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Sample records for attenuates pain hypersensitivity

  1. The potent, indirect adenosine monophosphate-activated protein kinase activator R419 attenuates mitogen-activated protein kinase signaling, inhibits nociceptor excitability, and reduces pain hypersensitivity in mice

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    Galo L. Mejia

    2016-07-01

    Full Text Available Abstract. There is a great need for new therapeutics for the treatment of pain. A possible avenue to development of such therapeutics is to interfere with signaling pathways engaged in peripheral nociceptors that cause these neurons to become hyperexcitable. There is strong evidence that mitogen-activated protein kinases and phosphoinositide 3-kinase (PI3K/mechanistic target of rapamycin signaling pathways are key modulators of nociceptor excitability in vitro and in vivo. Activation of adenosine monophosphate-activated protein kinase (AMPK can inhibit signaling in both of these pathways, and AMPK activators have been shown to inhibit nociceptor excitability and pain hypersensitivity in rodents. R419 is one of, if not the most potent AMPK activator described to date. We tested whether R419 activates AMPK in dorsal root ganglion (DRG neurons and if this leads to decreased pain hypersensitivity in mice. We find that R419 activates AMPK in DRG neurons resulting in decreased mitogen-activated protein kinase signaling, decreased nascent protein synthesis, and enhanced P body formation. R419 attenuates nerve growth factor (NGF-induced changes in excitability in DRG neurons and blocks NGF-induced mechanical pain amplification in vivo. Moreover, locally applied R419 attenuates pain hypersensitivity in a model of postsurgical pain and blocks the development of hyperalgesic priming in response to both NGF and incision. We conclude that R419 is a promising lead candidate compound for the development of potent and specific AMPK activation to inhibit pain hypersensitivity as a result of injury.

  2. Hypersensitivity to pain in congenital blindness

    DEFF Research Database (Denmark)

    Slimani, Hocine; Danti, Sabrina; Ricciardi, Emiliano

    2013-01-01

    Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds an...... that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing......., congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated...

  3. Visceral pain hypersensitivity in functional gastrointestinal disorders.

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    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.

  4. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

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    Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

    2015-12-02

    Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

  5. Minocycline Prevents Muscular Pain Hypersensitivity and Cutaneous Allodynia Produced by Repeated Intramuscular Injections of Hypertonic Saline in Healthy Human Participants.

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    Samour, Mohamad Samir; Nagi, Saad Saulat; Shortland, Peter John; Mahns, David Anthony

    2017-08-01

    Minocycline, a glial suppressor, prevents behavioral hypersensitivities in animal models of peripheral nerve injury. However, clinical trials of minocycline in human studies have produced mixed results. This study addressed 2 questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pretreatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty-seven healthy participants took part in this double-blind, placebo-controlled study, consisting of 6 test sessions across 2 weeks. At the beginning of every session, pressure-pain thresholds of the anterior muscle compartment of both legs were measured to determine the region distribution and intensity of muscle soreness. To measure changes in thermal sensitivity in the skin overlying the anterior muscle compartment of both legs, quantitative sensory testing was used to measure the cutaneous thermal thresholds (cold sensation, cold pain, warm sensation, and heat pain) and a mild cooling stimulus was applied to assess the presence of cold allodynia. To induce ongoing hypersensitivity, repeated injections of HS were administered into the right tibialis anterior muscle at 48-hour intervals. In the final 2 sessions (days 9 and 14), only sensory assessments were done to plot the recovery after cessation of HS administrations and drug washout. By day 9, nontreated participants experienced a significant bilateral increase in muscle soreness (P minocycline-treated participants experienced a bilateral 70% alleviation in muscle soreness (P minocycline-treated participants showed cold allodynia. This study showed that repeated injections of HS can induce a hypersensitivity that outlasts the acute response, and the development of this hypersensitivity can be reliably attenuated with minocycline pretreatment. Four repeated injections of HS at 48-hour intervals induce a state of persistent hypersensitivity in

  6. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

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    Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.

    2013-01-01

    The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. PMID:23989007

  7. A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury

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    Wu Ann

    2011-01-01

    Full Text Available Abstract Background A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. Results We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs or in astrocyte and microglia activation in the spinal dorsal and ventral horns. Conclusions These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.

  8. Analysis of deep tissue hypersensitivity to pressure pain in professional pianists with insidious mechanical neck pain

    Science.gov (United States)

    2011-01-01

    Background The aim of this study was to investigate whether pressure pain hyperalgesia is a feature of professional pianists suffering from neck pain as their main playing-related musculoskeletal disorder. Methods Twenty-three active expert pianists, 6 males and 17 females (age: 36 ± 12 years) with insidious neck pain and 23 pianists, 9 males and 14 females (age: 38 ± 10 years) without neck pain the previous year were recruited. A numerical pain rate scale, Neck Disability Index, hand size and pressure pain thresholds (PPT) were assessed bilaterally over the C5-C6 zygapophyseal joint, deltoid muscle, the second metacarpal and the tibialis anterior muscle in a blinded design. Results The results showed that PPT levels were significantly decreased bilaterally over the second metacarpal and tibialis anterior muscles (P 0.10), in pianists with neck pain as compared to healthy pianists. Pianists with neck pain had a smaller (P neck pain (mean: 188. 6 ± 13.1). PPT over the tibialis anterior muscles was negatively correlated with the intensity of neck pain. Conclusions Our findings revealed pressure pain hypersensitivity over distant non-symptomatic distant points but not over the symptomatic areas in pianists suffering from neck pain. In addition, pianists with neck pain also had smaller hand size than those without neck pain. Future studies are needed to further determine the relevance of these findings in the clinical course of neck pain as playing-related musculoskeletal disorder in professional pianists. PMID:22111912

  9. Analysis of deep tissue hypersensitivity to pressure pain in professional pianists with insidious mechanical neck pain

    Directory of Open Access Journals (Sweden)

    Linari-Melfi Marcela

    2011-11-01

    Full Text Available Abstract Background The aim of this study was to investigate whether pressure pain hyperalgesia is a feature of professional pianists suffering from neck pain as their main playing-related musculoskeletal disorder. Methods Twenty-three active expert pianists, 6 males and 17 females (age: 36 ± 12 years with insidious neck pain and 23 pianists, 9 males and 14 females (age: 38 ± 10 years without neck pain the previous year were recruited. A numerical pain rate scale, Neck Disability Index, hand size and pressure pain thresholds (PPT were assessed bilaterally over the C5-C6 zygapophyseal joint, deltoid muscle, the second metacarpal and the tibialis anterior muscle in a blinded design. Results The results showed that PPT levels were significantly decreased bilaterally over the second metacarpal and tibialis anterior muscles (P 0.10, in pianists with neck pain as compared to healthy pianists. Pianists with neck pain had a smaller (P Conclusions Our findings revealed pressure pain hypersensitivity over distant non-symptomatic distant points but not over the symptomatic areas in pianists suffering from neck pain. In addition, pianists with neck pain also had smaller hand size than those without neck pain. Future studies are needed to further determine the relevance of these findings in the clinical course of neck pain as playing-related musculoskeletal disorder in professional pianists.

  10. Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury

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    Nan Gu

    2016-07-01

    Full Text Available Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT by using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.

  11. Histographical presentation of frequency distribution of attenuation numbers of hypersensitivity pneumonitis

    International Nuclear Information System (INIS)

    Uchino, Akira; Nishitani, Hiromu; Onitsuka, Hideo; Baba, Hiromi; Kawahira, Kozaburo

    1981-01-01

    Based on the attenuation numbers in computed tomography of the chest, histograms for 5 patients with hypersensitivity pneumonitis were analysed. For analysis of histograms, we established 3 parameters: A, tan theta, and M. Of histograms in normal subjects, maximum inspiration scan was more stable than maximum expiration scan, and parameter A was most stable. In patients with hypersensitivity pneumonitis, histograms shifted to the range of higher attenuation numbers than normal subjects. Follow up studies showed decrease in the shift, but parameter A and M of maximum inspiration scan never reached to normal ranges. This suggested that organic parenchymal changes never disappeared completely, even in clinical remission stage. Therefore, parameter A or M of maximum inspiration scan was adequate for analysis, and histographic analysis of chest CT scan was considered to be useful also for early detections and follow-up studies of all diffuse pulmonary disorders. (author)

  12. Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input

    DEFF Research Database (Denmark)

    Slimani, H.; Plaghki, L.; Ptito, M.

    2016-01-01

    Background We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. Methods To study the contribution of Aδ- and C-fibres in pain perception, we measure...... The increased sensitivity to painful thermal stimulation in congenital blindness may be due to more efficient central processing of C-fibre–mediated input, which may help to avoid impending dangerous encounters with stimuli that threaten the bodily integrity....

  13. Disruption of δ-opioid receptor phosphorylation at threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.

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    Chen, Hai-Jing; Xie, Wei-Yan; Hu, Fang; Zhang, Ying; Wang, Jun; Wang, Yun

    2012-04-01

    Our previous study identified Threonine 161 (Thr-161), located in the second intracellular loop of the δ-opioid receptor (DOR), as the only consensus phosphorylation site for cyclin-dependent kinase 5 (Cdk5). The aim of this study was to assess the function of DOR phosphorylation by Cdk5 in complete Freund's adjuvant (CFA)-induced inflammatory pain and morphine tolerance. Dorsal root ganglion (DRG) neurons of rats with CFA-induced inflammatory pain were acutely dissociated and the biotinylation method was used to explore the membrane localization of phosphorylated DOR at Thr-161 (pThr-161-DOR), and paw withdrawal latency was measured after intrathecal delivery of drugs or Tat-peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory pain. Both the total amount and the surface localization of pThr-161-DOR were significantly enhanced in the ipsilateral DRG following CFA injection. Intrathecal delivery of the engineered Tat fusion-interefering peptide corresponding to the second intracellular loop of DOR (Tat-DOR-2L) increased inflammatory hypersensitivity, and inhibited DOR- but not µ-opioid receptor-mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced inflammatory pain. Phosphorylation of DOR at Thr-161 by Cdk5 attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA-induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr-161 attenuates morphine tolerance.

  14. Segmental hypersensitivity and spinothalamic function in spinal cord injury pain

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    Finnerup, Nanna Brix; Sørensen, Leif Hougaard; Biering-Sørensen, Fin

    2007-01-01

    The mechanisms underlying central pain following spinal cord injury (SCI) are unsettled. The purpose of the present study was to examine differences in spinothalamic tract function below injury level and evoked pain in incomplete SCI patients with neuropathic pain below injury level (central pain......-free group. The rostral-caudal extent of the lesion measured by MRI did not differ between the two patient groups, and there were no statistically significant differences in any of the predefined areas of interest on the axial plane images. This study suggests that neuronal hyperexcitability plays a key role...... in central SCI pain and furthermore - in contrast to previous findings - that loss of spinothalamic functions does not appear to be a predictor for central neuropathic pain in spinal cord injury....

  15. Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula

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    Harte, Steven E.; Ichesco, Eric; Hampson, Johnson P.; Peltier, Scott J.; Schmidt-Wilcke, Tobias; Clauw, Daniel J.; Harris, Richard E.

    2016-01-01

    Abstract Pain can be elicited through all mammalian sensory pathways yet cross-modal sensory integration, and its relationship to clinical pain, is largely unexplored. Centralized chronic pain conditions such as fibromyalgia are often associated with symptoms of multisensory hypersensitivity. In this study, female patients with fibromyalgia demonstrated cross-modal hypersensitivity to visual and pressure stimuli compared with age- and sex-matched healthy controls. Functional magnetic resonance imaging revealed that insular activity evoked by an aversive level of visual stimulation was associated with the intensity of fibromyalgia pain. Moreover, attenuation of this insular activity by the analgesic pregabalin was accompanied by concomitant reductions in clinical pain. A multivariate classification method using support vector machines (SVM) applied to visual-evoked brain activity distinguished patients with fibromyalgia from healthy controls with 82% accuracy. A separate SVM classification of treatment effects on visual-evoked activity reliably identified when patients were administered pregabalin as compared with placebo. Both SVM analyses identified significant weights within the insular cortex during aversive visual stimulation. These data suggest that abnormal integration of multisensory and pain pathways within the insula may represent a pathophysiological mechanism in some chronic pain conditions and that insular response to aversive visual stimulation may have utility as a marker for analgesic drug development. PMID:27101425

  16. Hypersensitivity to mechanical and intra-articular electrical stimuli in persons with painful temporomandibular joints

    DEFF Research Database (Denmark)

    Ayesh, Emad; Jensen, Troels Staehelin; Svensson, P

    2007-01-01

    This study tested whether persons with TMJ arthralgia have a modality-specific and site-specific hypersensitivity to somatosensory stimuli assessed by quantitative sensory tests (QST). Forty-three healthy persons and 20 with TMJ arthralgia participated. The QST consisted of: sensory and pain dete...... of sensitization of the TMJs as well as central nociceptive pathways. QST may facilitate a mechanism-based classification of temporomandibular disorders. Udgivelsesdato: 2007-Dec...

  17. The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury

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    Vega-Avelaira David

    2012-04-01

    Full Text Available Abstract Background Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behaviour. However, delayed pain can arise in man some considerable time after nerve damage and to examine this following early life nerve injury we have carried out a longer term follow up of rat pain behaviour into adolescence and adulthood. Results Spared nerve injury (SNI or sham surgery was performed on 10 day old (P10 rat pups and mechanical nociceptive reflex thresholds were analysed 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2–3 weeks post P10 surgery, after that time period, beginning at 21 days post surgery (P31, the SNI group developed following early life nerve injury significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive threshold was 2-fold below that of the contralateral and sham thresholds at 21 days post surgery (SNI-ipsilateral 28 (±5 g control groups 69 (±9 g, p Conclusions We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understand the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.

  18. The Edible Brown Seaweed Ecklonia cava Reduces Hypersensitivity in Postoperative and Neuropathic Pain Models in Rats

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    Jae Goo Kim

    2014-06-01

    Full Text Available The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05. Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats.

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

    OpenAIRE

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

    2015-01-01

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

  20. A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

    Science.gov (United States)

    Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

    2016-06-01

    The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P pain models (P pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

  1. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

    OpenAIRE

    Kiyatkin, Michael E.; Feng, Bin; Schwartz, Erica S.; Gebhart, G. F.

    2013-01-01

    The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined chann...

  2. Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

    Science.gov (United States)

    Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

    2017-09-01

    Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

  3. Bilateral widespread mechanical pain hypersensitivity as sign of central sensitization in patients with cluster headache.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Ortega-Santiago, Ricardo; Cuadrado, María L; López-de-Silanes, Carlos; Pareja, Juan A

    2011-03-01

    To investigate bilateral widespread pressure pain hyperalgesia in deep tissues over symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with cluster headache (CH). Central sensitization is claimed to play a relevant role in CH. No study has previously searched for widespread pressure hyperalgesia in deep tissues over both symptomatic (trigemino-cervical) and nonsymptomatic (distant pain-free) regions in patients with CH. Sixteen men (mean age: 43 ± 11 years) with CH in a remission phase and 16 matched controls were recruited. Pressure pain thresholds (PPTs) were bilaterally measured over the supra-orbital (V1), infra-orbital (V2), mental (V3), median (C5), radial (C6), and ulnar (C7) nerves, C5-C6 zygapophyseal joint, mastoid process, and tibialis anterior muscle by an assessor blinded to the subjects' condition. The results showed that PPT levels were significantly decreased bilaterally in patients with CH as compared with healthy controls (all sites, P < .001). A greater degree of sensitization over the mastoid process (P < .001) and a lower degree of sensitization over the tibialis anterior muscle (P < .01) was found. Our findings revealed bilateral widespread pressure pain hypersensitivity in patients with CH confirming the presence of central sensitization mechanisms in this headache condition. © 2010 American Headache Society.

  4. Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).

    Science.gov (United States)

    Benson, Curtis; Paylor, John W; Tenorio, Gustavo; Winship, Ian; Baker, Glen; Kerr, Bradley J

    2015-09-01

    Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Molecular Hydrogen Attenuates Neuropathic Pain in Mice

    Science.gov (United States)

    Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei

    2014-01-01

    Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting. PMID:24941001

  6. Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma

    Science.gov (United States)

    Wienemann, Tobias; Chantelau, Ernst A.; Koller, Armin

    2014-01-01

    Introduction and objective Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy). Design and methods A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®). Results In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively. Conclusion Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking. PMID:25397867

  7. Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia after acute foot trauma

    Directory of Open Access Journals (Sweden)

    Tobias Wienemann

    2014-11-01

    Full Text Available Introduction and objective: Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy. Design and methods: A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture. Cases were 12 patients (11 diabetic subjects with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT and deep pressure pain perception threshold (DPPPT were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®. Results: In the control group, post-traumatic DPPPT (but not CPPPT at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group; CPPPT did not decrease post-operatively. Conclusion: Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

  8. Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma.

    Science.gov (United States)

    Wienemann, Tobias; Chantelau, Ernst A; Koller, Armin

    2014-01-01

    Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy). A case-control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II(®)). In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15-25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15-20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively. Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to 'pull away' from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

  9. α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats

    Directory of Open Access Journals (Sweden)

    Sun Y

    2017-07-01

    treatment significantly downregulated NaV1.7 and NaV1.8 expression in colon DRGs from rats with diabetes. Conclusion: Our results suggest that ALA plays an analgesic role, which was likely mediated by downregulation of NaV1.7 and NaV1.8 expressions and functions, thus providing experimental evidence for using ALA to treat colonic hypersensitivity in patients with diabetic visceral pain. Keywords: diabetes, colonic hypersensitivity, dorsal root ganglion, voltage-gated sodium channels, α-lipoic acid

  10. Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

    Science.gov (United States)

    Imbe, Hiroki; Kimura, Akihisa

    2017-09-01

    The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

    Science.gov (United States)

    Kras, J V; Kartha, S; Winkelstein, B A

    2015-11-01

    The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  12. Comparative clinical study using laser and LED-therapy for orofacial pain relief: dentin hypersensitivity and cervicogenic headache

    Science.gov (United States)

    Lizarelli, Rosane F. Z.; Pizzo, Renata C. A.; Florez, Fernando L. E.; Grecco, Clovis; Speciali, Jose G.; Bagnato, Vanderlei S.

    2015-06-01

    Considering several clinical situations, low intensity laser therapy has been widely applied in pain relief or analgesia mechanism. With the advent of new LED-based (light emitting diode) light sources, the need of further clinical experiments aiming to compare the effectiveness among them is paramount. The LED system therapeutic use can be denominated as LEDT - Light Emitting Diode Therapy. This study proposed two clinical evaluations of pain relief effect: to dentin hypersensitivity and to cervicogenic headache using different sources of lasers (low and high intensity) and light emitting diodes (LEDs), one emitting at the spectral band of red (630+/- 5nm) and the other one at infrared band (880+/- 5nm). Two different clinical studies were performed and presented interesting results. Considering dentin hypersensitivity, red and infrared led were so effective than the control group (high intensity laser system); by the other side, considering cervicogenic headache, control group (infrared laser) was the best treatment in comparison to red and infrared led system.

  13. Berberine Attenuates Inflammation Associated with Delayed-Type Hypersensitivity via Suppressing Th1 Response and Inhibiting Apoptosis.

    Science.gov (United States)

    Wang, Zhigang; Chen, Zhe; Chen, Tao; Yi, Tao; Zheng, Zhou; Fan, Hong; Chen, Zebin

    2017-02-01

    Berberine, one of the active alkaloids from Rhizoma Coptidis, has been indicated to have anti-inflammatory and immunosuppressive properties. The aim of this study was to determine the role of berberine on ovalbumin (OVA)-induced delayed-type hypersensitivity (DTH) and its potential mechanisms. Berberine treatment significantly reduced footpad swelling, inflammatory cells infiltration, anti-OVA IgG levels, IgE concentration in serum, and the tetramer + CD8 + cells. In homogenized footpad tissue, the production of Th1-mediated cytokines including IFN-γ, TNF-α, and IL-2 were suppressed following the administration of berberine. Detailed studies revealed that berberine prevented differentiation into Th1 cells in the OVA-primed lymphocytes, resulting from suppressing the expression of T-bet and secretion of IFN-γ but not IL-4. Concanavalin A stimulation assay and MTT assay also indicated inhibiting effect of berberine treatment on IFN-γ production and decreased cytotoxicity in lymphocytes proliferation, respectively. Additionally, berberine obviously decreased the cell apoptosis and enzymatic activity of caspase-3, which was further confirmed by the facts that berberine clearly lowered Bax/Bcl-2 ratio and expression of cleaved caspase-3 protein. On correlation analysis, the percentage of apoptotic cells showed a significant positive relationship with IFN-γ/IL-4 ratio of supernatant from footpad tissue in berberine-treated DTH mice. These results demonstrated that berberine attenuated Th1-mediated inflammation in OVA-induced DTH by curbing Th1 response and inhibiting cell apoptosis, suggesting a therapeutic potential for berberine for the treatment of type IV hypersensitivity.

