

  14. Is there equity in use of healthcare services among immigrants, their descendents, and ethnic Danes?

    DEFF Research Database (Denmark)

    Nielsen, Signe S; Hempler, Nana F; Waldorff, Frans B

    2012-01-01

    Legislation in Denmark explicitly states the right to equal access to healthcare. Nevertheless, inequities may exist; accordingly evidence is needed. Our objective was to investigate whether differences in healthcare utilisation in immigrants, their descendents, and ethnic Danes could be explaine...

  15. Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

    Science.gov (United States)

    Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

    2018-01-01

    The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1's role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual's first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and 'SHAM-VL'), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here.

  16. Telecast of Astronaut Neil Armstrong descending ladder to surface of the moon

    Science.gov (United States)

    1969-01-01

    Astronaut Neil A. Armstrong, Apollo 11 commander, descends the ladder of the Apollo 11 Lunar Module prior to making the first step by man on the moon. This view is a black and white reproduction taken from a telecast by the Apollo 11 lunar surface camera during extravehicular activity. The black bar running through the center of the picture is an anamoly in the television ground data system at the Goldstone Tracking Station.

  17. Relevant Factors in the Process of Socialization, Involvement and Belonging of Descendants in Family Businesses

    Directory of Open Access Journals (Sweden)

    Melquicedec Lozano-Posso

    2016-12-01

    Full Text Available This research works toward the identification of the factors that comprise the process of socialization, involvement and initial belonging of descendants in family businesses and the key relationships between them. By means of a qualitative detailed study of four cases, complemented by a quantitative survey of 274 Colombian family businesses, the authors generate a new model that takes into account both factors explored in previous research as well as others identified in this study. Findings confirm the specific dependency of each stage on the subsequent ones; socialization influences involvement, which in turn influences the belonging of the descendants to the family business, with a strong presence of factors such as knowledge, leadership, mode, timing, and motivation. Those responsible for the orientation of potential successors may examine these findings in order to optimize their preparation efforts and support of family human resources for the continuity of the business.

  18. Experimental and numerical investigations of coke descending behavior in a coke dry quenching cooling shaft

    International Nuclear Information System (INIS)

    Feng Yanhui; Zhang Xinxin; Yu Quan; Shi Zhongyin; Liu Zhicheng; Zhang Hu; Liu Huafei

    2008-01-01

    A viscous flow model based on the Navier-Stokes equation is developed to describe coke descending behavior in the 1/7-scaled-down experimental setup of an actual 75 t/h cooling shaft. It is found that the internal friction due to cokes viscosity significantly influences the descending behavior of cokes in the lower part of the shaft, while the external wall friction dominates the sluggish flow of the cokes in the shaft. An asymptotic friction coefficient expression is proposed for granular mixtures flowing along the shaft wall modified from normal wall tress, and the concept of bulk solid viscosity is introduced to describe the internal friction between coke particles. The results simulated by the present model are compared with those by the potential flow and the kinematic model without friction. The viscous flow model is quite good to simulate the bulk coke flow as the physically important frictions are engaged

  19. Treatment of rat spinal cord injury with the neurotrophic factor albumin-oleic acid: translational application for paralysis, spasticity and pain.

    Directory of Open Access Journals (Sweden)

    Gerardo Avila-Martin

    Full Text Available Sensorimotor dysfunction following incomplete spinal cord injury (iSCI is often characterized by the debilitating symptoms of paralysis, spasticity and pain, which require treatment with novel pleiotropic pharmacological agents. Previous in vitro studies suggest that Albumin (Alb and Oleic Acid (OA may play a role together as an endogenous neurotrophic factor. Although Alb can promote basic recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on a known translational measure of SCI associated with symptoms of spasticity and change in nociception has not been studied. Following T9 spinal contusion injury in Wistar rats, intrathecal treatment with: i Saline, ii Alb (0.4 nanomoles, iii OA (80 nanomoles, iv Alb-Elaidic acid (0.4/80 nanomoles, or v Alb-OA (0.4/80 nanomoles were evaluated on basic motor function, temporal summation of noxious reflex activity, and with a new test of descending modulation of spinal activity below the SCI up to one month after injury. Albumin, OA and Alb-OA treatment inhibited nociceptive Tibialis Anterior (TA reflex activity. Moreover Alb-OA synergistically promoted early recovery of locomotor activity to 50 ± 10% of control and promoted de novo phasic descending inhibition of TA noxious reflex activity to 47 ± 5% following non-invasive electrical conditioning stimulation applied above the iSCI. Spinal L4-L5 immunohistochemistry demonstrated a unique increase in serotonin fibre innervation up to 4.2 ± 1.1 and 2.3 ± 0.3 fold within the dorsal and ventral horn respectively with Alb-OA treatment when compared to uninjured tissue, in addition to a reduction in NR1 NMDA receptor phosphorylation and microglia reactivity. Early recovery of voluntary motor function accompanied with tonic and de novo phasic descending inhibition of nociceptive TA flexor reflex activity following Alb-OA treatment, mediated via known endogenous spinal mechanisms of action, suggests a clinical application of this novel

  20. Uses of medicinal plants by Haitian immigrants and their descendants in the Province of Camagüey, Cuba

    Science.gov (United States)

    Volpato, Gabriele; Godínez, Daimy; Beyra, Angela; Barreto, Adelaida

    2009-01-01

    Background Haitian migrants played an important role shaping Cuban culture and traditional ethnobotanical knowledge. An ethnobotanical investigation was conducted to collect information on medicinal plant use by Haitian immigrants and their descendants in the Province of Camagüey, Cuba. Methods Information was obtained from semi-structured interviews with Haitian immigrants and their descendants, direct observations, and by reviewing reports of traditional Haitian medicine in the literature. Results Informants reported using 123 plant species belonging to 112 genera in 63 families. Haitian immigrants and their descendants mainly decoct or infuse aerial parts and ingest them, but medicinal baths are also relevant. Some 22 herbal mixtures are reported, including formulas for a preparation obtained using the fruit of Crescentia cujete. Cultural aspects related to traditional plant posology are addressed, as well as changes and adaptation of Haitian medicinal knowledge with emigration and integration over time. Conclusion The rapid disappearance of Haitian migrants' traditional culture due to integration and urbanization suggests that unrecorded ethnomedicinal information may be lost forever. Given this, as well as the poor availability of ethnobotanical data relating to traditional Haitian medicine, there is an urgent need to record this knowledge. PMID:19450279

  1. Specific alteration of rhythm in temperature-stressed rats possess features of abdominal pain in IBS patients

    Directory of Open Access Journals (Sweden)

    Yasuo Itomi

    2015-09-01

    Full Text Available It is known that specific alteration of rhythm in temperature (SART stress produces somatic pain. However, it remains to be investigated whether SART stress induces visceral pain. In this study, we investigated the visceral hypersensitivity in the SART stress model by pharmacological tools and heterotopical nociception. Four-week-old Sprague–Dawley rats were exposed to repeated cold stress. Visceral pain was measured by visceromotor response to colorectal distension, and the effects of alosetron and duloxetine on visceral pain were investigated in SART rats. Heterotopical nociception was given by capsaicin injection into the left forepaw to induce diffuse noxious inhibitory controls (DNIC. SART stress induced visceral hypersensitivity that was sustained at minimum for one week. In pharmacological analysis, alosetron and duloxetine improved SART stress-induced visceral hypersensitivity. Heterotopical nociception induced DNIC in normal conditions, but was disrupted in SART rats. On the other hand, RMCP-II mRNA in distal colon was not affected by SART stress. In conclusion, SART rats exhibit several features of visceral pain in IBS, and may be a useful model for investigating the central modification of pain control in IBS.

  2. Inhibitory effects of antimicrobial agents against Fusarium species.

    Science.gov (United States)

    Kawakami, Hideaki; Inuzuka, Hiroko; Hori, Nobuhide; Takahashi, Nobumichi; Ishida, Kyoko; Mochizuki, Kiyofumi; Ohkusu, Kiyofumi; Muraosa, Yasunori; Watanabe, Akira; Kamei, Katsuhiko

    2015-08-01

    We investigated the inhibitory effects of antibacterial, biocidal, and antifungal agents against Fusarium spp. Seven Fusarium spp: four F. falciforme (Fusarium solani species complex), one Fusarium spp, one Fusarium spp. (Fusarium incarnatum-equiseti species complex), and one F. napiforme (Gibberella fujikuroi species complex), isolated from eyes with fungal keratitis were used in this study. Their susceptibility to antibacterial agents: flomoxef, imipenem, gatifloxacin, levofloxacin, moxifloxacin, gentamicin, tobramycin, and Tobracin® (contained 3,000 μg/ml of tobramycin and 25 μg/ml of benzalkonium chloride (BAK), a biocidal agent: BAK, and antifungal agents: amphotericin B, pimaricin (natamycin), fluconazole, itraconazole, miconazole, voriconazole, and micafungin, was determined by broth microdilution tests. The half-maximal inhibitory concentration (IC50), 100% inhibitory concentration (IC100), and minimum inhibitory concentration (MIC) against the Fusarium isolates were determined. BAK had the highest activity against the Fusarium spp. except for the antifungal agents. Three fluoroquinolones and two aminoglycosides had inhibitory effects against the Fusarium spp. at relatively high concentrations. Tobracin® had a higher inhibitory effect against Fusarium spp. than tobramycin alone. Amphotericin B had the highest inhibitory effect against the Fusarium spp, although it had different degrees of activity against each isolate. Our findings showed that fluoroquinolones, aminoglycosides, and BAK had some degree of inhibitory effect against the seven Fusarium isolates, although these agents had considerably lower effect than amphotericin B. However, the inhibitory effects of amphotericin B against the Fusarium spp. varied for the different isolates. Further studies for more effective medications against Fusarium, such as different combinations of antibacterial, biocidal, and antifungal agents are needed. © The Author 2015. Published by Oxford University Press on

  3. 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.

  4. Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

    Science.gov (United States)

    Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

    2018-03-01

    Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (pvitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

  5. Enhanced inhibitory synaptic transmission in the spinal dorsal horn mediates antinociceptive effects of TC-2559

    Science.gov (United States)

    2011-01-01

    Background TC-2559 is a selective α4β2 subtype of nicotinic acetylcholine receptor (nAChR) partial agonist and α4β2 nAChR activation has been related to antinociception. The aim of this study is to investigate the analgesic effect of TC-2559 and its underlying spinal mechanisms. Results 1) In vivo bioavailability study: TC-2559 (3 mg/kg) had high absorption rate in rats with maximal total brain concentration reached over 4.6 μM within first 15 min after administration and eliminated rapidly with brain half life of about 20 min after injection. 2) In vivo behavioral experiments: TC-2559 exerts dose dependent antinociceptive effects in both formalin test in mice and chronic constriction injury (CCI) model in rats by activation of α4β2 nAChRs; 3) Whole-cell patch-clamp studies in the superficial dorsal horn neurons of the spinal cord slices: perfusion of TC-2559 (2 μM) significantly increased the frequency, but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). The enhancement of sIPSCs was blocked by pre-application of DHβE (2 μM), a selective α4β2 nicotinic receptor antagonist. Neither the frequency nor the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of spinal dorsal horn neurons were affected by TC-2559. Conclusions Enhancement of inhibitory synaptic transmission in the spinal dorsal horn via activation of α4β2 nAChRs may be one of the mechanisms of the antinociceptive effects of TC-2559 on pathological pain models. It provides further evidence to support the notion that selective α4β2 subtype nAChR agonist may be developed as new analgesic drug for the treatment of neuropathic pain. PMID:21816108

  6. Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans

    DEFF Research Database (Denmark)

    Vægter, Henrik Bjarke; Handberg, Gitte; Graven-Nielsen, Thomas

    2014-01-01

    Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesised that the spatial and temporal manifestations of EIH and CPM were comparable. Eighty healthy subjects (40 females), between 18......-65 years participated in this randomized repeated-measures crossover trial with data collection on two different days. CPM was assessed by two different cold pressor tests (hand,foot). EIH was assessed through two intensities of aerobic bicycling exercises and two intensities of isometric muscle...... tests and after all of the exercise conditions, except low intensity bicycling. EIH after bicycling was increased in women compared to men. CPM and the EIH response after isometric exercises were comparable in men and women and not affected by age. The EIH response was larger in the exercising body part...

  7. Math modeling for helicopter simulation of low speed, low altitude and steeply descending flight

    Science.gov (United States)

    Sheridan, P. F.; Robinson, C.; Shaw, J.; White, F.

    1982-01-01

    A math model was formulated to represent some of the aerodynamic effects of low speed, low altitude, and steeply descending flight. The formulation is intended to be consistent with the single rotor real time simulation model at NASA Ames Research Center. The effect of low speed, low altitude flight on main rotor downwash was obtained by assuming a uniform plus first harmonic inflow model and then by using wind tunnel data in the form of hub loads to solve for the inflow coefficients. The result was a set of tables for steady and first harmonic inflow coefficients as functions of ground proximity, angle of attack, and airspeed. The aerodynamics associated with steep descending flight in the vortex ring state were modeled by replacing the steady induced downwash derived from momentum theory with an experimentally derived value and by including a thrust fluctuations effect due to vortex shedding. Tables of the induced downwash and the magnitude of the thrust fluctuations were created as functions of angle of attack and airspeed.

  8. Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Distress Tolerance: A Preliminary Study.

    Science.gov (United States)

    Mariano, Timothy Y; van't Wout, Mascha; Jacobson, Benjamin L; Garnaat, Sarah L; Kirschner, Jason L; Rasmussen, Steven A; Greenberg, Benjamin D

    2015-08-01

    Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal ("inhibitory") stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli vs anodal stimulation. Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal vs anodal stimulation (P = 0.055) for participants self-completing the task. Pressure algometer (P = 0.81) and breath holding tolerance (P = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all P tDCS (P = 0.072). Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation. Wiley Periodicals, Inc.

  9. When Is Visual Information Used to Control Locomotion When Descending a Kerb?

    OpenAIRE

    Buckley, John G.; Timmis, Matthew A.; Scally, Andy J.; Elliott, David B.

    2011-01-01

    BACKGROUND: Descending kerbs during locomotion involves the regulation of appropriate foot placement before the kerb-edge and foot clearance over it. It also involves the modulation of gait output to ensure the body-mass is safely and smoothly lowered to the new level. Previous research has shown that vision is used in such adaptive gait tasks for feedforward planning, with vision from the lower visual field (lvf) used for online updating. The present study determined when lvf information is ...

  10. Self-restraint spillover: Inhibitory control disrupts appetite regulation among ruminators.

    Science.gov (United States)

    Schlinkert, Caroline; Koole, Sander L

    2017-10-23

    People can use inhibitory control to temporarily inhibit their personal preferences to achieve their long-term goals. According to the ego fixation model (Koole et al., 2014), ruminators have difficulties relaxing inhibitory control, leading them to continue inhibiting their personal needs, even when this is no longer required by the situation. Inhibitory control may thus disrupt healthy appetite regulation among ruminators. Among 324 Dutch undergraduate students (218 women; M age  = 21.5), different inhibitory control states were manipulated by varying whether or not participants exerted inhibitory control (Study 1) or priming high versus low inhibitory control (Study 2). All participants then performed a food-tasting task. Healthy appetite regulation was defined as a positive correlation between level of food deprivation and preference for high-calorie foods. For taste ratings, the interaction between inhibitory control and rumination was significant in each study: Inhibitory control disrupted healthy appetite regulation in taste preferences among ruminators, but not among non-ruminators. For eating behavior, the same interaction effect was significant when the two studies were combined. Inhibitory control disrupts healthy appetite regulation among ruminators. These findings suggest the need for caution in interventions that rely on inhibitory control, especially among samples with compulsive thought tendencies. © 2017 Wiley Periodicals, Inc.

  11. Flexible brain network reconfiguration supporting inhibitory control.

    Science.gov (United States)

    Spielberg, Jeffrey M; Miller, Gregory A; Heller, Wendy; Banich, Marie T

    2015-08-11

    The ability to inhibit distracting stimuli from interfering with goal-directed behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functional magnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties.

  12. Voluntary inhibitory motor control over involuntary tic movements.

    Science.gov (United States)

    Ganos, Christos; Rothwell, John; Haggard, Patrick

    2018-03-06

    Inhibitory control is crucial for normal adaptive motor behavior. In hyperkinesias, such as tics, disinhibition within the cortico-striato-thalamo-cortical loops is thought to underlie the presence of involuntary movements. Paradoxically, tics are also subject to voluntary inhibitory control. This puzzling clinical observation questions the traditional definition of tics as purely involuntary motor behaviors. Importantly, it suggests novel insights into tic pathophysiology. In this review, we first define voluntary inhibitory tic control and compare it with other notions of tic control from the literature. We then examine the association between voluntary inhibitory tic control with premonitory urges and review evidence linking voluntary tic inhibition to other forms of executive control of action. We discuss the somatotopic selectivity and the neural correlates of voluntary inhibitory tic control. Finally, we provide a scientific framework with regard to the clinical relevance of the study of voluntary inhibitory tic control within the context of the neurodevelopmental disorder of Tourette syndrome. We identify current knowledge gaps that deserve attention in future research. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  13. Pain Elimination during Injection with Newer Electronic Devices: A Comparative Evaluation in Children.

    Science.gov (United States)

    Bansal, Neha; Saha, Sonali; Jaiswal, Jn; Samadi, Firoza

    2014-05-01

    The present study was taken up to clinically evaluate and compare effectiveness of transcutaneous electrical nerve stimulator (TENS) and comfort control syringe (CCS) in various pediatric dental procedures as an alternative to the conventional method of local anesthesia (LA) administration. Ninety healthy children having at least one deciduous molar tooth indicated for extraction in either maxillary right or left quadrant in age group of 6 to 10 years were randomly divided into three equal groups having 30 subjects each. Group I: LA administration using conventional syringe, group II: LA administration using TENS along with the conventional syringe, group III: LA administration using CCS. After LA by the three techniques, pain, anxiety and heart rate were measured. The observations, thus, obtained were subjected to statistical analysis using analysis of variance (ANOVA), student t-test and paired t-test. The mean pain score was maximum in group I followed by group II, while group III revealed the minimum pain, where LA was administered using CCS. Mean anxiety score was maximum in group I followed by group II, while group III revealed the minimum score. Mean heart rate was maximum in group I followed in descending order by groups II and III. The study supports the belief that CCS could be a viable alternative in comparison to the other two methods of LA delivery in children. How to cite this article: Bansal N, Saha S, Jaiswal JN, Samadi F. Pain Elimination during Injection with Newer Electronic Devices: A Comparative Evaluation in Children. Int J Clin Pediatr Dent 2014;7(2):71-76.

  14. Endogenous analgesic effect of pregabalin: A double-blind and randomized controlled trial.

    Science.gov (United States)

    Sugimine, S; Saito, S; Araki, T; Yamamoto, K; Obata, H

    2017-07-01

    Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM. Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups. Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = -0.73, p CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R 2  = 0.51, p CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia. © 2017 European Pain Federation - EFIC®.

  15. Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy.

    Science.gov (United States)

    Granovsky, Yelena; Nahman-Averbuch, Hadas; Khamaisi, Mogher; Granot, Michal

    2017-05-01

    Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN). To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients. In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain. Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = -0.417; P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group ( P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics. Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to "normalize" with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

  16. Enhanced micronucleus formation in the descendants of {gamma}-ray-irradiated tobacco cells: Evidence for radiation-induced genomic instability in plant cells

    Energy Technology Data Exchange (ETDEWEB)

    Yokota, Yuichiro, E-mail: yokota.yuichiro@jaea.go.jp [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Funayama, Tomoo; Hase, Yoshihiro [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Hamada, Nobuyuki [Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, 2-11-1 Iwado-kita, Komae, Tokyo 201-8511 (Japan); Kobayashi, Yasuhiko; Tanaka, Atsushi; Narumi, Issay [Life Science and Biotechnology Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan)

    2010-09-10

    Ionizing radiation-induced genomic instability has been documented in various end points such as chromosomal aberrations and mutations, which arises in the descendants of irradiated mammalian or yeast cells many generations after the initial insult. This study aimed at addressing radiation-induced genomic instability in higher plant tobacco cells. We thus investigated micronucleus (MN) formation and cell proliferation in tobacco cells irradiated with {gamma}-rays and their descendants. In {gamma}-irradiated cells, cell cycle was arrested at G{sub 2}/M phase at around 24 h post-irradiation but released afterward. In contrast, MN frequency peaked at 48 h post-irradiation. Almost half of 40 Gy-irradiated cells had MN at 48 h post-irradiation, but proliferated as actively as sham-irradiated cells up to 120 h post-irradiation. Moreover, the descendants that have undergone at least 22 generations after irradiation still showed a two-fold MN frequency compared to sham-irradiated cells. This is the direct evidence for radiation-induced genomic instability in tobacco cells.

  17. Follow-up of pain processing recovery after ketamine in hyperalgesic fibromyalgia patients using brain perfusion ECD-SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Guedj, Eric; Cammilleri, Serge; Colavolpe, Cecile; Laforte, Catherine de; Mundler, Olivier [Assistance Publique des Hopitaux de Marseille, Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Marseille, Cedex 5 (France); Niboyet, Jean [Clinique La Phoceanne, Unite d' Etude et de Traitement de la Douleur, Marseille (France)

    2007-12-15

    The aim of this study was to determine whether the follow-up of pain processing recovery in hyperalgesic fibromyalgia (FM) could be objectively evaluated with brain perfusion ethyl cysteinate dimer single photon computerized tomography (ECD-SPECT) after administration of ketamine. We enrolled 17 hyperalgesic FM women patients (48.5 {+-} 11 years, range 25-63). After treatment with subcutaneous ketamine, 11 patients were considered as 'good responders', with a decrease in pain intensity, evaluated by visual analog scale (VAS), greater than 50%. On the other hand, six patients were considered as 'poor responders'. A voxel-based analysis of regional cerebral blood flow (rCBF) was conducted (p{sub voxel} < 0.001uc), in the two subgroups of patients, before and after treatment, in comparison to a group of ten healthy subjects, matched for age and gender. In comparison to baseline brain SPECT, midbrain rCBF showed a greater increase after ketamine in the responder group than in the nonresponder group (p{sub cluster} = 0.016c). In agreement with the clinical response, the change in midbrain rCBF after ketamine was highly correlated with the reduction of VAS pain score (r = 0.7182; p = 0.0041). This prospective study suggests that blockade of facilitatory descending modulation of pain with ketamine can be evaluated in the periaqueductal grey with brain perfusion SPECT. (orig.)

  18. Glycine transporter GlyT1, but not GlyT2, is expressed in rat dorsal root ganglion--Possible implications for neuropathic pain

    NARCIS (Netherlands)

    Schlösser, Lukas; Barthel, Franziska; Brandenburger, Timo; Neumann, Elena; Bauer, Inge; Eulenburg, Volker; Werdehausen, Robert; Hermanns, Henning

    2015-01-01

    Glycinergic inhibitory neurotransmission plays a pivotal role in the development of neuropathic pain. The glycine concentration in the synaptic cleft is controlled by the glycine transporters GlyT1 and GlyT2. GlyT1 is expressed throughout the central nervous system, while GlyT2 is exclusively

  19. Chronic idiopathic anal pain. Results of a diagnostic-therapeutic protocol in a colorectal referral unit.

    Science.gov (United States)

    Armañanzas, Laura; Arroyo, Antonio; Ruiz-Tovar, Jaime; López, Alberto; Santos, Jair; Moya, Pedro; Gómez, María Amparo; Candela, Fernando; Calpena, Rafael

    2015-01-01

    Chronic idiopathic anal pain (CIAP) remains a diagnosis of exclusion. Its study and management still lack a standardized protocol. The aim of this study is to evaluate the results obtained with the diagnostic-therapeutic protocol established in our service. We performed a retrospective study of patients diagnosed with CIAP at the Colorectal Unit of the General University Hospital of Elche, between 2005 and 2011. We evaluated 57 patients with a diagnosis of chronic anal pain for functional anorectal disease (FAD). After the application of our diagnostic protocol, final diagnosis of chronic anal pain (CAP) was achieved in 43 cases (75%), including 22 cases of descending perineum syndrome, 12 of proctalgia fugax, 2 of pudendal neuritis and 7 of coccydynia. In 14 patients exclusion diagnosis of CIAP was established. Among the therapies used on patients with CIAP, biofeedback combined with conservative measures improved symptoms in 43% of the cases. Sacral nerve stimulation was assessed in patients who did not respond to other treatments. Through proper anamnesis, physical examination and complementary tests, a specific diagnosis of the cause of CAP by FAD can be achieved, reducing exclusion diagnosis of CIAP to 25% of cases. Conservative measures combined with biofeedback achieved an improvement in pain in more than 40% of the cases of CIAP in our study. Sacral nerve stimulation can be considered as a treatment option in refractory cases. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Penetrating Atherosclerotic Ulcer of the Descending Thoracic Aorta: Treatment by Endovascular Stent-Graft

    International Nuclear Information System (INIS)

    Murgo, Salvatore; Dussaussois, Luc; Golzarian, Jafar; Cavenaile, Jean Christophe; Abada, Hicham Tarik; Ferreira, Jose; Struyven, Julien

    1998-01-01

    Purpose: To present four cases of penetrating ulcer of the descending thoracic aorta treated by transfemoral insertion of an endoluminal stent-graft. Methods: Four patients with penetrating aortic ulcers were reviewed. Three cases were complicated by rupture, false aneurysm, or retrograde dissection. All patients were treated by endovascular stent-graft and were followed by helical computed tomography (CT). Results: Endovascular stent-graft deployment was successful in all patients. However, in one case we observed a perigraft leak that spontaneously disappeared within the first month, and two interventions were needed for another patient. Following treatment, one episode of transient spinal ischemia was observed. The 30-day survival rate was 100%, but one patient died from pneumonia with cardiac failure 34 days after the procedure. In one patient, helical CT performed at 3 months showed a false aneurysm independent of the first ulcer. This patient refused any further treatment and suddenly died at home (unknown cause) after a 6-month follow-up period. Conclusion: Transluminal placement of endovascular stent-grafts for treatment of penetrating ulcers of the descending thoracic aorta appears to be a possible alternative to classical surgery. After treatment, follow-up by CT is essential to detect possible complications of the disease

  1. Electromyographic preactivation pattern of the gluteus medius during weight-bearing functional tasks in women with and without anterior knee pain.

    Science.gov (United States)

    Nakagawa, Theresa H; Muniz, Thiago B; Baldon, Rodrigo M; Maciel, Carlos D; Amorim, César F; Serrão, Fábio V

    2011-01-01

    Proximal factors have been proposed to influence the biomechanics of the patellofemoral joint. A delayed or diminished gluteus medius (GM) activation, before the foot contact on the ground during functional activities could lead to excessive femur adduction and internal rotation and be associated with anterior knee pain (AKP). There are few studies on this topic and the results were inconclusive, therefore, it is necessary to investigate the GM preactivation pattern during functional activities. To compare the GM electromyographic (EMG) preactivation pattern during walking, descending stairs and in single leg jump task in women with and without AKP. Nine women clinically diagnosed with AKP and ten control subjects with no history of knee injury participated in this study. We evaluated GM EMG linear envelope before the foot contact on the ground during walking and GM onset time and EMG linear envelope during descending stairs as well as in a single leg vertical jump. Mann-Whitney U tests were used to determine the between-group differences in GM EMG preactivation pattern. No between-group differences were observed in GM linear envelope during walking (P=0.41), GM onset time and linear envelope during descending stairs (P=0.17 and P=0.15) and single leg jump (P=0.81 and P=0.33). Women with AKP did not demonstrated altered GM preactivation pattern during functional weight bearing activities. Our results did not support the hypothesis that poor GM preactivation pattern could be associated with AKP.

  2. Lack of predictive power of trait fear and anxiety for conditioned pain modulation (CPM).

    Science.gov (United States)

    Horn-Hofmann, Claudia; Priebe, Janosch A; Schaller, Jörg; Görlitz, Rüdiger; Lautenbacher, Stefan

    2016-12-01

    In recent years the association of conditioned pain modulation (CPM) with trait fear and anxiety has become a hot topic in pain research due to the assumption that such variables may explain the low CPM efficiency in some individuals. However, empirical evidence concerning this association is still equivocal. Our study is the first to investigate the predictive power of fear and anxiety for CPM by using a well-established psycho-physiological measure of trait fear, i.e. startle potentiation, in addition to two self-report measures of pain-related trait anxiety. Forty healthy, pain-free participants (female: N = 20; age: M = 23.62 years) underwent two experimental blocks in counter-balanced order: (1) a startle paradigm with affective picture presentation and (2) a CPM procedure with hot water as conditioning stimulus (CS) and contact heat as test stimulus (TS). At the end of the experimental session, pain catastrophizing (PCS) and pain anxiety (PASS) were assessed. PCS score, PASS score and startle potentiation to threatening pictures were entered as predictors in a linear regression model with CPM magnitude as criterion. We were able to show an inhibitory CPM effect in our sample: pain ratings of the heat stimuli were significantly reduced during hot water immersion. However, CPM was neither predicted by self-report of pain-related anxiety nor by startle potentiation as psycho-physiological measure of trait fear. These results corroborate previous negative findings concerning the association between trait fear/anxiety and CPM efficiency and suggest that shifting the focus from trait to state measures might be promising.

  3. Synthesis and Analgesic Effects of μ-TRTX-Hhn1b on Models of Inflammatory and Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-08-01

    Full Text Available μ-TRTX-Hhn1b (HNTX-IV is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. μ-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of μ-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of μ-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that μ-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.

  4. Self-reported impulsivity and inhibitory control in problem gamblers.

    Science.gov (United States)

    Lorains, Felicity K; Stout, Julie C; Bradshaw, John L; Dowling, Nicki A; Enticott, Peter G

    2014-01-01

    Impulsivity is considered a core feature of problem gambling; however, self-reported impulsivity and inhibitory control may reflect disparate constructs. We examined self-reported impulsivity and inhibitory control in 39 treatment-seeking problem gamblers and 41 matched controls using a range of self-report questionnaires and laboratory inhibitory control tasks. We also investigated differences between treatment-seeking problem gamblers who prefer strategic (e.g., sports betting) and nonstrategic (e.g., electronic gaming machines) gambling activities. Treatment-seeking problem gamblers demonstrated elevated self-reported impulsivity, more go errors on the Stop Signal Task, and a lower gap score on the Random Number Generation task than matched controls. However, overall we did not find strong evidence that treatment-seeking problem gamblers are more impulsive on laboratory inhibitory control measures. Furthermore, strategic and nonstrategic problem gamblers did not differ from their respective controls on either self-reported impulsivity questionnaires or laboratory inhibitory control measures. Contrary to expectations, our results suggest that inhibitory dyscontrol may not be a key component for some treatment-seeking problem gamblers.

  5. Facilitated pronociceptive pain mechanisms in radiating back pain compared with localized back pain

    DEFF Research Database (Denmark)

    Vaegter, Henrik Bjarke; Palsson, Thorvaldur Skuli; Graven-Nielsen, Thomas

    2017-01-01

    Facilitated pain mechanisms and impaired pain inhibition are often found in chronic pain patients. This study compared clinical pain profiles, pain sensitivity, as well as pro-nociceptive and anti-nociceptive mechanisms in patients with localized low back pain (n=18), localized neck pain (n=17......), low back and radiating leg pain (n=18), or neck and radiating arm pain (n=17). It was hypothesized that patients with radiating pain had facilitated pain mechanisms and impaired pain inhibition compared with localized pain patients. Cuff algometry was performed on the non-painful lower leg to assess...... threshold (HPT) at the non-painful hand were also assessed. Clinical pain intensity, psychological distress, and disability were assessed with questionnaires. TSP was increased in patients with radiating back pain compared with localized back pain (Ppain or localized low...

  6. Miopatia ocular descendente Descending ocular myopathy: a case report

    Directory of Open Access Journals (Sweden)

    Marcos R. G. de Freitas

    1975-06-01

    Full Text Available Os autores apresentam caso de paciente jovem, do sexo feminino, com afecção muscular primária ocular e faríngea sem caráter familial. Foram feitos estudos eletromiográficos e histopatológicos musculares que confirmam o caráter miogênico do processo. É feita comparação entre a miopatia ocular e a miopatia ocular descendente, acreditando os autores que seriam variantesThe case of a 23 years old female patient, with primary involvement of the extraocular and faringeal muscles without familiar history is reported. Electromyographic and muscular biopsy studies proved the myogenic nature of the process. A clinical comparison between the ocular myopathy and the descending ocular myopathy is made, the authors thinking that both of them would be variants of the same muscle disease.

  7. Recruitment of activation receptors at inhibitory NK cell immune synapses.

    Directory of Open Access Journals (Sweden)

    Nicolas Schleinitz

    2008-09-01

    Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

  8. Axial compartmentation of descending and ascending thin limbs of Henle's loops.

    Science.gov (United States)

    Westrick, Kristen Y; Serack, Bradley; Dantzler, William H; Pannabecker, Thomas L

    2013-02-01

    In the inner medulla, radial organization of nephrons and blood vessels around collecting duct (CD) clusters leads to two lateral interstitial regions and preferential intersegmental fluid and solute flows. As the descending (DTLs) and ascending thin limbs (ATLs) pass through these regions, their transepithelial fluid and solute flows are influenced by variable transepithelial solute gradients and structure-to-structure interactions. The goal of this study was to quantify structure-to-structure interactions, so as to better understand compartmentation and flows of transepithelial water, NaCl, and urea and generation of the axial osmotic gradient. To accomplish this, we determined lateral distances of AQP1-positive and AQP1-negative DTLs and ATLs from their nearest CDs, so as to gauge interactions with intercluster and intracluster lateral regions and interactions with interstitial nodal spaces (INSs). DTLs express reduced AQP1 and low transepithelial water permeability along their deepest segments. Deep AQP1-null segments, prebend segments, and ATLs lie equally near to CDs. Prebend segments and ATLs abut CDs and INSs throughout much of their descent and ascent, respectively; however, the distal 30% of ATLs of the longest loops lie distant from CDs as they approach the outer medullary boundary and have minimal interaction with INSs. These relationships occur regardless of loop length. Finally, we show that ascending vasa recta separate intercluster AQP1-positive DTLs from descending vasa recta, thereby minimizing dilution of gradients that drive solute secretion. We hypothesize that DTLs and ATLs enter and exit CD clusters in an orchestrated fashion that is important for generation of the corticopapillary solute gradient by minimizing NaCl and urea loss.

  9. Bilingual Contexts Modulate the Inhibitory Control Network

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    Jing Yang

    2018-03-01

    Full Text Available The present functional magnetic resonance imaging (fMRI study investigated influences of language contexts on inhibitory control and the underlying neural processes. Thirty Cantonese–Mandarin–English trilingual speakers, who were highly proficient in Cantonese (L1 and Mandarin (L2, and moderately proficient in English (L3, performed a picture-naming task in three dual-language contexts (L1-L2, L2-L3, and L1-L3. After each of the three naming tasks, participants performed a flanker task, measuring contextual effects on the inhibitory control system. Behavioral results showed a typical flanker effect in the L2-L3 and L1-L3 condition, but not in the L1-L2 condition, which indicates contextual facilitation on inhibitory control performance by the L1-L2 context. Whole brain analysis of the fMRI data acquired during the flanker tasks showed more neural activations in the right prefrontal cortex and subcortical areas in the L2-L3 and L1-L3 condition on one hand as compared to the L1-L2 condition on the other hand, suggesting greater involvement of the cognitive control areas when participants were performing the flanker task in L2-L3 and L1-L3 contexts. Effective connectivity analyses displayed a cortical-subcortical-cerebellar circuitry for inhibitory control in the trilinguals. However, contrary to the right-lateralized network in the L1-L2 condition, functional networks for inhibitory control in the L2-L3 and L1-L3 condition are less integrated and more left-lateralized. These findings provide a novel perspective for investigating the interaction between bilingualism (multilingualism and inhibitory control by demonstrating instant behavioral effects and neural plasticity as a function of changes in global language contexts.

  10. Pain and pain behavior in burning mouth syndrome: a pain diary study.

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    Forssell, Heli; Teerijoki-Oksa, Tuija; Kotiranta, Ulla; Kantola, Rosita; Bäck, Marjaliina; Vuorjoki-Ranta, Tiina-Riitta; Siponen, Maria; Leino, Ari; Puukka, Pauli; Estlander, Ann-Mari

    2012-01-01

    To characterize pain related to primary burning mouth syndrome (BMS) in terms of intensity, interference, and distress caused by the pain, as well as factors influencing the pain across a period of 2 weeks, and to study the use of coping and management strategies on a daily basis. Fifty-two female patients with primary BMS completed a 2-week pain diary. Pain intensity, interference, distress, and mood on a 0 to 10 numeric rating scale (NRS), as well as pain amplifying and alleviating factors, were recorded three times a day. The use of treatments (medication or other means) and coping strategies were recorded at the end of each day. Coefficient of variation, repeated measures analysis of variance, and correlative methods were used to assess the between- and within-subject variation, pain patterns, and associations between various pain scores. The overall mean pain intensity score of the 14 diary days was 3.1 (SD: 1.7); there was considerable variation in pain intensity between patients. Most patients experienced intermittent pain. On average, pain intensity increased from the morning to the evening. Intercorrelations between pain intensity, interference, distress, and mood were high, varying between rs = .75 and rs = .93 (P < .001). Pungent or hot food or beverages, stress, and tiredness were the most frequently mentioned pain-amplifying factors. The corresponding pain-alleviating factors were eating, sucking pastilles, drinking cold beverages, and relaxation. Thirty (58%) patients used pain medication and 35% reported using other means to alleviate their BMS pain. There was large variation in the use of coping strategies -between subjects. There were considerable differences in pain, in factors influencing the pain, and in pain behavior across BMS patients. This indicates that patient information and education as well as treatment of BMS pain should be individualized.

  11. Decorrelation of Neural-Network Activity by Inhibitory Feedback

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    Einevoll, Gaute T.; Diesmann, Markus

    2012-01-01

    Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure. An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons. Recent studies demonstrate that spike correlations in recurrent neural networks are considerably smaller than expected based on the amount of shared presynaptic input. Here, we explain this observation by means of a linear network model and simulations of networks of leaky integrate-and-fire neurons. We show that inhibitory feedback efficiently suppresses pairwise correlations and, hence, population-rate fluctuations, thereby assigning inhibitory neurons the new role of active decorrelation. We quantify this decorrelation by comparing the responses of the intact recurrent network (feedback system) and systems where the statistics of the feedback channel is perturbed (feedforward system). Manipulations of the feedback statistics can lead to a significant increase in the power and coherence of the population response. In particular, neglecting correlations within the ensemble of feedback channels or between the external stimulus and the feedback amplifies population-rate fluctuations by orders of magnitude. The fluctuation suppression in homogeneous inhibitory networks is explained by a negative feedback loop in the one-dimensional dynamics of the compound activity. Similarly, a change of coordinates exposes an effective negative feedback loop in the compound dynamics of stable excitatory-inhibitory networks. The suppression of input correlations in finite networks is explained by the population averaged correlations in the linear network model: In purely inhibitory networks, shared-input correlations are canceled by negative spike-train correlations. In excitatory-inhibitory networks, spike-train correlations are typically positive. Here, the suppression of input correlations is not a result of the mere existence of correlations between

  12. Somatostatin-expressing inhibitory interneurons in cortical circuits

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    Iryna Yavorska

    2016-09-01

    Full Text Available Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons.

  13. Effects of Simvastatin Beyond Dyslipidemia: Exploring Its Antinociceptive Action in an Animal Model of Complex Regional Pain Syndrome-Type I

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    Graziela Vieira

    2017-09-01

    Full Text Available Simvastatin is a lipid-lowering agent that blocks the production of cholesterol through inhibition of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA reductase. In addition, recent evidence has suggested its anti-inflammatory and antinociceptive actions during inflammatory and pain disorders. Herein, we investigated the effects of simvastatin in an animal model of complex regional pain syndrome-type I, and its underlying mechanisms. Chronic post-ischemia pain (CPIP was induced by ischemia and reperfusion (IR injury of the left hind paw. Our findings showed that simvastatin inhibited mechanical hyperalgesia induced by CPIP model in single and repeated treatment schedules, respectively; however simvastatin did not alter inflammatory signs during CPIP model. The mechanisms underlying those actions are related to modulation of transient receptor potential (TRP channels, especially TRMP8. Moreover, simvastatin oral treatment was able to reduce the nociception induced by acidified saline [an acid-sensing ion channels (ASICs activator] and bradykinin (BK stimulus, but not by TRPA1, TRPV1 or prostaglandin-E2 (PGE2. Relevantly, the antinociceptive effects of simvastatin did not seem to be associated with modulation of the descending pain circuits, especially noradrenergic, serotoninergic and dopaminergic systems. These results indicate that simvastatin consistently inhibits mechanical hyperalgesia during neuropathic and inflammatory disorders, possibly by modulating the ascending pain signaling (TRPM8/ASIC/BK pathways expressed in the primary sensory neuron. Thus, simvastatin open-up new standpoint in the development of innovative analgesic drugs for treatment of persistent pain, including CRPS-I.

  14. Pain-relevant anxiety affects desire for pain relief, but not pain perception

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    Adriana Banozic

    2017-01-01

    Full Text Available Background: Pain context plays a significant role in the perception of pain. Despite recent interest in vicarious learning and anxiety in pain modulation, there have been no attempts to explore pain modulation by specific environmental cues. Aims: Therefore, the present study evaluated pain responses in the condition that was attributed as either anxiety relevant (AR or anxiety irrelevant. Materials and Methods: Participants were exposed to both conditions through social observational learning. Pain perception was assessed by means of a visual analog scale ranging from 0 = no pain to 10 = maximum imaginable pain. State anxiety, empathy, expectancy, and desire for pain relief were also measured at both neutral and emotionally inducing conditions. Results: No effect of relevancy of anxiety for the pain context on any of the pain-related constructs was found. However, participants in the AR condition reported an increased desire for pain relief. Maximizing similarities between observed and experienced pain context did not enhance observational learning effects in the emotionally inducing condition regardless of its relevance, but significant changes were found in comparison to the affectively neutral group. Conclusions: These results could have potentially significant clinical implications suggesting that even though observing painful procedures does not increase pain it could affect medication usage.

  15. Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

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    Gui-Lin Jin

    2018-01-01

    Full Text Available Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.

  16. Lack of endogenous modulation and reduced decay of prolonged heat pain in older adults.

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    Riley, Joseph L; King, Christopher D; Wong, Fong; Fillingim, Roger B; Mauderli, Andre P

    2010-07-01

    This study supports the hypothesis that healthy older adults exhibit decreased endogenous pain inhibition compared to younger healthy controls. Twenty-two older adults (56-77years of age) and 27 controls aged 20-49 participated in five experimental sessions following a training session. Each experimental session consisted of five 60-s trials in which the experimental heat stimulus was presented to the thenar eminence of the left palm with or without a conditioning stimulus (cold-water immersion of the foot). The temperature for the palm (44-49 degrees C) and foot (8-16 degrees C) was customized for each subject. The intensity of experimental pain produced by the contact thermode was continuously measured during the 60-s trial with an electronic visual analogue scale. No significant associations were found between subjects rating of concentration and the overall inhibitory effect. Older subjects failed to demonstrate conditioned pain modulation (CPM) and showed facilitation in the trials using painful concurrent immersion of the foot. A novel aspect of the study was that we recorded "pain offset" (i.e., after-sensations) and found that ratings for the older sample decreased at a slower rate than observed for the group of younger adults suggesting increased central sensitization among the older sample. Decrements in CPM could contribute to the greater prevalence of pain in older age. Since a number of neurotransmitter systems are involved in pain modulation, it is possible age-related differences in CPM are due to functional changes in these systems in a number of areas within the neuroaxis. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  17. Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy

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    Yelena Granovsky

    2017-06-01

    Conclusion:. Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to “normalize” with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

  18. Do detour tasks provide accurate assays of inhibitory control?

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    Whiteside, Mark A.; Laker, Philippa R.; Beardsworth, Christine E.

    2018-01-01

    Transparent Cylinder and Barrier tasks are used to purportedly assess inhibitory control in a variety of animals. However, we suspect that performances on these detour tasks are influenced by non-cognitive traits, which may result in inaccurate assays of inhibitory control. We therefore reared pheasants under standardized conditions and presented each bird with two sets of similar tasks commonly used to measure inhibitory control. We recorded the number of times subjects incorrectly attempted to access a reward through transparent barriers, and their latencies to solve each task. Such measures are commonly used to infer the differential expression of inhibitory control. We found little evidence that their performances were consistent across the two different Putative Inhibitory Control Tasks (PICTs). Improvements in performance across trials showed that pheasants learned the affordances of each specific task. Critically, prior experience of transparent tasks, either Barrier or Cylinder, also improved subsequent inhibitory control performance on a novel task, suggesting that they also learned the general properties of transparent obstacles. Individual measures of persistence, assayed in a third task, were positively related to their frequency of incorrect attempts to solve the transparent inhibitory control tasks. Neophobia, Sex and Body Condition had no influence on individual performance. Contrary to previous studies of primates, pheasants with poor performance on PICTs had a wider dietary breadth assayed using a free-choice task. Our results demonstrate that in systems or taxa where prior experience and differences in development cannot be accounted for, individual differences in performance on commonly used detour-dependent PICTS may reveal more about an individual's prior experience of transparent objects, or their motivation to acquire food, than providing a reliable measure of their inhibitory control. PMID:29593115

  19. Organizers of inhibitory synapses come of age.

    Science.gov (United States)

    Krueger-Burg, Dilja; Papadopoulos, Theofilos; Brose, Nils

    2017-08-01

    While the postsynaptic density of excitatory synapses is known to encompass a highly complex molecular machinery, the equivalent organizational structure of inhibitory synapses has long remained largely undefined. In recent years, however, substantial progress has been made towards identifying the full complement of organizational proteins present at inhibitory synapses, including submembranous scaffolds, intracellular signaling proteins, transsynaptic adhesion proteins, and secreted factors. Here, we summarize these findings and discuss future challenges in assigning synapse-specific functions to the newly discovered catalog of proteins, an endeavor that will depend heavily on newly developed technologies such as proximity biotinylation. Further advances are made all the more essential by growing evidence that links inhibitory synapses to psychiatric and neurological disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Fertility among descendants of immigrants in Belgium: The role of the partner

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    Lisa Van Landschoot

    2017-06-01

    Full Text Available Background: Research on the fertility behavior of descendants of immigrants has focused on female characteristics and has largely neglected those of the male partner. One key aspect is whether the partner is of same (endogamous or of different (exogamous ethnic origin. Moreover, the male partner may be born in the same country as the female partner, or he may have migrated to that country later in the life course. Consequently, both his ethnic origin and migration history may affect the fertility behavior of second-generation women. Objective: This study analyzes to what extent second and higher order births of second-generation women of Southern European, Turkish, or Moroccan origin in Belgium differ by the ethnic origin and migration history of the male partner. Methods: We apply event history methods using the 2001 Belgian Census, linked with the 2006 Belgian National Population Register. Results: Women of Turkish and Moroccan origin in an endogamous union experience higher second and subsequent birth rates than their counterparts in an exogamous union. However, no variation is found within the endogamous unions: Whether or not the endogamous partner has been born in the country of origin does not seem to affect second and higher order birth rates. For women of Southern European origin, second and higher order birth rates do not differ by origin and generation of their partner. Contribution: This study extends the literature on the fertility behavior of the descendants of immigrants by demonstrating the importance of male partner characteristics in explaining the transition to a second or a higher order birth.