  14. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Liang [Department of Immunology, Fourth Military Medical University, Xi' an 710032 (China); Zhao, Fang; Shen, Xuefeng [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Ouyang, Weiming [Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Bethesda, MD (United States); Liu, Xinqin; Xu, Yan; Yu, Tao [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Jin, Boquan [Department of Immunology, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

    2012-12-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p < 0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4{sup +}CD8{sup −} and peripheral CD4{sup +} T cells was significantly reduced, whereas, CD8{sup +} population was not affected. In contrast to conventional CD4{sup +} T cells, Foxp3{sup +} regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4{sup +} T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4{sup +} thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

  15. Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

    International Nuclear Information System (INIS)

    Fang, Liang; Zhao, Fang; Shen, Xuefeng; Ouyang, Weiming; Liu, Xinqin; Xu, Yan; Yu, Tao; Jin, Boquan; Chen, Jingyuan; Luo, Wenjing

    2012-01-01

    Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p + CD8 − and peripheral CD4 + T cells was significantly reduced, whereas, CD8 + population was not affected. In contrast to conventional CD4 + T cells, Foxp3 + regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4 + T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4 + thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

  16. TRPV1 antagonist attenuates postoperative hypersensitivity by central and peripheral mechanisms

    Czech Academy of Sciences Publication Activity Database

    Uchytilová, Eva; Špicarová, Diana; Paleček, Jiří

    2014-01-01

    Roč. 10, č. 2014 (2014), s. 67 ISSN 1744-8069 R&D Projects: GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LH12058; GA ČR(CZ) GPP303/12/P510 Institutional support: RVO:67985823 Keywords : SB366791 * TRPV1 * allodynia * hyperalgesia * surgical pain * spinal cord Subject RIV: FH - Neurology Impact factor: 3.654, year: 2014

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

    Science.gov (United States)

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

    2015-01-01

    Cervical radiculopathy represents aberrant mechanical hypersensitivity. Primary sensory neuron’s ability to sense mechanical force forms mechanotransduction. However, whether this property undergoes activity-dependent plastic changes and underlies mechanical hypersensitivity associated with cervical radiculopathic pain (CRP) is not clear. Here we show a new CRP model producing stable mechanical compression of dorsal root ganglion (DRG), which induces dramatic behavioral mechanical hypersensitivity. Amongst nociceptive DRG neurons, a mechanically sensitive neuron, isolectin B4 negative Aδ-type (IB4− Aδ) DRG neuron displays spontaneous activity with hyperexcitability after chronic compression of cervical DRGs. Focal mechanical stimulation on somata of IB4- Aδ neuron induces abnormal hypersensitivity. Upregulated HCN1 and HCN3 channels and increased Ih current on this subset of primary nociceptors underlies the spontaneous activity together with neuronal mechanical hypersensitivity, which further contributes to the behavioral mechanical hypersensitivity associated with CRP. This study sheds new light on the functional plasticity of a specific subset of nociceptive DRG neurons to mechanical stimulation and reveals a novel mechanism that could underlie the mechanical hypersensitivity associated with cervical radiculopathy. PMID:26577374

  18. Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception

    OpenAIRE

    Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G.; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

    2015-01-01

    Background Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. Results In this study, we showed that pre- or post-surgical expos...

  19. Addition of posttraumatic stress and sensory hypersensitivity more accurately estimates disability and pain than fear avoidance measures alone after whiplash injury.

    Science.gov (United States)

    Pedler, Ashley; Kamper, Steven J; Sterling, Michele

    2016-08-01

    The fear avoidance model (FAM) has been proposed to explain the development of chronic disability in a variety of conditions including whiplash-associated disorders (WADs). The FAM does not account for symptoms of posttraumatic stress and sensory hypersensitivity, which are associated with poor recovery from whiplash injury. The aim of this study was to explore a model for the maintenance of pain and related disability in people with WAD including symptoms of PTSD, sensory hypersensitivity, and FAM components. The relationship between individual components in the model and disability and how these relationships changed over the first 12 weeks after injury were investigated. We performed a longitudinal study of 103 (74 female) patients with WAD. Measures of pain intensity, cold and mechanical pain thresholds, symptoms of posttraumatic stress, pain catastrophising, kinesiophobia, and fear of cervical spine movement were collected within 6 weeks of injury and at 12 weeks after injury. Mixed-model analysis using Neck Disability Index (NDI) scores and average 24-hour pain intensity as the dependent variables revealed that overall model fit was greatest when measures of fear of movement, posttraumatic stress, and sensory hypersensitivity were included. The interactive effects of time with catastrophising and time with fear of activity of the cervical spine were also included in the best model for disability. These results provide preliminary support for the addition of neurobiological and stress system components to the FAM to explain poor outcome in patients with WAD.

  20. Localized Sympathectomy Reduces Mechanical Hypersensitivity by Restoring Normal Immune Homeostasis in Rat Models of Inflammatory Pain.

    Science.gov (United States)

    Xie, Wenrui; Chen, Sisi; Strong, Judith A; Li, Ai-Ling; Lewkowich, Ian P; Zhang, Jun-Ming

    2016-08-17

    Some forms of chronic pain are maintained or enhanced by activity in the sympathetic nervous system (SNS), but attempts to model this have yielded conflicting findings. The SNS has both pro- and anti-inflammatory effects on immunity, confounding the interpretation of experiments using global sympathectomy methods. We performed a "microsympathectomy" by cutting the ipsilateral gray rami where they entered the spinal nerves near the L4 and L5 DRG. This led to profound sustained reductions in pain behaviors induced by local DRG inflammation (a rat model of low back pain) and by a peripheral paw inflammation model. Effects of microsympathectomy were evident within one day, making it unlikely that blocking sympathetic sprouting in the local DRGs or hindpaw was the sole mechanism. Prior microsympathectomy greatly reduced hyperexcitability of sensory neurons induced by local DRG inflammation observed 4 d later. Microsympathectomy reduced local inflammation and macrophage density in the affected tissues (as indicated by paw swelling and histochemical staining). Cytokine profiling in locally inflamed DRG showed increases in pro-inflammatory Type 1 cytokines and decreases in the Type 2 cytokines present at baseline, changes that were mitigated by microsympathectomy. Microsympathectomy was also effective in reducing established pain behaviors in the local DRG inflammation model. We conclude that the effect of sympathetic fibers in the L4/L5 gray rami in these models is pro-inflammatory. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some chronic inflammatory pain conditions. Sympathetic blockade is used for many pain conditions, but preclinical studies show both pro- and anti-nociceptive effects. The sympathetic nervous system also has both pro- and anti-inflammatory effects on immune tissues and cells. We examined effects of a very localized sympathectomy. By cutting the gray rami to the spinal nerves near the lumbar sensory

  1. 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

  2. N-acetylcysteine attenuates hexavalent chromium-induced hypersensitivity through inhibition of cell death, ROS-related signaling and cytokine expression.

    Directory of Open Access Journals (Sweden)

    Yu-Hsuan Lee

    Full Text Available Chromium hypersensitivity (chromium-induced allergic contact dermatitis is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI can activate the Akt, Nuclear factor κB (NF-κB, and Mitogen-activated protein kinase (MAPK pathways and induce cell death, via the effects of reactive oxygen species (ROS. Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α and interleukin-1 (IL-1. However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells and a guinea pig (GP model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI activated the Akt, NF-κB and MAPK pathways thereby increasing IL-1α and TNF-α production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression.

  3. Copper hypersensitivity

    DEFF Research Database (Denmark)

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-01-01

    hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common...

  4. Hypersensitivity vasculitis

    Science.gov (United States)

    Cutaneous small vessel vasculitis; Allergic vasculitis; Leukocytoclastic vasculitis ... Hypersensitivity vasculitis, or cutaneous small vessel vasculitis, is caused by: An allergic reaction to a drug or other foreign ...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Spinal cord stimulation attenuates temporal summation in patients with neuropathic pain.

    Science.gov (United States)

    Eisenberg, Elon; Burstein, Yulia; Suzan, Erica; Treister, Roi; Aviram, Joshua

    2015-03-01

    Evidence has shown that electrical stimulation at the dorsal columns attenuated the "wind-up" phenomenon in dorsal horn neurons in nerve-injured rats. This study was aimed to test the effect of spinal cord stimulation (SCS) on temporal summation (TS), the clinical correlate of the wind-up phenomenon in patients with radicular leg pain. Eighteen patients with SCS implants were tested both 30 minutes after SCS activation ("ON") and 2 hours after turning it off ("OFF"), in a random order. Temporal summation was evaluated in the most painful site in the affected leg and in the corresponding area in the contralateral leg by applying a tonic painful heat stimulus (46.5°C; 120 seconds) and simultaneous recording of the perceived heat pain intensity. Patients were also requested to report their clinical pain intensity (0-100 numerical pain scale) during SCS "ON" and "OFF". The Wilcoxon signed rank test was used in the comparisons between SCS "ON" and "OFF". Spinal cord stimulation activation significantly attenuated clinical pain intensity (from 66 ± 18 to 27 ± 31, P spinal cord neurons, is a possible mechanism underlying SCS analgesia in patients with neuropathic pain.

  7. Spinal SIRT1 activation attenuates neuropathic pain in mice.

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Hypersensitivity of hypoxia grown Mycobacterium smegmatis to DNA damaging agents: implications of the DNA repair deficiencies in attenuation of mycobacteria.

    Science.gov (United States)

    Rex, Kervin; Kurthkoti, Krishna; Varshney, Umesh

    2013-10-01

    Mycobacteria are an important group of pathogenic bacteria. We generated a series of DNA repair deficient strains of Mycobacterium smegmatis, a model organism, to understand the importance of various DNA repair proteins (UvrB, Ung, UdgB, MutY and Fpg) in survival of the pathogenic strains. Here, we compared tolerance of the M. smegmatis strains to genotoxic stress (ROS and RNI) under aerobic, hypoxic and recovery conditions of growth by monitoring their survival. We show an increased susceptibility of mycobacteria to genotoxic stress under hypoxia. UvrB deficiency led to high susceptibility of M. smegmatis to the DNA damaging agents. Ung was second in importance in strains with single deficiencies. Interestingly, we observed that while deficiency of UdgB had only a minor impact on the strain's susceptibility, its combination with Ung deficiency resulted in severe consequences on the strain's survival under genotoxic stress suggesting a strong interdependence of different DNA repair pathways in safeguarding genomic integrity. Our observations reinforce the possibility of targeting DNA repair processes in mycobacteria for therapeutic intervention during active growth and latency phase of the pathogen. High susceptibility of the UvrB, or the Ung/UdgB deficient strains to genotoxic stress may be exploited in generation of attenuated strains of mycobacteria. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Carbenoxolone as a novel therapy for attenuation of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah

    2018-01-01

    to elucidate the underlying mechanisms using the two specific blockers 37,43Gap27 and 43Gap26. Compared with vehicle treatment, chronic systemic administration of 20 mg/kg or 40 mg/kg carbenoxolone caused a significantly later onset and attenuation of movement-evoked and on-going pain, assessed with limb use...... and weight-bearing respectively. In addition, the carbenoxolone-treated groups demonstrated a significant delay in time to reach the humane endpoint. Acute intrathecal administration of 37,43Gap27 significantly attenuated both limb use and weight-bearing, whereas 43Gap26 had a less pronounced effect...

  11. Intrathecal administration of rapamycin inhibits the phosphorylation of DRG Nav1.8 and attenuates STZ-induced painful diabetic neuropathy in rats.

    Science.gov (United States)

    He, Wan-You; Zhang, Bin; Xiong, Qing-Ming; Yang, Cheng-Xiang; Zhao, Wei-Cheng; He, Jian; Zhou, Jun; Wang, Han-Bing

    2016-04-21

    The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation and protein synthesis, and it is specifically inhibited by rapamycin. In chronic pain conditions, mTOR-mediated local protein synthesis is crucial for neuronal hyperexcitability and synaptic plasticity. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 plays a major role in action potential initiation and propagation and cellular excitability in DRG (dorsal root ganglion) neurons. In this study, we investigated if mTOR modulates the phosphorylation of Nav1.8 that is associated with neuronal hyperexcitability and behavioral hypersensitivity in STZ-induced diabetic rats. Painful diabetic neuropathy (PDN) was induced in Sprague-Dawley rats by intraperitoneal injection with streptozotocin (STZ) at 60mg/kg. After the onset of PDN, the rats received daily intrathecal administrations of rapamycin (1μg, 3μg, or 10μg/day) for 7 days; other diabetic rats received the same volumes of dimethyl sulfoxide (DMSO). Herein, we demonstrate a marked increase in protein expression of total mTOR and phospho-mTOR (p-mTOR) together with the up-regulation of phosphor-Nav1.8 (p-Nav1.8) prior to the mechanical withdrawal threshold reaching a significant reduction in dorsal root ganglions (DRGs). Furthermore, the intrathecal administration of rapamycin, inhibiting the activity of mTOR, suppressed the phosphorylation of DRG Nav1.8, reduced the TTX-R current density, heightened the voltage threshold for activation and lowered the voltage threshold for inactivation and relieved mechanical hypersensitivity in diabetic rats. An intrathecal injection (i.t.) of rapamycin inhibited the phosphorylation and enhanced the functional availability of DRG Nav1.8 attenuated STZ-induced hyperalgesia. These results suggest that rapamycin is a potential therapeutic intervention for clinical PDN. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. TrpA1 activation in peripheral sensory neurons underlies the ionic basis of pain hypersensitivity in response to vinca alkaloids.

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    Nina Boiko

    Full Text Available Chemotherapy induced peripheral neuropathy (CIPN, a side effect of many anti-cancer drugs including the vinca alkaloids, is characterized by a severe pain syndrome that compromises treatment in many patients. Currently there are no effective treatments for this pain syndrome except for the reduction of anti-cancer drug dose. Existing data supports the model that the pain associated with CIPN is the result of anti-cancer drugs augmenting the function of the peripheral sensory nociceptors but the cellular mechanisms underlying the effects of anti-cancer drugs on sensory neuron function are not well described. Studies from animal models have suggested a number of disease etiologies including mitotoxicity, axonal degeneration, immune signaling, and reduced sensory innervations but these outcomes are the result of prolonged treatment paradigms and do not necessarily represent the early formative events associated with CIPN. Here we show that acute exposure to vinca alkaloids results in an immediate pain syndrome in both flies and mice. Furthermore, we demonstrate that exposure of isolated sensory neurons to vinca alkaloids results in the generation of an inward sodium current capable of depolarizing these neurons to threshold resulting in neuronal firing. These neuronal effects of vinca alkaloids require the transient receptor potential ankyrin-1 (TrpA1 channel, and the hypersensitization to painful stimuli in response to the acute exposure to vinca alkaloids is reduced in TrpA1 mutant flies and mice. These findings demonstrate the direct excitation of sensory neurons by CIPN-causing chemotherapy drugs, and identify TrpA1 as an important target during the pathogenesis of CIPN.

  13. Pharmacological evaluation of NSAID-induced gastropathy as a "Translatable" model of referred visceral hypersensitivity.

    Science.gov (United States)

    Hummel, Michele; Knappenberger, Terri; Reilly, Meghan; Whiteside, Garth T

    2017-09-07

    To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice ( n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated. These mechanisms included: transient receptor potential (TRP), sodium and acid-sensing ion channels (ASICs) as well as opioid receptors and guanylate cyclase C (GC-C). Results showed that two opioids and a GC-C agonist, morphine, asimadoline and linaclotide, respectively, the TRP antagonists, AMG9810 and HC-030031 and the sodium channel blocker, carbamazepine, elicited a dose- and/or time-dependent attenuation of referred visceral hypersensitivity, while the ASIC blocker, amiloride, was ineffective at all doses tested. Together, these findings implicate opioid receptors, GC-C, and sodium and TRP channel activation as possible mechanisms associated with visceral hypersensitivity. More importantly, these findings also validate NSAID-induced gastropathy as a sensitive and clinically predictive mouse model suitable for assessing novel molecules with potential pain-attenuating properties.

  14. HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in a rat model of bone cancer pain by restoring μ-opioid receptor in spinal cord.

    Science.gov (United States)

    Hou, Xinran; Weng, Yingqi; Ouyang, Bihan; Ding, Zhuofeng; Song, Zongbin; Zou, Wangyuan; Huang, Changsheng; Guo, Qulian

    2017-08-15

    Bone cancer pain (BCP) is a common complication with inadequate management in patients suffering from advanced cancer. Histone deacetylase inhibitors showed significant analgesic effect in multiple inflammatory and neuropathic pain models, but their effect in bone cancer pain has never been explored. In this study, we utilized a BCP rat model with intra-tibial inoculation of Walker 256 mammary gland carcinoma cells, which developed progressive mechanical hypersensitivity but not thermal hypersensitivity. Intrathecal application of trichostatin A (TSA), a classic pan-HDAC inhibitor, ameliorated tactile hypersensitivity and enhanced the analgesic effect of morphine in BCP rats. The analgesic effect of TSA was blocked by co-administration of CTAP, a specific MOR antagonist, confirming the involvement of mu-opioid receptor (MOR). A reduction of MOR expression was observed in the lumbar spinal cord of BCP rats and TSA treatment was able to partially reverse it. In vitro study in PC12 cells also demonstrated the dose-dependent enhancement of MOR expression by TSA treatment. Taking all into consideration, we could draw the conclusion that HDAC inhibitor TSA ameliorates mechanical hypersensitivity and potentiates analgesic effect of morphine in BCP rats, probably by restoring MOR expression in spinal cord. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A comparative study of attenuation of propofol-induced pain by lignocaine, ondansetron, and ramosetron

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    Gangur Basappa Sumalatha

    2016-01-01

    Full Text Available Background and Aims: Propofol is widely used for induction of anaesthesia, although the pain during its injection remains a concern for all anaesthesiologists. A number of techniques have been adopted to minimise propofol-induced pain. Various 5-hydroxytryptamine-3 antagonists have shown to reduce propofol-induced pain. Hence, this placebo-controlled study was conducted to compare the efficacy of ondansetron, ramosetron and lignocaine in terms of attenuation of propofol-induced pain during induction of anaesthesia. Methods: Hundred and fifty adult patients, aged 18–60 years, posted for various elective surgical procedures under general anaesthesia were randomly assigned to three groups of 50 each. Group R received 0.3 mg of ramosetron, Group L received 0.5 mg/kg of 2% lignocaine and Group O received 4 mg of ondansetron. After intravenous (IV pre-treatment of study drug, manual occlusion of venous drainage was done at mid-arm with the help of an assistant for 1 min. This was followed by administration of propofol (1% after release of venous occlusion. Pain was assessed with a four-point scale. Unpaired Student's t-test and Chi-square test/Fisher's exact test were used to analyse results. Results: The overall incidence and intensity of pain were significantly less in Groups L and R compared to Group O (P ≤ 0.001. The incidence of mild to moderate pain in Groups O, R and L was 56%, 26% and 20%, respectively. The incidence of score '0' (no pain was significantly higher in Group L (76% and Group R (72% than Group O (34% (P < 0.001. Conclusion: Pre-treatment with IV ramosetron 0.3 mg is equally effective as 0.5 mg/kg of 2% lignocaine in preventing propofol-induced pain and both were better than ondansetron.

  16. Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

    Science.gov (United States)

    Kamimura, Rantaro; Hossain, Mohammad Z; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Takahashi, Kojiro; Otake, Masanori; Saito, Isao; Kitagawa, Junichi

    2018-03-24

    Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

  17. Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

    Science.gov (United States)

    Iacovides, S; Avidon, I; Baker, F C

    2015-07-01

    Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

  18. Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus).

    Science.gov (United States)

    Kang, Stacey C; Jampachaisri, Katechan; Seymour, Travis L; Felt, Stephen A; Pacharinsak, Cholawat

    2017-01-01

    The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days -1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.

  19. Hypersensitive tourists

    DEFF Research Database (Denmark)

    Jensen, Martin Trandberg

    2016-01-01

    This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests that aller......This research note sets forth a new agendum for sensuous tourism scholarship. It departs in the neglected study of the embodied life of hypersensitive tourists, and argues that the ambiguousness of the sensuous be better understood. To contextualise this argument the following suggests...... that allergic tourists make up a contemporary and increasingly relevant empirical field through which to illuminate the dark sides of the sensuous. Finally, the note develops four analytical dimensions that structure critical sensuous scholarship....

  20. Metronidazole hypersensitivity.

    Science.gov (United States)

    Knowles, S; Choudhury, T; Shear, N H

    1994-03-01

    To report a case of a possible hypersensitivity reaction induced by metronidazole. An Asian woman with a history of recurrent vaginitis had previously developed localized erythema while on intravaginal metronidazole and nystatin. While receiving oral metronidazole for treatment of a current bacterial vaginosis, she developed chills, fever, generalized erythema, and a rash within 60 minutes of the first dose. Treatment with diphenhydramine was instituted. The following day while in the hospital, the patient's condition worsened; she experienced shortness of breath and increased edema of the extremities. Methylprednisolone was administered with diphenhydramine and her condition improved over the next 5 days. The patient's vaginitis was treated with gentian violet and she was discharged on a tapering dosage of prednisone. Metronidazole-induced cutaneous reactions and systemic hypersensitivity reactions are reviewed. Alternatives to metronidazole and other potential cross-reactive drugs are suggested for the treatment of recurrent vaginitis. Although the patient's initial reaction to metronidazole represented a rare event, written documentation and communication in the patient's native language may have prevented the subsequent severe hypersensitivity reaction.