  1. Cyclooxygenase inhibitory compounds from Gymnosporia heterophylla aerial parts.

    Science.gov (United States)

    Ochieng, Charles O; Opiyo, Sylvia A; Mureka, Edward W; Ishola, Ismail O

    2017-06-01

    Gymnosporia heterophylla (Celastraceae) is an African medicinal plants used to treat painful and inflammatory diseases with partial scientific validation. Solvent extractions followed by repeated chromatographic purification of the G. heterophylla aerial parts led to the isolation of one new β-dihydroagarofuran sesquiterpene alkaloid (1), and two triterpenes (2-3). In addition, eight known compounds including one β-dihydroagarofuran sesquiterpene alkaloid (4), and six triterpenes (5-10) were isolated. All structures were determined through extensive analysis of the NMR an MS data as well as by comparison with literature data. These compounds were evaluated for the anti-inflammatory activities against COX-1 and -2 inhibitory potentials. Most of the compound isolated showed non selective COX inhibitions except for 3-Acetoxy-1β-hydroxyLupe-20(29)-ene (5), Lup-20(29)-ene-1β,3β-diol (6) which showed COX-2 selective inhibition at 0.54 (1.85), and 0.45 (2.22) IC 50 , in mM (Selective Index), respectively. The results confirmed the presence of anti-inflammatory compounds in G. heterophylla which are important indicators for development of complementary medicine for inflammatory reactions; however, few could be useful as selective COX-2 inhibitor. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Anesthetic management of descending thoracic aortobifemoral bypass for aortoiliac occlusive disease: Our experience

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    Anjum Saiyed

    2014-01-01

    Full Text Available Background: Complete obstruction of the abdominal aorta at the renal artery level is a difficult surgical problem. Aortic clamping and declamping can lead to profound haemodynamic changes, myocardial infarction, ventricular failure or even death may result. These complications are important challenges in anesthetic management of these patients. Methods :0 Between August, 2010 and April, 2012, descending thoracic aorta to femoral artery bypass grafting was used to revascularize lower limbs in 11 patients in our institute. The anesthetic management of these patients is described here. Epidural catheter placement was done in T 5-6 or T 6-7 space for post operative pain relief. Induction was done by, Inj. Glycopyrolate 0.2 mg, Inj. Fentanyl 5 μg/kg., Inj. Pentothal sodium 5 mg/kg, Inj. Rocuronium 0.9 mg/kg, IPPV done. Left sided double lumen tube was inserted, Maintenance of Anesthesia was done by O 2 + N 2 O (30:70. Increments of Vecuronium and Fentanyl were given Monitoring of Heart rate, arterial pressure, central venous pressure were continuously displayed. The available pharmacological agents were used when there is deviation of more than 15% from base line. Results: In our study, inspite of measures taken to control rise in blood pressure during aortic cross clamping, a rise of 90 mm of Hg in one patient and 60-80 mm of Hg in four patients was observed, which was managed by sodium nitropruside infusion. At the end of surgery seven patients were extubated on the operation table. In remaining four patients DLT was replaced by single lumen endotracheal tube and were shifted to ICU on IPPV. They weaned off gradually in 3-5 hours. In our series blood loss was 400 ml to 1000 ml. There was no mortality in the first 24 hours. Postoperative bleeding was reported in one case which was re-explored and stood well. Conclusion: The anesthetic technique during aortic surgery is directed at minimizing the hemodynamic effects of cross clamping in order to

  3. Conditioned pain modulation in patients with nonspecific chronic back pain with chronic local pain, chronic widespread pain, and fibromyalgia.

    Science.gov (United States)

    Gerhardt, Andreas; Eich, Wolfgang; Treede, Rolf-Detlef; Tesarz, Jonas

    2017-03-01

    Findings considering conditioned pain modulation (CPM) in chronic back pain (CBP) are contradictory. This might be because many patients with CBP report pain in further areas of the body, and altered CPM might influence spatial extent of pain rather than CBP per se. Therefore, we compared CPM in patients with CBP with different pain extent. Patients with fibromyalgia syndrome (FMS), for whom CPM impairment is reported most consistently, were measured for comparison. Based on clinical evaluation and pain drawings, patients were categorized into chronic local back pain (CLP; n = 53), chronic widespread back pain (CWP; n = 32), and FMS (n = 92). Conditioned pain modulation was measured by the difference in pressure pain threshold (test stimuli) at the lower back before and after tonic heat pain (conditioning stimulus). We also measured psychosocial variables. Pressure pain threshold was significantly increased in CLP patients after tonic heat pain (P pain modulation in CLP was significantly higher than that in CWP and FMS (P painful areas (0-10) were associated with lower CPM (r = 0.346, P = 0.001) in CBP but not in FMS (r = -0.013, P = 0.903). Anxiety and depression were more pronounced in FMS than in CLP or CWP (P values pain inhibition seem to be more indicated the higher the pain extent.

  4. A pilot investigation of acute inhibitory control training in cocaine users.

    Science.gov (United States)

    Alcorn, Joseph L; Pike, Erika; Stoops, William S; Lile, Joshua A; Rush, Craig R

    2017-05-01

    Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals. Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using the stop-signal task and visual-probe task with eye tracking, respectively. Training condition groups did not differ on demographics, inhibitory control training performance, response inhibition, or cocaine-cue attentional bias. Response inhibition performance improved as a function of inhibitory control training in both conditions. Cocaine-cue attentional bias was observed, but did not change as a function of inhibitory control training in either condition. Response inhibition in cocaine-using individuals was augmented by acute inhibitory control training, which may improve treatment outcomes through better behavioral inhibition. Future studies should investigate longer-term implementation of inhibitory control training, as well as combining inhibitory control training with other treatment modalities. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Inhibitory ability of children with developmental dyscalculia.

    Science.gov (United States)

    Zhang, Huaiying; Wu, Hanrong

    2011-02-01

    Inhibitory ability of children with developmental dyscalculia (DD) was investigated to explore the cognitive mechanism underlying DD. According to the definition of developmental dyscalculia, 19 children with DD-only and 10 children with DD&RD (DD combined with reading disability) were selected step by step, children in two control groups were matched with children in case groups by gender and age, and the match ratio was 1:1. Psychological testing software named DMDX was used to measure inhibitory ability of the subjects. The differences of reaction time in number Stroop tasks and differences of accuracy in incongruent condition of color-word Stroop tasks and object inhibition tasks between DD-only children and their controls reached significant levels (P<0.05), and the differences of reaction time in number Stroop tasks between dyscalculic and normal children did not disappear after controlling the non-executive components. The difference of accuracy in color-word incongruent tasks between children with DD&RD and normal children reached significant levels (P<0.05). Children with DD-only confronted with general inhibitory deficits, while children with DD&RD confronted with word inhibitory deficits only.

  6. Responses to selection for body weight in descendants of x-irradiated rats

    International Nuclear Information System (INIS)

    Gianola, D.; Chapman, A.B.; Rutledge, J.J.

    1979-01-01

    Th effectiveness of selection for high and low body weight at six weeks of age was studied in descendants of x-irradiated (R) and nonirradiated (C) inbred rats. There were two replicates of each of the direction of selection--irradiation treatments. In C lines, there were no consistent responses to selection, probably due to a low level of genetic variability. In R rats, selection was effective only for decreased body weight. The results of this experiment do not suggest the use of irradiation combined with selection as a means of enhancing responses to selection in animals

  7. [The assimilation of Italians and their descendants in Argentine society (1880-1925)].

    Science.gov (United States)

    Nascimbene, M C

    1996-09-01

    "The impact of massive immigration in the post-1870 period produced major changes in... Argentine society. Integration of immigrant groups (Italians, Spaniards, the French and others) was nevertheless fiercely opposed by local elites. The essay is firstly concerned with size and development of immigration flows; secondly it deals with the characteristics of local reaction against the immigrants; thirdly it reveals how, in spite of the latter, the Italians' integration did take place in the Argentine middle classes. Finally, a particular case-study is presented, in connection with integration of immigrants and their descendants in the national army." (SUMMARY IN ENG AND FRE) excerpt

  8. Dynamics of circadian thalamocortical flow of information during a peripheral neuropathic pain condition

    Directory of Open Access Journals (Sweden)

    Helder eCardoso-Cruz

    2011-08-01

    Full Text Available It is known that the thalamocortical loop plays a crucial role in the encoding of sensory-discriminative features of painful stimuli. However, only a few studies have addressed the changes in thalamocortical dynamics that may occur after the onset of chronic pain. Our goal was to evaluate how the induction of chronic neuropathic pain affected the flow of information within the thalamocortical loop throughout the brain states of the sleep-wake cycle. To address this issue we recorded local field potentials – LFPs – both before and after the establishment of neuropathic pain in awake freely moving adult rats chronically implanted with arrays of multielectrodes in the lateral thalamus and primary somatosensory cortex. Our results show that the neuropathic injury induced changes in the number of wake and slow-wave-sleep state episodes, and especially in the total number of transitions between brain states. Moreover, partial directed coherence – PDC – analysis revealed that the amount of information flow between cortex and thalamus in neuropathic animals decreased significantly, indicating that the overall thalamic activity had less weight over the cortical activity. However, thalamocortical LFPs displayed higher phase-locking during awake and slow-wave-sleep episodes after the nerve lesion, suggesting faster transmission of relevant information along the thalamocortical loop. The observed changes are in agreement with the hypothesis of thalamic dysfunction after the onset of chronic pain, and may result from diminished inhibitory effect of the primary somatosensory cortex over the lateral thalamus.

  9. Scuba diving, acute left anterior descending artery occlusion and normal ECG

    Science.gov (United States)

    Doll, Sébastien Xavier; Rigamonti, Fabio; Roffi, Marco; Noble, Stéphane

    2013-01-01

    We report the case of an acute proximal occlusion of the left anterior descending coronary (LAD) artery following a scuba diving decompression accident and associated with normal ECG. Following uneventful thromboaspiration and coronary stenting, the patient was discharged on day  4 with secondary preventative therapies. A transthoracic echocardiography performed at this point showed a complete recovery compared with an initial localised akinesia involving the anterior and apical portion of the left ventricle upon admission. This case highlights that significant acute coronary lesions involving the LAD can occur without any ECG anomaly. The presence of acute and persistent angina associated with troponin elevation should prompt physicians to consider coronary angiography without delay, independently of the ECG results. PMID:23376677

  10. Painful Intercourse Is Significantly Associated with Evoked Pain Perception and Cognitive Aspects of Pain in Women with Pelvic Pain

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    Meryl J. Alappattu, DPT, PhD

    2015-03-01

    Conclusions: Differences in local pain ratings suggest that women with pelvic pain perceive stimuli in this region as more painful than pain-free women although the magnitude of stimuli does not differ. Alappattu MJ, George SZ, Robinson ME, Fillingim RB, Moawad N, LeBrun EW, and Bishop MD. Painful intercourse is significantly associated with evoked pain perception and cognitive aspects of pain in women with pelvic pain. Sex Med 2015;3:14–23.

  11. Anterior knee pain and evidence of osteoarthritis of the patellofemoral joint should not be considered contraindications to mobile-bearing unicompartmental knee arthroplasty: a 15-year follow-up.

    Science.gov (United States)

    Hamilton, T W; Pandit, H G; Maurer, D G; Ostlere, S J; Jenkins, C; Mellon, S J; Dodd, C A F; Murray, D W

    2017-05-01

    It is not clear whether anterior knee pain and osteoarthritis (OA) of the patellofemoral joint (PFJ) are contraindications to medial unicompartmental knee arthroplasty (UKA). Our aim was to investigate the long-term outcome of a consecutive series of patients, some of whom had anterior knee pain and PFJ OA managed with UKA. We assessed the ten-year functional outcomes and 15-year implant survival of 805 knees (677 patients) following medial mobile-bearing UKA. The intra-operative status of the PFJ was documented and, with the exception of bone loss with grooving to the lateral side, neither the clinical or radiological state of the PFJ nor the presence of anterior knee pain were considered a contraindication. The impact of radiographic findings and anterior knee pain was studied in a subgroup of 100 knees (91 patients). There was no relationship between functional outcomes, at a mean of ten years, or 15-year implant survival, and pre-operative anterior knee pain, or the presence or degree of cartilage loss documented intra-operatively at the medial patella or trochlea, or radiographic evidence of OA in the medial side of the PFJ. In 6% of cases there was full thickness cartilage loss on the lateral side of the patella. In these cases, the overall ten-year function and 15-year survival was similar to those without cartilage loss; however they had slightly more difficulty with descending stairs. Radiographic signs of OA seen in the lateral part of the PFJ were not associated with a definite compromise in functional outcome or implant survival. Severe damage to the lateral side of the PFJ with bone loss and grooving remains a contraindication to mobile-bearing UKA. Less severe damage to the lateral side of the PFJ and damage to the medial side, however severe, does not compromise the overall function or survival, so should not be considered to be a contraindication. However, if a patient does have full thickness cartilage loss on the lateral side of the PFJ they may

  12. Collateralization of descending spinal pathways from red nucleus and other brainstem cell groups in rat, cat and monkey

    NARCIS (Netherlands)

    A.M. Huisman (Margriet)

    1983-01-01

    textabstractThe somatotopically organized rubrospinal pathway is the major component of the laterally descending brainstem pathways, and is especially involved in steering of fractionated movements of the distal parts of the limbs. Electrophysiological studies in cat showed that this fiber

  13. Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats

    Science.gov (United States)

    Kim, Jae Hyo; Kim, Hee Young; Chung, Kyungsoon

    2011-01-01

    Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the α-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through α-adrenergic descending inhibitory systems at the spinal level. PMID:21389301

  14. An extinct vertebrate preserved by its living hybridogenetic descendant.

    Science.gov (United States)

    Dubey, Sylvain; Dufresnes, Christophe

    2017-10-06

    Hybridogenesis is a special mode of hybrid reproduction where one parental genome is eliminated and the other is transmitted clonally. We propose that this mechanism can perpetuate the genome of extinct species, based on new genetic data from Pelophylax water frogs. We characterized the genetic makeup of Italian hybridogenetic hybrids (P. kl. hispanicus and esculentus) and identified a new endemic lineage of Eastern-Mediterranean origin as one parental ancestor of P. kl. hispanicus. This taxon is nowadays extinct in the wild but its germline subsists through its hybridogenetic descendant, which can thus be considered as a "semi living fossil". Such rare situation calls for realistic efforts of de-extinction through selective breeding without genetic engineering, and fuels the topical controversy of reviving long extinct species. "Ghost" species hidden by taxa of hybrid origin may be more frequent than suspected in vertebrate groups that experienced a strong history of hybridization and semi-sexual reproduction.

  15. Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding

    Directory of Open Access Journals (Sweden)

    Claudia Marcela Garcia-Peña

    2014-06-01

    Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.

  16. Nutritional profile in children under five years of Afro-descendant communities in Paraguay

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    Susana Sánchez-Bernal

    2015-12-01

    Full Text Available Background: In Paraguay, little is known about the Afro-descendant population. It is important to know about their nutritional status, mainly in childhood, to guide appropriate action. Objective: To determine the nutritional profile of children under five years from the African descendants’ communities in Paraguay and its associated factors. Material and methods: A cross-sectional and observational design with analytical component was developed. It involved healthy male and female children under five years old, with at least one African descendant as immediate family. Dietary habits and nutritional status (WHO criteria were assessed. WHO Anthro and SPSS 16.0 software were used. Results: 150 children were included. The median of age was 26.9 months (1.2-59.9 m, and 50.7% were males. The median maternal age was 28.3 years (16-49 years. Children with Exclusive Breast Feeding (EBF, n=119 had a mean duration of 3.5±1.8 months (1-7m. 26.9% were exclusively breastfed during six months. The starting of complementary feeding was on average 5.2 months. The underweight prevalence (UW, zP/E 0.05. Children with UW had a lower average of age of onset of complementary feeding (1.7 vs 4.9 months, p˂0.0001 compare with their pairs without malnutrition. Conclusion: Chronic malnutrition was the most prevalent chronic disease affecting over 1 in 10 children. Early initiation of complementary feeding could be a risk factor for malnutrition.

  17. [Neurolitic block of the lumbar sympathetic chain improves chronic pain in a patient with critical lower limb ischemia].

    Science.gov (United States)

    Barreto Junior, Elton Pereira de Sá; Nascimento, Jedson Dos Santos; de Castro, Anita Perpetua Carvalho Rocha

    Sympathectomy is one of the therapies used in the treatment of chronic obstructive arterial disease (COAD). Although not considered as first-line strategy, it should be considered in the management of pain difficult to control. This clinical case describes the evolution of a patient with inoperable COAD who responded properly to the lumbar sympathetic block. A female patient, afro-descendant, 69 years old, ASA II, admitted to the algology service due to refractory ischemic pain in the lower limbs. The patient had undergone several surgical procedures and conservative treatments without success. Vascular surgery considered the case as out of therapeutic possibility, unless limb amputation. At that time, sympathectomy was indicated. After admission to the operating room, the patient was monitored, positioned and sedated. The blockade was performed with the aid of radioscopy, bilaterally, at L2-L3-L4 right and L3 left levels. On the right side, at each level cited, 3mL of absolute alcohol with 0.25% bupivacaine were injected without vasoconstrictor, and on the left side only local anesthetic. The procedure was performed uneventfully. The patient was discharged with complete remission of the pain. Neurolitic block of the lumbar sympathetic chain is an effective and safe treatment option for pain control in patients with critical limb ischemia patients in whom the only possible intervention would be limb amputation. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

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    Shohei Sakuda

    2014-03-01

    Full Text Available Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control.

  19. Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

    Science.gov (United States)

    Sakuda, Shohei; Prabowo, Diyan Febri; Takagi, Keiko; Shiomi, Kazuro; Mori, Mihoko; Ōmura, Satoshi; Nagasawa, Hiromichi

    2014-01-01

    Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A) inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III) and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control. PMID:24674936

  20. Brain activity modifications following spinal cord stimulation for chronic neuropathic pain: A systematic review.

    Science.gov (United States)

    Bentley, L D; Duarte, R V; Furlong, P L; Ashford, R L; Raphael, J H

    2016-04-01

    Spinal cord stimulation (SCS) is believed to exert supraspinal effects; however, these mechanisms are still far from fully elucidated. This systematic review aims to assess existing neurophysiological and functional neuroimaging literature to reveal current knowledge regarding the effects of SCS for chronic neuropathic pain on brain activity, to identify gaps in knowledge, and to suggest directions for future research. Electronic databases and hand-search of reference lists were employed to identify publications investigating brain activity associated with SCS in patients with chronic neuropathic pain, using neurophysiological and functional neuroimaging techniques (fMRI, PET, MEG, EEG). Studies investigating patients with SCS for chronic neuropathic pain and studying brain activity related to SCS were included. Demographic data (age, gender), study factors (imaging modality, patient diagnoses, pain area, duration of SCS at recording, stimulus used) and brain areas activated were extracted from the included studies. Twenty-four studies were included. Thirteen studies used neuroelectrical imaging techniques, eight studies used haemodynamic imaging techniques, two studies employed both neuroelectrical and haemodynamic techniques separately, and one study investigated cerebral neurobiology. The limited available evidence regarding supraspinal mechanisms of SCS does not allow us to develop any conclusive theories. However, the studies included appear to show an inhibitory effect of SCS on somatosensory evoked potentials, as well as identifying the thalamus and anterior cingulate cortex as potential mediators of the pain experience. The lack of substantial evidence in this area highlights the need for large-scale controlled studies of this kind. © 2015 European Pain Federation - EFIC®

  1. An evolutionary scenario for gonadotrophin-inhibitory hormone in chordates.

    Science.gov (United States)

    Osugi, T; Ubuka, T; Tsutsui, K

    2015-06-01

    In 2000, we discovered a novel hypothalamic neuropeptide that actively inhibits gonadotrophin release in quail and termed it gonadotrophin-inhibitory hormone (GnIH). GnIH peptides have subsequently been identified in most representative species of gnathostomes. They all share a C-terminal LPXRFamide (X = L or Q) motif. GnIH can inhibit gonadotrophin synthesis and release by decreasing the activity of GnRH neuroes, as well as by directly inhibiting pituitary gonadotrophin secretion in birds and mammals. To investigate the evolutionary origin of GnIH and its ancestral function, we identified a GnIH precursor gene encoding GnIHs from the brain of sea lamprey, the most ancient lineage of vertebrates. Lamprey GnIHs possess a C-terminal PQRFamide motif. In vivo administration of one of lamprey GnIHs stimulated the expression of lamprey GnRH in the hypothalamus and gonadotophin β mRNA in the pituitary. Thus, GnIH may have emerged in agnathans as a stimulatory neuropeptide that subsequently diverged to an inhibitory neuropeptide during the course of evolution from basal vertebrates to later-evolved vertebrates, such as birds and mammals. From a structural point of view, pain modulatory neuropeptides, such as neuropeptide FF (NPFF) and neuropeptide AF, share a C-terminal PQRFamide motif. Because agnathans possess both GnIH and NPFF genes, the origin of GnIH and NPFF genes may date back before the emergence of agnathans. More recently, we identified a novel gene encoding RFamide peptides in the amphioxus. Molecular phylogenetic analysis and synteny analysis indicated that this gene is closely related to the genes of GnIH and NPFF of vertebrates. The results suggest that the identified protochordate gene is similar to the common ancestor of GnIH and NPFF genes, indicating that the origin of GnIH and NPFF may date back to the time of the emergence of early chordates. The GnIH and NPFF genes may have diverged by whole-genome duplication during the course of vertebrate

  2. Colorectal surgery patients' pain status, activities, satisfaction, and beliefs about pain and pain management.

    Science.gov (United States)

    Brown, Carolyn; Constance, Kristel; Bédard, Denise; Purden, Margaret

    2013-12-01

    This study describes surgical colorectal cancer patients' pain levels, recovery activities, beliefs and expectations about pain, and satisfaction with pain management. A convenience sample of 50 adult inpatients who underwent colorectal surgery for cancer participated. Patients were administered the modified American Pain Society Patient Outcome Questionnaire on postoperative day 2 and asked to report on their status in the preceding 24 hours. Patients reported low current (mean 1.70) and average (mean 2.96) pain scores but had higher scores and greater variation for worst pain (mean 5.48). Worst pain occurred mainly while turning in bed or mobilizing, and 25% of patients experienced their worst pain at rest. Overall, patients expected to have pain after surgery and were very satisfied with pain management. Patients with worst pain scores >7 reported interference with recovery activities, mainly general activity (mean 5.67) and walking ability (mean 5.15). These patients were likely to believe that "people can get addicted to pain medication easily" (mean 3.39 out of 5) and that "pain medication should be saved for cases where pain gets worse" (mean 3.20 out of 5). These beliefs could deter patients from seeking pain relief and may need to be identified and addressed along with expectations about pain in the preoperative nursing assessment. Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  3. Descending Necrotising Mediastinitis: A Case Report Illustrating a Trend in Conservative Management

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    B. A. P. Jayasekera

    2012-01-01

    Full Text Available The mortality rate from descending necrotising mediastinitis (DNM has declined since its first description in 1938. The decline in mortality has been attributed to earlier diagnosis by way of contrast-enhanced computed tomographic (CT scanning and aggressive surgical intervention in the form of transthoracic drainage. We describe a case of DNM with involvement of anterior and posterior mediastinum down to the diaphragm, managed by cervicotomy and transverse cervical drainage with placement of corrugated drains and a pleural chest drain, with a delayed mediastinoscopy and mediastinal drain placement. We advocate a conservative approach with limited debridement and emphasis on drainage of infection in line with published case series.

  4. Small-scale modelling of cementation by descending silica-bearing fluids: Explanation of the origin of arenitic caves in South American tepuis

    Science.gov (United States)

    Aubrecht, R.; Lánczos, T.; Schlögl, J.; Audy, M.

    2017-12-01

    Geoscientific research was performed on South American table mountains (tepuis) and in their sandstone cave systems. To explain speleogenesis in these poorly soluble rocks, two theories were introduced: a) arenization theory implying selective weathering of quartz along grain boundaries and releasing of sand grains, b) selective lithification theory implying cementation by descending silica-bearing fluid flow. The latter theory presumes that the descending fluid flow becomes unstable on the interface between two layers with different porosity and splits to separate flow channels (so-called ;finger flow;). The arenites outside these channels remain uncemented. To verify the latter theory, small-scale modelling was performed, using layered sands and sodium-silicate solution. Fine to medium sand was used (0.08-0.5 mm), along with a coarse sand fraction (0.5-1.5 mm). The sands were layered and compacted in a transparent plastic boxes. Three liters of sodium-silicate solution (so-called water glass) were left to drip for several hours to the top of the sediment. The fine-grained layers were perfectly laterally impregnated, whereas the descending fluid flows split to ;fingers; in the coarse-grained layers due their higher hydraulic conductivity. This small-scale laboratory simulation mimics the real diagenesis by descending silica-bearing fluids and matches the real phenomena observed on the tepuis. The resulting cemented constructions closely mimic many geomorphological features observed on tepuis and inside their caves, e.g. ;finger-flow; pillars, overhangs, imperfectly formed (aborted) pillars in forms of hummocks hanging from ceilings, locally also thicker central pillars that originated by merging of smaller fluid-flow channels. The modelling showed that selective lithification theory can explain most of the geomorphological aspects related to the speleogenesis in tepuis.

  5. Dancing in pain: pain appraisal and coping in dancers.

    Science.gov (United States)

    Anderson, Ruth; Hanrahan, Stephanie J

    2008-01-01

    This study investigated the relationships between the type of pain experienced (performance pain and injury pain), the cognitive appraisal of pain and pain coping styles in dancers. Fifty-one professional ballet and contemporary dancers (17 males and 34 females), with the mean age of 25.9 years, completed a general pain questionnaire, the Pain Appraisal Inventory, the Survey of Pain Attitudes Control Subscale, and the Sports Inventory for Pain. Multivariate analyses of variance indicated that both the cognitive appraisal of the pain and pain coping styles did not differ according to the type of pain experienced or the pain severity. However, it was found that dancers with performance pain of either low or high severity were more likely to dance in pain than dancers experiencing injury pain. Multiple regression analyses indicated that the appraisal of pain as threatening was predictive of the use of avoidance and catastrophizing pain coping styles. Overall, results indicated that dancers may not differentiate between performance pain and injury pain, or modify their appraisal and coping strategies according to the characteristics of the pain experienced. The study highlighted an opportunity for increased education for dancers in recognizing the difference between pain considered to be a routine aspect of training and pain which is a signal of serious injury.

  6. Dissecting aneurysm of arch and descending thoracic aorta presenting as a left sided hemorrhagic pleural effusion

    Directory of Open Access Journals (Sweden)

    Shamim Shelley

    2010-01-01

    Full Text Available The most common cause of massive hemorrhagic effusion is malignancy. Herein we present a case of dissecting aneurysm of descending thoracic aorta presenting initially with shortness of breath due to left sided massive pleural effusion. Effusion was hemorrhagic in nature with high hematocrit value. CT scan of thorax with CT angiogram was done and that revealed the diagnosis.

  7. Fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome.

    Science.gov (United States)

    Simons, Laura E

    2016-02-01

    A significant proportion of children and adolescents with chronic pain endorse elevated pain-related fear. Pain-related fear is associated with high levels of disability, depressive symptoms, and school impairment. Because of faulty nerve signaling, individuals with neuropathic pain and complex regional pain syndrome may be more prone to develop pain-related fear as they avoid use of and neglect the affected body area(s), resulting in exacerbated symptoms, muscle atrophy, maintenance of pain signaling, and ongoing pain-related disability. Not surprisingly, effective treatments for elevated pain-related fears involve exposure to previously avoided activities to downregulate incorrect pain signaling. In the context of intensive interdisciplinary pain treatment of youth with neuropathic pain, decreasing pain-related fear is associated with improved physical and psychological functioning, whereas high initial pain-related fear is a risk factor for less treatment responsiveness. An innovative approach to targeting pain-related fear and evidence of a neural response to treatment involving decoupling of the amygdala with key fear circuits in youth with complex regional pain syndrome suggest breakthroughs in our ability to ameliorate these issues.

  8. Spontaneous pain attacks: neuralgic pain

    NARCIS (Netherlands)

    de Bont, L.G.

    2006-01-01

    Paroxysmal orofacial pains can cause diagnostic problems, especially when different clinical pictures occur simultaneously. Pain due to pulpitis, for example, may show the same characteristics as pain due to trigeminal neuralgia would. Moreover, the trigger point of trigeminal neuralgia can either

  9. Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: synthesis and neuropharmacology.

    Science.gov (United States)

    Yogeeswari, Perumal; Sharma, Monika; Samala, Ganesh; Gangadhar, Matharasala; Karthick, Srirama; Mallipeddi, Saketh; Semwal, Arvind; Sriram, Dharmarajan

    2013-08-01

    We disclose the discovery of a novel series of tetrahydropyrido-pyrazoles that are potent inhibitors of tumour necrosis factor-alpha (TNF-α), nitric oxide and cannabinoid receptor subtype 1 (CB₁). We report herein the synthesis and neuropharmacological screening results of the titled compounds in two acute pain and two neuropathic pain models in rodents. Particularly the analogue N-(4-bromophenyl)-3-tert-butyl-5-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide (8a) exhibited pronounced acute antinociceptive efficacy, also being effective in chronic constriction injury (ED₅₀ = 23.8 mg/kg) and partial sciatic nerve injury (ED₅₀ = 29.0 mg/kg) models with CB₁ receptor activity (IC₅₀ = 49.6 nM) and inhibitory effect on TNF-α (86.4% inhibition at 100 mg/kg). These results suggest the importance of the development of this lead as multi-targeted treatment strategy for neuropathic pain. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Allosteric Inhibition of Macrophage Migration Inhibitory Factor Revealed by Ibudilast

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Y.; Crichlow, G; Vermeire, J; Leng, L; Du, X; Hodsdon, M; Bucala, R; Cappello, M; Gross, M; et al.

    2010-01-01

    AV411 (ibudilast; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) is an antiinflammatory drug that was initially developed for the treatment of bronchial asthma but which also has been used for cerebrovascular and ocular indications. It is a nonselective inhibitor of various phosphodiesterases (PDEs) and has varied antiinflammatory activity. More recently, AV411 has been studied as a possible therapeutic for the treatment of neuropathic pain and opioid withdrawal through its actions on glial cells. As described herein, the PDE inhibitor AV411 and its PDE-inhibition-compromised analog AV1013 inhibit the catalytic and chemotactic functions of the proinflammatory protein, macrophage migration inhibitory factor (MIF). Enzymatic analysis indicates that these compounds are noncompetitive inhibitors of the p-hydroxyphenylpyruvate (HPP) tautomerase activity of MIF and an allosteric binding site of AV411 and AV1013 is detected by NMR. The allosteric inhibition mechanism is further elucidated by X-ray crystallography based on the MIF/AV1013 binary and MIF/AV1013/HPP ternary complexes. In addition, our antibody experiments directed against MIF receptors indicate that CXCR2 is the major receptor for MIF-mediated chemotaxis of peripheral blood mononuclear cells.

  11. Myostatin inhibitory region of fish (Paralichthys olivaceus) myostatin-1 propeptide.

    Science.gov (United States)

    Lee, Sang Beum; Kim, Jeong Hwan; Jin, Deuk-Hee; Jin, Hyung-Joo; Kim, Yong Soo

    2016-01-01

    Myostatin (MSTN) is a potent negative regulator of skeletal muscle growth, and its activity is suppressed by MSTN propeptide (MSTNpro), the N-terminal part of MSTN precursor cleaved during post-translational MSTN processing. The current study examined which region of flatfish (Paralichthys olivaceus) MSTN-1 propeptide (MSTN1pro) is critical for MSTN inhibition. Six different truncated forms of MSTN1pro containing N-terminal maltose binding protein (MBP) as a fusion partner were expressed in Escherichia coli, and partially purified by an affinity chromatography for MSTN-inhibitory activity examination. Peptides covering different regions of flatfish MSTN1pro were also synthesized for MSTN-inhibitory activity examination. A MBP-fused MSTN1pro region consisting of residues 45-100 had the same MSTN-inhibitory potency as the full sequence flatfish MSTN1pro (residues 23-265), indicating that the region of flatfish MSTN1pro consisting of residues 45-100 is sufficient to maintain the full MSTN-inhibitory capacity. A MBP-fused MSTN1pro region consisting of residues 45-80 (Pro45-80) also showed MSTN-inhibitory activity with a lower potency, and the Pro45-80 demonstrated its MSTN binding capacity in a pull-down assay, indicating that the MSTN-inhibitory capacity of Pro45-80 is due to its binding to MSTN. Flatfish MSTN1pro synthetic peptides covering residues 45-65, 45-70, and 45-80 demonstrated MSTN-inhibitory activities, but not the synthetic peptide covering residues 45-54, indicating that residues 45-65 of flatfish MSTN1pro are essential for MSTN inhibition. In conclusion, current study show that like the mammalian MSTNpro, the MSTN-inhibitory region of flatfish MSTN1pro resides near its N-terminus, and imply that smaller sizes of MSTNpro can be effectively used in various applications designed for MSTN inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Subclinical recurrent neck pain and its treatment impacts motor training-induced plasticity of the cerebellum and motor cortex

    Science.gov (United States)

    Baarbé, Julianne K.; Yielder, Paul; Haavik, Heidi; Holmes, Michael W. R.

    2018-01-01

    The cerebellum processes pain inputs and is important for motor learning. Yet, how the cerebellum interacts with the motor cortex in individuals with recurrent pain is not clear. Functional connectivity between the cerebellum and motor cortex can be measured by a twin coil transcranial magnetic stimulation technique in which stimulation is applied to the cerebellum prior to stimulation over the motor cortex, which inhibits motor evoked potentials (MEPs) produced by motor cortex stimulation alone, called cerebellar inhibition (CBI). Healthy individuals without pain have been shown to demonstrate reduced CBI following motor acquisition. We hypothesized that CBI would not reduce to the same extent in those with mild-recurrent neck pain following the same motor acquisition task. We further hypothesized that a common treatment for neck pain (spinal manipulation) would restore reduced CBI following motor acquisition. Motor acquisition involved typing an eight-letter sequence of the letters Z,P,D,F with the right index finger. Twenty-seven neck pain participants received spinal manipulation (14 participants, 18–27 years) or sham control (13 participants, 19–24 years). Twelve healthy controls (20–27 years) also participated. Participants had CBI measured; they completed manipulation or sham control followed by motor acquisition; and then had CBI re-measured. Following motor acquisition, neck pain sham controls remained inhibited (58 ± 33% of test MEP) vs. healthy controls who disinhibited (98 ± 49% of test MEP, Pneck pain sham vs. healthy control groups suggests that neck pain may change cerebellar-motor cortex interaction. The change to facilitation suggests that spinal manipulation may reverse inhibitory effects of neck pain. PMID:29489878

  13. Coronary heart disease clinical manifestation and risk factors in Japanese immigrants and their descendents in the city of São Paulo

    Directory of Open Access Journals (Sweden)

    Amato Reynaldo Vicente

    2003-01-01

    Full Text Available OBJECTIVE: To assess whether a difference exists in coronary heart disease clinical manifestations and the prevalence of risk factors between Japanese immigrants and their descendents in the city of São Paulo. METHODS: Retrospective analysis of coronary artery disease clinical manifestations and the prevalence of risk factors, comparing 128 Japanese immigrants (Japanese group with 304 Japanese descendents (Nisei group. RESULTS: The initial manifestation of the disease was earlier in the Nisei group (mean = 53 years, a difference of 12 years when compared with that in the Japanese group (mean = 65 years (P<0.001. Myocardial infarction was the first manifestation in both groups (P = 0.83. The following parameters were independently associated with early coronary events: smoking (OR = 2.25; 95% CI = 1.35-3.77; P<0.002; Nisei group (OR = 10.22; 95% CI = 5.64-18.5; P<0.001; and female sex (OR = 5.04; 95% CI = 2.66-9.52; P<0.001. CONCLUSION: The clinical presentation of coronary heart disease in the Japanese and their descendents in the city of São Paulo was similar, but coronary heart disease onset occurred approximately 12 years earlier in the Nisei group than in the Japanese group.

  14. Pain-related worry in patients with chronic orofacial pain.

    Science.gov (United States)

    Davis, C Ervin; Stockstill, John W; Stanley, William D; Wu, Qiang

    2014-07-01

    Pain-related worry is distinct from, but related to, pain catastrophizing (PC) and anxiety. Worry and its relationship with other variables have been studied in people with chronic pain but not in people with chronic orofacial pain. The authors explored the prevalence of trait, general and pain-related worry and the association of worry with higher pain levels and other variables. The authors assessed people who had a diagnosis of chronic orofacial pain by using nonpain-related trait worry, state anxiety, trait anxiety, PC and pain measures. The participants' answers to an open-ended question about what they were most worried about led to the identification of worry domains, including worry about pain. The authors found that worrying about pain was related significantly to worst and least pain levels, pain interference and pain duration, as well as moderated trait worry in predicting pain interference. Although trait worry was not correlated directly with pain, when moderated by PC, it made substantial contributions in predicting pain interference. Participants with chronic orofacial pain reported experiencing substantial levels of trait worry, anxiety, PC and worry about pain that related to pain ratings directly and indirectly. Clinicians should assess pain-related worry in patients with chronic orofacial pain to understand the effects of worry on pain and functioning. Clinicians could treat these patients more effectively by helping them reduce their levels of pain-related worry and focusing on improved coping.

  15. Pain Adaptability in Individuals With Chronic Musculoskeletal Pain Is Not Associated With Conditioned Pain Modulation.

    Science.gov (United States)

    Wan, Dawn Wong Lit; Arendt-Nielsen, Lars; Wang, Kelun; Xue, Charlie Changli; Wang, Yanyi; Zheng, Zhen

    2018-03-27

    Healthy humans can be divided into the pain adaptive (PA) and the pain nonadaptive (PNA) groups; PA showed a greater decrease in pain rating to a cold pressor test (CPT) than PNA. This study examined if the dichotomy of pain adaptability existed in individuals with chronic musculoskeletal pain. CPTs at 2°C and 7°C were used to assess the status of pain adaptability in participants with either chronic nonspecific low back pain or knee osteoarthritis. The participants' potency of conditioned pain modulation (CPM) and local inhibition were measured. The strengths of pain adaptability at both CPTs were highly correlated. PA and PNA did not differ in their demographic characteristics, pain thresholds from thermal and pressure stimuli, or potency of local inhibition or CPM. PA reached their maximum pain faster than PNA (t 41 = -2.76, P adaptability exists in musculoskeletal pain patients. Consistent with the healthy human study, the strength of pain adaptability and potency of CPM are not related. Pain adaptability could be another form of endogenous pain inhibition of which clinical implication is yet to be understood. The dichotomy of pain adaptability was identified in healthy humans. The current study confirms that this dichotomy also exists in individuals with chronic musculoskeletal pain, and could be reliably assessed with CPTs at 2°C and 7°C. Similar to the healthy human study, pain adaptability is not associated with CPM, and may reflect the temporal aspect of pain inhibition. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  16. Maintenance of Pain in Children With Functional Abdominal Pain.

    Science.gov (United States)

    Czyzewski, Danita I; Self, Mariella M; Williams, Amy E; Weidler, Erica M; Blatz, Allison M; Shulman, Robert J

    2016-03-01

    A significant proportion of children with functional abdominal pain develop chronic pain. Identifying clinical characteristics predicting pain persistence is important in targeting interventions. We examined whether child anxiety and/or pain-stooling relations were related to maintenance of abdominal pain frequency and compared the predictive value of 3 methods for assessing pain-stooling relations (ie, diary, parent report, child report). Seventy-six children (7-10 years old at baseline) who presented for medical treatment of functional abdominal pain were followed up 18 to 24 months later. Baseline anxiety and abdominal pain-stooling relations based on pain and stooling diaries and child- and parent questionnaires were examined in relationship to the persistence of abdominal pain frequency. Children's baseline anxiety was not related to persistence of pain frequency. Children who, however, displayed irritable bowel syndrome (IBS) symptoms at baseline maintained pain frequency at follow-up, whereas in children in whom there was no relationship between pain and stooling, pain frequency decreased. Pain and stool diaries and parent report of pain-stooling relations were predictive of pain persistence but child-report questionnaires were not. The presence of IBS symptoms in school-age children with functional abdominal pain appears to predict persistence of abdominal pain over time, whereas anxiety does not. Prospective pain and stooling diaries and parent report of IBS symptoms were predictors of pain maintenance, but child report of symptoms was not.

  17. Angiotensin I-Converting Enzyme (ACE Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

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    Małgorzata Darewicz

    2014-08-01

    Full Text Available The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes and ex vivo digestion (with human gastrointestinal enzymes. Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50% of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes.

  18. Percutaneous Stent Implantation for Treating Multivessel Coronary Disease in Patients with and without Involvement of the Proximal Segment of the Anterior Descending Coronary Artery

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    Salgueiro Sandro

    2002-01-01

    Full Text Available OBJECTIVE: To assess coronary stent placement in patients with multivessel coronary disease and involvement of the proximal portion of the anterior descending coronary artery. METHODS: We retrospectively analyzed the in-hospital and late evolution of 189 patients with multivessel coronary disease, who underwent percutaneous coronary stent placement. These patients were divided into 2 groups as follows: group I (GI - 59 patients with involvement of the proximal segment of the anterior descending coronary artery; and group II (GII - 130 patients without involvement of the proximal segment of the anterior descending coronary artery. RESULTS: No significant difference was observed in the success rate of the procedure (91.5% versus 97.6%, p=0.86, nor in the occurrence of major adverse cardiac events (5.1% versus 1.5%, p=0.38, nor in the occurrence of major vascular complications (1.7% versus 0%, p=0.69 in the in-hospital phase. In the late follow-up, the incidence of major adverse cardiac events (15.4% versus 13.7%, p=0.73 and the need for new revascularization (13.5% versus 10.3%, p=0.71 were similar for both groups. CONCLUSION: The in-hospital and late evolution of patients with multivessel coronary disease with and without involvement of the proximal segment of the anterior descending coronary artery treated with coronary stent placement did not differ. This suggests that this revascularization method is an effective procedure and a valuable option for treating these types of patients.

  19. Altering gender role expectations: effects on pain tolerance, pain threshold, and pain ratings.

    Science.gov (United States)

    Robinson, Michael E; Gagnon, Christine M; Riley, Joseph L; Price, Donald D

    2003-06-01

    The literature demonstrating sex differences in pain is sizable. Most explanations for these differences have focused on biologic mechanisms, and only a few studies have examined social learning. The purpose of this study was to examine the contribution of gender-role stereotypes to sex differences in pain. This study used experimental manipulation of gender-role expectations for men and women. One hundred twenty students participated in the cold pressor task. Before the pain task, participants were given 1 of 3 instructional sets: no expectation, 30-second performance expectation, or a 90-second performance expectation. Pain ratings, threshold, and tolerance were recorded. Significant sex differences in the "no expectation" condition for pain tolerance (t = 2.32, df = 38, P differ in their pain tolerance, pain threshold, or pain ratings. This is the first empirical study to show that manipulation of expectations alters sex differences in laboratory pain.

  20. Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.

    Science.gov (United States)

    Povarov, I S; Kondratenko, R V; Derevyagin, V I; Ostrovskaya, R U; Skrebitskii, V G

    2015-01-01

    Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons.

  1. Neural manual vs. robotic assisted mobilization to improve motion and reduce pain hypersensitivity in hand osteoarthritis: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Villafañe, Jorge Hugo; Valdes, Kristin; Imperio, Grace; Borboni, Alberto; Cantero-Téllez, Raquel; Galeri, Silvia; Negrini, Stefano

    2017-05-01

    [Purpose] The aim of the present study is to detail the protocol for a randomised controlled trial (RCT) of neural manual vs. robotic assisted on pain in sensitivity as well as analyse the quantitative and qualitative movement of hand in subjects with hand osteoarthritis. [Subjects and Methods] Seventy-two patients, aged 50 to 90 years old of both genders, with a diagnosis of hand Osteoarthritis (OA), will be recruited. Two groups of 36 participants will receive an experimental intervention (neurodynamic mobilization intervention plus exercise) or a control intervention (robotic assisted passive mobilization plus exercise) for 12 sessions over 4 weeks. Assessment points will be at baseline, end of therapy, and 1 and 3 months after end of therapy. The outcomes of this intervention will be pain and determine the central pain processing mechanisms. [Result] Not applicable. [Conclusion] If there is a reduction in pain hypersensitivity in hand OA patients it can suggest that supraspinal pain-inhibitory areas, including the periaqueductal gray matter, can be stimulated by joint mobilization.