  1. Fast Green FCF Alleviates Pain Hypersensitivity and Down-Regulates the Levels of Spinal P2X4 Expression and Pro-inflammatory Cytokines in a Rodent Inflammatory Pain Model

    Directory of Open Access Journals (Sweden)

    Fang Xu

    2018-05-01

    Full Text Available Fast Green FCF (FGF, a biocompatible dye, recently drew attention as a potential drug to treat amyloid-deposit diseases due to its effects against amyloid fibrillogenesis in vitro and a high degree of safety. However, its role in inflammatory pain is unknown. Our study aimed to investigate the effect of FGF in the inflammatory pain model induced by complete Freund’s adjuvant (CFA and to identify the associated mechanisms. We found that systemic administration of FGF reversed mechanical and thermal pain hypersensitivity evoked by CFA in a dose-dependent manner. FGF treatment decreased purinergic spinal P2X4 expression in the spinal cord of CFA-inflamed mice. FGF also down-regulated spinal and peripheral pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, and interleukin-6 (IL-6], but did not alter the spinal level of nerve growth factor (NGF or brain-derived neurotrophic factor (BDNF. In conclusion, our results suggest the potential of FGF for controlling the progress of inflammatory pain.

  2. Dexmedetomidine attenuates persistent postsurgical pain by upregulating K+–Cl− cotransporter-2 in the spinal dorsal horn in rats

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    Dai S

    2018-05-01

    Full Text Available Shuhong Dai,1 Yu Qi,1 Jie Fu,1 Na Li,1 Xu Zhang,1 Juan Zhang,2 Wei Zhang,2 Haijun Xu,1 Hai Zhou,1 Zhengliang Ma2 1Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China; 2The Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China Background: Dexmedetomidine (DEX could have an analgesic effect on pain transmission through the modulation of brain-derived neurotrophic factor (BDNF. In addition, KCC2-induced shift in neuronal Cl- homeostasis is crucial for postsynaptic inhibition mediated by GABAA receptors. Accumulating evidence shows that nerve injury, peripheral inflammation and stress activate the spinal BDNF/TrkB signal, which results in the downregulation of KCC2 transport and expression, eventually leads to GAGAergic disinhibition and hyperalgesia. The aim of this experiment was to explore the interaction between DEX and KCC2 at a molecular level in rats in the persistent postsurgical pain (PPSP. Methods: PPSP in rats was evoked by the skin/muscle incision and retraction (SMIR. Mechanical hypersensitivity was assessed with the Dynamic Plantar Aesthesiometer. Western blot and immunofluorescence assay were used to assess the expressions of related proteins. Results: In the first part of our experiment, the results revealed that the BDNF/TrkB-KCC2 signal plays a critical role in the development of SMIR-evoked PPSP; the second part showed that intraperitoneal administrations of 40 µg/kg DEX at 15 min presurgery and 1 to 3 days post-surgery significantly attenuated SMIR-evoked PPSP. Simultaneously, SMIR-induced KCC2 downregulation was partly reversed, which coincided with the inhibition of the BDNF/TrkB signal in the spinal dorsal horn. Moreover, intrathecal administrations of KCC2 inhibitor VU0240551 significantly reduced the analgesic effect of DEX on SMIR-evoked PPSP. Conclusion: The results of our study indicated that DEX attenuated PPSP by restoring KCC2 function through reducing BDNF

  3. A unique inbred rat strain with sustained cephalic hypersensitivity as a model of chronic migraine-like pain

    DEFF Research Database (Denmark)

    Munro, Gordon; Petersen, Steffen; Jansen-Olesen, Inger

    2018-01-01

    Animal models of migraine-like pain enabling ongoing study of behaviour typically involve the systemic administration of chemical vasodilators or dural administration of inflammatory algogens. However, neither method mediates prolonged effects on behavior indicative of enduring pathophysiological...... in preclinical migraine drug discovery....

  4. Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy.

    Science.gov (United States)

    Altmann, Christine; Hardt, Stefanie; Fischer, Caroline; Heidler, Juliana; Lim, Hee-Young; Häussler, Annett; Albuquerque, Boris; Zimmer, Béla; Möser, Christine; Behrends, Christian; Koentgen, Frank; Wittig, Ilka; Schmidt, Mirko H H; Clement, Albrecht M; Deller, Thomas; Tegeder, Irmgard

    2016-12-01

    Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confirmed in primary sensory neurons. Autophagy and survival were impaired in progranulin-deficient neurons and improved in progranulin overexpressing neurons. Nerve injury in vivo caused an accumulation of LC3b-EGFP positive bodies in neurons of the dorsal root ganglia and nerves suggesting an impairment of autophagic flux. Overexpression of progranulin in these neurons was associated with a reduction of the stress marker ATF3, fewer protein aggregates in the injured nerve and enhanced stump healing. At the behavioral level, further inhibition of the autophagic flux by hydroxychloroquine intensified cold and heat nociception after sciatic nerve injury and offset the pain protection provided by progranulin. We infer that progranulin may assist in removal of protein waste and thereby helps to resolve neuropathic pain after nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Severe pain as a possible cause of dropped head syndrome that was attenuated after amputation of an ischemic lower limb.

    Science.gov (United States)

    Maki, Satoshi; Koda, Masao; Furuya, Takeo; Takahashi, Kazuhisa; Yamazaki, Masashi

    2016-03-02

    Dropped head syndrome (DHS) is defined as weakness of the neck extensor muscles causing a correctable chin-on-the-chest deformity. Here we report the case of a patient with severe pain from lower leg ischemia showing DHS whose symptoms were attenuated by pain relief after amputation of the severely ischemic lower leg. To our knowledge this is the first report indicating that severe pain can cause DHS. A 64-year-old Asian woman was referred to our department with a 1-month history of DHS. She also suffered from severe right foot pain because of limb ischemia. She began to complain of DHS as her gangrenous foot pain worsened. She had neck pain and difficulty with forward gaze. We found no clinical or laboratory findings of neuromuscular disorder or isolated neck extensor myopathy. We amputated her leg below the knee because of progressive foot gangrene. Her severe foot pain resolved after the surgery and her DHS was attenuated. Severe pain can cause DHS. If a patient with DHS has severe pain in another part of the body, we recommend considering aggressive pain relief as a treatment option.

  6. Tanshinone IIA Attenuates Diabetic Peripheral Neuropathic Pain in Experimental Rats via Inhibiting Inflammation

    Directory of Open Access Journals (Sweden)

    Baojian Zhang

    2018-01-01

    Full Text Available Diabetic peripheral neuropathic pain (DPNP is a common and intractable complication of diabetes. Conventional therapies are always not ideal; development of novel drugs is still needed to achieve better pain relief. Recent evidences have demonstrated that inflammation is involved in the onset and maintenance of DPNP. The anti-inflammatory property of Tanshinone IIA (TIIA makes it a promising candidate to block or alter the pain perception. This study was conducted to investigate whether TIIA could attenuate DPNP in streptozotocin- (STZ- induced rats model and its potential mechanisms. TIIA was administered to STZ-induced diabetic rats at the dose of 40 mg/kg once a day for 3 weeks. The effects of TIIA on thermal hyperalgesia and mechanical allodynia were investigated using behavioral tests. The mRNA level and expression of interleukin- (IL- 1β, interleukin- (IL- 6, tumor necrosis factor- (TNF- α, and interleukin- (IL- 10 in the fourth to sixth segments of the dorsal root ganglion (L4–6 DRG were detected by quantitative real-time PCR (qPCR and Western blot. TIIA treatment significantly attenuated mechanical allodynia and thermal hyperalgesia in diabetic rats. In addition, the expression of the proinflammatory cytokines IL-1β, IL-6, and TNF-α was inhibited, and the level of the anti-inflammatory cytokine IL-10 was increased by TIIA. This study demonstrated that TIIA has significant antiallodynic and antihyperalgesic effects in a rat model of STZ-induced DPNP, and the effect may be associated with its anti-inflammation property.

  7. Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: modulation by hippocampal sigma receptors.

    Science.gov (United States)

    Kotagale, Nandkishor Ramdas; Shirbhate, Saurabh Haridas; Shukla, Pradeep; Ugale, Rajesh Ramesh

    2013-08-15

    Present study investigated the influence of the sigma (σ₁ and σ₂) receptors within hippocampus on the agmatine induced antinociception in neuropathic rats. Animals were subjected to sciatic nerve ligation for induction of neuropathic pain and observed the paw withdrawal latency in response to thermal hyperalgesia, cold allodynia and the mechanical hyperalgesia. Intrahippocampal (i.h.) as well as intraperitoneal (i.p.) administration of agmatine attenuated neuropathic pain in sciatic nerve ligated rats. Intrahippocampal administration of σ₁ agonist (+)-pentazocine or σ₂ agonist PB28 sensitized whereas, σ₁ antagonist BD1063 or σ₂ antagonist SM21 potentiated antinociceptive effect of agmatine. The behavioral effects correlated with hippocampal tumor necrosis factor-α (TNF-α) levels observed by western blot analysis. These results suggest that both the σ₁ and σ₂ receptor subunits within hippocampus play an important role in antinociceptive action of agmatine against neuropathic pain. © 2013 Elsevier B.V. All rights reserved.

  8. Modelling Affective Pain in Mice: Effects of Inflammatory Hypersensitivity on Place Escape/Avoidance Behaviour, Anxiety and Hedonic State

    DEFF Research Database (Denmark)

    Refsgaard, Louise Konradsen; Hoffmann-Petersen, Julie; Sahlholt, Maj

    2016-01-01

    and the dark area of a box while being stimulated with a suprathreshold filament on the untreated or treated paw, respectively. This was followed by a 30-min test with unrestricted movement. Anxiety-like behaviour, locomotor activity, and hedonic state were assessed with the elevated zero maze (EZM), an open...... PEAP and other behavioural responses, namely anxiety-like behaviour, locomotor activity, and hedonic state. New Method A novel paradigm assessing the affective component of pain in mice was developed by modifying the setup known from rat studies: Animals were forced to stay 2x5 min in the light...... field setup, and a saccharin preference test, respectively, and correlated with the PEAP behaviour to examine potentially confounding parameters of the novel paradigm. Results In the PEAP, CFA-treated animals spent more time in the light area. CFA also increased anxiety-like behaviour significantly...

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

    OpenAIRE

    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...

  10. Comparative study of attenuation of the pain caused by propofol intravenous injection, by granisetron, magnesium sulfate and nitroglycerine

    Directory of Open Access Journals (Sweden)

    Dhananjay Kumar Singh

    2011-01-01

    Full Text Available Background: Propofol has the disadvantage of causing pain or discomfort on injection. The aim of the study was to assess the efficacy of pretreatment with various drugs to alleviate the propofol injection pain. Methods: One hundred American Society of Anesthesiology (ASA I and II adults, scheduled for various elective surgical procedures under general anesthesia (GA, were included in the study. They were randomly divided into four groups having 25 patients in each group. Group A received pretreatment with intravenous (i.v. magnesium sulfate, group B received i.v. granisetron, group C received i.v. nitroglycerine and group D was the control group. One-fourth of the total calculated induction dose of propofol was administered over a period of 5 seconds. The patients were asked about the pain on injection. The intensity of pain was assessed using verbal response. A score of 0-3 which corresponds to no, mild, moderate and severe pain was recorded. Results: All the three drugs reduced the incidence and intensity of pain on propofol injection but the order of efficacy in attenuation of pain on the propofol injection was granisetron > nitroglycerine > magnesium sulfate > control. Conclusion: Granisetron was the most effective followed by nitroglycerine and magnesium sulfate in attenuating pain on propofol intravenous injection.

  11. Attenuation of TRPV1 and TRPV4 Expression and Function in Mouse Inflammatory Pain Models Using Electroacupuncture

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    Wei-Hsin Chen

    2012-01-01

    Full Text Available Although pain is a major human affliction, our understanding of pain mechanisms is limited. TRPV1 (transient receptor potential vanilloid subtype 1 and TRPV4 are two crucial receptors involved in inflammatory pain, but their roles in EA- (electroacupuncture- mediated analgesia are unknown. We injected mice with carrageenan (carra or a complete Freund’s adjuvant (CFA to model inflammatory pain and investigated the analgesic effect of EA using animal behavior tests, immunostaining, Western blotting, and a whole-cell recording technique. The inflammatory pain model mice developed both mechanical and thermal hyperalgesia. Notably, EA at the ST36 acupoint reversed these phenomena, indicating its curative effect in inflammatory pain. The protein levels of TRPV1 and TRPV4 in DRG (dorsal root ganglion neurons were both increased at day 4 after the initiation of inflammatory pain and were attenuated by EA, as demonstrated by immunostaining and Western blot analysis. We verified DRG electrophysiological properties to confirm that EA ameliorated peripheral nerve hyperexcitation. Our results indicated that the AP (action potential threshold, rise time, and fall time, and the percentage and amplitude of TRPV1 and TRPV4 were altered by EA, indicating that EA has an antinociceptive role in inflammatory pain. Our results demonstrate a novel role for EA in regulating TRPV1 and TRPV4 protein expression and nerve excitation in mouse inflammatory pain models.

  12. Mast cell deficiency attenuates acupuncture analgesia for mechanical pain using c-kit gene mutant rats.

    Science.gov (United States)

    Cui, Xiang; Liu, Kun; Xu, Dandan; Zhang, Youyou; He, Xun; Liu, Hao; Gao, Xinyan; Zhu, Bing

    2018-01-01

    Acupuncture therapy plays a pivotal role in pain relief, and increasing evidence demonstrates that mast cells (MCs) may mediate acupuncture analgesia. The present study aims to investigate the role of MCs in acupuncture analgesia using c-kit gene mutant-induced MC-deficient rats. WsRC-Ws/Ws rats and their wild-type (WT) littermates (WsRC-+/+) were used. The number of MCs in skin of ST36 area was compared in two rats after immunofluorescence labeling. Mechanical withdrawal latency (MWL), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were measured on bilateral plantar for pain threshold evaluation before and after each stimulus. Acupuncture- and moxibustion-like stimuli (43°C, 46°C heat, 1 mA electroacupuncture [EA], 3 mA EA, and manual acupuncture [MA]) were applied randomly on different days. Fewer MCs were observed in the skin of ST36 in mutant rats compared to WT rats ( P 0.05). Bilateral MWL and MWT in WsRC-+/+ rats increased significantly after each stimulus compared to baseline ( P <0.01, P <0.001). In WsRC-Ws/Ws rats, only noxious stimuli could produce anti-nociceptive effects for mechanical pain (46°C, 3 mA EA, MA) ( P <0.01, P <0.001). Additionally, the net increases in MWL and MWT induced by most stimuli were greater in WT than in mutant rats ( P <0.05). For thermal nociception, either high- or low-intensity stimuli could significantly augment TWL in two rats ( P <0.001), and the net increases of TWL evoked by most stimuli were to the same extent in two genetic variants. MCs influence the basic mechanical but not thermal pain threshold. MCs participate in acupuncture analgesia in mechanical but not in thermal nociception, in that MC deficiency may attenuate the mechanical analgesia evoked by high-intensity stimuli and eliminate analgesia provoked by low-intensity stimuli.

  13. Macrophage-to-sensory neuron crosstalk mediated by Angiotensin II type-2 receptor elicits neuropathic pain

    OpenAIRE

    Krause, Eric; Shepherd, Andrew; Mickle, Aaron; Copits, Bryan; Karlsson, Pall; Kadunganattil, Suraj; Golden, Judith; Tadinada, Satya; Mack, Madison; Haroutounian, Simon; De Kloet, Annette; Samineni, Vijay; Valtcheva, Manouela; Mcilvried, Lisa; Sheahan, Tayler

    2017-01-01

    Peripheral nerve damage initiates a complex series of cellular and structural processes that culminate in chronic neuropathic pain. Our study defines local angiotensin signaling via activation of the Angiotensin II (Ang II) type-2 receptor (AT2R) on macrophages as the critical trigger of neuropathic pain. An AT2R-selective antagonist attenuates neuropathic, but not inflammatory pain hypersensitivity in mice, and requires the cell damage-sensing ion channel transient receptor potential family-...

  14. 5-HT6 receptor antagonist attenuates the memory deficits associated with neuropathic pain and improves the efficacy of gabapentinoids.

    Science.gov (United States)

    Jayarajan, Pradeep; Nirogi, Ramakrishna; Shinde, Anil; Goura, Venkatesh; Babu, Vuyyuru Arun; Yathavakilla, Sumanth; Bhyrapuneni, Gopinadh

    2015-10-01

    Memory deficit is a co-morbid disorder in patients suffering from neuropathic pain. Gabapentin and pregabalin (gabapentinoids) are among the widely prescribed medications for the treatment of neuropathic pain. Memory loss and sedation are the commonly reported side effects with gabapentinoids. Improving the cognitive functions and attenuating drug-induced side effects may play a crucial role in the management of pain. We evaluated the effects of 5-HT6 receptor antagonists on the memory deficits associated with neuropathy. We also studied the effects of 5-HT6 receptor antagonists on the side effects, and the analgesic effects of gabapentinoids. 5-HT6 receptor antagonists attenuated the cognitive deficits in neuropathic rats. Neuropathic rats co-treated with 5-HT6 receptor antagonist and gabapentinoids showed improvement in memory. 5-HT6 receptor antagonists enhanced the analgesic effects of gabapentinoids but had no effect on the motor side effects. The observed effects may not be due to pharmacokinetic interactions. 5-HT6 receptor antagonist attenuate the cognitive deficits associated with neuropathy, and this effect is also seen when co-treated with gabapentinoids. Since, 5-HT6 antagonists improved the effectiveness of gabapentinoids, reduction in the dosage and frequency of gabapentinoids treatment may reduce the side effects. Combining 5-HT6 receptor antagonist with gabapentinoids may offer a novel treatment strategy for neuropathic pain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Anandamide attenuates Th-17 cell-mediated delayed-type hypersensitivity response by triggering IL-10 production and consequent microRNA induction.

    Directory of Open Access Journals (Sweden)

    Austin R Jackson

    Full Text Available Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions. However, their role in the regulation of Th17 cells has not been studied previously. In the current study, we used methylated Bovine Serum Albumin [mBSA]-induced delayed type hypersensitivity [DTH] response in C57BL/6 mice, mediated by Th17 cells, as a model to test the anti-inflammatory effects of endocannabinoids. Administration of anandamide [AEA], a member of the endocannabinoid family, into mice resulted in significant mitigation of mBSA-induced inflammation, including foot pad swelling, cell infiltration, and cell proliferation in the draining lymph nodes [LN]. AEA treatment significantly reduced IL-17 and IFN-γ production, as well as decreased RORγt expression while causing significant induction of IL-10 in the draining LNs. IL-10 was critical for the AEA-induced mitigation of DTH response inasmuch as neutralization of IL-10 reversed the effects of AEA. We next analyzed miRNA from the LN cells and found that 100 out of 609 miRNA species were differentially regulated in AEA-treated mice when compared to controls. Several of these miRNAs targeted proinflammatory mediators. Interestingly, many of these miRNA were also upregulated upon in vitro treatment of LN cells with IL-10. Together, the current study demonstrates that AEA may suppress Th-17 cell-mediated DTH response by inducing IL-10 which in turn triggers miRNA that target proinflammatory pathways.

  16. Mast cell deficiency attenuates acupuncture analgesia for mechanical pain using c-kit gene mutant rats

    Directory of Open Access Journals (Sweden)

    Cui X

    2018-03-01

    effects for mechanical pain (46°C, 3 mA EA, MA (P<0.01, P<0.001. Additionally, the net increases in MWL and MWT induced by most stimuli were greater in WT than in mutant rats (P<0.05. For thermal nociception, either high- or low-intensity stimuli could significantly augment TWL in two rats (P<0.001, and the net increases of TWL evoked by most stimuli were to the same extent in two genetic variants. Conclusion: MCs influence the basic mechanical but not thermal pain threshold. MCs participate in acupuncture analgesia in mechanical but not in thermal nociception, in that MC deficiency may attenuate the mechanical analgesia evoked by high-intensity stimuli and eliminate analgesia provoked by low-intensity stimuli. Keywords: WsRC-Ws/Ws rats, tryptase, stimulus intensity, mechanical withdrawal threshold, thermal withdrawal latency

  17. Adrenergic β2-receptors mediates visceral hypersensitivity induced by heterotypic intermittent stress in rats.

    Directory of Open Access Journals (Sweden)

    Chunhua Zhang

    Full Text Available Chronic visceral pain in patients with irritable bowel syndrome (IBS has been difficult to treat effectively partially because its pathophysiology is not fully understood. Recent studies show that norepinephrine (NE plays an important role in the development of visceral hypersensitivity. In this study, we designed to investigate the role of adrenergic signaling in visceral hypersensitivity induced by heterotypical intermittent stress (HIS. Abdominal withdrawal reflex scores (AWRs used as visceral sensitivity were determined by measuring the visceromoter responses to colorectal distension. Colon-specific dorsal root ganglia neurons (DRGs were labeled by injection of DiI into the colon wall and were acutely dissociated for whole-cell patch-clamp recordings. Blood plasma level of NE was measured using radioimmunoassay kits. The expression of β2-adrenoceptors was measured by western blotting. We showed that HIS-induced visceral hypersensitivity was attenuated by systemic administration of a β-adrenoceptor antagonist propranolol, in a dose-dependent manner, but not by a α-adrenoceptor antagonist phentolamine. Using specific β-adrenoceptor antagonists, HIS-induced visceral hypersensitivity was alleviated by β2 adrenoceptor antagonist but not by β1- or β3-adrenoceptor antagonist. Administration of a selective β2-adrenoceptor antagonist also normalized hyperexcitability of colon-innervating DRG neurons of HIS rats. Furthermore, administration of β-adrenoceptor antagonist suppressed sustained potassium current density (IK without any alteration of fast-inactivating potassium current density (IA. Conversely, administration of NE enhanced the neuronal excitability and produced visceral hypersensitivity in healthy control rats, and blocked by β2-adrenoceptor antagonists. In addition, HIS significantly enhanced the NE concentration in the blood plasma but did not change the expression of β2-adrenoceptor in DRGs and the muscularis externa of the

  18. Curcumin attenuates the expression of NMDAR-NR1 in Chronic Constructive Injury model of neuropathic pain

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    Xiangdi Yu

    2015-03-01

    Full Text Available Objective: Neuropathic pain is a prevalent desease that greatly impairs the patients’ quality of life. A lack of the understanding of its aetiology, inadequate relief, and development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptic effect of curcumin and its effect on expression of N-methyl-D-aspartate (NMDA receptor in spinal dorsal horn and dorsal root ganglion in chronic constriction injury (CCI mode of neuropathic pain of rats. Methods: Paw withdrawal mechanical threshold (PWMT and paw withdrawal thermal latency (PWTL of rats were measured on 2th pre-operative and 1, 3, 5, 7, 10, 14 post-operative days, and the expression of NMDAR NR-1 in spinal dorsal horn and DRG was measured by Immunohistochemical staining and western-blot. Results: CCI rats exhibited significant hyperalgesia after operation as compared with control rats. Chronic treatment with curcumin 100mg/kg/day for 14days starting from the 1 th day after CCI operation significantly attenuated PWMT and PWTL. Curcumin also inhibited the expression of NMDAR NR-1 in spinal dorsal horn and DRG. Conclusion: These results indicate an antinociceptive activity of curcumin possibly through its inhibitory action on expression of NMDAR NR-1 in spinal dorsal horn and DRG and point towards its potential to attenuate neuropathic pain.