  2. Predicting postoperative pain by preoperative pressure pain assessment.

    Science.gov (United States)

    Hsu, Yung-Wei; Somma, Jacques; Hung, Yu-Chun; Tsai, Pei-Shan; Yang, Chen-Hsien; Chen, Chien-Chuan

    2005-09-01

    The goal of this study was to evaluate whether preoperative pressure pain sensitivity testing is predictive of postoperative surgical pain. Female subjects undergoing lower abdominal gynecologic surgery were studied. A pressure algometer was used preoperatively to determine the pressure pain threshold and tolerance. A visual analog scale (VAS) was used to assess postoperative pain. A State-Trait Anxiety Inventory was used to assess patients' anxiety. Subjects received intravenous patient-controlled analgesia for postoperative pain control. The preoperative pain threshold and tolerance were compared with the postoperative VAS pain score and morphine consumption. Forty women were enrolled. Their preoperative pressure pain threshold and tolerance were 141 +/- 65 kPa and 223 +/- 62 kPa, respectively. The VAS pain score in the postanesthesia care unit and at 24 h postoperatively were 81 +/- 24 and 31 +/- 10, respectively. Highly anxious patients had higher VAS pain scores in the postanesthesia care unit (P pain tolerance was significantly correlated with the VAS at 24 h postoperatively (P pain tolerance after fentanyl administration (mean, 272 +/- 68 kPa) correlated significantly with morphine consumption in the first 24 h postoperatively (P pain tolerance is significantly correlated with the level of postoperative pain. Pain tolerance assessment after fentanyl was administered and fentanyl sensitivity predicted the dose of analgesics used in the first 24 h after surgery. The algometer is thus a simple, useful tool for predicting postoperative pain and analgesic consumption.

  3. Pain and the ethics of pain management.

    Science.gov (United States)

    Edwards, R B

    1984-01-01

    In this article I clarify the concepts of 'pain', 'suffering', 'pains of body', 'pains of soul'. I explore the relevance of an ethic to the clinical setting which gives patients a strong prima facie right to freedom from unnecessary and unwanted pain and which places upon medical professionals two concomitant moral obligations to patients. First, there is the duty not to inflict pain and suffering beyond what is necessary for effective diagnosis, treatment and research. Next, there is the duty to do all that can be done to relieve all the pain and suffering which can be alleviated. I develop in some detail that individuality of pain sensitivity must be taken into account in fulfilling these obligations. I explore the issue of the relevance of informed consent and the right to refuse treatment to the matter of pain relief. And I raise the question of what conditions, if any, should override the right to refuse treatment where pain relief is of paramount concern.

  4. Improvement of burn pain management through routine pain monitoring and pain management protocol.

    Science.gov (United States)

    Yang, Hyeong Tae; Hur, Giyeun; Kwak, In-Suk; Yim, Haejun; Cho, Yong Suk; Kim, Dohern; Hur, Jun; Kim, Jong Hyun; Lee, Boung Chul; Seo, Cheong Hoon; Chun, Wook

    2013-06-01

    Pain management is an important aspect of burn management. We developed a routine pain monitoring system and pain management protocol for burn patients. The purpose of this study is to evaluate the effectiveness of our new pain management system. From May 2011 to November 2011, the prospective study was performed with 107 burn patients. We performed control group (n=58) data analysis and then developed the pain management protocol and monitoring system. Next, we applied our protocol to patients and performed protocol group (n=49) data analysis, and compared this to control group data. Data analysis was performed using the Numeric Rating Scale (NRS) of background pain and procedural pain, Clinician-Administered PTSD Scale (CAPS), Hamilton Depression Rating Scale (HDRS), State-Trait Anxiety Inventory Scale (STAIS), and Holmes and Rahe Stress Scale (HRSS). The NRS of background pain for the protocol group was significantly decreased compared to the control group (2.8±2.0 versus 3.9±1.9), and the NRS of procedural pain of the protocol group was significantly decreased compared to the control group (4.8±2.8 versus 3.7±2.5). CAPS and HDRS were decreased in the protocol group, but did not have statistical significance. STAIS and HRSS were decreased in the protocol group, but only the STAIS had statistical significance. Our new pain management system was effective in burn pain management. However, adequate pain management can only be accomplished by a continuous and thorough effort. Therefore, pain control protocol and pain monitoring systems need to be under constant revision and improvement using creative ideas and approaches. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  5. Residential Mobility, Inhibitory Control, and Academic Achievement in Preschool

    Science.gov (United States)

    Schmitt, Sara A.; Finders, Jennifer K.; McClelland, Megan M.

    2015-01-01

    Research Findings: The present study investigated the direct effects of residential mobility on children's inhibitory control and academic achievement during the preschool year. It also explored fall inhibitory control and academic skills as mediators linking residential mobility and spring achievement. Participants included 359 preschool children…

  6. Characterizing individual painDETECT symptoms by average pain severity

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    Sadosky A

    2016-07-01

    Full Text Available Alesia Sadosky,1 Vijaya Koduru,2 E Jay Bienen,3 Joseph C Cappelleri4 1Pfizer Inc, New York, NY, 2Eliassen Group, New London, CT, 3Outcomes Research Consultant, New York, NY, 4Pfizer Inc, Groton, CT, USA Background: painDETECT is a screening measure for neuropathic pain. The nine-item version consists of seven sensory items (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure, a pain course pattern item, and a pain radiation item. The seven-item version consists only of the sensory items. Total scores of both versions discriminate average pain-severity levels (mild, moderate, and severe, but their ability to discriminate individual item severity has not been evaluated.Methods: Data were from a cross-sectional, observational study of six neuropathic pain conditions (N=624. Average pain severity was evaluated using the Brief Pain Inventory-Short Form, with severity levels defined using established cut points for distinguishing mild, moderate, and severe pain. The Wilcoxon rank sum test was followed by ridit analysis to represent the probability that a randomly selected subject from one average pain-severity level had a more favorable outcome on the specific painDETECT item relative to a randomly selected subject from a comparator severity level.Results: A probability >50% for a better outcome (less severe pain was significantly observed for each pain symptom item. The lowest probability was 56.3% (on numbness for mild vs moderate pain and highest probability was 76.4% (on cold/heat for mild vs severe pain. The pain radiation item was significant (P<0.05 and consistent with pain symptoms, as well as with total scores for both painDETECT versions; only the pain course item did not differ.Conclusion: painDETECT differentiates severity such that the ability to discriminate average pain also distinguishes individual pain item severity in an interpretable manner. Pain

  7. Genetic polymorphisms of human platelet antigens in Euro-African and Japanese descendants from Parana, Southern Brazil.

    Science.gov (United States)

    Silvestre, Ana Paula Avenia; Zacarias, Joana Maira Valentini; Guelsin, Gláucia Andréia Soares; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

    2017-09-01

    The frequency distributions of HPA-1 to HPA-6 and HPA-15 were evaluated in two Brazilian populations from Parana: a mixed population of predominantly Caucasians and a population of Japanese descendants. Genotyping was performed by PCR-SSP in 364 unrelated individuals. Differences in the distribution of HPA highlight diversity in Brazilian miscegenation and the importance of formation of the HPA panel composed of regional blood donors.

  8. Population activity structure of excitatory and inhibitory neurons.

    Science.gov (United States)

    Bittner, Sean R; Williamson, Ryan C; Snyder, Adam C; Litwin-Kumar, Ashok; Doiron, Brent; Chase, Steven M; Smith, Matthew A; Yu, Byron M

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  9. Population activity structure of excitatory and inhibitory neurons.

    Directory of Open Access Journals (Sweden)

    Sean R Bittner

    Full Text Available Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

  10. Population activity structure of excitatory and inhibitory neurons

    Science.gov (United States)

    Doiron, Brent

    2017-01-01

    Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure. PMID:28817581

  11. Intrinsically-generated fluctuating activity in excitatory-inhibitory networks

    Science.gov (United States)

    Mastrogiuseppe, Francesca; Ostojic, Srdjan

    2017-01-01

    Recurrent networks of non-linear units display a variety of dynamical regimes depending on the structure of their synaptic connectivity. A particularly remarkable phenomenon is the appearance of strongly fluctuating, chaotic activity in networks of deterministic, but randomly connected rate units. How this type of intrinsically generated fluctuations appears in more realistic networks of spiking neurons has been a long standing question. To ease the comparison between rate and spiking networks, recent works investigated the dynamical regimes of randomly-connected rate networks with segregated excitatory and inhibitory populations, and firing rates constrained to be positive. These works derived general dynamical mean field (DMF) equations describing the fluctuating dynamics, but solved these equations only in the case of purely inhibitory networks. Using a simplified excitatory-inhibitory architecture in which DMF equations are more easily tractable, here we show that the presence of excitation qualitatively modifies the fluctuating activity compared to purely inhibitory networks. In presence of excitation, intrinsically generated fluctuations induce a strong increase in mean firing rates, a phenomenon that is much weaker in purely inhibitory networks. Excitation moreover induces two different fluctuating regimes: for moderate overall coupling, recurrent inhibition is sufficient to stabilize fluctuations; for strong coupling, firing rates are stabilized solely by the upper bound imposed on activity, even if inhibition is stronger than excitation. These results extend to more general network architectures, and to rate networks receiving noisy inputs mimicking spiking activity. Finally, we show that signatures of the second dynamical regime appear in networks of integrate-and-fire neurons. PMID:28437436

  12. Spinal SIRT1 activation attenuates neuropathic pain in mice.

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    Haijun Shao

    Full Text Available Abnormal histone acetylation occurs during neuropathic pain through an epigenetic mechanism. Silent information regulator 1 (sir2 or SIRT1, a NAD-dependent deacetylase, plays complex systemic roles in a variety of processes through deacetylating acetylated histone and other specific substrates. But the role of SIRT1 in neuropathic pain is not well established yet. The present study was intended to detect SIRT1 content and activity, nicotinamide (NAM and nicotinamide adenine dinucleotide (NAD in the spinal cord using immunoblotting or mass spectroscopy over time in mice following chronic constriction injury (CCI or sham surgery. In addition, the effect of intrathecal injection of NAD or resveratrol on thermal hyperalgesia and mechanical allodynia was evaluated in CCI mice. Finally, we investigated whether SIRT1 inhibitor EX-527 could reverse the anti-nociceptive effect of NAD or resveratrol. It was found that spinal SIRT1 expression, deacetylase activity and NAD/NAM decreased significantly 1, 3, 7, 14 and 21 days after CCI surgery as compared with sham group. In addition, daily intrathecal injection of 5 µl 800 mM NAD 1 h before and 1 day after CCI surgery or single intrathecal injection of 5 µl 90 mM resveratrol 1 h before CCI surgery produced a transient inhibitory effect on thermal hyperalgesia and mechanical allodynia in CCI mice. Finally, an intrathecal injection of 5 µl 1.2 mM EX-527 1 h before NAD or resveratrol administration reversed the anti-nociceptive effect of NAD or resveratrol. These data indicate that the reduction in SIRT1 deacetylase activity may be a factor contributing to the development of neuropathic pain in CCI mice. Our findings suggest that the enhancement of spinal NAD/NAM and/or SIRT1 activity may be a potentially promising strategy for the prevention or treatment of neuropathic pain.

  13. Gene Transfer of Glutamic Acid Decarboxylase 67 by Herpes Simplex Virus Vectors Suppresses Neuropathic Pain Induced by Human Immunodeficiency Virus gp120 Combined with ddC in Rats.

    Science.gov (United States)

    Kanao, Megumi; Kanda, Hirotsugu; Huang, Wan; Liu, Shue; Yi, Hyun; Candiotti, Keith A; Lubarsky, David A; Levitt, Roy C; Hao, Shuanglin

    2015-06-01

    Human immunodeficiency virus (HIV)-related painful sensory neuropathies primarily consist of the HIV infection-related distal sensory polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides only partial relief of pain in patients with HIV/acquired immune deficiency syndrome because little is known about the exact neuropathological mechanisms for HIV-associated neuropathic pain (NP). Hypofunction of γ-aminobutyric acid (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve injury. In this study, we tested the hypothesis that HIV gp120 combined with antiretroviral therapy reduces spinal GABAergic inhibitory tone and that restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat model. The application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical allodynia. The hind paws of rats were inoculated with replication-defective herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the decarboxylation of glutamate to GABA. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The expression of GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of spinal GABA, pCREB, and pC/EBPβ was tested using immunohistochemistry. In the gp120 with ddC-induced neuropathic pain model, GAD67 expression mediated by the HSV vector caused an elevation of mechanical threshold that was apparent on day 3 after vector inoculation. The antiallodynic effect of the single HSV vector inoculation expressing GAD67 lasted >28 days. The area under the time-effect curves in the HSV vector expressing GAD67 was increased compared with that in the

  14. Right Coronary Artery Originated from the Left Anterior Descending Artery in a Patient with Congenital Pulmonary Valvular Stenosis

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    Yusuf Hoşoğlu

    2013-01-01

    Full Text Available The single coronary artery, anomalous origin of the right coronary artery from the left anterior descending artery, is a benign and very rare coronary artery anomaly. We firstly present a case with this type of single coronary artery and congenital pulmonary valvular stenosis with large poststenotic dilatation.

  15. Enzyme inhibitory activity of selected Philippine plants

    International Nuclear Information System (INIS)

    Sasotona, Joseph S.; Hernandez, Christine C.

    2015-01-01

    In the Philippines, the number one cause of death are cardiovascular diseases. Diseases linked with inflammation are proliferating. This research aims to identify plant extracts that have potential activity of cholesterol-lowering, anti-hypertension, anti-gout, anti-inflammatory and fat blocker agents. Although there are commercially available drugs to treat the aforementioned illnesses, these medicine have adverse side-effects, aside from the fact that they are expensive. The results of this study will serve as added knowledge to contribute to the development of cheaper, more readily available, and effective alternative medicine. 100 plant extracts from different areas in the Philippines have been tested for potential inhibitory activity against Hydroxymethylglutaryl-coenzyme A (HMG-CoA), Lipoxygenase, and Xanthine Oxidase. The plant samples were labeled with codes and distributed to laboratories for blind testing. The effective concentration of the samples tested for Xanthine oxidase is 100 ppm. Samples number 9, 11, 14, 29, 43, 46, and 50 have shown significant inhibitory activity at 78.7%, 78.4%, 70%, 89.2%, 79%, 67.4%, and 67.5% respectively. Samples tested for Lipoxygenase inhibition were set at 33ppm. Samples number 2, 37, 901, 1202, and 1204 have shown significant inhibitory activity at 66, 84.9%, 88.55%, 93.3%, and 84.7% respectively. For HMG-CoA inhibition, the effective concentration of the samples used was 100 ppm. Samples number 1 and 10 showed significant inhibitory activity at 90.1% and 81.8% respectively. (author)

  16. A rare case of acyanotic congenital heart disease, large patent ductus arteriosus with pre-ductal coarctation of descending thoracic aorta with patent ductus arteriosus closure and extra anatomical bypass grafting.

    Science.gov (United States)

    Wani, Zara; Tiwari, Deepak; Gehlot, Rajeev; Kumar, Deepak; Chhabra, Sushil; Sharma, Meenaxi

    2017-01-01

    We report a case of 18-year-old female patient with large patent ductus arteriosus (PDA)-preductal coarctation of descending thoracic aorta. She underwent large PDA closure with a prosthetic graft from ascending aorta to descending thoracic aorta by mid-sternotomy on cardiopulmonary bypass machine under total hypothermic circulatory arrest.

  17. Time Course of Brain Network Reconfiguration Supporting Inhibitory Control.

    Science.gov (United States)

    Popov, Tzvetan; Westner, Britta U; Silton, Rebecca L; Sass, Sarah M; Spielberg, Jeffrey M; Rockstroh, Brigitte; Heller, Wendy; Miller, Gregory A

    2018-05-02

    Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test sample n = 96, replication sample n = 237, total N = 333, both sexes) who performed a color-word Stroop task. Time-frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal-parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation. SIGNIFICANCE STATEMENT Hemodynamic neuroimaging research has recently clarified regional structures in brain networks supporting inhibitory control. However, due to

  18. The comparison respond of braking torque control between PID and SMC controller for electric powered wheelchair descending on slope condition

    Science.gov (United States)

    Asyraf, S. M.; Heerwan, P. M.; Izhar, I. M.

    2018-04-01

    During descending on a slope, the speed of Electric Powered Wheelchair (EPW) tends to changed rapidly. Normally, most EPW is provided with mechanical braking system which transfers human pulling force of the lever creating friction at the tire. However, the task is difficult for the users are elderly or paralyses. However, even for normal user with good strength, in fear condition they tend to give sudden braking which leads to tire locking up and skidding, eventually EPW unstable. These problems will cause accident and injuries to the users if speed does not properly control. In this paper, the automated braking torque control method was proposed in EPW as alternative to solve this problem and increase the mobility and stability especially during descending on slope in other to help the user of the EPW as their daily transportation. In this research, Proportional-Integral-Derivative and Sliding Mode Control controller are compared to determine the best response for torque braking control. The rapid change of speed can be controlled by the braking torque using proposed controllers based on the desired constant speed set by the control designer. Moreover, the sudden braking that caused tire to lock up and skid can be avoided. Furthermore, result from SMC shows this controller have good time respond to maintain the speed based on desired value when descending at slope condition by controlling the braking torque compared to the PID controller.

  19. Expectation values of descendent fields in the Bullough-Dodd model and related perturbed conformal field theories

    International Nuclear Information System (INIS)

    Baseilhac, P.; Stanishkov, M.

    2001-01-01

    The exact vacuum expectation values of the second level descendent fields 2 (∂-barφ 2 e aφ in the Bullough-Dodd model are calculated. By performing quantum group restrictions, we obtain -2 L-bar -2 PHI lk > in the PHI 12 , PHI 21 and PHI 15 perturbed minimal CFTs. In particular, the exact expectation value is found to be proportional to the square of the bulk free energy

  20. The influence of children's pain memories on subsequent pain experience.

    Science.gov (United States)

    Noel, Melanie; Chambers, Christine T; McGrath, Patrick J; Klein, Raymond M; Stewart, Sherry H

    2012-08-01

    Healthy children are often required to repeatedly undergo painful medical procedures (eg, immunizations). Although memory is often implicated in children's reactions to future pain, there is a dearth of research directly examining the relationship between the 2. The current study investigated the influence of children's memories for a novel pain stimulus on their subsequent pain experience. One hundred ten healthy children (60 boys) between the ages of 8 and 12 years completed a laboratory pain task and provided pain ratings. Two weeks later, children provided pain ratings based on their memories as well as their expectancies about future pain. One month following the initial laboratory visit, children again completed the pain task and provided pain ratings. Results showed that children's memory of pain intensity was a better predictor of subsequent pain reporting than their actual initial reporting of pain intensity, and mediated the relationship between initial and subsequent pain reporting. Children who had negatively estimated pain memories developed expectations of greater pain prior to a subsequent pain experience and showed greater increases in pain ratings over time than children who had accurate or positively estimated pain memories. These findings highlight the influence of pain memories on healthy children's expectations of future pain and subsequent pain experiences and extend predictive models of subsequent pain reporting. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Pain adaptability in individuals with chronic musculoskeletal pain is not associated with conditioned pain modulation

    DEFF Research Database (Denmark)

    Wan, Dawn Wong Lit; Arendt-Nielsen, Lars; Wang, Kelun

    2018-01-01

    (MSK). CPTs at 2°C and 7°C were used to assess the status of pain adaptability in participants with either chronic non-specific low back pain or knee osteoarthritis. The participants' potency of conditioned pain modulation (CPM) and local inhibition were measured. The strengths of pain adaptability...... at both CPTs were highly correlated. PA and PNA did not differ in their demographics, pain thresholds from thermal and pressure stimuli, or potency of local inhibition or CPM. PA reached their maximum pain faster than PNA (t41=-2.76, p... days whereas PNA did not (F (6,246) = 3.01, p = 0.01). The dichotomy of pain adaptability exists in MSK patients. Consistent with the healthy human study, the strength of pain adaptability and potency of CPM are not related. Pain adaptability could be another form of endogenous pain inhibition which...

  2. Subclinical recurrent neck pain and its treatment impacts motor training-induced plasticity of the cerebellum and motor cortex.

    Directory of Open Access Journals (Sweden)

    Julianne K Baarbé

    Full Text Available The cerebellum processes pain inputs and is important for motor learning. Yet, how the cerebellum interacts with the motor cortex in individuals with recurrent pain is not clear. Functional connectivity between the cerebellum and motor cortex can be measured by a twin coil transcranial magnetic stimulation technique in which stimulation is applied to the cerebellum prior to stimulation over the motor cortex, which inhibits motor evoked potentials (MEPs produced by motor cortex stimulation alone, called cerebellar inhibition (CBI. Healthy individuals without pain have been shown to demonstrate reduced CBI following motor acquisition. We hypothesized that CBI would not reduce to the same extent in those with mild-recurrent neck pain following the same motor acquisition task. We further hypothesized that a common treatment for neck pain (spinal manipulation would restore reduced CBI following motor acquisition. Motor acquisition involved typing an eight-letter sequence of the letters Z,P,D,F with the right index finger. Twenty-seven neck pain participants received spinal manipulation (14 participants, 18-27 years or sham control (13 participants, 19-24 years. Twelve healthy controls (20-27 years also participated. Participants had CBI measured; they completed manipulation or sham control followed by motor acquisition; and then had CBI re-measured. Following motor acquisition, neck pain sham controls remained inhibited (58 ± 33% of test MEP vs. healthy controls who disinhibited (98 ± 49% of test MEP, P<0.001, while the spinal manipulation group facilitated (146 ± 95% of test MEP, P<0.001. Greater inhibition in neck pain sham vs. healthy control groups suggests that neck pain may change cerebellar-motor cortex interaction. The change to facilitation suggests that spinal manipulation may reverse inhibitory effects of neck pain.

  3. Pain Control After Surgery: Pain Medicines

    Science.gov (United States)

    ... Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality Birth Control Family Health Infants and Toddlers Kids and Teens ... Bracing: What Works? Home Prevention and Wellness Pain Control After Surgery: Pain Medicines Pain Control After Surgery: ...

  4. Electronic diary assessment of pain-related fear, attention to pain, and pain intensity in chronic low back pain patients.

    NARCIS (Netherlands)

    Roelofs, J.; Peters, M.L.; Patijn, J.; Schouten, E.G.; Vlaeyen, J.W.

    2004-01-01

    The present study investigated the relationships between pain-related fear, attention to pain, and pain intensity in daily life in patients with chronic low back pain. An experience sampling methodology was used in which electronic diary data were collected by means of palmtop computers from 40

  5. Altered Pain Sensitivity in Elderly Women with Chronic Neck Pain

    Science.gov (United States)

    Uthaikhup, Sureeporn; Prasert, Romchat; Paungmali, Aatit; Boontha, Kritsana

    2015-01-01

    Background Age-related changes occur in both the peripheral and central nervous system, yet little is known about the influence of chronic pain on pain sensitivity in older persons. The aim of this study was to investigate pain sensitivity in elders with chronic neck pain compared to healthy elders. Methods Thirty elderly women with chronic neck pain and 30 controls were recruited. Measures of pain sensitivity included pressure pain thresholds, heat/cold pain thresholds and suprathreshold heat pain responses. The pain measures were assessed over the cervical spine and at a remote site, the tibialis anterior muscle. Results Elders with chronic neck pain had lower pressure pain threshold over the articular pillar of C5-C6 and decreased cold pain thresholds over the cervical spine and tibialis anterior muscle when compared with controls (p pain thresholds and suprathreshold heat pain responses (p > 0.05). Conclusion The presence of pain hypersensitivity in elderly women with chronic neck pain appears to be dependent on types of painful stimuli. This may reflect changes in the peripheral and central nervous system with age. PMID:26039149

  6. A rare case of acyanotic congenital heart disease, large patent ductus arteriosus with pre-ductal coarctation of descending thoracic aorta with patent ductus arteriosus closure and extra anatomical bypass grafting

    Directory of Open Access Journals (Sweden)

    Zara Wani

    2017-01-01

    Full Text Available We report a case of 18-year-old female patient with large patent ductus arteriosus (PDA-preductal coarctation of descending thoracic aorta. She underwent large PDA closure with a prosthetic graft from ascending aorta to descending thoracic aorta by mid-sternotomy on cardiopulmonary bypass machine under total hypothermic circulatory arrest.

  7. Pain Sensitivity and Pain Catastrophizing are Associated with Persistent Pain and Disability after Lumbar Spine Surgery

    Science.gov (United States)

    Coronado, Rogelio A.; George, Steven Z.; Devin, Clinton J.; Wegener, Stephen T.; Archer, Kristin R.

    2015-01-01

    Objective To examine whether pain sensitivity and pain catastrophizing are associated with persistent pain and disability after lumbar spine surgery. Design Prospective observational cohort study. Setting Academic medical center. Participants Patients (N = 68, mean ± SD age = 57.9 ± 13.1 years, N female = 40 (58.8%)) undergoing spine surgery for a degenerative condition from March 1, 2012 to April 30, 2013 were assessed 6 weeks, 3 months, and 6 months after surgery. Interventions Not applicable. Main Outcome Measure(s) The main outcome measures were persistent back pain intensity, pain interference, and disability. Patients with persistent back pain intensity, pain interference, or disability were identified as those patients reporting Brief Pain Inventory scores ≥ 4 and Oswestry Disability Index scores ≥ 21 at all postoperative time points. Results From 6 weeks to 6 months after surgery, approximately 12.9%, 24.2%, and 46.8% of patients reported persistent back pain intensity, pain interference, or disability, respectively. Increased pain sensitivity at 6 weeks was associated with having persistent back pain intensity (OR = 2.0, 95% CI = 1.0; 4.1) after surgery. Increased pain catastrophizing at 6 weeks was associated with having persistent back pain intensity (OR = 1.1, 95% CI = 1.0; 1.2), pain interference (OR = 1.1, 95% CI = 1.0; 1.2), and disability (OR = 1.3, 95% CI = 1.1; 1.4). An interaction effect was not found between pain sensitivity and pain catastrophizing on persistent outcomes (p > 0.05). Conclusion(s) Findings suggest the importance of early postoperative screening for pain sensitivity and pain catastrophizing in order to identify patients at-risk for poor postoperative pain intensity, interference, and/or disability outcomes. Future research should consider the benefit of targeted therapeutic strategies for patients with these postoperative prognostic factors. PMID:26101845

  8. Pain chronification: what should a non-pain medicine specialist know?

    Science.gov (United States)

    Morlion, Bart; Coluzzi, Flaminia; Aldington, Dominic; Kocot-Kepska, Magdalena; Pergolizzi, Joseph; Mangas, Ana Cristina; Ahlbeck, Karsten; Kalso, Eija

    2018-04-12

    Pain is one of the most common reasons for an individual to consult their primary care physician, with most chronic pain being treated in the primary care setting. However, many primary care physicians/non-pain medicine specialists lack enough awareness, education and skills to manage pain patients appropriately, and there is currently no clear, common consensus/formal definition of "pain chronification". This article, based on an international Change Pain Chronic Advisory Board meeting which was held in Wiesbaden, Germany, in October 2016, provides primary care physicians/non-pain medicine specialists with a narrative overview of pain chronification, including underlying physiological and psychosocial processes, predictive factors for pain chronification, a brief summary of preventive strategies, and the role of primary care physicians and non-pain medicine specialists in the holistic management of pain chronification. Based on currently available evidence, we propose the following consensus-based definition of pain chronification which provides a common framework to raise awareness among non-pain medicine specialists: "Pain chronification describes the process of transient pain progressing into persistent pain; pain processing changes as a result of an imbalance between pain amplification and pain inhibition; genetic, environmental and biopsychosocial factors determine the risk, the degree, and time-course of chronification." Early intervention plays an important role in preventing pain chronification and, as key influencers in the management of patients with acute pain, it is critical that primary care physicians are equipped with the necessary awareness, education and skills to manage pain patients appropriately.

  9. Pain as social glue: shared pain increases cooperation.

    Science.gov (United States)

    Bastian, Brock; Jetten, Jolanda; Ferris, Laura J

    2014-11-01

    Even though painful experiences are employed within social rituals across the world, little is known about the social effects of pain. We examined the possibility that painful experiences can promote cooperation within social groups. In Experiments 1 and 2, we induced pain by asking some participants to insert their hands in ice water and to perform leg squats. In Experiment 3, we induced pain by asking some participants to eat a hot chili pepper. Participants performed these tasks in small groups. We found evidence for a causal link: Sharing painful experiences with other people, compared with a no-pain control treatment, promoted trusting interpersonal relationships by increasing perceived bonding among strangers (Experiment 1) and increased cooperation in an economic game (Experiments 2 and 3). Our findings shed light on the social effects of pain, demonstrating that shared pain may be an important trigger for group formation. © The Author(s) 2014.

  10. Pain-related guilt in low back pain.

    Science.gov (United States)

    Serbic, Danijela; Pincus, Tamar

    2014-12-01

    Identifying mechanisms that mediate recovery is imperative to improve outcomes in low back pain (LBP). Qualitative studies suggest that guilt may be such a mechanism, but research on this concept is scarce, and reliable instruments to measure pain-related guilt are not available. We addressed this gap by developing and testing a Pain-related Guilt Scale (PGS) for people with LBP. Two samples of participants with LBP completed the scale and provided data on rates of depression, anxiety, pain intensity, and disability. Three factors were identified using exploratory factor analysis (n=137): "Social guilt," (4 items) relating to letting down family and friends; "Managing condition/pain guilt," (5 items) relating to failing to overcome and control pain; and "Verification of pain guilt," (3 items) relating to the absence of objective evidence and diagnosis. This factor structure was confirmed using confirmatory factor analysis (n=288), demonstrating an adequate to good fit with the data (AGFI=0.913, RMSEA=0.061). The PGS subscales positively correlated with depression, anxiety, pain intensity, and disability. After controlling for depression and anxiety the majority of relationships between the PGS subscales and disability and pain intensity remained significant, suggesting that guilt shared unique variance with disability and pain intensity independent of depression and anxiety. High levels of guilt were reported by over 40% of participants. The findings suggest that pain-related guilt is common and is associated with clinical outcomes. Prospective research is needed to examine the role of guilt as a predictor, moderator, and mediator of patients' outcomes.

  11. Pain Intensity Moderates the Relationship Between Age and Pain Interference in Chronic Orofacial Pain Patients.

    Science.gov (United States)

    Boggero, Ian A; Geiger, Paul J; Segerstrom, Suzanne C; Carlson, Charles R

    2015-01-01

    BACKGROUND/STUDY CONTEXT: Chronic pain is associated with increased interference in daily functioning that becomes more pronounced as pain intensity increases. Based on previous research showing that older adults maintain well-being in the face of pain as well as or better than their younger counterparts, the current study examined the interaction of age and pain intensity on interference in a sample of chronic orofacial pain patients. Data were obtained from the records of 508 chronic orofacial pain patients being seen for an initial evaluation from 2008 to 2012. Collected data included age (range: 18-78) and self-reported measures of pain intensity and pain interference. Bivariate correlations and regression models were used to assess for statistical interactions. Regression analyses revealed that pain intensity positively predicted pain interference (R(2) = .35, B = 10.40, SE = 0.62, t(507) = 16.70, p theories, including socioemotional selectivity theory, which posits that as people age, they become more motivated to maximize positive emotions and minimize negative ones. The results highlight the importance of studying the mechanisms older adults use to successfully cope with pain.

  12. Headache attributed to masticatory myofascial pain: impact on facial pain and pressure pain threshold.

    Science.gov (United States)

    Costa, Y M; Porporatti, A L; Stuginski-Barbosa, J; Bonjardim, L R; Speciali, J G; Conti, P C R

    2016-03-01

    There is no clear evidence on how a headache attributed to temporomandibular disorder (TMD) can hinder the improvement of facial pain and masticatory muscle pain. The aim of this study was to measure the impact of a TMD-attributed headache on masticatory myofascial (MMF) pain management. The sample was comprised of adults with MMF pain measured according to the revised research diagnostic criteria for temporomandibular disorders (RDC/TMD) and additionally diagnosed with (Group 1, n = 17) or without (Group 2, n = 20) a TMD-attributed headache. Both groups received instructions on how to implement behavioural changes and use a stabilisation appliance for 5 months. The reported facial pain intensity (visual analogue scale--VAS) and pressure pain threshold (PPT--kgf cm(-2)) of the anterior temporalis, masseter and right forearm were measured at three assessment time points. Two-way anova was applied to the data, considering a 5% significance level. All groups had a reduction in their reported facial pain intensity (P 0·100). A TMD-attributed headache in patients with MMF pain does not negatively impact pain management, but does change the pattern for muscle pain improvement. © 2015 John Wiley & Sons Ltd.

  13. When pain meets … pain-related choice behavior and pain perception in different goal conflict situations.

    Science.gov (United States)

    Schrooten, Martien G S; Wiech, Katja; Vlaeyen, Johan W S

    2014-11-01

    Individuals in pain often face the choice between avoiding pain and pursuing other equally valued goals. However, little is known about pain-related choice behavior and pain perception in goal conflict situations. Seventy-eight healthy volunteers performed a computerized task requiring repeated choices between incompatible options, differing in their effect on probability to receive painful stimulation and money. Depending on group assignment, participants chose between increased pain probability versus decreased money probability (avoidance-avoidance conflict situation); decreased pain probability versus increased money probability (approach-approach conflict situation); or decrease versus increase in both probabilities (double approach/avoidance conflict situation). During the choice task, participants rated painfulness, unpleasantness, threat, and fearfulness associated with the painful stimulation and how they felt. Longer choice latency and more choice switching were associated with higher retrospective ratings of conflict and of decision difficulty, and more equal importance placed on pain avoidance and earning money. Groups did not differ in choice behavior, pain stimulus ratings, or affect. Across groups, longer choice latencies were nonsignificantly associated with higher pain, unpleasantness, threat, and fearfulness. In the avoidance-avoidance group, more choice switching was associated with higher pain-related threat and fearfulness, and with more negative affect. These results of this study suggest that associations between choice behaviors, pain perception, and affect depend on conflict situation. We present a first experimental demonstration of the relationship between pain-related choice behaviors, pain, and affect in different goal conflict situations. This experimental approach allows us to examine these relationships in a controlled fashion. Better understanding of pain-related goal conflicts and their resolution may lead to more effective pain

  14. [Pain and Christianity. A symbol for overcoming pain?].

    Science.gov (United States)

    Markschies, C

    2007-08-01

    Pain and Christianity appear to belong together: Christ's pain stands at the centre of God's healing; his pain leads to the salvation of mankind. We can learn from Jesus' example how to bear suffering and pain. In early Christian times, the belief that Jesus Christ suffered pain on the cross was usually not accepted. In line with the "apathy axiom", freedom from emotion was something to strive for at that time. Only after the acceptance of Christianity as the state religion of the Roman Empire in 380 AD did the pain of Christ again stand in the centre of the Christian doctrine of salvation. The memory of the fact that Jesus himself had to undergo the worst pain can still help people to overcome their pain and comfort them.

  15. [Domains of physical activity in slave-descendant communities in Southwest Bahia State, Brazil: a population-based study].

    Science.gov (United States)

    Bezerra, Vanessa Moraes; Andrade, Amanda Cristina de Souza; César, Cibele Comini; Caiaffa, Waleska Teixeira

    2015-06-01

    This study aimed to describe the prevalence of physical activity (PA) and associated factors in various domains (leisure-time, work, home, and commuting) among quilombolas (descendants of African slaves) in Bahia State, Brazil. This was a cross-sectional study of 797 individuals from 18 to 100 years of age. The study adopted a cutoff point of 150 minutes of PA per week. A hierarchical Poisson model was used. The highest prevalence of PA was at work (42.1%), followed by the home environment (39.3%), commuting (35.5%), and leisure time (13.1%). PA at work was associated with male gender, lower age, higher schooling, and consumption of alcohol and fruits. PA in the household domain was associated with female gender, lower age, marital status (married), and negative self-rated health. In commuting, PA was associated with male gender and lower age bracket, and during leisure time with safety, male gender, lower age, and higher schooling. The study concludes that this slave-descendant community displays a profile of PA that is characteristic of rural groups (more active at work, with little leisure-time activity). The determinants of PA were similar to those seen in urban groups.

  16. Competing effects of pain and fear of pain on postural control in low back pain?

    NARCIS (Netherlands)

    Mazaheri, M.; Heidari, E.; Mostmand, J.; Negahban, H.; van Dieen, J.H.

    2014-01-01

    STUDY DESIGN. A cross-sectional, observational study. OBJECTIVE. To determine whether pain and fear of pain have competing effects on postural sway in patients with low back pain (LBP). SUMMARY OF BACKGROUND DATA. Competing effects of pain and pain-related fear on postural control can be proposed as

  17. Virtual restorative environment therapy as an adjunct to pain control during burn dressing changes: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Small, Charlotte; Stone, Robert; Pilsbury, Jane; Bowden, Michael; Bion, Julian

    2015-08-05

    The pain of a severe burn injury is often characterised by intense background pain, coupled with severe exacerbations associated with essential procedures such as dressing changes. The experience of pain is affected by patients' psychological state and can be enhanced by the anxiety, fear and distress caused by environmental and visual inputs. Virtual Reality (VR) distraction has been used with success in areas such as burns, paediatrics and oncology. The underlying principle of VR is that attention is diverted from the painful stimulus by the use of engaging, dynamic 3D visual content and associated auditory stimuli. Functional magnetic resonance imaging (fMRI) studies undertaken during VR distraction from experimental pain have demonstrated enhancement of the descending cortical pain-control system. The present study will evaluate the feasibility of introducing a novel VR system to the Burns Unit at the Queen Elizabeth Hospital Birmingham for dressing changes: virtual restorative environment therapy (VRET). The study will also explore the system's impact on pain during and after the dressing changes compared to conventional analgesia for ward-based burn dressing changes. A within-subject crossover design will be used to compare the following three conditions: 1. Interactive VRET plus conventional analgesics. 2. Passive VRET with conventional analgesics. 3. Conventional analgesics alone. Using the Monte Carlo method, and on the basis of previous local audit data, a sample size of 25 will detect a clinically significant 33 % reduction in worst pain scores experienced during dressing changes. The study accrual rate is currently slower than predicted by previous audits of admission data. A review of the screening log has found that recruitment has been limited by the nature of burn care, the ability of burn inpatients to provide informed consent and the ability of patients to use the VR equipment. Prior to the introduction of novel interactive technologies for

  18. Comparative phytochemical and growth inhibitory studies on the leaf ...

    African Journals Online (AJOL)

    Comparative phytochemical and growth inhibitory studies on the leaf and root bark extracts of securinega Virosa (roxb ex. Willd) baill ... The growth inhibitory tests were carried out between 1-30 mg/ in a period of 24-96 h while the phytochemical screening was carried out on the plant parts using standard methods. At 24 h ...

  19. Inhibitory control in childhood stuttering

    NARCIS (Netherlands)

    Eggers, K.; de Nil, L.; Van den Bergh, B.R.H.

    2013-01-01

    Purpose The purpose of this study was to investigate whether previously reported parental questionnaire-based differences in inhibitory control (IC; Eggers, De Nil, & Van den Bergh, 2010) would be supported by direct measurement of IC using a computer task. Method Participants were 30 children who

  20. Menopause affects pain depending on pain type and characteristics.

    Science.gov (United States)

    Meriggiola, Maria Cristina; Nanni, Michela; Bachiocco, Valeria; Vodo, Stellina; Aloisi, Anna M

    2012-05-01

    Women are more affected than men by many chronic pain conditions, suggesting the effect of sex-related mechanisms in their occurrence. The role of gonadal hormones has been studied but with contrasting results depending on the pain syndrome, reproductive status, and hormone considered. The aim of the present study was to evaluate the pain changes related to the menopausal transition period. In this observational study, postmenopausal women were asked to evaluate the presence of pain in their life during the premenopausal and postmenopausal periods and its modification with menopause. One hundred one women were enrolled and completed questionnaires on their sociodemographic status, pain characteristics, and evolution. The most common pain syndromes were headache (38%), osteoarticular pain (31%), and cervical/lumbar pain (21%). Pain was present before menopause in 66 women, ceased with menopause in 17, and started after menopause in 18. Data were used for cluster analysis, which allowed the division of participants into four groups. In the first, all women experienced headaches that disappeared or improved with menopause. The second group included osteoarticular pain; the pain improved in half of these women and remained stable in the other half. The third group had cervical/lumbar pain, which disappeared or improved with menopause in all. The fourth group presented different kinds of moderate pain, which worsened in all. The present study provides preliminary data suggesting that menopause can affect pain depending on the painful condition experienced by the woman. This underlines the different interactions of menopause-related events with body structures involved in pain.

  1. Pain perception and modulation in acute and chronic pain states

    NARCIS (Netherlands)

    Oudejans, L.C.J.

    2016-01-01

    This thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain phenotypes are determined in patients with chronic pain. The ability of patients with acute pain after

  2. The periodontal pain paradox: Difficulty on pain assesment in dental patients (The periodontal pain paradox hypothesis

    Directory of Open Access Journals (Sweden)

    Haryono Utomo

    2006-12-01

    Full Text Available In daily dental practice, the majority of patients’ main complaints are related to pain. Most patients assume that all pains inside the oral cavity originated from the tooth. One particular case is thermal sensitivity; sometimes patients were being able to point the site of pain, although there is neither visible caries nor secondary caries in dental radiograph. In this case, gingival recession and dentin hypersensitivity are first to be treated to eliminate the pain. If these treatments failed, pain may misdiagnose as pulpal inflammation and lead to unnecessary root canal treatment. Study in pain during periodontal instrumentation of plaque-related periodontitis revealed that the majority of patients feel pain and discomfort during probing and scaling. It seems obvious because an inflammation, either acute or chronic is related to a lowered pain threshold. However, in contrast, in this case report, patient suffered from chronic gingivitis and thermal sensitivity experienced a relative pain-free sensation during probing and scaling. Lowered pain threshold which accompanied by a blunted pain perception upon periodontal instrumentation is proposed to be termed as the periodontal pain paradox. The objective of this study is to reveal the possibility of certain factors in periodontal inflammation which may involved in the periodontal pain paradox hypothesis. Patient with thermal hypersensitivity who was conducted probing and scaling, after the relative pain-free instrumentation, thermal hypersensitivity rapidly disappeared. Based on the successful periodontal treatment, it is concluded that chronic gingivitis may modulate periodontal pain perception which termed as periodontal pain paradox

  3. Optimization of inhibitory decision rules relative to length and coverage

    KAUST Repository

    Alsolami, Fawaz; Chikalov, Igor; Moshkov, Mikhail; Zielosko, Beata

    2012-01-01

    The paper is devoted to the study of algorithms for optimization of inhibitory rules relative to the length and coverage. In contrast with usual rules that have on the right-hand side a relation "attribute ≠ value", inhibitory rules have a relation

  4. Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery

    DEFF Research Database (Denmark)

    Mangione, Fernanda Marinho; Biering-Sørensen, Tor; Nochioka, Kotaro

    2017-01-01

    OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to b...

  5. INHIBITORY EFFECT OF SALVIA SCLAREA

    African Journals Online (AJOL)

    rakoe

    2011-11-02

    Nov 2, 2011 ... This study demonstrated anti-herpes simplex virus (HSV) activity of lavender, sage and ... Green monkey kidney cells were protected from HSV-2 infection by ... The highest inhibitory effect against HSV-2 was observed after treatment ..... some nuclear-replicating eukaryotic DNA viruses with large genomes.

  6. Pain Scores Are Not Predictive of Pain Medication Utilization

    Directory of Open Access Journals (Sweden)

    Suzanne Galloway

    2011-01-01

    Full Text Available Objective. To compare Visual Analogue Scale (VAS scores with overall postoperative pain medication requirements including cumulative dose and patterns of medication utilization and to determine whether VAS scores predict pain medication utilization. Methods. VAS scores and pain medication data were collected from participants in a randomized trial of the utility of phenazopyridine for improved pain control following gynecologic surgery. Results. The mean age of the 219 participants was 54 (range19 to 94. We did not detect any association between VAS and pain medication utilization for patient-controlled anesthesia (PCA or RN administered (intravenous or oral medications. We also did not detect any association between the number of VAS scores recorded and mean pain scores. Conclusion. Postoperative VAS scores do not predict pain medication use in catheterized women inpatients following gynecologic surgery. Increased pain severity, as reflected by higher VAS scores, is not associated with an increase in pain assessment. Our findings suggest that VAS scores are of limited utility for optimal pain control. Alternative or complimentary methods may improve pain management.