  19. Viral vectors encoding endomorphins and serine histogranin attenuate neuropathic pain symptoms after spinal cord injury in rats.

    Science.gov (United States)

    Nasirinezhad, Farinaz; Gajavelli, Shyam; Priddy, Blake; Jergova, Stanislava; Zadina, James; Sagen, Jacqueline

    2015-01-07

    The treatment of spinal cord injury (SCI)-induced neuropathic pain presents a challenging healthcare problem. The lack of available robust pharmacological treatments underscores the need for novel therapeutic methods and approaches. Due to the complex character of neuropathic pain following SCI, therapies targeting multiple mechanisms may be a better choice for obtaining sufficient long-term pain relief. Previous studies in our lab showed analgesic effects using combinations of an NMDA antagonist peptide [Ser1]histogranin (SHG), and the mu-opioid peptides endomorphins (EMs), in several pain models. As an alternative to drug therapy, this study evaluated the analgesic potential of these peptides when delivered via gene therapy. Lentiviruses encoding SHG and EM-1 and EM-2 were intraspinally injected, either singly or in combination, into rats with clip compression SCI 2 weeks following injury. Treated animals showed significant reduction in mechanical and thermal hypersensitivity, compared to control groups injected with GFP vector only. The antinociceptive effects of individually injected components were modest, but the combination of EMs and SHG produced robust and sustained antinociception. The onset of the analgesic effects was observed between 1-5 weeks post-injection and sustained without decrement for at least 7 weeks. No adverse effects on locomotor function were observed. The involvement of SHG and EMs in the observed antinociception was confirmed by pharmacologic inhibition using intrathecal injection of either the opioid antagonist naloxone or an anti-SHG antibody. Immunohistochemical analysis showed the presence of SHG and EMs in the spinal cord of treated animals, and immunodot-blot analysis of CSF confirmed the presence of these peptides in injected animals. In a separate group of rats, delayed injection of viral vectors was performed in order to mimic a more likely clinical scenario. Comparable and sustained antinociceptive effects were observed in

  20. Dentine hypersensitivity: real or imagined | Gbadebo | Nigerian ...

    African Journals Online (AJOL)

    Background: Dentine hypersensitivity is a common presentation of cause of pain and or discomfort with mastication which has been shown to affect the quality of life of the affected individual. It is also a common cause of presentation at the dental clinics. However, the cause, diagnosis and possible management to give relief ...

  1. Investigation of Seminal Plasma Hypersensitivity Reactions

    Science.gov (United States)

    1998-10-01

    diseases, chronic vaginal candidiasis ); 3) establish the prevalence of BSS and localized/systemic seminal plasma protein hypersensitivity among the GW...of further investigation as our population grows. Subsequent pharmacologic treatment of this female for chronic vaginal candidiasis with an...partner.2Ř Subsequently, women experiencing localized vaginal inflammation, characterized by burning and pain and occurring immediately after contact

  2. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.

    Science.gov (United States)

    Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina

    2016-09-08

    Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.

  3. Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

    Directory of Open Access Journals (Sweden)

    Mehmet Fidanboylu

    Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

  4. Tanshinone IIA attenuates neuropathic pain via inhibiting glial activation and immune response.

    Science.gov (United States)

    Cao, Fa-Le; Xu, Min; Wang, Yan; Gong, Ke-Rui; Zhang, Jin-Tao

    2015-01-01

    Neuropathic pain, characterized by spontaneous pain, hyperalgesia and allodynia, is a devastating neurological disease that seriously affects patients' quality of life. We have previously shown that tanshinone IIA (TIIA), an important lipophilic component of Danshen, had significant anti-nociceptive effect in somatic and visceral pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA on neuropathic pain and the underlying mechanisms. Therefore, in the present study, by using spinal nerve ligation (SNL) pain model, the antinociceptive and antihyperalgesic effects of TIIA on neuropathic pain were evaluated by intraperitoneal administration in rats. The results indicated that TIIA dose-dependently inhibited SNL-induced mechanical hyperalgesia. As revealed by OX42 levels, TIIA effectively repressed the activation of spinal microglial activation in SNL-induced neuropathic pain. Meanwhile, TIIA also decreased the expressions of inflammatory cytokines TNF-α and IL-1β in the spinal cord. Furthermore, TIIA inhibited oxidative stress by significantly rescuing the superoxide dismutase (SOD) activity and decreasing the malondialdehyde (MDA). Moreover, TIIA depressed SNL-induced MAPKs activation in spinal cord. Taken together, our study provides evidence that TIIA inhibited SNL-induced neuropathic pain through depressing microglial activation and immune response by the inhibition of mitogen-activated protein kinases (MAPKs) pathways. Our findings suggest that TIIA might be a promising agent in the treatment of neuropathic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Suppression of asparaginyl endopeptidase attenuates breast cancer-induced bone pain through inhibition of neurotrophin receptors.

    Science.gov (United States)

    Yao, Peng; Ding, Yuanyuan; Han, Zhenkai; Mu, Ying; Hong, Tao; Zhu, Yongqiang; Li, Hongxi

    2017-01-01

    Objective Cancer-induced bone pain is a common clinical problem in breast cancer patients with bone metastasis. However, the mechanisms driving cancer-induced bone pain are poorly known. Recent studies show that a novel protease, asparaginyl endopeptidase (AEP) plays crucial roles in breast cancer metastasis and progression. We aim to determine the functions and targeted suppress of AEP in a mouse model of breast cancer-induced bone pain. Methods Breast cancer cells with AEP knocked-down or overexpression were constructed and implanted into the intramedullary space of the femur to induce pain-like behavior in mice. AEP-specific inhibitors or purified AEP proteins were further used in animal model. The histological characters of femur and pain ethological changes were measured. The expressions of AEP and neurotrophin receptors (p75NTR and TrkA) in dorsal root ganglion and spinal cord were examined. Results Femur radiographs and histological analysis revealed that cells with AEP knocked-down reduced bone destruction and pain behaviors. However, cells with AEP overexpression elevated bone damage and pain behaviors. Further, Western blot results found that the expressions of p75NTR and TrkA in dorsal root ganglions and spinal cords were reduced in mice inoculated with AEP knocked-down cells. Targeted suppression of AEP with specific small compounds significantly reduced the bone pain while purified recombinant AEP proteins increased bone pain. Conclusions AEP aggravate the development of breast cancer bone metastasis and bone pain by increasing the expression of neurotrophin receptors. AEP might be an effective target for treatment of breast cancerinduced bone pain.

  6. Comparsion of Intravenous Lignocaine, Tramadol and Keterolac for Attenuation of Propofol Injection Pain.

    Science.gov (United States)

    Madan, Harprit Kaur; Singh, Rajinder; Sodhi, Gurdip Singh

    2016-07-01

    Propofol possesses many characteristics of an ideal intravenous anaesthetic agent, providing a smooth induction and a rapid recovery. However, it has been reported to evoke considerable pain on injection in 10-100% of patients. The cause of pain upon intravenous injection of propofol remains a mystery. To study and compare the efficacy of Lignocaine, Tramadol and Ketorolac in minimizing the propofol injection pain. Hundred adult patients (ASA grade I and grade II) scheduled for elective surgery under general anaesthesia with propofol as an inducing agent were considered for the study. Patients were randomly divided into 4 groups of 25 patients each Group L (lignocaine) Group T (tramadol) Group K (ketorolac) and Group N (normal saline). Pain scores were measured by the investigator immediately following injection of propofol. All patients' responses were graded by a verbal pain score. All the results were tabulated and analysed using the one-way ANOVA and z-test. There was no statistically significant difference among group L (24%), T (28%) and K (28%) for pain on injection, but significant difference of all 3 groups was there when compared with group N. Intravenous lignocaine, tramadol and ketorolac all 3 drugs significantly reduce propofol injection pain. However, lignocaine appears to be more acceptable cause of less pain and fewer side effects as compared to tramadol and ketorolac.

  7. Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.

    Science.gov (United States)

    Chen, Jun; Joshi, Shailen K; DiDomenico, Stanley; Perner, Richard J; Mikusa, Joe P; Gauvin, Donna M; Segreti, Jason A; Han, Ping; Zhang, Xu-Feng; Niforatos, Wende; Bianchi, Bruce R; Baker, Scott J; Zhong, Chengmin; Simler, Gricelda H; McDonald, Heath A; Schmidt, Robert G; McGaraughty, Steve P; Chu, Katharine L; Faltynek, Connie R; Kort, Michael E; Reilly, Regina M; Kym, Philip R

    2011-05-01

    Despite the increasing interest in TRPA1 channel as a pain target, its role in cold sensation and body temperature regulation is not clear; the efficacy and particularly side effects resulting from channel blockade remain poorly understood. Here we use a potent, selective, and bioavailable antagonist to address these issues. A-967079 potently blocks human (IC(50): 51 nmol/L, electrophysiology, 67 nmol/L, Ca(2+) assay) and rat TRPA1 (IC(50): 101 nmol/L, electrophysiology, 289 nmol/L, Ca(2+) assay). It is >1000-fold selective over other TRP channels, and is >150-fold selective over 75 other ion channels, enzymes, and G-protein-coupled receptors. Oral dosing of A-967079 produces robust drug exposure in rodents, and exhibits analgesic efficacy in allyl isothiocyanate-induced nocifensive response and osteoarthritic pain in rats (ED(50): 23.2 mg/kg, p.o.). A-967079 attenuates cold allodynia produced by nerve injury but does not alter noxious cold sensation in naive animals, suggesting distinct roles of TRPA1 in physiological and pathological states. Unlike TRPV1 antagonists, A-967079 does not alter body temperature. It also does not produce locomotor or cardiovascular side effects. Collectively, these data provide novel insights into TRPA1 function and suggest that the selective TRPA1 blockade may present a viable strategy for alleviating pain without untoward side effects. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  8. Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus).

    Science.gov (United States)

    Seymour, Travis L; Adams, Sean C; Felt, Stephen A; Jampachaisri, Katechan; Yeomans, David C; Pacharinsak, Cholawat

    2016-01-01

    Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

  9. Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats.

    Science.gov (United States)

    Chao, Yu-Chieh; Xie, Fang; Li, Xueyang; Guo, Ruijuan; Yang, Ning; Zhang, Chen; Shi, Rong; Guan, Yun; Yue, Yun; Wang, Yun

    2016-07-01

    Repeated administration of morphine may result in opioid-induced hypersensitivity (OIH), which involves altered expression of numerous genes, including brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) neurons. Yet, it remains unclear how BDNF expression is increased in DRG neurons after repeated morphine treatment. DNA methylation is an important mechanism of epigenetic control of gene expression. In the current study, we hypothesized that the demethylation regulation of certain BDNF gene promoters in DRG neurons may contribute to the development of OIH. Real-time RT-PCR was used to assess changes in the mRNA transcription levels of major BDNF exons including exon I, II, IV, VI, as well as total BDNF mRNA in DRGs from rats after repeated morphine administration. The levels of exon IV and total BDNF mRNA were significantly upregulated by repeated morphine administration, as compared to that in saline control group. Further, ELISA array and immunocytochemistry study revealed a robust upregulation of BDNF protein expression in DRG neurons after repeated morphine exposure. Correspondingly, the methylation levels of BDNF exon IV promoter showed a significant downregulation by morphine treatment. Importantly, intrathecal administration of a BDNF antibody, but not control IgG, significantly inhibited mechanical hypersensitivity that developed in rats after repeated morphine treatment. Conversely, intrathecal administration of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-aza-dC) markedly upregulated the BDNF protein expression in DRG neurons and enhanced the mechanical allodynia after repeated morphine exposure. Together, our findings suggest that demethylation regulation of BDNF gene promoter may be implicated in the development of OIH through epigenetic control of BDNF expression in DRG neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Upregulation of the sodium channel NaVβ4 subunit and its contributions to mechanical hypersensitivity and neuronal hyperexcitability in a rat model of radicular pain induced by local DRG inflammation

    Science.gov (United States)

    Xie, Wenrui; Tan, Zhi-Yong; Barbosa, Cindy; Strong, Judith A.; Cummins, Theodore R.; Zhang, Jun-Ming

    2016-01-01

    High frequency spontaneous firing in myelinated sensory neurons plays a key role in initiating pain behaviors in several different models, including the radicular pain model in which the rat lumbar dorsal root ganglia (DRG) are locally inflamed. The sodium channel isoform NaV1.6 contributes to pain behaviors and spontaneous activity in this model. Among all the isoforms in adult DRG, NaV1.6 is the main carrier of TTX-sensitive resurgent Na currents that allow high-frequency firing. Resurgent currents flow after a depolarization or action potential, as a blocking particle exits the pore. In most neurons the regulatory β4 subunit is potentially the endogenous blocker. We used in vivo siRNA mediated knockdown of NaVβ4 to examine its role in the DRG inflammation model. NaVβ4 but not control siRNA almost completely blocked mechanical hypersensitivity induced by DRG inflammation. Microelectrode recordings in isolated whole DRGs showed that NaVβ4 siRNA blocked the inflammation-induced increase in spontaneous activity of Aβ neurons, and reduced repetitive firing and other measures of excitability. NaVβ4 was preferentially expressed in larger diameter cells; DRG inflammation increased its expression and this was reversed by NaVβ4 siRNA, based on immunohistochemistry and Western blotting. NaVβ4 siRNA also reduced immunohistochemical NaV1.6 expression. Patch clamp recordings of TTX-sensitive Na currents in acutely cultured medium diameter DRG neurons showed that DRG inflammation increased transient and especially resurgent current; effects blocked by NaVβ4 siRNA. NaVβ4 may represent a more specific target for pain conditions that depend on myelinated neurons expressing NaV1.6. PMID:26785322

  11. Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

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    Mao-yin Zhang

    2015-01-01

    Full Text Available Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI. Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg were administrated intragastrically at early phase of postoperation (before pain appearance and later phase of postoperation (after pain appearance, respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1β increase. Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

  12. Kinesthetic illusions attenuate experimental muscle pain, as do muscle and cutaneous stimulation.

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    Gay, André; Aimonetti, Jean-Marc; Roll, Jean-Pierre; Ribot-Ciscar, Edith

    2015-07-30

    In the present study, muscle pain was induced experimentally in healthy subjects by administrating hypertonic saline injections into the tibialis anterior (TA) muscle. We first aimed at comparing the analgesic effects of mechanical vibration applied to either cutaneous or muscle receptors of the TA or to both types simultaneously. Secondly, pain alleviation was compared in subjects in whom muscle tendon vibration evoked kinesthetic illusions of the ankle joint. Muscle tendon vibration, which primarily activated muscle receptors, reduced pain intensity by 30% (p<0.01). In addition, tangential skin vibration reduced pain intensity by 33% (p<0.01), primarily by activating cutaneous receptors. Concurrently stimulating both sensory channels induced stronger analgesic effects (-51%, p<0.01), as shown by the lower levels of electrodermal activity. The strongest analgesic effects of the vibration-induced muscle inputs occurred when illusory movements were perceived (-38%, p=0.01). The results suggest that both cutaneous and muscle sensory feedback reduce muscle pain, most likely via segmental and supraspinal processes. Further clinical trials are needed to investigate these new methods of muscle pain relief. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.

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    Philpott, Holly T; OʼBrien, Melissa; McDougall, Jason J

    2017-12-01

    Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.

  14. GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury.

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    Falnikar, Aditi; Hala, Tamara J; Poulsen, David J; Lepore, Angelo C

    2016-03-01

    Development of neuropathic pain occurs in a major portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. Following SCI, chronic dysregulation of extracellular glutamate homeostasis has been shown to play a key role in persistent central hyperexcitability of superficial dorsal horn neurons that mediate pain neurotransmission, leading to various forms of neuropathic pain. Astrocytes express the major CNS glutamate transporter, GLT1, which is responsible for the vast majority of functional glutamate uptake, particularly in the spinal cord. In our unilateral cervical contusion model of mouse SCI that is associated with ipsilateral forepaw heat hypersensitivity (a form of chronic at-level neuropathic pain-related behavior), we previously reported significant and long-lasting reductions in GLT1 expression and functional GLT1-mediated glutamate uptake in cervical spinal cord dorsal horn. To therapeutically address GLT1 dysfunction following cervical contusion SCI, we injected an adeno-associated virus type 8 (AAV8)-Gfa2 vector into the superficial dorsal horn to increase GLT1 expression selectively in astrocytes. Compared to both contusion-only animals and injured mice that received AAV8-eGFP control injection, AAV8-GLT1 delivery increased GLT1 protein expression in astrocytes of the injured cervical spinal cord dorsal horn, resulting in a significant and persistent reversal of already-established heat hypersensitivity. Furthermore, AAV8-GLT1 injection significantly reduced expression of the transcription factor and marker of persistently increased neuronal activation, ΔFosB, in superficial dorsal horn neurons. These results demonstrate that focal restoration of GLT1 expression in the superficial dorsal horn is a promising target for treating chronic neuropathic pain following SCI. © 2015 Wiley Periodicals, Inc.

  15. A comparison of granisetron and nitroglycerine for attenuating rocuronium pain: A double-blinded randomized, placebo controlled trial

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    Rohit Goyal

    2014-01-01

    Full Text Available Background: The incidence of pain reported in literature after IV administration of rocuronium is 50-80%. The aim of our study was to determine whether pre-treatment with intravenous granisetron and nitroglycerine would reduce rocuronium-induced pain. Methods: One hundred fifty patients of either sex, aged 18-65 years, American society of Anaesthesiologist grading (ASA I-II, scheduled for various surgeries under general anesthesia were randomly assigned to one of the groups. Group G: received 2 granisetron (1mg/ml diluted with 3 ml of 0.9% normal saline while the Group C: received 5 ml of 0.9% normal saline. Group N: received 200΅g of nitroglycerine diluted to a total of 5 ml(with 0.9% normal saline. It was accompanied by manual venous occlusion for 20 seconds. Then 0.06mg/kg of rocuronium was injected through same cannula over 10-15 sec.Patients were asked by a blinded investigator to score the pain on injection of rocuronium using visual analogue scale (0-10 with 0-no pain,1-3 mild pain, 4-6 moderate and >=7 severe pain. At the same time discomfort in the form of patient′s movement, such as no movement (grade 0, movement only wrist (grade 1, movement to the upper arm and shoulder of injected arm (grade 2 or generalized movements (grade3 was observed. Statistical analysis using independent t test, Mann-Whitney test and reverse ANOVA was done. Results: 1. At 0 seconds, in group G number of patients who experienced withdrawl score of 0-1 were 92%,group N were 82% while only 26% of patients in group C had favourable withdrawl score.74% of patients in group C had score of 2-3 at same time. 2. At 0 sec, in group G number of patients who experienced VAS score of 0-3 were 96%, group N 72%. At same time Group C 48 % of patients had VAS score of 2-3. Conclusion: We conclude that pre-treatment with granisetron or nitroglycerine both are highly effective in attenuation of rocuronium induced pain.

  16. Preventive Treatment with Ketamine Attenuates the Ischaemia-Reperfusion Response in a Chronic Postischaemia Pain Model

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    Suryamin Liman

    2015-01-01

    Full Text Available Ischemia and inflammation may be pathophysiological mechanisms of complex regional pain syndrome (CRPS. Ketamine has proposed anti-inflammatory effects and has been used for treating CRPS. This study aimed to evaluate anti-inflammatory and analgesic effects of ketamine after ischaemia-reperfusion injury in a chronic postischaemia pain (CPIP model of CRPS-I. Using this model, ischemia was induced in the hindlimbs of male Sprague-Dawley rats. Ketamine, methylprednisolone, or saline was administered immediately after reperfusion. Physical effects, (oedema, temperature, and mechanical and cold allodynia in the bilateral hindpaws, were assessed from 48 hours after reperfusion. Fewer (56% rats in the ketamine group developed CPIP at the 48th hour after reperfusion (nonsignificant. Ketamine treated rats showed a significantly lower temperature in the ischaemic hindpaw compared to saline (P<0.01 and methylprednisolone (P<0.05 groups. Mechanical and cold allodynia were significantly lower in the ischaemic side in the ketamine group (P<0.05. Proinflammatory cytokines TNF-α and IL-2 were significantly lower at the 48th hour after reperfusion in ketamine and methylprednisolone groups, compared to saline (all P<0.05. In conclusion, immediate administration of ketamine after an ischaemia-reperfusion injury can alleviate pain and inflammation in the CPIP model and has potential to treat postischaemic pain.