  7. Characterizing neuropathic pain profiles: enriching interpretation of painDETECT

    Directory of Open Access Journals (Sweden)

    Cappelleri JC

    2016-07-01

    Full Text Available Joseph C Cappelleri,1 Vijaya Koduru,2 E Jay Bienen,3 Alesia Sadosky4 1Pfizer Inc, Groton, CT, USA; 2Eliassen Group, New London, CT, USA; 3Outcomes Research Consultant, New York, NY, USA; 4Pfizer Inc, New York, NY, USA Purpose: To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropathic pain (NeP, for discriminating among sensory pain symptoms (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure. Methods: The seven-item version of painDETECT provides an overall score that targets only sensory symptoms, while the nine-item version adds responses on two items to the overall score, covering pain course pattern and pain radiation. Both versions have relevance in terms of characterizing broad NeP. The nine- and seven-item versions of painDETECT were administered to subjects with confirmed NeP across six conditions identified during office visits to US community-based physicians. Responses on the sensory symptom items were dichotomized into “at least moderate” (ie, moderate, strongly, very strongly relative to the combined other responses (never, hardly noticed, slightly. Logistic regression of dichotomized variables on the total painDETECT score provided probabilities of experiencing each symptom across the range of painDETECT scores. Results: Both painDETECT versions discriminated among the symptoms with similar probabilities across the score ranges. Using these data, the probability of moderately experiencing each pain sensory item was estimated for a particular score, providing a pain profile. Additionally, the likelihood of experiencing each sensation was determined for a discrete increase in score, ie, the odds of at least a moderate sensation of burning (versus less than a moderate sensation was 1.29 for a 1-point increase, 3.52 for a 5-point increase, and 12.42 for every 10-point increase in the nine-item painDETECT score

  8. Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose–response curves in mice

    Directory of Open Access Journals (Sweden)

    Raghda A.M. Salama

    2016-07-01

    Full Text Available Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose–response curves. This study aims at identifying the equivalent intraperitoneal (i.p. doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose–response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.. The dose–response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents, the area under the ‘change in mechanical threshold’-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations.

  9. Spinal pain

    International Nuclear Information System (INIS)

    Izzo, R.; Popolizio, T.; D’Aprile, P.; Muto, M.

    2015-01-01

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  10. Spinal pain

    Energy Technology Data Exchange (ETDEWEB)

    Izzo, R., E-mail: roberto1766@interfree.it [Neuroradiology Department, A. Cardarelli Hospital, Naples (Italy); Popolizio, T., E-mail: t.popolizio1@gmail.com [Radiology Department, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (Fg) (Italy); D’Aprile, P., E-mail: paoladaprile@yahoo.it [Neuroradiology Department, San Paolo Hospital, Bari (Italy); Muto, M., E-mail: mutomar@tiscali.it [Neuroradiology Department, A. Cardarelli Hospital, Napoli (Italy)

    2015-05-15

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  11. COMPARATIVE EVALUATION OF INHIBITORY ACTIVITY OF ...

    African Journals Online (AJOL)

    Osondu

    2013-02-26

    Feb 26, 2013 ... especially the four bacteria isolates used in this study are present in the epiphgram of both normal and ... Keyword: Albino snail, Archachatina marginata, Inhibitory activity, Epiphgram, Bacteria isolate. Introduction .... evolution.

  12. Inhibitory Effect of Gamma-Irradiated Chitosan on the Growth of Denitrifiers

    Directory of Open Access Journals (Sweden)

    Javier Vilcáez

    2009-01-01

    Full Text Available In order to find an environmentally benign substitute to hazardous inhibitory agents, the inhibitory effect of -irradiated chitosans against a mixed culture of denitrifying bacteria was experimentally evaluated. Unlike other studies using pure aerobic cultures, the observed effect was not a complete inhibition but a transient inhibition reflected by prolonged lag phases and reduced growth rates. Raw chitosan under acid conditions (pH 6.3 exerted the strongest inhibition followed by the 100 kGy and 500 kGy irradiated chitosans, respectively. Therefore, because the molecular weight of chitosan decreases with the degree of -irradiation, the inhibitory properties of chitosan due to its high molecular weight were more relevant than the inhibitory properties gained due to the modification of the surface charge and/or chemical structure by -irradiation. High dosage of -irradiated appeared to increase the growth of mixed denitrifying bacteria in acid pH media. However, in neutral pH media, high dosage of -irradiation appeared to enhance the inhibitory effect of chitosan.

  13. Reward and motivation in pain and pain relief

    Science.gov (United States)

    Navratilova, Edita; Porreca, Frank

    2015-01-01

    Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain. PMID:25254980

  14. Pain and pain tolerance in professional ballet dancers.

    Science.gov (United States)

    Tajet-Foxell, B; Rose, F D

    1995-01-01

    Pain experience in sport had been the subject of increasing research in recent years. While sports professionals have generally been found to have higher pain thresholds than control subjects the reasons for this are not entirely clear. The present study seeks to investigate one possible explanatory factor, the importance of the popular image of the physical activity and of the self-image of its participants, by examining pain experience in professional ballet dancers. Like sports professionals, dancers were found to have higher pain and pain tolerance thresholds than age matched controls in the Cold Pressor Test. However, they also reported a more acute experience of the sensory aspects of the pain. Explanations of this apparent paradox are discussed both in terms of the neuroticism scores of the two groups and in terms of the dancers' greater experience of pain and its relationship with physical activity. The results illustrated the importance of using multidimensional measures of pain in this type of investigation. PMID:7788215

  15. Inhibitory Effect of Corn Silk on Skin Pigmentation

    OpenAIRE

    Sang Yoon Choi; Yeonmi Lee; Sung Soo Kim; Hyun Min Ju; Ji Hwoon Baek; Chul-Soo Park; Dong-Hyuk Lee

    2014-01-01

    In this study, the inhibitory effect of corn silk on melanin production was evaluated. This study was performed to investigate the inhibitory effect of corn silk on melanin production in Melan-A cells by measuring melanin production and protein expression. The corn silk extract applied on Melan-A cells at a concentration of 100 ppm decreased melanin production by 37.2% without cytotoxicity. This was a better result than arbutin, a positive whitening agent, which exhibited a 26.8% melanin prod...

  16. Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality

    Directory of Open Access Journals (Sweden)

    Toria Herd

    2018-02-01

    Full Text Available Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents’ inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent’s secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.

  17. Inhibitory Control Mediates the Association between Perceived Stress and Secure Relationship Quality.

    Science.gov (United States)

    Herd, Toria; Li, Mengjiao; Maciejewski, Dominique; Lee, Jacob; Deater-Deckard, Kirby; King-Casas, Brooks; Kim-Spoon, Jungmeen

    2018-01-01

    Past research has demonstrated negative associations between exposure to stressors and quality of interpersonal relationships among children and adolescents. Nevertheless, underlying mechanisms of this association remain unclear. Chronic stress has been shown to disrupt prefrontal functioning in the brain, including inhibitory control abilities, and evidence is accumulating that inhibitory control may play an important role in secure interpersonal relationship quality, including peer problems and social competence. In this prospective longitudinal study, we examine whether changes in inhibitory control, measured at both behavioral and neural levels, mediate the association between stress and changes in secure relationship quality with parents and peers. The sample included 167 adolescents (53% males) who were first recruited at age 13 or 14 years and assessed annually three times. Adolescents' inhibitory control was measured by their behavioral performance and brain activities, and adolescents self-reported perceived stress levels and relationship quality with mothers, fathers, and peers. Results suggest that behavioral inhibitory control mediates the association between perceived stress and adolescent's secure relationship quality with their mothers and fathers, but not their peers. In contrast, given that stress was not significantly correlated with neural inhibitory control, we did not further test the mediation path. Our results highlight the role of inhibitory control as a process through which stressful life experiences are related to impaired secure relationship quality between adolescents and their mothers and fathers.

  18. Identification of dipeptidyl peptidase-IV inhibitory peptides from mare whey protein hydrolysates.

    Science.gov (United States)

    Song, J J; Wang, Q; Du, M; Ji, X M; Mao, X Y

    2017-09-01

    Inhibition of dipeptidyl peptidase-IV (DPP-IV) activity is a promising strategy for treatment of type 2 diabetes. In the current study, DPP-IV inhibitory peptides were identified from mare whey protein hydrolysates obtained by papain. The results showed that all the mare whey protein hydrolysates obtained at various hydrolysis durations possessed more potent DPP-IV inhibitory activity compared with intact whey protein. The 4-h hydrolysates showed the greatest DPP-IV inhibitory activity with half-maximal inhibitory concentration of 0.18 mg/mL. The 2 novel peptides from 4-h hydrolysate fractions separated by successive chromatographic steps were characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. The novel peptides Asn-Leu-Glu-Ile-Ile-Leu-Arg and Thr-Gln-Met-Val-Asp-Glu-Glu-Ile-Met-Glu-Lys-Phe-Arg, which corresponded to β-lactoglobulin 1 f(71-77) and β-lactoglobulin 1 f(143-155), demonstrated DPP-IV inhibitory activity with half-maximal inhibitory concentrations of 86.34 and 69.84 μM, respectively. The DPP-IV inhibitory activity of the 2 peptides was retained or even improved after simulated gastrointestinal digestion in vitro. Our findings indicate that mare whey protein-derived peptides may possess potential as functional food ingredients in the management of type 2 diabetes. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Pain genes.

    Directory of Open Access Journals (Sweden)

    Tom Foulkes

    2008-07-01

    Full Text Available Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors signal the existence of tissue damage to the central nervous system (CNS, where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

  20. Cancer pain management: Basic information for the young pain physicians

    Directory of Open Access Journals (Sweden)

    SPS Rana

    2011-01-01

    Full Text Available Cancer pain is multifactorial and complex. The impact of cancer pain is devastating, with increased morbidity and poor quality of life, if not treated adequately. Cancer pain management is a challenging task both due to disease process as well as a consequence of treatment-related side-effects. Optimization of analgesia with oral opioids, adjuvant analgesics, and advanced pain management techniques is the key to success for cancer pain. Early access of oral opioid and interventional pain management techniques can overcome the barriers of cancer pain, with improved quality of life. With timely and proper anticancer therapy, opioids, nerve blocks, and other non-invasive techniques like psychosocial care, satisfactory pain relief can be achieved in most of the patients. Although the WHO Analgesic Ladder is effective for more than 80% cancer pain, addition of appropriate adjuvant drugs along with early intervention is needed for improved Quality of Life. Effective cancer pain treatment requires a holistic approach with timely assessment, measurement of pain, pathophysiology involved in causing particular type of pain, and understanding of drugs to relieve pain with timely inclusion of intervention. Careful evaluation of psychosocial and mental components with good communication is necessary. Barriers to cancer pain management should be overcome with an interdisciplinary approach aiming to provide adequate analgesia with minimal side-effects. Management of cancer pain should comprise not only a physical component but also psychosocial and mental components and social need of the patient. With risk-benefit analysis, interventional techniques should be included in an early stage of pain treatment. This article summarizes the need for early and effective pain management strategies, awareness regarding pain control, and barriers of cancer pain.

  1. Multidimensional features of pain in patients with chronic neck pain

    Directory of Open Access Journals (Sweden)

    Fabianna Resende de Jesus-Moraleida

    Full Text Available Abstract Introduction: Chronic neck pain is associated with significant health costs and loss of productivity at work. Objective: to assess pain and disability in individuals with chronic neck pain. Methods: 31 volunteers with chronic neck pain, mean age 29, 65 years, were assessed using the McGill Pain Questionnaire in Brazilian version (Br-MPQ and Neck Disability Index (NDI. The Br-MPQ analysis was performed based on the numerical values associated with the words selected to describe the experience of pain (Pain Rating Index - PRI, and present pain intensity (PPI. NDI was used to evaluate the influence of neck pain in performance of everyday tasks. Finally, we investigated the association between PPI and NDI. Results: PRI revealed that the most significant dimension was the sensory pain (70%, and the number of chosen words was 10 (2,62 out of 20 words. Mean PPI value was 1,23 (0,76 in five points; 40% of participants described pain intensity as moderate. NDI score was 9,77 (3,34, indicating mild disability. There was a positive association between disability and pain intensity (r = 0,36; p =0,046. Pain intensity and duration of pain were not associated. Conclusions: Findings of this study identified important information related to neck pain experienced by patients when suffering from chronic neck pain, moreover, the association between disability and pain intensity reinforces the importance of complementary investigation of these aspects to optimize function in them.

  2. Quantification of progression and regression of descending thoracic aortic wall thickness by enhanced computed tomography

    International Nuclear Information System (INIS)

    Yokoyama, Kenichi; Takasu, Junichiro; Yamamoto, Rie; Taguchi, Rie; Itani, Yasutaka; Ito, Yuichi; Watanabe, Shigeru; Masuda, Yoshiaki

    2001-01-01

    The purpose of this study is to verify the usefulness of the quantification of aortic wall involvement by enhanced computed tomography (CT). One-hundred thirteen Japanese patients underwent two enhanced CT of the descending thoracic aorta at intervals. We sliced the descending thoracic aorta continuously from the level of the tracheal bifurcation with 1 cm intervals, and we defined aortic wall volume (AWV) (cm 3 ) as the sum of a 7-slice area of aortic wall involving calcification. The average of AWV increased from 7.95±2.92 cm 3 to 8.70±2.98 cm 3 . The developmental rate of AWV (ΔAWV) was 0.270±0.281 cm 3 /year. ΔAWV did not have a significant correlation with any risk factor at the baseline. ΔAWV had significant correlation with total cholesterol, (LDL-C) low-density lipoprotein cholesterol and LDL-C/(HDL-C) high-density lipoprotein cholesterol ratio at the follow-up, and by multivariate analysis with only the LDL-C/HDL-C ratio. ΔAWV was not correlated with the intake status of hypoglycemic, antihypertensive or lipid-lowering drugs. The cut-off level of total cholesterol with the most significant odds ratio for progression of aortic wall was 190 mg/dl, and that of LDL-C was 130 mg/dl. This method proved to be useful for the non-invasive assessment of aortic wall thickness. (author)

  3. Postoperative pain

    DEFF Research Database (Denmark)

    Kehlet, H; Dahl, J B

    1993-01-01

    also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree......Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...

  4. Alexithymic trait, painful heat stimulation and everyday pain experience

    Directory of Open Access Journals (Sweden)

    Olga ePollatos

    2015-10-01

    Full Text Available Background: Alexithymia was found to be associated with a variety of somatic complaints including somatoform pain symptoms. This study addressed the question of whether the different facets of alexithymia are related to responses in heat pain stimulation and its interrelations with levels of everyday pain as assessed by self report. Methods: In the study, sensitivity to heat pain was assessed in fifty healthy female participants. Alexithymia facets were assessed by the Toronto Alexithymia Scale. Pain threshold and tolerance were determined using a testing the limits procedure. Participants furthermore rated subjective intensities and unpleasantness of tonic heat stimuli (45.5 C to 47.5 C on visual analogue scales and on a questionnaire. Possible confounding with temperature sensitivity and mood was controlled. Everyday pain was assessed by self-report addressing everyday pain frequency, intensity and impairment experienced over the last two months. Results: Main results were that the facets of alexithymia were differentially associated with pain perception. The affective scale difficulties in describing feelings was associated with hyposensitivity to pain as indicated by higher pain tolerance scores. Furthermore, everyday pain frequency was related to increased alexithymia values on the affective scale difficulties in identifying feelings, whereas higher values on the cognitive alexithymia scale externally oriented thinking were related to lower pain impairment and intensity. Conclusions: We conclude that the different facets of alexithymia are related to alternations in pain processing. Further research on clinical samples is necessary to elucidate whether different aspects of alexithymia act as vulnerability factor for the development of pain symptoms.

  5. Histamine release inhibitory activity of Piper nigrum leaf.

    Science.gov (United States)

    Hirata, Noriko; Naruto, Shunsuke; Inaba, Kazunori; Itoh, Kimihisa; Tokunaga, Masashi; Iinuma, Munekazu; Matsuda, Hideaki

    2008-10-01

    Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.

  6. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  7. Performa Inhibitory Control dengan Induksi Sing-a-Song Stress Test pada Dewasa Awal

    Directory of Open Access Journals (Sweden)

    Akhmad Kurniawan

    2018-04-01

    Full Text Available Inhibitory control is able to control attention by inhibiting internal tendencies and external influences. Inhibitory control is controlled by dorsolateral prefrontal cortex and anterior cingulate cortex, that can be affected by stress variable. Sing-a-Song Stress Test (SSST is a current method to induce stress that has never been practiced in study of inhibitory control. This study aimed to determine the effect of SSST against inhibitory control in early adult. Between subjects design was applied in this study. A number of 35 participants with age range from 17 to 21 years old were randomly assigned into experimental group (n = 17 and control group (n = 18. Inhibitory control was measured using Computerized Stroop Color-Word Test (CSCWT. Positive Affect and Negative Affect Schedule (PANAS was used to conduct a manipulation check. Independent-Samples T Test explained no significant effect of stress on inhibitory control (t = -0,117; p > 0,05.

  8. The role of emotional inhibitory control in specific internet addiction - an fMRI study.

    Science.gov (United States)

    Dieter, Julia; Hoffmann, Sabine; Mier, Daniela; Reinhard, Iris; Beutel, Martin; Vollstädt-Klein, Sabine; Kiefer, Falk; Mann, Karl; Leménager, Tagrid

    2017-05-01

    Addicts to specific internet applications involving communication features showed increased social anxiety, emotional competence deficits and impaired prefrontal-related inhibitory control. The dorsal Anterior Cingulate Cortex (dACC) likely plays an important role in cognitive control and negative affect (such as social exclusion, pain or anxiety). To assess (social) anxiety-related inhibitory control in specific internet addiction (addicted use of games and social networks) and its relation to altered dACC activation. N=44 controls and n=51 specific internet addicts completed an anxious words-based Affective Go/No-Go task (AGN). A subsample of n=23 healthy controls and n=25 specific internet addicts underwent functional Magnetic Resonance Imaging (fMRI) while completing an Emotional Stroop Task (EST) with socially anxious, positive, negative and neutral words. Subgroups of internet gaming and social network addicts were exploratively assessed. Psychometric measures of social anxiety, emotional competence and impulsivity were additionally explored. Specific internet addicts showed higher impulsivity, social anxiety and reduced emotional competence. Between-group differences in AGN and EST behavioral measures were not detected. No group differences were found in the dACC, but explorative analyses revealed decreased left middle and superior temporal gyrus activation during interference of socially anxious words in internet gaming and relative to social network addicts. Given the function of the left middle temporal gyrus in the retrieval of words or expressions during communication, our findings give a first hint that social words might be less retrievable in the semantic storage of internet gaming addicts, possibly indicating deficiencies in handling speech in social situations. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats.

    Science.gov (United States)

    Miranda, J; Lamana, S M S; Dias, E V; Athie, M; Parada, C A; Tambeli, C H

    2015-02-12

    We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain. Copyright © 2014 IBRO

  10. Sexual pain.

    Science.gov (United States)

    Boardman, Lori A; Stockdale, Colleen K

    2009-12-01

    Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain.

  11. On minimal inhibitory rules for almost all k-valued information systems

    KAUST Repository

    Moshkov, Mikhail; Skowron, Andrzej; Suraj, Zbigniew

    2009-01-01

    The minimal inhibitory rules for information systems can be used for construction of classifiers. We show that almost all information systems from a certain large class of information systems have relatively short minimal inhibitory rules. However

  12. The Fear of Pain Questionnaire (FOPQ): assessment of pain-related fear among children and adolescents with chronic pain.

    Science.gov (United States)

    Simons, Laura E; Sieberg, Christine B; Carpino, Elizabeth; Logan, Deirdre; Berde, Charles

    2011-06-01

    An important construct in understanding pain-related disability is pain-related fear. Heightened pain-related fear may result in behavioral avoidance leading to disuse, disability, and depression; whereas confrontation of avoided activities may result in a reduction of fear over time and reengagement with activities of daily living. Although there are several measures to assess pain-related fear among adults with chronic pain, none exist for children and adolescents. The aim of the current study was to develop a new tool to assess avoidance and fear of pain with pediatric chronic pain patients: the Fear of Pain Questionnaire, child report (FOPQ-C), and Fear of Pain Questionnaire, parent proxy report (FOPQ-P). After initial pilot testing, the FOPQ-C and FOPQ-P were administered to 299 youth with chronic pain and their parents at an initial multidisciplinary pain treatment evaluation. The FOPQ demonstrated very strong internal consistency of .92 for the child and parent versions. One-month stability estimates were acceptable and suggested responsivity to change. For construct validity, the FOPQ correlated with generalized anxiety, pain catastrophizing, and somatization. Evidence of criterion-related validity was found with significant associations for the FOPQ with pain, healthcare utilization, and functional disability. These results support the FOPQ as a psychometrically sound measure. Pain-related fear plays an important role in relation to emotional distress and pain-related disability among children and adolescents with chronic pain. Identification of patients with high levels of fear avoidance of pain with the FOPQ will inform how to proceed with psychological and physical therapy interventions for chronic pain. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. Cancer Pain Management Education Rectifies Patients' Misconceptions of Cancer Pain, Reduces Pain, and Improves Quality of Life.

    Science.gov (United States)

    Koh, Su-Jin; Keam, Bhumsuk; Hyun, Min Kyung; Ju Seo, Jeong; Uk Park, Keon; Oh, Sung Yong; Ahn, Jinseok; Lee, Ja Youn; Kim, JinShil

    2018-03-26

    More than half of the patients have reported improper management of breakthrough cancer pain. Empirical evidence is lacking concerning the effectiveness of cancer pain education on breakthrough pain control. This study aimed to examine the effects of individual pain education on pain control, use of short-acting analgesics for breakthrough pain, quality of life outcomes, and rectification of patients' misconceptions regarding cancer pain. A quasi-experimental design was used. In total, 176 (102 inpatients and 74 outpatients) and 163 (93 inpatients and 70 outpatients) cancer patients completed questionnaires on pain intensity, quality of life, use of short-acting medication for breakthrough pain, and misconceptions about cancer pain and opioid use before and immediately and/or seven days after individual pain education. The mean age of the participants was 60.9 years (±11.2), and 56.3% were male. The most common cancers were lung cancer (17.0%), colon cancer (15.9%), and breast cancer (12.5%). The subjects' reasons for attrition were conditional deterioration, death, or voluntary withdrawal (N = 13, 7.4%). Following the education, there was a significant reduction in overall pain intensity over 24 hours (P < 0.001). The outpatients showed more use of short-acting analgesics for breakthrough pain. Sleep quality change was most significantly associated with intervention; other quality of life aspects (e.g., general feelings and life enjoyment) also improved. Pain education also significantly reduced misconceptions regarding cancer pain management. The present educational intervention was effective in encouraging short-acting analgesic use for breakthrough pain, improving quality of life outcomes, and rectifying patients' misconceptions about analgesic use.

  14. Daytime descending intermediate layers observed over a sub-tropical Indian station Waltair during low-solar activity period

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    K. Niranjan

    2010-03-01

    Full Text Available Study on daytime descending intermediate layer over subtropical Indian station Waltair (17.7° N, 83.3° E geographic, 6.4° N, 10° E geomagnetic, 20° N dip located in the equatorial anomaly transition region, using an IPS 42 Digital Ionosonde during the low solar activity year 2004 showed that the layers occur in the altitude range of 140–160 km with maximum occurrence during winter solstice. The layers observed during daytime occur with a double peak variation throughout the year with less occurrence probability and shorter duration presence during forenoon hours. The morning layer descent was associated with a density increase where as during afternoon hours a decrease in density was observed. The downward drift velocity was about 8 km/h during morning hours and between 7–11 km/h during afternoon hours, with a low descent rate of around 4.5 km/h during summer morning hours. The results indicate the presence of a 6 h tide at this location as observed from the characteristics of the descending layers, unlike at majority of locations where a significant semi diurnal trend is observed. The study brings out the complex nature of the tidal interaction at different locations.

  15. Extended right hemicolectomy and left hemicolectomy for colorectal cancers between the distal transverse and proximal descending colon.

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    Gravante, G; Elshaer, M; Parker, R; Mogekwu, A C; Drake, B; Aboelkassem, A; Rahman, E U; Sorge, R; Alhammali, T; Gardiner, K; Al-Hamali, S; Rashed, M; Kelkar, A; Agarwal, R; El-Rabaa, S

    2016-05-01

    We report our experience with extended right hemicolectomy (ERH) and left hemicolectomy (LH) for the treatment of cancers located between the distal transverse and the proximal descending colon, and compare postoperative morbidity, mortality, pathological results and survival for the two techniques. A retrospective review was performed of a single institution series over ten years. Patients who underwent different operations, had benign disease or received palliative resections were excluded. Data collected were patient demographics, type and duration of surgery, tumour site, postoperative complications and histology results. Ninety-eight patients were analysed (64 ERHs, 34 LHs). ERH was conducted using an open approach in 93.8% of cases compared with 73.5% for LH. The anastomotic leak rate was similar for both groups (ERH: 6.3%, LH: 5.9%). This was also the case for other postoperative complications, mortality (ERH: 1.6%, LH: 2.9%) and overall survival (ERH: 50.4 months, LH: 51.8 months). All but one patient in the ERH cohort had clear surgical margins. Nodal evaluation for staging was adequate in 78.1% of ERH cases and 58.8% of LH cases. In our experience, both ERH and LH are adequate for tumours located between the distal transverse and the proximal descending colon.

  16. Waning of "conditioned pain modulation": a novel expression of subtle pronociception in migraine.

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    Nahman-Averbuch, Hadas; Granovsky, Yelena; Coghill, Robert C; Yarnitsky, David; Sprecher, Elliot; Weissman-Fogel, Irit

    2013-01-01

    To assess the decay of the conditioned pain modulation (CPM) response along repeated applications as a possible expression of subtle pronociception in migraine. One of the most explored mechanisms underlying the pain modulation system is "diffuse noxious inhibitory controls," which is measured psychophysically in the lab by the CPM paradigm. There are contradicting reports on CPM response in migraine, questioning whether migraineurs express pronociceptive pain modulation. Migraineurs (n = 26) and healthy controls (n = 35), all females, underwent 3 stimulation series, consisting of repeated (1) "test-stimulus" (Ts) alone that was given first followed by (2) parallel CPM application (CPM-parallel), and (3) sequential CPM application (CPM-sequential), in which the Ts is delivered during or following the conditioning-stimulus, respectively. In all series, the Ts repeated 4 times (0-3). In the CPM series, repetition "0" consisted of the Ts-alone that was followed by 3 repetitions of the Ts with a conditioning-stimulus application. Although there was no difference between migraineurs and controls for the first CPM response in each series, we found waning of CPM-parallel efficiency along the series for migraineurs (P = .005 for third vs first CPM), but not for controls. Further, greater CPM waning in the CPM-sequential series was correlated with less reported extent of pain reduction by episodic medication (r = 0.493, P = .028). Migraineurs have subtle deficits in endogenous pain modulation which requires a more challenging test protocol than the commonly used single CPM. Waning of CPM response seems to reveal this pronociceptive state. The clinical relevance of the CPM waning effect is highlighted by its association with clinical parameters of migraine. © 2013 American Headache Society.

  17. Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders

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    2016-12-01

    1 AWARD NUMBER: W81XWH-14-1-0433 TITLE: Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders PRINCIPAL INVESTIGATOR: Anis...SUBTITLE 5a. CONTRACT NUMBER Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders 5b. GRANT NUMBER W81XWH-14-1-0433 5c. PROGRAM...chloride co-transporters that control EGABA could be used as a corrective strategy for the synaptic and circuit disruptions demonstrated in the

  18. A Contribution to the Understanding of Pain in Fibromyalgia Based on Cerebrospinal Fluid Investigations

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    Henning Værøy

    1996-01-01

    Full Text Available Fibromyalgia is established in current practice as a condition with widespread pain and a number of specific tender points, as well as symptoms of limb stiffness, lack of refreshing sleep and depression. Musculoskeletal correlations with the syndrome have generally been disappointing. Chemical changes in the cerebrospinal fluid are of interest and seem to show significant relationships with fibromyalgia, both with respect to opioid peptides and substance P. The nature of these relationships and their possible linkage with neuronal plasticity at the spinal cord level are discussed. The influence of both peripheral sensitization and reduced presynaptic inhibitory feedback is considered in this connection.

  19. Pain-related psychological correlates of pediatric acute post-surgical pain

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    Pagé MG

    2012-11-01

    Full Text Available M Gabrielle Pagé,1 Jennifer Stinson,2,3 Fiona Campbell,2,4 Lisa Isaac,2,4 Joel Katz1,4,51Department of Psychology, Faculty of Health, York University, 2Department of Anesthesia and Pain Medicine, Hospital for Sick Children, 3Lawrence S Bloomberg Faculty of Nursing, University of Toronto, 4Department of Anesthesia, Faculty of Medicine, University of Toronto, 5Department of Psychology, Hospital for Sick Children, Toronto, ON, CanadaBackground: Post-surgical pain is prevalent in children, yet is significantly understudied. The goals of this study were to examine gender differences in pain outcomes and pain-related psychological constructs postoperatively and to identify pain-related psychological correlates of acute post-surgical pain (APSP and predictors of functional disability 2 weeks after hospital discharge.Methods: Eighty-three children aged 8–18 (mean 13.8 ± 2.4 years who underwent major orthopedic or general surgery completed pain and pain-related psychological measures 48–72 hours and 2 weeks after surgery.Results: Girls reported higher levels of acute postoperative anxiety and pain unpleasantness compared with boys. In addition, pain anxiety was significantly associated with APSP intensity and functional disability 2 weeks after discharge, whereas pain catastrophizing was associated with APSP unpleasantness.Conclusion: These results highlight the important role played by pain-related psychological factors in the experience of pediatric APSP by children and adolescents.Keywords: acute post-surgical pain, children, adolescents, pain anxiety, pain catastrophizing

  20. Lactoferricin B-derived peptides with inhibitory effects on ECE-dependent vasoconstriction.

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    Fernández-Musoles, Ricardo; López-Díez, José Javier; Torregrosa, Germán; Vallés, Salvador; Alborch, Enrique; Manzanares, Paloma; Salom, Juan B

    2010-10-01

    Endothelin-converting enzyme (ECE), a key peptidase in the endothelin (ET) system, cleaves inactive big ET-1 to produce active ET-1, which binds to ET(A) receptors to exert its vasoconstrictor and pressor effects. ECE inhibition could be beneficial in the treatment of hypertension. In this study, a set of eight lactoferricin B (LfcinB)-derived peptides, previously characterized in our laboratory as angiotensin-converting enzyme (ACE) inhibitory peptides, was examined for their inhibitory effects on ECE. In vitro inhibitory effects on ECE activity were assessed using both the synthetic fluorogenic peptide substrate V (FPS V) and the natural substrate big ET-1. To study vasoactive effects, an ex vivo functional assay was developed using isolated rabbit carotid artery segments. With FPS V, only four LfcinB-derived peptides induced inhibition of ECE activity, whereas the eight peptides showed ECE inhibitory effects with big ET-1 as substrate. Regarding the ex vivo assays, six LfcinB-derived peptides showed inhibition of big ET-1-induced, ECE-dependent vasoconstriction. A positive correlation between the inhibitory effects of LfcinB-derived peptides on ECE activity when using big ET-1 and the inhibitory effects on ECE-dependent vasoconstriction was shown. ECE-independent vasoconstriction induced by ET-1 was not affected, thus discarding effects of LfcinB-derived peptides on ET(A) receptors or intracellular signal transduction mechanisms. In conclusion, a combined in vitro and ex vivo method to assess the effects of potentially antihypertensive peptides on the ET system has been developed and applied to show the inhibitory effects on ECE-dependent vasoconstriction of six LfcinB-derived peptides, five of which were dual vasopeptidase (ACE/ECE) inhibitors. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. The Fear of Movement/Pain in Musculoskeletal Pain-A Review

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    Behnam Akhbari

    2012-07-01

    Full Text Available Objective: To investigate and review psychological influences of pain such as kinesiophobia and pain-related fear on patients with musculoskeletal pain and on rehabilitation outcomes. Materials & Methods: Fear is a universal and powerful emotion and, as a result, it can have a profound impact on human behavior. the fear-motivated behavior has the potential to adversely impact rehabilitation outcomes for patients with musculoskeletal pain. cross-sectional studies consistently documented a positive association between elevated pain-related fear and increased pain intensity and disability. in addition, several longitudinal studies indicated that elevated pain-related fear is a precursor to poor clinical outcomes. existence of catastrophizing in patients effect on the fear of movement/ (reinjury. this fear contributes to avoidance behaviors and subsequent disuse, depression, and disability. it has been established that kinesiophobia plays a negative role in the outcome of the rehabilitation of acute and chronic low back pain, chronic fatigue syndrome and fibromyalgia syndrome. Results: The recent studies suggest that physical therapists should consider the role of pain-related fear and avoidance behaviors in patients' function and they should assess these cognitive and behavioral factors. or (physical therapists should assess pain-related fear when rehabilitating certain individuals with musculoskeletal pain. currently, there is a lot of evidence for the assessment of pain-related fear in patients with musculoskeletal pain. self-report questionnaires are readily available for assessment and investigation of pain-related fear and several studies have found support for their validity and reliability. recent research indicated that besides fear-avoidance responses, endurance-related responses lead to chronic pain via physical overload. the existence of mental kinesiophobia has been established in patients with chronic stress complaints, and this

  2. Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum leaf.

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    Hirata, Noriko; Tokunaga, Masashi; Naruto, Shunsuke; Iinuma, Munekazu; Matsuda, Hideaki

    2007-12-01

    Previously we reported that Piper nigrum leaf extract showed a potent stimulation effect on melanogenesis and that (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2) were isolated as active constituents. As a part of our continuous studies on Piper species for the development of cosmetic hair-care agents, testosterone 5alpha-reductase inhibitory activity of aqueous ethanolic extracts obtained from several different parts of six Piper species, namely Piper nigrum, P. methysticum, P. betle, P. kadsura, P. longum, and P. cubeba, were examined. Among them, the extracts of P. nigrum leaf, P. nigrum fruit and P. cubeba fruit showed potent inhibitory activity. Activity-guided fractionation of P. nigrum leaf extract led to the isolation of 1 and 2. Fruits of P. cubeba contain 1 as a major lignan, thus inhibitory activity of the fruit may be attributable to 1. As a result of further assay on other known constituents of the cited Piper species, it was found that piperine, a major alkaloid amide of P. nigrum fruit, showed potent inhibitory activity, thus a part of the inhibitory activity of P. nigrum fruit may depend on piperine. The 5alpha-reductase inhibitory activities of 1 and piperine were found for the first time. In addition, the P. nigrum leaf extract showed in vivo anti-androgenic activity using the hair regrowth assay in testosterone sensitive male C57Black/6CrSlc strain mice.

  3. Potent Inhibitory Effect of Chinese Dietary Spices on Fatty Acid Synthase.

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    Jiang, Bing; Liang, Yan; Sun, Xuebing; Liu, Xiaoxin; Tian, Weixi; Ma, Xiaofeng

    2015-09-01

    Dietary spices have been adopted in cooking since ancient times to enhance flavor and also as food preservatives and disease remedies. In China, the use of spices and other aromatic plants as food flavoring is an integral part of dietary behavior, but relatively little is known about their functions. Fatty acid synthase (FAS) has been recognized as a remedy target, and its inhibitors might be applied in disease treatment. The present work was designed to assess the inhibitory activities on FAS of spices extracts in Chinese menu. The in vitro inhibitory activities on FAS of 22 extracts of spices were assessed by spectrophotometrically monitoring oxidation of NADPH at 340 nm. Results showed that 20 spices extracts (90.9 %) exhibited inhibitory activities on FAS, with half inhibition concentration (IC(50)) values ranging from 1.72 to 810.7 μg/ml. Among them, seven spices showed strong inhibitory effect with IC(50) values lower than 10 μg/ml. These findings suggest that a large proportion of the dietary spices studied possess promising inhibitory activities on FAS, and subsequently might be applied in the treatment of obesity and obesity-related human diseases.

  4. Preparation of ACE Inhibitory Peptides from Mytilus coruscus Hydrolysate Using Uniform Design

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    Jin-Chao Wu

    2013-01-01

    Full Text Available The angiotensin-I-converting enzyme (ACE inhibitory peptides from mussel, Mytilus coruscus, were investigated and the variable factors, protease concentration, hydrolysis time, pH, and temperature, were optimized using Uniform Design, a new statistical experimental method. The results proved that the hydrolysate of alkali proteases had high ACE-inhibitory activity, especially the alkali protease E1. Optimization by Uniform Design showed that the best hydrolysis conditions for preparation of ACE-inhibitory peptides from Mytilus coruscus were protease concentration of 36.0 U/mL, hydrolysis time of 2.7 hours, pH 8.2, and Temperature at 59.5°C, respectively. The verification experiments under optimum conditions showed that the ACE-inhibitory activity (91.3% were agreed closely with the predicted activity of 90.7%. The amino acid composition analysis of Mytilus coruscus ACE-inhibitory peptides proved that it had high percent of lysine, leucine, glycine, aspartic acid, and glutamic acid.

  5. Basal μ-opioid receptor availability in the amygdala predicts the inhibition of pain-related brain activity during heterotopic noxious counter-stimulation.

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    Piché, Mathieu; Watanabe, Nobuhiro; Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Ishiwata, Kiichi; Hotta, Harumi

    2014-01-01

    The aim of this study was to investigate the association between the magnitude of anti-nociceptive effects induced by heterotopic noxious counter-stimulation (HNCS) and the basal μ-opioid receptor availability in the amygdala. In 8 healthy volunteers (4 females and 4 males), transcutaneous electrical stimulation was applied to the right sural nerve to produce the nociceptive flexion reflex (RIII-reflex), moderate pain, and scalp somatosensory evoked potentials (SEPs). Immersion of the left hand in cold water for 20min was used as HNCS. In a separate session, basal μ-opioid receptor availability was measured using positron emission tomography with the radiotracer [(11)C]carfentanil. HNCS produced a reduction of the P260 amplitude (pbasal μ-opioid receptor availability in the amygdala on the right (R(2)=0.55, p=0.03) with a similar trend on the left (R(2)=0.24, p=0.22). Besides, HNCS did not induce significant changes in pain and RIII-reflex amplitude (p>0.05). These results suggest that activation of μ-opioid receptors in the amygdala may contribute to the anti-nociceptive effects of HNCS. The lack of RIII-reflex modulation further suggests that μ-opioid receptor activation in the amygdala contributes to decrease pain-related brain activity through a cerebral mechanism independent of descending modulation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  6. Differential pain modulation in patients with peripheral neuropathic pain and fibromyalgia.

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    Gormsen, Lise; Bach, Flemming W; Rosenberg, Raben; Jensen, Troels S

    2017-12-29

    Background The definition of neuropathic pain has recently been changed by the International Association for the Study of Pain. This means that conditions such as fibromyalgia cannot, as sometimes discussed, be included in the neuropathic pain conditions. However, fibromyalgia and peripheral neuropathic pain share common clinical features such as spontaneous pain and hypersensitivity to external stimuli. Therefore, it is of interest to directly compare the conditions. Material and methods In this study we directly compared the pain modulation in neuropathic pain versus fibromyalgia by recording responses to a cold pressor test in 30 patients with peripheral neuropathic pain, 28 patients with fibromyalgia, and 26 pain-free age-and gender-matched healthy controls. Patients were asked to rate their spontaneous pain on a visual analog scale (VAS (0-100 mm) immediately before and immediately after the cold pressor test. Furthermore the duration (s) of extremity immersion in cold water was used as a measure of the pain tolerance threshold, and the perceived pain intensity at pain tolerance on the VAS was recorded on the extremity in the water after the cold pressor test. In addition, thermal (thermo tester) and mechanical stimuli (pressure algometer) were used to determine sensory detection, pain detection, and pain tolerance thresholds in different body parts. All sensory tests were done by the same examiner, in the same room, and with each subject in a supine position. The sequence of examinations was the following: (1) reaction time, (2) pressure thresholds, (3) thermal thresholds, and (4) cold pressor test. Reaction time was measured to ensure that psychomotoric inhibitions did not influence pain thresholds. Results Pain modulation induced by a cold pressor test reduced spontaneous pain by 40% on average in neuropathic pain patients, but increased spontaneous pain by 2.6% in fibromyalgia patients. This difference between fibromyalgia and neuropathic pain patients was

  7. EFFECTIVENESS OF INTEGRATED NEUROMUSCULAR INHIBITORY TECHNIQUE (INIT WITH SPECIFIC STRENGTH TRAINING EXERCISES IN SUBJECTS WITH UPPER TRAPEZIUS TRIGGER POINTS

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    B. Jyothirmai

    2015-10-01

    Full Text Available Background: Upper trapezius trigger points is a common cause for neck pain, decreased cervical range of motion and functional activities. The purpose of the study was to evaluate the effectiveness of integrated neuromuscular inhibitory technique (INIT along with specific strength training exercises in reducing pain, improving ROM and functional activities in subjects with upper trapezius trigger point. Methods: Thirty subjects were diagnosed with upper trapezius trigger points were included in the study. These patients were randomly allocated to intervention group (n=15, which underwent a 4- weeks training program of INIT along with specific strength training & control group (n=15 that received INIT alone. The outcome measures were taken before and after treatment. Outcomes were measured by visual analogue scale, cervical range of motion and neck disability index. Within the groups VAS, NDI, and cervical lateral flexion and rotation showed significant change in the mean value. The comparison of pre and post VAS in experimental group and control group showed a significant change in the experimental group .Paired sample t- test was used to analyze changes from before and after intervention programmed. Results: There is a statistically significant (p<0.00 improvement in both variables from baseline to 4th week in experimental group and control group but compared to control group, experimental group shows highly significant values in all parameters. Conclusion: INIT along with specific strength training is proved to be effective in reducing pain, decreasing disability and improving range of motion in individuals with upper trapezius trigger points.

  8. Enhanced Brain Responses to Pain-Related Words in Chronic Back Pain Patients and Their Modulation by Current Pain.

    Science.gov (United States)

    Ritter, Alexander; Franz, Marcel; Puta, Christian; Dietrich, Caroline; Miltner, Wolfgang H R; Weiss, Thomas

    2016-08-10

    Previous functional magnetic resonance imaging (fMRI) studies in healthy controls (HC) and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP) patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain activations induced by pain-related adjectives. Subjects viewed pain-related, negative, positive, and neutral words; subjects were asked to generate mental images related to these words during fMRI scanning. Brain activation was compared between CBP patients and HC in response to the different word categories and examined in relation to current pain in CBP patients. Pain-related words vs. neutral words activated a network of brain regions including cingulate cortex and insula in subjects and patients. There was stronger activation in medial and dorsolateral prefrontal cortex (DLPFC) and anterior midcingulate cortex in CPB patients than in HC. The magnitude of activation for pain-related vs. negative words showed a negative linear relationship to CBP patients' current pain. Our findings confirm earlier observations showing that pain-related words activate brain networks similar to noxious stimulation. Importantly, CBP patients show even stronger activation of these structures while merely processing pain-related words. Current pain directly influences on this activation.

  9. Dogs' reaction to inequity is affected by inhibitory control.

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    Brucks, Désirée; Range, Friederike; Marshall-Pescini, Sarah

    2017-11-17

    Inequity aversion is thought to act as a mechanism to ensure cooperation and has been studied in many different species, consistently revealing inter-individual variation. Inhibitory control has been proposed to act as one factor responsible for this variation since individuals need to inhibit performing the required action and/or refuse rewards in order to exhibit inequity aversion. Here, we investigated if dogs' sensitivity to inequity is affected by their capacity for inhibitory control, assessed in a test battery and questionnaire. Overall, dogs showing high compulsivity scores (i.e. repetitive behaviours independent of feedback) were more motivated to participate in the inequity task independent of the rewarding scheme. Dogs were more sensitive to inequity and individual contrast if they exhibited a slower decision speed in the inhibition tasks. Furthermore, less persistent and more impulsive dogs were more sensitive to reward inequity, potentially due to having a lower tolerance level for frustration. Results indicate that aspects of inhibitory control can explain the variation in dogs' inequity response, highlighting one of the mechanisms underlying responses to inequity. Emphasising the importance to design paradigms, which allow us to disentangle capacities to recognise inequity from the inability to react to it due to poor inhibitory control abilities.

  10. Ancestor–descendant relationships in evolution: origin of the extant pygmy right whale, Caperea marginata

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    Tsai, Cheng-Hsiu; Fordyce, R. Ewan

    2015-01-01

    Ancestor–descendant relationships (ADRs), involving descent with modification, are the fundamental concept in evolution, but are usually difficult to recognize. We examined the cladistic relationship between the only reported fossil pygmy right whale, †Miocaperea pulchra, and its sole living relative, the enigmatic pygmy right whale Caperea marginata, the latter represented by both adult and juvenile specimens. †Miocaperea is phylogenetically bracketed between juvenile and adult Caperea marginata in morphologically based analyses, thus suggesting a possible ADR—the first so far identified within baleen whales (Cetacea: Mysticeti). The †Miocaperea–Caperea lineage may show long-term morphological stasis and, in turn, punctuated equilibrium. PMID:25589485

  11. Botulinum Toxin Type A—A Modulator of Spinal Neuron–Glia Interactions under Neuropathic Pain Conditions

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    Ewelina Rojewska

    2018-04-01

    Full Text Available Neuropathic pain represents a significant clinical problem because it is a chronic condition often refractory to available therapy. Therefore, there is still a strong need for new analgesics. Botulinum neurotoxin A (BoNT/A is used to treat a variety of clinical diseases associated with pain. Glia are in continuous bi-directional communication with neurons to direct the formation and refinement of synaptic connectivity. This review addresses the effects of BoNT/A on the relationship between glia and neurons under neuropathic pain. The inhibitory action of BoNT/A on synaptic vesicle fusion that blocks the release of miscellaneous pain-related neurotransmitters is known. However, increasing evidence suggests that the analgesic effect of BoNT/A is mediated through neurons and glial cells, especially microglia. In vitro studies provide evidence that BoNT/A exerts its anti-inflammatory effect by diminishing NF-κB, p38 and ERK1/2 phosphorylation in microglia and directly interacts with Toll-like receptor 2 (TLR2. Furthermore, BoNT/A appears to have no more than a slight effect on astroglia. The full activation of TLR2 in astroglia appears to require the presence of functional TLR4 in microglia, emphasizing the significant interaction between those cell types. In this review, we discuss whether and how BoNT/A affects the spinal neuron–glia interaction and reduces the development of neuropathy.