  17. Dexmedetomidine attenuates neuropathic pain in chronic constriction injury by suppressing NR2B, NF-κB, and iNOS activation

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    Feng Liang

    2017-05-01

    Full Text Available The effective treatment of patients suffering from neuropathic pain remains challenging. Dexmedetomidine (DEX possesses anti-inflammatory activity. However, the role of DEX in neuropathic pain is still unclear. The aim of the present study was to examine DEX an α2-adrenoceptor agonist could improve pain hypersensitivity and reduce inflammatory in a chronic constriction injury (CCI model of the sciatic nerve in Sprague-Dawley rats. Dex was intrathecally administrated 1-h after operation. The paw mechanical withdrawal threshold (MWT and paw withdrawal thermal latency (PWTL were measured on day 1 before operation and on days 1, 7, 14 and 21 after operation, respectively. On day 21, all the rats were decapitated to collect the L4-6 segments of the spinal cord to examine IL-1, TNF-α, IL-6, NR2B, NF-κB, and iNOS mRNA levels using RT-PCR. The postoperative MWT and PWTL were significantly decreased in CCI, and DEX groups as compared to those before surgery and Sham group (P < 0.05. And DEX reversed this trend (P < 0.05. Interleukin 1 (IL-1, tumor necrosis factor α (TNF-α, IL-6 mRNA expression significantly increased postsurgery in CCI group as compared to that of Sham group (P < 0.05; DEX blocked increased IL-1, TNF-α, IL-6, N-methyl-D-aspartate (NMDA receptor 2B (NR2B, nuclear factor κB (NF-κB, and inducible isoform of nitric oxide synthase (iNOS mRNA levels (P < 0.05. DEX may alleviate neuropathic hypersensitivity and inflammation partially by inhibiting NR2B, NF-κB, and iNOS expression in the spinal cord of rats with neuropathic pain resulting from CCI of the sciatic nerve.

  18. Association between Severity of Tooth Wear and Dentinal Hypersensitivity

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    Ashok Ayer

    2016-11-01

    Full Text Available Background & Objectives: Tooth wear (attrition, abrasion, erosion, and abfraction is perceived globally as ever increasing problem. Several outcome of the tooth wear are hypersensitivity, esthetic problems, functional impairment, annoyance to the patient, and fracture of the tooth. Among these, the measurable and more commonly reported outcome is hypersensitivity to stimuli. Although dentin hypersensitivity is a common clinical condition and is generally reported by the patient after experiencing a sharp, short pain caused by one of the several different external stimuli, it is often inadequately understood. None of the scientific literature available till date attempted to establish the relationship between tooth wear and dentin hypersensitivity which could be a key factor in monitoring those patients.  The aim of the study was to estimate the association between severity of teeth wear and sensitivity in the patients with reported dentinal hypersensitivity.Materials & Methods: Fifty patients with dentin hypersensitivity were investigated for tooth wear. Tooth wear measured using exact tooth wear index and level of sensitivity to stimuli was recorded using a numerical rating scale. Results: Enamel wear at cervical region of teeth showed a positive correlation (p=.010, similarly, dentin wear at cervical region of teeth showed positive correlation and significant association (p<.001 with dentinal hypersensitivity.Conclusion: The observation supports a significant association between severities of tooth surface wear and dentinal hypersensitivity.

  19. Dentin Hypersensitivity: Recent Concepts in Management

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    Vijay Mantri

    2011-01-01

    Full Text Available Tooth sensitivity is a very common clinical presentation which can cause considerable concern for patients. Dentin hypersensitivity (DH is characterized by short sharp pain arising from exposed dentin in response to stimuli. The most widely accepted theory of how the pain occurs is Brannstrom′s hydrodynamic theory, fluid movement within the dentinal tubules. The condition generally involves the facial surfaces of teeth near the cervical aspect and is very common in premolars and canines. This condition is frequently encountered by dentists, periodontists, hygienists and dental therapists. Some dental professionals lack confidence in treating DH. The management of this condition requires a good understanding of the complexity of the problem, as well as the variety of treatments available. This review considers the etiopathogenesis, incidence, diagnosis, prevention and management of dentinal hypersensitivity. DH is diagnosed after elimination of other possible causes of the pain. Any treatment plan for DH should include identifying and eliminating predisposing etiologic factors. Professionals should appreciate the role causative factors play in localizing and initiating hypersensitive lesions. It is important to identify these factors so that prevention can be included in the treatment plan. Treatments can be self-administered by the patient at home or be applied by a dental professional in the dental office. At-home methods tend to be simple and inexpensive and can treat simultaneously generalized DH affecting many teeth Desensitizing treatment should be delivered systematically, beginning with prevention and at-home treatments. The latter may be supplemented with in-office modalities.

  20. The prevalence of dentin hypersensitivity in general dental practices in the northwest United States.

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    Cunha-Cruz, Joana; Wataha, John C; Heaton, Lisa J; Rothen, Marilynn; Sobieraj, Martin; Scott, JoAnna; Berg, Joel

    2013-03-01

    The prevalence of dentin hypersensitivity is uncertain, yet appropriate diagnosis and treatment of dentin hypersensitivity require accurate knowledge regarding its prevalence. The authors conducted a study to estimate the prevalence of dentin hypersensitivity in general dental practices and to investigate associated risk factors. The authors conducted a cross-sectional survey of 787 adult patients from 37 general dental practices within Northwest Practice-based Research Collaborative in Evidence-based DENTistry (PRECEDENT). Dentin hypersensitivity was diagnosed by means of participants' responses to a question regarding pain in their teeth and gingivae, and practitioner-investigators conducted a clinical examination to rule out alternative causes of pain. Participants recorded their pain level on a visual analog scale and the Seattle Scales in response to a one-second air blast. The authors used generalized estimating equation log-linear models to estimate the prevalence and the prevalence ratios. The prevalence of dentin hypersensitivity was 12.3 percent; patients with hypersensitivity had, on average, 3.5 hypersensitive teeth. The prevalence of dentin hypersensitivity was higher among 18- to 44-year olds than among participants 65 years or older; it also was higher in women than in men, in participants with gingival recession than in those without gingival recession and in participants who underwent at-home tooth whitening than in those who did not. Hypersensitivity was not associated with obvious occlusal trauma, noncarious cervical lesions or aggressive toothbrushing habits. One in eight participants from general practices had dentin hypersensitivity, which was a chronic condition causing intermittent, low-level pain. Patients with hypersensitivity were more likely to be younger, to be female and to have a high prevalence of gingival recession and at-home tooth whitening. Given dentin hypersensitivity's prevalence, clinicians should diagnose it only after

  1. Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.

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    Song, Zhen-Peng; Xiong, Bing-Rui; Guan, Xue-Hai; Cao, Fei; Manyande, Anne; Zhou, Ya-Qun; Zheng, Hua; Tian, Yu-Ke

    2016-06-01

    To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

  2. Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats.

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    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

  3. Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK

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    Shao-Jun Wang

    2012-01-01

    Full Text Available Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36 and Shangjuxu (ST37 in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.

  4. Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation.

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    Sun, Rao; Zhang, Wei; Bo, Jinhua; Zhang, Zuoxia; Lei, Yishan; Huo, Wenwen; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

    2017-03-06

    The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. The experiments were conducted in a rat model of single prolonged stress (SPS), an established model of PTSD-pain comorbidity. We found that SPS exposure produced persistent mechanical allodynia. Immunohistochemical and enzyme-linked immuno sorbent assay analysis showed that SPS also induced elevated activation of glia cells (including microglia and astrocytes) and accumulation of pro-inflammatory cytokines in spinal cord. In another experiment, we found that intrathecal injection of PHA-543613, a selective α7 nAchR agonist, attenuated the SPS-evoked allodynia in a dose dependent manner. However, this anti-hyperalgesic effect was blocked by pretreatment with methyllycaconitine (MLA), a selective α7 nAchR antagonist. Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain

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    Tillu Dipti V

    2012-01-01

    Full Text Available Abstract Background Despite advances in our understanding of basic mechanisms driving post-surgical pain, treating incision-induced pain remains a major clinical challenge. Moreover, surgery has been implicated as a major cause of chronic pain conditions. Hence, more efficacious treatments are needed to inhibit incision-induced pain and prevent the transition to chronic pain following surgery. We reasoned that activators of AMP-activated protein kinase (AMPK may represent a novel treatment avenue for the local treatment of incision-induced pain because AMPK activators inhibit ERK and mTOR signaling, two important pathways involved in the sensitization of peripheral nociceptors. Results To test this hypothesis we used a potent and efficacious activator of AMPK, resveratrol. Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity. Interleukin-6 (IL-6 is thought to play an important role in incision-induced pain and resveratrol potently inhibited IL-6-mediated signaling to ERK in sensory neurons and blocked IL-6-mediated allodynia in vivo through a local mechanism of action. Using a model of incision-induced allodynia in mice, we further demonstrate that local injection of resveratrol around the surgical wound strongly attenuates incision-induced allodynia. Intraplantar IL-6 injection and plantar incision induces persistent nociceptive sensitization to PGE2 injection into the affected paw after the resolution of allodynia to the initial stimulus. We further show that resveratrol treatment at the time of IL-6 injection or plantar incision completely blocks the development of persistent nociceptive sensitization consistent with the blockade of a transition to a chronic pain state by resveratrol treatment. Conclusions These results highlight the importance of signaling

  6. Pharmacological Modulation of the Mitochondrial Electron Transport Chain in Paclitaxel-Induced Painful Peripheral Neuropathy.

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    Griffiths, Lisa A; Flatters, Sarah J L

    2015-10-01

    Paclitaxel is an effective first-line chemotherapeutic with the major dose-limiting side effect of painful neuropathy. Mitochondrial dysfunction and oxidative stress have been implicated in paclitaxel-induced painful neuropathy. Here we show the effects of pharmacological modulation of mitochondrial sites that produce reactive oxygen species using systemic rotenone (complex I inhibitor) or antimycin A (complex III inhibitor) on the maintenance and development of paclitaxel-induced mechanical hypersensitivity in adult male Sprague Dawley rats. The maximally tolerated dose (5 mg/kg) of rotenone inhibited established paclitaxel-induced mechanical hypersensitivity. However, some of these inhibitory effects coincided with decreased motor coordination; 3 mg/kg rotenone also significantly attenuated established paclitaxel-induced mechanical hypersensitivity without any motor impairment. The maximally tolerated dose (.6 mg/kg) of antimycin A reversed established paclitaxel-induced mechanical hypersensitivity without any motor impairment. Seven daily doses of systemic rotenone or antimycin A were given either after paclitaxel administration or before and during paclitaxel administration. Rotenone had no significant effect on the development of paclitaxel-induced mechanical hypersensitivity. However, antimycin A significantly inhibited the development of paclitaxel-induced mechanical hypersensitivity when given before and during paclitaxel administration but had no effect when given after paclitaxel administration. These studies provide further evidence of paclitaxel-evoked mitochondrial dysfunction in vivo, suggesting that complex III activity is instrumental in paclitaxel-induced pain. This study provides further in vivo evidence that mitochondrial dysfunction is a key contributor to the development and maintenance of chemotherapy-induced painful neuropathy. This work also indicates that selective modulation of the electron transport chain can induce antinociceptive

  7. Neuropathic pain and cytokines: current perspectives

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    Clark AK

    2013-11-01

    Full Text Available Anna K Clark, Elizabeth A Old, Marzia Malcangio Wolfson Centre for Age Related Diseases, King's College London, London, UK Abstract: Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention. Keywords: anti-inflammatory cytokines, proinflammatory cytokines, microglia, astrocytes, first pain synapse

  8. Chronic hypersensitivity pneumonitis.

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    Pereira, Carlos Ac; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

    2016-01-01

    Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary.

  9. Double blind randomized control trial to evaluate the efficacy of ketoprofen patch to attenuate pain during venous cannulation

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    Kumar, Sanjay; Sanjeev, Omprakash; Agarwal, Anil; Shamshery, Chetna; Gupta, Rakhi

    2018-01-01

    Background Venipuncture pain is an uncomfortable suffering to the patient. It creates anxiety, fear and dissatisfaction. The ketoprofen transdermal patch is a proven treatment for musculoskeletal and arthritic pain. We planned this study to evaluate the efficacy of the ketoprofen patch to reduce venipuncture pain. Methods Two hundred adult patients, aged 18–60 years, of either sex, ASA grade I or II, were enrolled. Presuming that therapy would decrease venipuncture pain by 30%, a power calcul...

  10. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

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    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity. © 2015 The Authors. European Journal of Neuroscience published by Federation of

  11. Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ya-Qiong [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Jin, Shao-Ju [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Luohe Medical College, Luohe 462002, Henan Province (China); Liu, Ning [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Li, Yu-Xiang [College of Nursing, Ningxia Medical University, Yinchuan 750004 (China); Zheng, Jie [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Ma, Lin [Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004 (China); Du, Juan; Zhou, Ru [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Zhao, Cheng-Jun [Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750000 (China); Niu, Yang [Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004 (China); Sun, Tao [Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004 (China); Yu, Jian-Qiang, E-mail: Yujq910315@163.com [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Luohe Medical College, Luohe 462002, Henan Province (China)

    2014-09-05

    Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.

  12. Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

    International Nuclear Information System (INIS)

    Xu, Ya-Qiong; Jin, Shao-Ju; Liu, Ning; Li, Yu-Xiang; Zheng, Jie; Ma, Lin; Du, Juan; Zhou, Ru; Zhao, Cheng-Jun; Niu, Yang; Sun, Tao; Yu, Jian-Qiang

    2014-01-01

    Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway

  13. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  14. Perineural pretreatment of bee venom attenuated the development of allodynia in the spinal nerve ligation injured neuropathic pain model; an experimental study.

    Science.gov (United States)

    Koh, Won Uk; Choi, Seong Soo; Lee, Jong Hyuk; Lee, So Hee; Lee, Sun Kyung; Lee, Yoon Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

    2014-11-04

    Diluted bee venom (BV) is known to have anti-nociceptive and anti-inflammatory effects. We therefore assessed whether perineural bee venom pretreatment could attenuate the development of neuropathic pain in the spinal nerve ligation injured animal model. Neuropathic pain was surgically induced in 30 male Sprague Dawley rats by ligation of the L5 and L6 spinal nerves, with 10 rats each treated with saline and 0.05 and 0.1 mg BV. Behavioral testing for mechanical, cold, and thermal allodynia was conducted on postoperative days 3 to 29. Three rats in each group and 9 sham operated rats were sacrificed on day 9, and the expression of transient receptor potential vanilloid type 1 (TRPV1), ankyrin type 1 (TRPA1), and melastatin type 8 (TRPM8) receptors in the ipsilateral L5 dorsal root ganglion was analyzed. The perineural administration of BV to the spinal nerves attenuated the development of mechanical, thermal, and cold allodynia, and the BV pretreatment reduced the expression of TRPV1, TRPA1, TRPM8 and c - Fos in the ipsilateral dorsal root ganglion. The current study demonstrates that the perineural pretreatment with diluted bee venom before the induction of spinal nerve ligation significantly suppresses the development of neuropathic pain. Furthermore, this bee venom induced suppression was strongly related with the involvement of transient receptor potential family members.

  15. Cutaneous and systemic hypersensitivity reactions to metallic implants

    DEFF Research Database (Denmark)

    Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

    2011-01-01

    Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous....... However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis...

  16. Food hypersensitivity by inhalation

    Directory of Open Access Journals (Sweden)

    Bahna Sami L

    2009-02-01

    Full Text Available Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.

  17. Chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Pereira CA

    2016-09-01

    Full Text Available Carlos AC Pereira,1 Andréa Gimenez,2 Lilian Kuranishi,2 Karin Storrer 2 1Interstitial Lung Diseases Program, 2Pulmonology Postgraduate, Federal University of São Paulo, São Paulo, Brazil Abstract: Hypersensitivity pneumonitis (HSP is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. Keywords: interstitial lung diseases, extrinsic allergic alveolitis, diffuse lung disease, lung immune response, HRCT, farmers lung

  18. The scientific rationale and development of an optimized dentifrice for the treatment of dentin hypersensitivity.

    Science.gov (United States)

    Tavss, Edward A; Fisher, Steven W; Campbell, Shannon; Bonta, Yolanda; Darcy-Siegel, Joann; Blackwell, Bernie L; Volpe, Anthony R; Miller, Steven E

    2004-02-01

    To describe the development of a new dentin hypersensitivity treatment, Colgate Sensitive Maximum Strength dentifrice, containing 5% potassium nitrate as the anti-hypersensitivity active agent. The objective was to develop a home-use hypersensitivity dentifrice that would be superior to the market leader, improving on what is available, which also contains 5% potassium nitrate as the anti-hypersensitivity active agent. In vivo (clinicals, taste evaluation and rat caries), in vitro (potassium flux) and analytical (rheology, dispensed volume, scanning electron microscopy, electron scanning chemical analysis and radioactive dentin abrasion) methods were performed. The objective was accomplished with the development of a new activated silica technology that resulted in enhanced potassium ion activity. In vitro documentation, supported by clinical studies, demonstrated that the resulting formula is more effective than the market leader for relief of hypersensitivity pain. Fast pain relief in less than 2 weeks and long-lasting protection against pain with regular use have also been clinically documented. Furthermore, FDA-required in vivo and in vitro studies indicate that this formula, which contains 0.45% stannous fluoride (1100 ppm fluoride) as the anti-caries active agent, is effective against caries. Good taste, acceptable rheology, acceptable abrasivity, and cosmetic and chemical stability have all been engineered into this unique dentin hypersensitivity treatment. In summary, a highly efficacious consumer friendly treatment for dentin hypersensitivity has been developed.

  19. Suppression of Pax2 attenuates allodynia and hyperalgesia through ET-1-ETAR-NFAT5 signaling in a rat model of neuropathic pain.

    Science.gov (United States)

    Tai, Lydia Wai; Pan, Zhiqiang; Sun, Liting; Li, Haobo; Gu, Pan; Wong, Stanley Sau Ching; Chung, Sookja K; Cheung, Chi Wai

    2018-05-27

    Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, may regulate ET-1. Therefore, we hypothesized that ET-1 axis may be regulated by Pax2 or NFAT5 in the development of neuropathic pain. After partial sciatic nerve ligation (pSNL), rats displayed allodynia and hyperalgesia, which was associated with increased mRNA and protein expressions of spinal Pax2, NFAT5, and mRNA levels of ET-1 and ETAR, but not ETBR. Knockdown of Pax2 or NFAT5 with siRNA, or inhibition of ETAR with BQ-123 attenuated pSNL-induced pain-like behaviors. At molecular level, Pax2 siRNA, but not NFAT5 siRNA, downregulated ET-1 and ETAR, while ETAR inhibitor reduced NFAT5, indicating Pax2 in the upstream of ET-1 axis with NFAT5 in the downstream. Further, suppression of Pax2 (inhibiting ET-1) or impairment of ET-1 signaling (inhibition of ETAR and/or decrease of NFAT5) deactivated mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, supporting the significance of functional regulation of ET-1 axis in neuropathic pain signaling. These findings demonstrate that Pax2 targeting ET-1-ETAR-NFAT5 is a novel regulatory mechanism underlying neuropathic pain. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Metal hypersensitivity after knee arthroplasty: fact or fiction?

    Science.gov (United States)

    Innocenti, Massimo; Vieri, Berti; Melani, Tommaso; Paoli, Tommaso; Carulli, Christian

    2017-06-07

    Hypersensitivity to metals in the general population has an incidence of about 15%, and in rising also for the higher number of joint replacements in the last decades. Total Knee Arthroplasty (TKA) represents the most performed orthopaedic procedure during last years, and it seems to be particularly associated with sensitization after surgery. On the other hand, there is a rising amount of patients with painful but well implanted and functioning TKAs: in certain cases, after the exclusion of the most frequent causes of failure, a condition of hypersensitivity may be found, and a revision with anallergic implants is mandatory. The present study is a review of the potential problems related to hypersensitivity in TKA, its possible diagnostic procedures, and the surgical options to date available. Medical history, patch testing, and other specific laboratory assays are useful to assess a status of metals hypersensitivity before surgery in subjects undergoing a knee replacement, or even after TKA in patients complaining pain in otherwise well implanted and aligned prostheses. However, few groups worlwide deal with such condition, and all proposed diagnostic protocols may be considered still today conjectural. On the other hand, these represent the most updated knowledge of this condition, and may be useful for both the patient and the orthopaedic surgeon. Once assessed a possible or ascertained allergy to metals, several options are available for primary andr revision knee surgery, in order to avoid the risk of hypersensitivity. A review of the recent publications on this topic and an overview of the related aspects has been made to understand a condition to date considered negligible. Hypersensitivity to metals has not to be nowadays considered a "fiction", but rather a possible preoperative risk or a postoperative cause of failure of TKA. Crucial is the information of patients and the medical history, associated in suspect cases to laboratory testings. Today in the

  1. Modulation of Cervical Facet Joint Nociception and Pain Attenuates Physical and Psychological Features of Chronic Whiplash: A Prospective Study.

    Science.gov (United States)

    Smith, Ashley Dean; Jull, Gwendolen; Schneider, Geoff M; Frizzell, Bevan; Hooper, Robert A; Sterling, Michele

    2015-09-01

    To investigate changes in clinical (physical and psychological) features of individuals with chronic whiplash-associated disorder who had previously undergone cervical radiofrequency neurotomy at the time point when the effects of radiofrequency neurotomy had dissipated and pain returned. Prospective cohort observational trial of consecutive patients. Tertiary spinal intervention centre in Calgary, Alberta, Canada. A total of 53 consecutive individuals with chronic whiplash-associated disorder. Individuals underwent radiofrequency neurotomy and were assessed before radiofrequency neurotomy, at 1 and 3 months postprocedure, and then after the return of pain (approximately 10 months postprocedure). Quantitative sensory tests (pressure; thermal pain thresholds; brachial plexus provocation test), nociceptive flexion reflex, and motor function (cervical range of movement; craniocervical flexion test) were measured. Self-reported disability, psychological distress, pain catastrophization, and posttraumatic stress disorder symptoms also were measured. Upon the return of pain after radiofrequency neurotomy, levels of disability increased (P .22). There were no significant changes in pressure hyperalgesia (P > .054) or craniocervical flexion test performance (P > .07) after the return of pain. Psychological distress and pain catastrophizing increased significantly after the return of pain (P .13). However, there was no difference in number or severity of posttraumatic stress symptoms after the return of pain (P > .30). Physical and psychological features of chronic whiplash-associated disorder are modulated dynamically with cervical radiofrequency neurotomy. These findings indicate that peripheral nociception is involved in the manifestations of chronic whiplash-associated disorder in this cohort of individuals. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  2. Metal Hypersensitivity in Orthodontic Patients

    Directory of Open Access Journals (Sweden)

    Sandhya Maheshwari Sanjeev K

    2015-06-01

    Full Text Available Orthodontic treatment of individuals with metal hypersensitivity is a matter of concern for the orthodontist. Orthodontic appliances contain metals like Nickel, Cobalt and Chromium etc. Metals may cause allergic reactions and are known as allergens. Reaction to these metals is due to biodegradation of metals in the oral cavity. This may lead to the formation of corrosion products and their exposure to the patient. Nickel is the most common metal to cause hypersensitivity reaction. Chromium ranks second among the metals, known to trigger allergic reactions. The adverse biological reactions to these metals may include hypersensitivity, dermatitis and asthma. In addition, a significant carcinogenic and mutagenic potential has been demonstrated. The orthodontist must be familiar with the best possible alternative treatment modalities to provide the safest, most effective care possible in these cases. The present article focuses on the issue of metal hypersensitivity and its management in orthodontic

  3. Resveratrol attenuates bone cancer pain through regulating the expression levels of ASIC3 and activating cell autophagy.

    Science.gov (United States)

    Zhu, Haili; Ding, Jieqiong; Wu, Ji; Liu, Tingting; Liang, Jing; Tang, Qiong; Jiao, Ming

    2017-11-01

    Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4-L6 dorsal root ganglion. Then, resveratrol, which was intraperitoneally injected into the BCP rats on post-operative Day 21, dose-dependently increased the paw withdrawal threshold of BCP rats, reversed the pain behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH-SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in a dose- and time-dependent manner. Meanwhile, resveratrol also had an antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3-transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK-SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats, SIRT1 and LC3-II were also down-regulated. These findings provide new evidence for the use of resveratrol as a therapeutic treatment during BCP states. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis.

    Science.gov (United States)

    Zhang, Liping; Kline, Robert H; McNearney, Terry A; Johnson, Michael P; Westlund, Karin N

    2014-11-17

    Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in several studies with inflammatory and neuropathic preclinical pain models. In this study, the analgesic efficacy of a novel, highly selective CB2 receptor agonist, LY3038404 HCl, is investigated in a chronic pancreatitis pain model, induced with an alcohol/high fat (AHF) diet. Rats fed the AHF diet developed visceral pain-like behaviors detectable by week 3 and reached a maximum at week 5 that persists as long as the diet is maintained. Rats with AHF induced chronic pancreatitis were treated with LY3038404 HCl (10 mg/kg, orally, twice a day for 9 days). The treated animals demonstrated significantly alleviated pain related behaviors after 3 days of dosing, including increased paw withdrawal thresholds (PWT), prolonged abdominal withdrawal latencies (ABWL), and decreased nocifensive responses to noxious 44°C hotplate stimuli. Terminal histological analysis of pancreatic tissue sections from the AHF chronic pancreatitis animals demonstrated extensive injury, including a global pancreatic gland degeneration (cellular atrophy), vacuolization (fat deposition), and fibrosis. After the LY3038404 HCl treatment, pancreatic tissue was significantly protected from severe damage and fibrosis. LY3038404 HCl affected neither open field exploratory behaviors nor dark/light box preferences as measures

  5. MiR-30b Attenuates Neuropathic Pain by Regulating Voltage-Gated Sodium Channel Nav1.3 in Rats

    Directory of Open Access Journals (Sweden)

    Songxue Su

    2017-05-01

    Full Text Available Nav1.3 is a tetrodotoxin-sensitive isoform among voltage-gated sodium channels that are closely associated with neuropathic pain. It can be up-regulated following nerve injury, but its biological function remains uncertain. MicroRNAs (miRNAs are endogenous non-coding RNAs that can regulate post-transcriptional gene expression by binding with their target mRNAs. Using Target Scan software, we discovered that SCN3A is the major target of miR-30b, and we then determined whether miR-30b regulated the expression of Nav1.3 by transfecting miR-30b agomir through the stimulation of TNF-α or by transfecting miR-30b antagomir in primary dorsal root ganglion (DRG neurons. The spinal nerve ligation (SNL model was used to determine the contribution of miR-30b to neuropathic pain, to evaluate changes in Nav1.3 mRNA and protein expression, and to understand the sensitivity of rats to mechanical and thermal stimuli. Our results showed that miR-30b agomir transfection down-regulated Nav1.3 mRNA stimulated with TNF-α in primary DRG neurons. Moreover, miR-30b overexpression significantly attenuated neuropathic pain induced by SNL, with decreases in the expression of Nav1.3 mRNA and protein both in DRG neurons and spinal cord. Activation of Nav1.3 caused by miR-30b antagomir was identified. These data suggest that miR-30b is involved in the development of neuropathic pain, probably by regulating the expression of Nav1.3, and might be a novel therapeutic target for neuropathic pain.Perspective: This study is the first to explore the important role of miR-30b and Nav1.3 in spinal nerve ligation-induced neuropathic pain, and our evidence may provide new insight for improving therapeutic approaches to pain.

  6. Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: an exploratory study in chronic whiplash patients.

    Science.gov (United States)

    Schneider, Geoff M; Smith, Ashley D; Hooper, Allen; Stratford, Paul; Schneider, Kathryn J; Westaway, Michael D; Frizzell, Bevan; Olson, Lee

    2010-02-09

    The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD) and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity). Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB) procedure in the cervical spine. Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST) consisting of pressure pain thresholds (PPT's) and cold pain thresholds (CPT's). In patients with chronic WAD (n = 18), the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18) was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. At baseline, PPT's were decreased at all three sites in the WAD group (p < 0.001). Cold pain thresholds were increased in the cervical spine in the WAD group (p < 0.001). Post-MBB, the WAD group showed significant increases in PPT's at all sites (p < 0.05), and significant decreases in CPT's at the cervical spine (p < 0.001). The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical

  7. Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

    OpenAIRE

    Feng, Bin; La, Jun-ho; Schwartz, Erica S.; Tanaka, Takahiro; McMurray, Timothy P.; Gebhart, G. F.

    2012-01-01

    Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the di...

  8. Plant derived aporphinic alkaloid S-(+-dicentrine induces antinociceptive effect in both acute and chronic inflammatory pain models: evidence for a role of TRPA1 channels.

    Directory of Open Access Journals (Sweden)

    Deise Prehs Montrucchio

    Full Text Available S-(+-dicentrine is an aporphinic alkaloid found in several plant species, mainly from Lauraceae family, which showed significant antinociceptive activity in an acute model of visceral pain in mice. In this work, we extended the knowledge on the antinociceptive properties of S-(+-dicentrine and showed that this alkaloid also attenuates mechanical and cold hypersensitivity associated with cutaneous inflammation induced by Complete Freund's Adjuvant in mice. Given orally, S-(+-dicentrine (100 mg/kg reversed CFA-induced mechanical hypersensitivity, evaluated as the paw withdrawal threshold to von Frey hairs, and this effect lasted up to 2 hours. S-(+-dicentrine also reversed CFA-induced cold hypersensitivity, assessed as the responses to a drop of acetone in the injured paw, but did not reverse the heat hypersensitivity, evaluated as the latency time to paw withdrawal in the hot plate (50°C. Moreover, S-(+-dicentrine (100 mg/kg, p.o. was effective in inhibit nociceptive responses to intraplantar injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by capsaicin, a TRPV1 activator. When administered either by oral or intraplantar routes, S-(+-dicentrine reduced the licking time (spontaneous nociception and increased the latency time to paw withdrawal in the cold plate (cold hypersensitivity, both induced by the intraplantar injection of cinnamaldehyde. Taken together, our data adds information about antinociceptive properties of S-(+-dicentrine in inflammatory conditions, reducing spontaneous nociception and attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent mechanism. It also indicates that S-(+-dicentrine might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain, especially under inflammatory conditions.

  9. Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Bo Hu

    2018-05-01

    Full Text Available Background/Aims: Paeoniflorin (PF is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund’s complete adjuvant (CFA-induced inflammatory pain and explore the underlying molecular mechanism. Methods: An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1β and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot. Results: PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro. Conclusion: These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.

  10. The inhibition of nitric oxide-activated poly(ADP-ribose) synthetase attenuates transsynaptic alteration of spinal cord dorsal horn neurons and neuropathic pain in the rat.

    Science.gov (United States)

    Mao, J; Price, D D; Zhu, J; Lu, J; Mayer, D J

    1997-09-01

    Transsynaptic alteration of spinal cord dorsal horn neurons characterized by hyperchromatosis of cytoplasm and nucleoplasm (so-called 'dark' neurons) occurs in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the common sciatic nerve. The incidence of dark neurons in CCI rats has been proposed to be mediated by glutamate-induced neurotoxicity. In the present study, we examined whether the inhibition of the nitric oxide (NO)-activated poly(ADP-ribose) synthetase (PARS), a nuclear enzyme critical to glutamate-induced neurotoxicity, would both reduce the incidence of dark neurons and attenuate behavioral manifestations of neuropathic pain in CCI rats. Dark neurons were observed bilaterally (with ipsilateral predominance) within the spinal cord dorsal horn, particularly in laminae I-II, of rats 8 days after unilateral sciatic nerve ligation as compared to sham operated rats. The number of dark neurons in the dorsal horn was dose-dependently reduced in CCI rats receiving once daily intrathecal (i.t.) treatment with the PARS inhibitor benzamide (200 or 400 nmol, but not 100 nmol benzamide or saline) for 7 days. Consistent with the histological improvement, thermal hyperalgesia, mechanical hyperalgesia, and low threshold mechano-allodynia also were reliably reduced in CCI rats treated with either 200 or 400 nmol benzamide. Neither dark neurons nor neuropathic pain behaviors were reliably affected by i.t. administration of either 800 nmol novobiocin (a mono(ADP-ribose) synthetase) or 800 nmol benzoic acid (the backbone structure of benzamide), indicating a selective effect of benzamide. Intrathecal treatment with an NO synthase inhibitor NG-nitro-L-arginine methyl ester (40 nmol, but not its inactive D-isomer) utilizing the same benzamide treatment regimen resulted in similar reductions of both dark neurons and neuropathic pain behaviors in CCI rats. These results provide, for the first time, in vivo evidence indicating that benzamide is

  11. Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: An exploratory study in chronic whiplash patients

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    Stratford Paul

    2010-02-01

    Full Text Available Abstract Background The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity. Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB procedure in the cervical spine. Methods Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST consisting of pressure pain thresholds (PPT's and cold pain thresholds (CPT's. In patients with chronic WAD (n = 18, the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18 was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. Results At baseline, PPT's were decreased at all three sites in the WAD group (p Conclusions The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical zygapophyseal joints.

  12. Pain

    OpenAIRE

    H.W. Snyman

    1980-01-01

    The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  13. Pain

    Directory of Open Access Journals (Sweden)

    H.W. Snyman

    1980-09-01

    Full Text Available The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  14. Selective Cathepsin S Inhibition with MIV-247 Attenuates Mechanical Allodynia and Enhances the Antiallodynic Effects of Gabapentin and Pregabalin in a Mouse Model of Neuropathic Pain.

    Science.gov (United States)

    Hewitt, Ellen; Pitcher, Thomas; Rizoska, Biljana; Tunblad, Karin; Henderson, Ian; Sahlberg, Britt-Louise; Grabowska, Urszula; Classon, Björn; Edenius, Charlotte; Malcangio, Marzia; Lindström, Erik

    2016-09-01

    Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation. MIV-247, gabapentin, or pregabalin were administered alone or in combination via oral gavage. Mechanical allodynia was assessed using von Frey hairs. Neurobehavioral side effects were evaluated by assessing beam walking. MIV-247, gabapentin, and pregabalin concentrations in various tissues were measured. Oral administration of MIV-247 (100-200 µmol/kg) dose-dependently attenuated mechanical allodynia by up to approximately 50% reversal when given as a single dose or when given twice daily for 5 days. No behavioral deficits were observed at any dose of MIV-247 tested. Gabapentin (58-350 µmol/kg) and pregabalin (63-377 µmol/kg) also inhibited mechanical allodynia with virtually complete reversal at the highest doses tested. The minimum effective dose of MIV-247 (100 µmol/kg) in combination with the minimum effective dose of pregabalin (75 µmol/kg) or gabapentin (146 µmol/kg) resulted in enhanced antiallodynic efficacy without augmenting side effects. A subeffective dose of MIV-247 (50 µmol/kg) in combination with a subeffective dose of pregabalin (38 µmol/kg) or gabapentin (73 µmol/kg) also resulted in substantial efficacy. Plasma levels of MIV-247, gabapentin, and pregabalin were similar when given in combination as to when given alone. Cathepsin S inhibition with MIV-247 exerts significant antiallodynic efficacy alone, and also enhances the effect of gabapentin and pregabalin without increasing side effects or inducing pharmacokinetic interactions. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Olea Europea-derived phenolic products attenuate antinociceptive morphine tolerance: an innovative strategic approach to treat cancer pain.

    Science.gov (United States)

    Muscoli, C; Lauro, F; Dagostino, C; D'Agostino, C; Ilari, S; Giancotti, L A; Gliozzi, M; Costa, N; Carresi, C; Musolino, V; Casale, F; Ventrice, D; Oliverio, M; Oliverio, E; Palma, E; Nisticò, S; Nistico', S; Procopio, A; Rizzo, M; Mollace, V

    2014-01-01

    Morphine and related opioid drugs are currently the major drugs for severe pain. Their clinical utility is limited in the management of severe cancer pain due to the rapid development of tolerance. Restoring opioid efficacy is therefore of great clinical importance. A great body of evidence suggests the key role of free radicals and posttranslational modulation in the development of tolerance to the analgesic activity of morphine. Epidemiological studies have shown a relationship between the Mediterranean diet and a reduced incidence of pathologies such as coronary heart disease and cancer. A central hallmark of this diet is the high consumption of virgin olive oil as the main source of fat which contains antioxidant components in the non-saponifiable fraction, including phenolic compounds absent in seed oils. Here, we show that in a rodent model of opiate tolerance, removal of the free radicals with phenolic compounds of olive oil such as hydroxytyrosol and oleuropein reinstates the analgesic action of morphine. Chronic injection of morphine in mice led to the development of tolerance and this was associated with increased nitrotyrosin and malondialdehyde (MDA) formation together with nitration and deactivation of MnSOD in the spinal cord. Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine tolerance by inhibiting nitration and MDA formation and replacing the MnSOD activity. The phenolic fraction of virgin olive oil exerts antioxidant activities in vivo and free radicals generation occurring during chronic morphine administration play a crucial role in the development of opioid tolerance. Our data suggest novel therapeutic approach in the management of chronic cancer pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance.

  16. Ethanolic extract of Aconiti Brachypodi Radix attenuates nociceptive pain probably via inhibition of voltage-dependent Na⁺ channel.

    Science.gov (United States)

    Ren, Wei; Yuan, Lin; Li, Jun; Huang, Xian-Ju; Chen, Su; Zou, Da-Jiang; Liu, Xiangming; Yang, Xin-Zhou

    2012-01-01

    Aconiti Brachypodi Radix, belonging to the genus of Aconitum (Family Ranunculaceae), are used clinically as anti-rheumatic, anti-inflammatory and anti-nociceptive in traditional medicine of China. However, its mechanism and influence on nociceptive threshold are unknown and need further investigation. The analgesic effects of ethanolic extract of Aconiti Brachypodi Radix (EABR) were thus studied in vivo and in vitro. Three pain models in mice were used to assess the effect of EABR on nociceptive threshold. In vitro study was conducted to clarify the modulation of the extract on the tetrodotoxin-sensitive (TTX-S) sodium currents in rat's dorsal root ganglion (DRG) neurons using whole-cell patch clamp technique. The results showed that EABR (5-20 mg/kg, i.g.) could produce dose-dependent analgesic effect on hot-plate tests as well as writhing response induced by acetic acid. In addition, administration of 2.5-10 mg/kg EABR (i.g.) caused significant decrease in pain responses in the first and second phases of formalin test without altering the PGE₂ production in the hind paw of the mice. Moreover, EABR (10 µg/ml -1 mg/ml) could suppress TTX-S voltage-gated sodium currents in a dose-dependent way, indicating the underlying electrophysiological mechanism of the analgesic effect of the folk plant medicine. Collectively, our results indicated that EABR has analgesic property in three pain models and useful influence on TTX-S sodium currents in DRG neurons, suggesting that the interference with pain messages caused by the modulation of EABR on TTX-S sodium currents in DRG neurones may explain some of its analgesic effect.

  17. TO STUDY EFFECT OF GABAPENTIN ON ATTENUATION OF PRESSOR RESPONSE TO DIRECT LARYNGOSCOPY AND TRACHEAL INTUBATION AND ON PERIOPERATIVE PAIN

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    Sarita Chandapet

    2017-05-01

    Full Text Available BACKGROUND Endotracheal intubation was first described by Rowbotham and Magill in 1921. 1 In 1940 Reid and Brace first described hemodynamic response to Laryngoscopy and Intubation due to Noxious stimuli. 2 The circulatory responses to laryngeal and tracheal stimulation are due to sympathoadrenal stimulation. 3 Laryngoscopy and Tracheal Intubation induces changes in circulating Catecholamine levels significantly. Norepinephrine, Epinephrine and Dopamine levels rise, but the raise in Norepinephrine levels is consistently associated with elevation of Blood pressure and Heart rate. 4 Even though the elevation in Blood pressure and Heart rate due to Laryngoscopy and Intubation are brief, they may have detrimental effects in high risk patients including Myocardial Infarction, Cardiac failure, Intracranial haemorrhage and increases in Intracranial pressure. 5 Many strategies have been advocated to minimize these hemodynamic adverse responses and aimed at different levels of the reflex arc. 6 Block of the peripheral sensory receptors and afferent input is by topical application and infiltration of Local Anaesthetic to Superior laryngeal nerve. Block of central mechanism of integration and sensory input by drugs like Fentanyl, Morphine etc. Block of efferent pathway and effector sites IV Lignocaine, Beta blockers, Calcium channel blockers, Hydralazine etc. No single drug or technique is satisfactory. The aim of this study is to evaluate the efficacy of Gabapentin in attenuating hemodynamic response to laryngoscopy and intubation in a placebo controlled double blind study. MATERIALS AND METHODS A clinical comparative study of attenuation of sympathetic response to laryngoscopy and intubation was done in 150 patients posted for elective surgery divided into two groups and were randomly allocated Group 1 – placebo capsules with sugar and Group 2 – Gabapentin 300 mg capsules. Heart rate, systolic, diastolic blood pressure, mean arterial pressure were

  18. The periodontal pain paradox: Difficulty on pain assesment in dental patients (The periodontal pain paradox hypothesis

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    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

  19. Morus alba L. Stem Extract Attenuates Pain and Articular Cartilage Damage in the Anterior Cruciate Ligament Transection-Induced Rat Model of Osteoarthritis.

    Science.gov (United States)

    Khunakornvichaya, Arada; Lekmeechai, Sujinna; Pham, Phi Phuong; Himakoun, Wanwisa; Pitaksuteepong, Tasana; Morales, Noppawan Phumala; Hemstapat, Warinkarn

    2016-01-01

    This study was designed to investigate the anti-nociceptive effect of Morus alba stem extract as well as its cartilage protective effect in the anterior cruciate ligament transection (ACLT)-induced rat model of osteoarthritis (OA). The anti-nociceptive effect of this plant extract was determined by measuring hind limb weight bearing, while the severity of cartilage damage to the knee joints was evaluated using the modified Mankin grading system. Oral administration of M. alba stem extract (56 and 560 mg/kg) significantly attenuated joint pain as indicated by a significant (p alba stem extract at 56 and 560 mg/kg when compared to those of the vehicle-treated OA-induced group. In addition, a significant improvement in the Mankin score was also observed in rats treated with 560 mg/kg M. alba stem extract, which was in agreement with its pain-relieving effect. The results showed that M. alba stem extract exhibited an anti-nociceptive effect as well as cartilage protection in the ACLT-induced rat model of OA, supporting its potential use as a therapeutic treatment for OA. © 2016 S. Karger AG, Basel.

  20. 355-nm hypersensitization of optical fibers

    NARCIS (Netherlands)

    Canagasabey, A.; Canning, J.; Groothoff, N.

    2003-01-01

    A study is presented on 355-nm hypersensitization of optical fibers. It is found that the intrinsic 244-nm photosensitivity of boron-codoped germanosilicate optical fibers is enhanced by 355-nm hypersensitization. Hypersensitization through standard polymer coating is also demonstrated.

  1. Duloxetine and 8-OH-DPAT, but not fluoxetine, reduce depression-like behaviour in an animal model of chronic neuropathic pain.

    Science.gov (United States)

    Hu, Bing; Doods, Henri; Treede, Rolf-Detlef; Ceci, Angelo

    2016-04-21

    The current study assessed whether antidepressant and/or antinociceptive drugs, duloxetine, fluoxetine as well as (±)-8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), are able to reverse depression-like behaviour in animals with chronic neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve in rats was selected as neuropathic pain model. Mechanical hypersensitivity and depression-like behaviour were evaluated 4 weeks after surgery by "electronic algometer" and forced swimming test (FST), which measured the time of immobility, and active behaviours climbing and swimming. The selective noradrenergic and serotonergic uptake blocker duloxetine (20mg/kg) and the selective 5-HT1A agonist 8-OH-DPAT (0.5mg/kg) significantly reversed both mechanical hypersensitivity and depression-like behaviour in CCI animals. Duloxetine significantly reversed depression-like behaviour in CCI rats by increasing the time of climbing and swimming, while 8-OH-DPAT attenuated depression-like behaviour mainly by increasing the time of swimming. However, the selective serotonergic uptake blocker fluoxetine (20mg/kg) failed to attenuate mechanical hypersensitivity and depression-like behaviour, possibly due to confounding pro-nociceptive actions at 5-HT3 receptors. These data suggest to target noradrenergic and 5-HT1A receptors for treatment of chronic pain and its comorbidity depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Gelofen Induced Hypersensitivity: A Rare Case Report

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    M. Nikkhah Rankohie

    2016-07-01

    Full Text Available Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs are drugs commonly pre-scribed in dental practice for the management of pain and swelling. But, rarely hypersensitiv-ity reactions are reported. Case Report: A 28 year old woman underwent periodontal plastic surgery (gingival graft. Postoperative analgesics (400 mg Gelofen ,oral and antibiotics were administrated for the patient. Three hours after discharge of patient, she complained of redness, itching , rapid swelling of her eyes in 10 minutes, and watery eye discharge 1 hour after taking the drugs. She was treated with 8mg/2ml mg Dexamethasone IM at the dental department and with Hy-drocortisone 100mg/ml IM and antihistamine drugs at the hospital. Conclusion: There are no published protocols and sensitivity and specifity of skin pick testing and patch testing for Gelofen. So avoidance of re-exposure is the best management strategy. The use of Cox-2 specific medications would be a proper alternative for pain relief. (Sci J Hamadan Univ Med Sci 2016; 23 (2:179-183

  3. Expression of TRPV1 channels after nerve injury provides an essential delivery tool for neuropathic pain attenuation.

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    Hossain Md Zakir

    Full Text Available Increased expression of the transient receptor potential vanilloid 1 (TRPV1 channels, following nerve injury, may facilitate the entry of QX-314 into nociceptive neurons in order to achieve effective and selective pain relief. In this study we hypothesized that the level of QX-314/capsaicin (QX-CAP--induced blockade of nocifensive behavior could be used as an indirect in-vivo measurement of functional expression of TRPV1 channels. We used the QX-CAP combination to monitor the functional expression of TRPV1 in regenerated neurons after inferior alveolar nerve (IAN transection in rats. We evaluated the effect of this combination on pain threshold at different time points after IAN transection by analyzing the escape thresholds to mechanical stimulation of lateral mental skin. At 2 weeks after IAN transection, there was no QX-CAP mediated block of mechanical hyperalgesia, implying that there was no functional expression of TRPV1 channels. These results were confirmed immunohistochemically by staining of regenerated trigeminal ganglion (TG neurons. This suggests that TRPV1 channel expression is an essential necessity for the QX-CAP mediated blockade. Furthermore, we show that 3 and 4 weeks after IAN transection, application of QX-CAP produced a gradual increase in escape threshold, which paralleled the increased levels of TRPV1 channels that were detected in regenerated TG neurons. Immunohistochemical analysis also revealed that non-myelinated neurons regenerated slowly compared to myelinated neurons following IAN transection. We also show that TRPV1 expression shifted towards myelinated neurons. Our findings suggest that nerve injury modulates the TRPV1 expression pattern in regenerated neurons and that the effectiveness of QX-CAP induced blockade depends on the availability of functional TRPV1 receptors in regenerated neurons. The results of this study also suggest that the QX-CAP based approach can be used as a new behavioral tool to detect

  4. Improved reactive nanoparticles to treat dentin hypersensitivity.

    Science.gov (United States)

    Toledano-Osorio, Manuel; Osorio, Estrella; Aguilera, Fátima S; Luis Medina-Castillo, Antonio; Toledano, Manuel; Osorio, Raquel

    2018-05-01

    The aim of this study was to evaluate the effectiveness of different nanoparticles-based solutions for dentin permeability reduction and to determine the viscoelastic performance of cervical dentin after their application. Four experimental nanoparticle solutions based on zinc, calcium or doxycycline-loaded polymeric nanoparticles (NPs) were applied on citric acid etched dentin, to facilitate the occlusion and the reduction of the fluid flow at the dentinal tubules. After 24 h and 7 d of storage, cervical dentin was evaluated for fluid filtration. Field emission scanning electron microscopy, energy dispersive analysis, AFM and Nano-DMA analysis were also performed. Complex, storage, loss modulus and tan delta (δ) were assessed. Doxycycline-loaded NPs impaired tubule occlusion and fluid flow reduction trough dentin. Tubules were 100% occluded in dentin treated with calcium-loaded NPs or zinc-loaded NPs, analyzed at 7 d. Dentin treated with both zinc-NPs and calcium-NPs attained the highest reduction of dentinal fluid flow. Moreover, when treating dentin with zinc-NPs, complex modulus values attained at intertubular and peritubular dentin were higher than those obtained after applying calcium-NPs. Zinc-NPs are then supposed to fasten active dentin remodeling, with increased maturity and high mechanical properties. Zinc-based nanoparticles are then proposed for effective dentin remineralization and tubular occlusion. Further research to finally prove for clinical benefits in patients with dentin hypersensitivity using Zn-doped nanoparticles is encouraged. Erosion from acids provokes dentin hypersensitivity (DH) which presents with intense pain of short duration. Open dentinal tubules and demineralization favor DH. Nanogels based on Ca-nanoparticles and Zn-nanoparticles produced an efficient reduction of fluid flow. Dentinal tubules were filled by precipitation of induced calcium-phosphate deposits. When treating dentin with Zn-nanoparticles, complex modulus

  5. [Anticonvulsant hypersensitivity syndrome and lamotrigine-associated anticonvulsant hypersensitivity syndrome].

    Science.gov (United States)

    Taillia, H; Alla, P; Fournier, B; Bounolleau, P; Ouologem, M; Ricard, D; Sallansonnet-Froment, M; de Greslan, T; Renard, J-L

    2009-10-01

    Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.

  6. The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

    Science.gov (United States)

    Farmer, Adam D; Ruffle, James K; Aziz, Qasim

    2017-02-01

    The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

  7. Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

    Science.gov (United States)

    Ding, Hao; Liu, Xiao-Chang; Mei, Qiao; Xu, Jian-Ming; Hu, Xiang-Yang; Hu, Jing

    2014-04-07

    Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

  8. Minocycline through attenuation of oxidative stress and inflammatory response reduces the neuropathic pain in a rat model of chronic constriction injury

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    Abolfazl Abbaszadeh

    2018-02-01

    Full Text Available Objective(s: Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI. Materials and Methods: In this study four groups (n = 6–8 of rats were used as follows: Sham, CCI, CCI + minocycline (MIN 10 mg/Kg (IP and CCI + MIN 30 mg/Kg (IP. On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1β, Glutathione peroxidase (GPx, Superoxide dismutase (SOD and Malondialdehyde (MDA. Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated. Results: Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1β. Antioxidative enzymes (SOD, MDA, and GPx were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline. Conclusion: It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress.

  9. Purple sweet potato (Ipomea Batatas P. as dentin hypersensitivity desensitization gel

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    Chariza Hanum Mayvita Iskandar

    2015-12-01

    Full Text Available Background: Dentin hypersensitivity is a short sharp sense of pain in the teeth when exposed to excitatory stimulus. A total of 74% of world population experiencing dentin hypersensitivity. Home treatment topical desensitization is rarely found in Indonesia. The use of dentrifice is less practical because it must be done with regular brushing. Indonesia has abundant natural resources, one of which is purple sweet potato. Purple sweet potato (Ipomea Batatas P. has highest potasium ions compared to other foodstuffs. Potassium ions can be a solution of dentin hypersensitivity by temporary blocking the suffix pulp nerve impulses. Purpose: The research objective was to determine the effectiveness of the 10% purple sweet potato extract gel of the dental pain threshold score. Method: An experimental study carried out by dental pain threshold score measurements using vitality tester into the teeth with gum recession. Samples included 32 respondents with a single blind and pre-post test control group design. They were divided into treatment group and negative control group. Paired T-test and Wilcoxon were used as data analysis. Result: The results showed dental pain threshold score increasing either in treatment group and negative control, although not as significant as in the treatment group. Conclusion: 10% purple sweet potato extract gel containing potassium ions is able to reduce the pain of dentin hypersensitivity.

  10. Electromagnetic hypersensitivity: Fact or fiction?

    International Nuclear Information System (INIS)

    Genuis, Stephen J.; Lipp, Christopher T.

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: ► Many people report symptoms when near devices emanating electromagnetic fields(EMF). ► Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. ► Recent evidence suggests pathophysiological change in some individuals with EHS. ► EHS patients consistently report profound social and personal challenges. ► Clinicians need to be apprised of the EHS condition and potential interventions.

  11. Climate hypersensitivity to solar forcing?

    Directory of Open Access Journals (Sweden)

    W. Soon

    2000-05-01

    Full Text Available We compare the equilibrium climate responses of a quasi-dynamical energy balance model to radiative forcing by equivalent changes in CO2, solar total irradiance (Stot and solar UV (SUV. The response is largest in the SUV case, in which the imposed UV radiative forcing is preferentially absorbed in the layer above 250 mb, in contrast to the weak response from global-columnar radiative loading by increases in CO2 or Stot. The hypersensitive response of the climate system to solar UV forcing is caused by strongly coupled feedback involving vertical static stability, tropical thick cirrus ice clouds and stratospheric ozone. This mechanism offers a plausible explanation of the apparent hypersensitivity of climate to solar forcing, as suggested by analyses of recent climatic records. The model hypersensitivity strongly depends on climate parameters, especially cloud radiative properties, but is effective for arguably realistic values of these parameters. The proposed solar forcing mechanism should be further confirmed using other models (e.g., general circulation models that may better capture radiative and dynamical couplings of the troposphere and stratosphere.Key words: Meteorology and atmospheric dynamics (climatology · general or miscellaneous · Solar physics · astrophysics · and astronomy (ultraviolet emissions

  12. Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology

    Science.gov (United States)

    Bannister, Kirsty; Sikandar, Shafaq; Bauer, Claudia S.; Dolphin, Annette C.; Porreca, Frank; Dickenson, Anthony H.

    2011-01-01

    Background Opioid induced hyperalgesia is recognised in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid induced hyperalgesia. Methods Sprague-Dawley rats (180-200 g) were implanted with morphine (90μg · μl−1 · hr−1) or saline (0.9% w/v) filled osmotic mini-pumps. On days 7-10 in isoflurane anaesthetized animals we evaluated the effects of (a) systemic pregabalin on spinal neuronal and visceromotor responses and (b) spinal ondansetron on dorsal horn neuronal responses. The messenger RNA levels of α2δ-1, 5HT3A and mu-opioid receptor in the dorsal root ganglia of all animals were analysed. Results In morphine-treated animals the evoked spinal neuronal responses were enhanced to a sub-set of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%), and the visceromotor response to a sub-set of colorectal distension pressures was attenuated by pregabalin (52.8%) (n = 8 for all measures, P < 0.05). Messenger RNA levels were unchanged. Conclusions The inhibitory action of pregabalin in opioid induced hyperalgesia animals is not neuropathy-dependent nor reliant on up-regulation of the α2δ-1 subunit of voltage gated calcium channels, mechanisms proposed essential for pregabalin’s efficacy in neuropathy. In opioid induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be upregulated creating an environment that’s permissive for pregabalin-mediated analgesia without peripheral pathology. PMID:21602662

  13. Does the kappa opioid receptor system contribute to pain aversion?

    Directory of Open Access Journals (Sweden)

    Catherine M Cahill

    2014-11-01

    Full Text Available The kappa opioid receptor (KOR and the endogenous peptide-ligand dynorphin have received significant attention due the involvement in mediating a variety of behavioral and neurophysiological responses, including opposing the rewarding properties of drugs of abuse including opioids. Accumulating evidence indicates this system is involved in regulating states of motivation and emotion. Acute activation of the KOR produces an increase in motivational behavior to escape a threat, however, KOR activation associated with chronic stress leads to the expression of symptoms indicative of mood disorders. It is well accepted that KOR can produce analgesia and is engaged in chronic pain states including neuropathic pain. Spinal studies have revealed KOR-induced analgesia in reversing pain hypersensitivities associated with peripheral nerve injury. While systemic administration of KOR agonists attenuates nociceptive sensory transmission, this effect appears to be a stress-induced effect as anxiolytic agents, including delta opioid receptor agonists, mitigate KOR agonist-induced analgesia. Additionally, while the role of KOR and dynorphin in driving the dysphoric and aversive components of stress and drug withdrawal has been well characterized, how this system mediates the negative emotional states associated with chronic pain is relatively unexplored. This review provides evidence that dynorphin and the KOR system contribute to the negative affective component of pain and that this receptor system likely contributes to the high comorbidity of mood disorders associated with chronic neuropathic pain.

  14. Electromagnetic hypersensitivity: Fact or fiction?

    Energy Technology Data Exchange (ETDEWEB)

    Genuis, Stephen J., E-mail: sgenuis@ualberta.ca [University of Alberta (Canada); Lipp, Christopher T. [Faculty of Medicine at the University of Calgary (Canada)

    2012-01-01

    As the prevalence of wireless telecommunication escalates throughout the world, health professionals are faced with the challenge of patients who report symptoms they claim are connected with exposure to some frequencies of electromagnetic radiation (EMR). Some scientists and clinicians acknowledge the phenomenon of hypersensitivity to EMR resulting from common exposures such as wireless systems and electrical devices in the home or workplace; others suggest that electromagnetic hypersensitivity (EHS) is psychosomatic or fictitious. Various organizations including the World Health Organization as well as some nation states are carefully exploring this clinical phenomenon in order to better explain the rising prevalence of non-specific, multi-system, often debilitating symptoms associated with non-ionizing EMR exposure. As well as an assortment of physiological complaints, patients diagnosed with EHS also report profound social and personal challenges, impairing their ability to function normally in society. This paper offers a review of the sparse literature on this perplexing condition and a discussion of the controversy surrounding the legitimacy of the EHS diagnosis. Recommendations are provided to assist health professionals in caring for individuals complaining of EHS. - Highlights: Black-Right-Pointing-Pointer Many people report symptoms when near devices emanating electromagnetic fields(EMF). Black-Right-Pointing-Pointer Electromagnetic hypersensitivity (EHS) research has generated conflicting outcomes. Black-Right-Pointing-Pointer Recent evidence suggests pathophysiological change in some individuals with EHS. Black-Right-Pointing-Pointer EHS patients consistently report profound social and personal challenges. Black-Right-Pointing-Pointer Clinicians need to be apprised of the EHS condition and potential interventions.

  15. Symptoms of Fibromyalgia According to the 2016 Revised Fibromyalgia Criteria in Chronic Pain Patients Referred to Multidisciplinary Pain Rehabilitation: Influence on Clinical and Experimental Pain Sensitivity

    DEFF Research Database (Denmark)

    Plesner, Karin Bruun; Vaegter, Henrik Bjarke

    2018-01-01

    Fibromyalgia is a condition with chronic widespread pain and signs of generalized pain hypersensitivity. FM has previously been classified according to the ACR1990 criteria, where the presence of hypersensitivity is estimated by a tender point examination. Due to the limitations of these classifi......Fibromyalgia is a condition with chronic widespread pain and signs of generalized pain hypersensitivity. FM has previously been classified according to the ACR1990 criteria, where the presence of hypersensitivity is estimated by a tender point examination. Due to the limitations...... of these classification criteria, new diagnostic criteria have been proposed, abandoning this examination. This cross-sectional study investigated the prevalence of FM according to the revised 2016 FM criteria in a large cohort of chronic pain patients. Pain drawings, the Fibromyalgia Symptom Severity Scale...

  16. Genetic evidence for involvement of neuronally expressed S1P₁ receptor in nociceptor sensitization and inflammatory pain.

    Directory of Open Access Journals (Sweden)

    Norbert Mair

    2011-02-01

    Full Text Available Sphingosine-1-phosphate (S1P is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P₁ receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P₁ receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P₁ receptor. Our data show that neuronally expressed S1P₁ receptors play a significant role in regulating nociceptor function and that S1P/S1P₁ signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation.

  17. Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

    Science.gov (United States)

    Asante, Curtis O; Wallace, Victoria C; Dickenson, Anthony H

    2009-01-01

    Background The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR) dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via mRNA translation and thus protein

  18. Formalin-induced behavioural hypersensitivity and neuronal hyperexcitability are mediated by rapid protein synthesis at the spinal level

    Directory of Open Access Journals (Sweden)

    Wallace Victoria C

    2009-06-01

    Full Text Available Abstract Background The mammalian target of rapamycin (mTOR is a key regulator of mRNA translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity. Specific to pain, shifts in pain thresholds and responsiveness are an expression of neuronal plasticity and this likely contributes to persistent pain. We investigated this by inhibiting the activity of mTOR with rapamycin at the spinal level, of rats that were subjected to the formalin test, using both behavioural and electrophysiological techniques. Results For in vivo electrophysiology, Sprague Dawley rats were fully anaesthetised and single-unit extracellular recordings were obtained from lamina V wide dynamic range (WDR dorsal horn spinal neurones at the region where input is received from the hind paw. Neuronal responses from naive rats showed that rapamycin-sensitive pathways were important in nociceptive-specific C-fibre mediated transmission onto WDR neurones as well mechanically-evoked responses since rapamycin was effective in attenuating these measures. Formalin solution was injected into the hind paw prior to which, rapamycin or vehicle was applied directly onto the exposed spinal cord. When rapamycin was applied to the spinal cord prior to hind paw formalin injection, there was a significant attenuation of the prolonged second phase of the formalin test, which comprises continuing afferent input to the spinal cord, neuronal hyperexcitability and an activated descending facilitatory drive from the brainstem acting on spinal neurones. In accordance with electrophysiological data, behavioural studies showed that rapamycin attenuated behavioural hypersensitivity elicited by formalin injection into the hind paw. Conclusion We conclude that mTOR has a role in maintaining persistent pain states via m

  19. Amalgam Contact Hypersensitivity Lesion: An Unusual Presentation ...

    African Journals Online (AJOL)

    Contact allergic reactions due to hypersensitivity to dental materials in professionals and ... Keywords: Amalgam, Amalgam contact hypersensitivity lesion, Lichenoid reaction, Oral mucosa ... was associated with mild burning sensation. The patient did ... OLLD in which oral and/or skin lesions appear in temporal association ...

  20. Cutaneous and systemic hypersensitivity reactions to metallic implants.

    Science.gov (United States)

    Basko-Plluska, Juliana L; Thyssen, Jacob P; Schalock, Peter C

    2011-01-01

    Cutaneous reactions to metal implants, orthopedic or otherwise, are well documented in the literature. The first case of a dermatitis reaction over a stainless steel fracture plate was described in 1966. Most skin reactions are eczematous and allergic in nature, although urticarial, bullous, and vasculitic eruptions may occur. Also, more complex immune reactions may develop around the implants, resulting in pain, inflammation, and loosening. Nickel, cobalt, and chromium are the three most common metals that elicit both cutaneous and extracutaneous allergic reactions from chronic internal exposure. However, other metal ions as well as bone cement components can cause such hypersensitivity reactions. To complicate things, patients may also develop delayed-type hypersensitivity reactions to metals (ie, in-stent restenosis, prosthesis loosening, inflammation, pain, or allergic contact dermatitis) following the insertion of intravascular stents, dental implants, cardiac pacemakers, or implanted gynecologic devices. Despite repeated attempts by researchers and clinicians to further understand this difficult area of medicine, the association between metal sensitivity and cutaneous allergic reactions remains to be fully understood. This review provides an update of the current knowledge in this field and should be valuable to health care providers who manage patients with conditions related to this field.

  1. Hypersensitivity pneumonitis: an immunopathology review.

    Science.gov (United States)

    Woda, Bruce A

    2008-02-01

    Hypersensitivity pneumonitis (HSP) is an immunologically mediated alveolar and interstitial lung disease caused by repeated inhalation of organic dusts and some occupational agents. The pathogenesis of HSP is uncertain. A number of unexplained features of HSP remain, namely (1) why do so few exposed individuals develop clinical HSP, (2) what triggers an acute episode after prolonged periods of previous sensitization, and (3) what leads to disease progression. This article considers these issues and aims to discuss and clarify current concepts in pathogenesis. Pertinent literature review in conjunction with the author's personal interpretive opinion. Current data suggest that individuals with a T(H)1 dominant response are likely to develop clinical disease. There is also some evidence that genetic factors such as polymorphisms in the major histocompatibility complex, tumor necrosis factor alpha, and tissue inhibitor of metalloproteinase 3 are associated with the development of or resistance to the disease.

  2. Hypersensitivity reactions in patients receiving hemodialysis.

    Science.gov (United States)

    Butani, Lavjay; Calogiuri, Gianfranco

    2017-06-01

    To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. The effects of an intraperitoneal single low dose of ketamine in attenuating the postoperative skin/muscle incision and retraction-induced pain related to the inhibition of N-methyl-D-aspartate receptors in the spinal cord.

    Science.gov (United States)

    Shen, Yu; Xu, Li; Liu, Ming; Lei, Yishan; Gu, Xiaoping; Ma, Zhengliang

    2016-03-11

    Chronic postoperative pain (CPOP) is a common clinical problem which might be related to central sensitization. It has been widely accepted that NMDA (N-methyl-D-aspartate) receptors are among the triggers of central sensitization. Ketamine is a non-competitive NMDA receptor antagonist that is widely used in alleviating postoperative pain, but its effect on CPOP has been rarely reported. In the present study, the skin/muscle incision and retraction (SMIR) model was used to investigate the role of NMDARs in chronic postoperative pain and the effect of an intraperitoneal single low dose ketamine (10mg/kg) of attenuating SMIR-induced CPOP. We assessed pain behaviours after a SMIR operation by paw withdrawal threshold (PWMT) and paw withdrawal latency (PWMTL). Western blotting were performed to examine the role of NMDARs in SMIR-induced CPOP and the effect of ketamine on the expression and phosphorylation of NMDARs. The SMIR operation induced long-lasting mechanical hyperalgesia, and the up-regulation of phosphorylated NMDARs and total NMDARs at the spinal level. A single intraperitoneal administration of low dose ketamine (10mg/kg) during surgery alleviated pain behaviors and inhibited the up-regulation of phosphorylated NMDARs and total NMDARs. Our datas suggested that NMDARs play important roles in SMIR-induced CPOP. A single intraperitoneal low dose of ketamine could attenuate SMIR-induced CPOP, which might be associated with the inhibition of NMDARs. Our finding might provide a new, simple method of addressing CPOP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Hypersensitivity to contrast media and dyes.

    Science.gov (United States)

    Brockow, Knut; Sánchez-Borges, Mario

    2014-08-01

    This article updates current knowledge on hypersensitivity reactions to diagnostic contrast media and dyes. After application of a single iodinated radiocontrast medium (RCM), gadolinium-based contrast medium, fluorescein, or a blue dye, a hypersensitivity reaction is not a common finding; however, because of the high and still increasing frequency of those procedures, patients who have experienced severe reactions are nevertheless frequently encountered in allergy departments. Evidence on allergologic testing and management is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein. Skin tests can be helpful in the diagnosis of patients with hypersensitivity reactions to these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Cutaneous drug hypersensitivity : Immunological and genetic perspective

    Directory of Open Access Journals (Sweden)

    Kisalay Ghosh

    2011-01-01

    Full Text Available Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity.

  6. Immediate-type hypersensitivity to polyethylene glycols

    DEFF Research Database (Denmark)

    Wenande, E; Garvey, L H

    2016-01-01

    Polyethylene glycols (PEGs) or macrogols are polyether compounds widely used in medical and household products. Although generally considered biologically inert, cases of mild to life-threatening immediate-type PEG hypersensitivity are reported with increasing frequency. Nevertheless, awareness...

  7. Dentinal hypersensitivity following scaling and root planing: comparison of low-level laser and topical fluoride treatment.

    Science.gov (United States)

    Pesevska, Snezana; Nakova, Marija; Ivanovski, Kiro; Angelov, Nikola; Kesic, Ljiljana; Obradovic, Radmila; Mindova, Sonja; Nares, Salvador

    2010-09-01

    The aim of this study is to compare the effectiveness of low-level laser irradiation to traditional topical fluoride treatment for treatment choices of dentinal hypersensitivity following scaling and root planing. The experimental group (15 patients) was treated with low-energy-level diode laser at each site of dentinal hypersensitivity following scaling and root planning. The control group (15 patients) received topical fluoride treatment (protective varnish for desensitization). All the patients were treated at baseline visit, and then at day 2 and 4 after the initial treatment; the pain was subjectively assessed by the patients as strong, medium, medium low, low, or no pain. Total absence of the dental hypersensitivity was reported in 26.66% of the examined group even after the second visit, compared to the control group where complete resolution of the hypersensitivity was not present after the second visit in any of the treated cases. Complete absence of pain was achieved in 86.6% of patients treated with laser and only in 26.6% in the fluoride treated group, after the third visit. Based on our findings, we conclude that low-energy biostimulative laser treatment can be successfully used for treatment of dental hypersensitivity following scaling and root planing.

  8. Classification and pathophysiology of radiocontrast media hypersensitivity.

    Science.gov (United States)

    Brockow, Knut; Ring, Johannes

    2010-01-01

    Hypersensitivity reactions to radiocontrast media (RCM) are unpredictable and are a concern for radiologists and cardiologists. Immediate hypersensitivity reactions manifest as anaphylaxis, and an allergic IgE-mediated mechanism has been continuously discussed for decades. Non-immediate reactions clinically are exanthemas resembling other drug-induced non-immediate hypersensitivities. During the past years, evidence is increasing that some of these reactions may be immunological. Repeated reactions after re-exposure, positive skin tests, and presence of specific IgE antibodies as well as positive basophil activation tests in some cases, and positive lymphocyte transformation or lymphocyte activation tests in others, indicate that a subgroup of both immediate and non-immediate reactions are of an allergic origin, although many questions remain unanswered. Recently reported cases highlight that pharmacological premedication is not safe to prevent RCM hypersensitivity in patients with previous severe reactions. These insights may have important consequences. A large multicenter study on the value of skin tests in RCM hypersensitivity concluded that skin testing is a useful tool for diagnosis of RCM allergy. It may have a role for the selection of a safe product in previous reactors, although confirmatory validation data is still scarce. In vitro tests to search for RCM-specific cell activation still are in development. In conclusion, recent data indicate that RCM hypersensitivity may have an allergic mechanism and that allergological testing is useful and may indicate tolerability. Copyright 2010 S. Karger AG, Basel.

  9. Loin pain hematuria syndrome.

    Science.gov (United States)

    Taba Taba Vakili, Sahar; Alam, Tausif; Sollinger, Hans

    2014-09-01

    Loin pain hematuria syndrome is a rare disease with a prevalence of ∼0.012%. The most prominent clinical features include periods of severe intermittent or persistent unilateral or bilateral loin pain accompanied by either microscopic or gross hematuria. Patients with loin pain hematuria syndrome initially present with hematuria, flank pain, or most often both hematuria and flank pain. Kidney biopsies from patients with loin pain hematuria typically reveal only minor pathologic abnormalities. Further, loin pain hematuria syndrome is not associated with loss of kidney function or urinary tract infections. Loin pain hematuria syndrome-associated hematuria and pain are postulated to be linked to vascular disease of the kidney, coagulopathy, renal vasospasm with microinfarction, hypersensitivity, complement activation on arterioles, venocalyceal fistula, abnormal ureteral peristalsis, and intratubular deposition of calcium or uric acid microcrystals. Many patients with loin pain hematuria syndrome also meet criteria for a somatoform disorder, and analgesic medications, including narcotics, commonly are used to treat loin pain hematuria syndrome-associated pain. Interventional treatments include renal denervation, kidney autotransplantation, and nephrectomy; however, these methods should be used only as a last resort when less invasive measures have been tried unsuccessfully. In this review article, we discuss and critique current clinical practices related to loin pain hematuria syndrome pathophysiology, diagnosis, treatment, and prognosis. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  10. Incidence of hypersensitivity and anaphylaxis with sugammadex.

    Science.gov (United States)

    Min, K Chris; Woo, Tiffany; Assaid, Christopher; McCrea, Jacqueline; Gurner, Deborah M; Sisk, Christine McCrary; Adkinson, Franklin; Herring, W Joseph

    2018-06-01

    To evaluate the incidence of hypersensitivity and anaphylaxis after administration of sugammadex. Retrospective analysis. Sugammadex clinical development program and post-marketing experience. Surgical patients and healthy volunteers who received sugammadex or placebo/comparator with anesthesia and/or neuromuscular blockade (NMB). Sugammadex administered as 2.0 mg/kg at reappearance of the second twitch, 4.0 mg/kg at 1-2 post-tetanic count, or 16.0 mg/kg at 3 min after rocuronium 1.2 mg/kg. Three analytical methods were used: 1) automated MedDRA queries; 2) searches of adverse events (AEs) consistent with treatment-related hypersensitivity reactions as diagnosed by the investigator; and 3) a retrospective adjudication of AEs suggestive of hypersensitivity by a blinded, independent adjudication committee (AC). In addition, a search of all post-marketing reports of events of hypersensitivity was performed, and events were retrospectively adjudicated by an independent AC. Anaphylaxis was determined according to Sampson Criterion 1. The pooled dataset included 3519 unique subjects who received sugammadex and 544 who received placebo. The automated MedDRA query method showed no apparent increase in hypersensitivity or anaphylaxis with sugammadex as compared to placebo or neostigmine. Similarly, there was a low overall incidence of AEs of treatment-related hypersensitivity (sugammadex and placebo or neostigmine. Finally, the retrospective adjudication of AEs suggestive of hypersensitivity showed a low incidence of hypersensitivity (0.56% and 0.21% for sugammadex 2 mg/kg and 4 mg/kg, respectively), with an incidence similar to subjects who received placebo (0.55%). There were no confirmed cases of anaphylaxis in the pooled studies. During post-marketing use, spontaneous reports of anaphylaxis occurred with approximately 0.01% of sugammadex doses. Subjects who received sugammadex with general anesthesia and/or NMB had a low overall incidence of

  11. Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling

    Directory of Open Access Journals (Sweden)

    Enrique J. Cobos

    2018-01-01

    Full Text Available Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. Ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity, whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type.

  12. Wu-Tou Decoction Inhibits Chronic Inflammatory Pain in Mice: Participation of TRPV1 and TRPA1 Ion Channels

    Directory of Open Access Journals (Sweden)

    Chao Wang

    2015-01-01

    Full Text Available Wu-tou decoction (WTD is a classic traditional Chinese medicine formula and has been used effectively to treat joint diseases clinically. Previous reports indicated that WTD possesses anti-inflammatory activity; however, its actions on pain have not been clarified. Here, we investigated the antinociceptive activity of WTD in CFA-induced mice, and its possible mechanism of the action associated with transient receptor potential (TRP ion channels was also explored. Our results showed that 1.58, 3.15, and 6.30 g/kg WTD significantly attenuated mechanical, cold, and heat hypersensitivities. Moreover, WTD effectively inhibited spontaneous nociceptive responses to intraplantar injections of capsaicin and cinnamaldehyde, respectively. WTD also effectively suppressed jumping and wet-dog-shake behaviors to intraperitoneal injection of icilin. Additionally, WTD significantly reduced protein expression of TRPV1 and TRPA1 in dorsal root ganglia and skins of injured paw. Collectively, our data demonstrate firstly that WTD exerts antinociceptive activity in inflammatory conditions by attenuating mechanical, cold, and heat hypersensitivities. This antinociceptive effect may result in part from inhibiting the activities of TRPV1, TRPA1, and TRPM8, and the suppression of TRPV1 and TRPA1 protein by WTD was also highly effective. These findings suggest that WTD might be an attractive and suitable therapeutic agent for the management of chronic inflammatory pain.

  13. 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

  14. Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

    Science.gov (United States)

    Chen, Longtu; Ilham, Sheikh J.; Feng, Bin

    2017-01-01

    Context Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects. Evidence of Acquisition In this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia. Results Certain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract. Conclusions Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target

  15. Endogenous Opioid-Masked Latent Pain Sensitization

    DEFF Research Database (Denmark)

    Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B

    2015-01-01

    UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development of chr...

  16. Increased Auditory Startle Reflex in Children with Functional Abdominal Pain

    NARCIS (Netherlands)

    Bakker, Mirte J.; Boer, Frits; Benninga, Marc A.; Koelman, Johannes H. T. M.; Tijssen, Marina A. J.

    2010-01-01

    Objective To test the hypothesis that children with abdominal pain-related functional gastrointestinal disorders have a general hypersensitivity for sensory stimuli. Study design Auditory startle reflexes were assessed in 20 children classified according to Rome III classifications of abdominal

  17. Increased Auditory Startle Reflex in Children with Functional Abdominal Pain

    NARCIS (Netherlands)

    Bakker, Mirte J.; Boer, Frits; Benninga, Marc A.; Koelman, Johannes H. T. M.; Tijssen, Marina A. J.

    Objective To test the hypothesis that children with abdominal pain-related functional gastrointestinal disorders have a general hypersensitivity for sensory stimuli. Study design Auditory startle reflexes were assessed in 20 children classified according to Rome III classifications of abdominal

  18. Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

    OpenAIRE

    Bai, Tao; Li, Ying; Xia, Jing; Jiang, Yudong; Zhang, Lei; Wang, Huan; Qian, Wei; Song, Jun; Hou, Xiaohua

    2017-01-01

    Background/Aims Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins express...

  19. Voluntary Exercise Training: Analysis of Mice in Uninjured, Inflammatory, and Nerve-Injured Pain States.

    Directory of Open Access Journals (Sweden)

    Tayler D Sheahan

    Full Text Available Both clinical and animal studies suggest that exercise may be an effective way to manage inflammatory and neuropathic pain conditions. However, existing animal studies commonly use forced exercise paradigms that incorporate varying degrees of stress, which itself can elicit analgesia, and thus may complicate the interpretation of the effects of exercise on pain. We investigated the analgesic potential of voluntary wheel running in the formalin model of acute inflammatory pain and the spared nerve injury model of neuropathic pain in mice. In uninjured, adult C57BL/6J mice, 1 to 4 weeks of exercise training did not alter nociceptive thresholds, lumbar dorsal root ganglia neuronal excitability, or hindpaw intraepidermal innervation. Further, exercise training failed to attenuate formalin-induced spontaneous pain. Lastly, 2 weeks of exercise training was ineffective in reversing spared nerve injury-induced mechanical hypersensitivity or in improving muscle wasting or hindpaw denervation. These findings indicate that in contrast to rodent forced exercise paradigms, short durations of voluntary wheel running do not improve pain-like symptoms in mouse models of acute inflammation and peripheral nerve injury.

  20. Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

    Science.gov (United States)

    Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

    2007-04-01

    Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

  1. Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

    Science.gov (United States)

    Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

    2007-04-01

    Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

  2. Repetitive Treatment with Diluted Bee Venom Attenuates the Induction of Below-Level Neuropathic Pain Behaviors in a Rat Spinal Cord Injury Model.

    Science.gov (United States)

    Kang, Suk-Yun; Roh, Dae-Hyun; Choi, Jung-Wan; Ryu, Yeonhee; Lee, Jang-Hern

    2015-07-10

    The administration of diluted bee venom (DBV) into an acupuncture point has been utilized traditionally in Eastern medicine to treat chronic pain. We demonstrated previously that DBV has a potent anti-nociceptive efficacy in several rodent pain models. The present study was designed to examine the potential anti-nociceptive effect of repetitive DBV treatment in the development of below-level neuropathic pain in spinal cord injury (SCI) rats. DBV was applied into the Joksamli acupoint during the induction and maintenance phase following thoracic 13 (T13) spinal hemisection. We examined the effect of repetitive DBV stimulation on SCI-induced bilateral pain behaviors, glia expression and motor function recovery. Repetitive DBV stimulation during the induction period, but not the maintenance, suppressed pain behavior in the ipsilateral hind paw. Moreover, SCI-induced increase in spinal glia expression was also suppressed by repetitive DBV treatment in the ipsilateral dorsal spinal cord. Finally, DBV injection facilitated motor function recovery as indicated by the Basso-Beattie-Bresnahan rating score. These results indicate that the repetitive application of DBV during the induction phase not only decreased neuropathic pain behavior and glia expression, but also enhanced locomotor functional recovery after SCI. This study suggests that DBV acupuncture can be a potential clinical therapy for SCI management.

  3. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization.

    Science.gov (United States)

    Sutton, Blair C; Opp, Mark R

    2014-03-01

    Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased

  4. Entomologic evaluation of insect hypersensitivity in horses.

    Science.gov (United States)

    Greiner, E C

    1995-04-01

    Potential methods of incriminating insects as the cause of insect hypersensitivity are presented. A listing of the biting midges known to attack horses in North America is presented also. An example of how species may be determined to be the cause of the hypersensitivity is given using data from a recent study in Florida. Light trap collections indicated the temporal and geographic distribution of potential contributing species and collections made by vacuuming horses further delineated species by proving they feed on horses and the correct locations on the horses to match lesion distribution. Culicoides hypersensitivity in horses in Florida seems to be caused by a series of species active and feeding on the horses at different times of the year.

  5. Drug hypersensitivity in clonal mast cell disorders

    DEFF Research Database (Denmark)

    Bonadonna, P; Pagani, M; Aberer, W

    2015-01-01

    and severity of immediate hypersensitivity reactions. Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. Fatal anaphylaxis has been described particularly following hymenoptera stings, but also occasionally after the intake of drugs such as nonsteroidal anti-inflammatory drugs......, opioids and drugs in the perioperative setting. However, data on the frequency of drug hypersensitivity in mastocytosis and vice versa are scarce and evidence for an association appears to be limited. Nevertheless, clonal MC disorders should be ruled out in cases of severe anaphylaxis: basal serum...... tryptase determination, physical examination for cutaneous mastocytosis lesions, and clinical characteristics of anaphylactic reaction might be useful for differential diagnosis. In this position paper, the ENDA group performed a literature search on immediate drug hypersensitivity reactions in clonal MC...

  6. Hypersensitivity Reactions from Excipients in Systemic Glucocorticoid Formulations

    DEFF Research Database (Denmark)

    Calogiuri, Gianfranco; Garvey, Lene H; Romita, Paolo

    2016-01-01

    Glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, however these drugs themselves and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate-type hypersensitivity reactions. Reactions involving excipients have been...

  7. Systemic Immediate Hypersensitive Reactions after Treatment with Sweet Bee Venom: A Case Report

    Directory of Open Access Journals (Sweden)

    NaYoung Jo

    2015-12-01

    Full Text Available Objectives: A previous study showed that bee venom (BV could cause anaphylaxis or other hypersensitivity reactions. Although hypersensitivity reactions due to sweet bee venom (SBV have been reported, SBV has been reported to be associated with significantly reduced sensitization compared to BV. Although no systemic immediate hypersensitive response accompanied by abnormal vital signs has been reported with respect to SBV, we report a systemic immediate hypersensitive response that we experienced while trying to use SBV clinically. Methods: The patient had undergone BV treatment several times at other Oriental medicine clinics and had experienced no adverse reactions. She came to acupuncture & moxibustion department at Semyung university hospital of Oriental medicine (Je-cheon, Korea complaining of facial hypoesthesia and was treated using SBV injections, her first SBV treatment. SBV, 0.05 cc, was injected at each of 8 acupoints, for a total of 0.40 cc: Jichang (ST4, Daeyeong (ST5, Hyeopgeo (ST6, Hagwan (ST7, Yepung (TE17, Imun (TE21, Cheonghoe (GB2, and Gwallyeo (SI18. Results: The patient showed systemic immediate hypersensitive reactions. The main symptoms were abdominal pain, nausea and perspiration, but common symptoms associated with hypersensitivity, such as edema, were mild. Abdominal pain was the most long-lasting symptom and was accompanied by nausea. Her body temperature decreased due to sweating. Her diastolic blood pressure could not be measured on three occasions. She remained alert, though the symptoms persisted. The following treatments were conducted in sequence; intramuscular epinephrine, 1 mg/mL, injection, intramuscular dexamethasone, 5 mg/mL, injection, intramuscular buscopan, 20 mg/mL, injection, oxygen (O2 inhalation therapy, 1 L/minutes, via a nasal prong, and intravascular injection of normal saline, 1 L. After 12 hours of treatment, the symptoms had completely disappeared. Conclusion: This case shows that the use of SBV

  8. Algometry with a clothes peg compared to an electronic pressure algometer: a randomized cross-sectional study in pain patients

    OpenAIRE

    Egloff, Niklaus; Klingler, Nicole; von Känel, Roland; Cámara, Rafael JA; Curatolo, Michele; Wegmann, Barbara; Marti, Elizabeth; Ferrari, Marie-Louise Gander

    2011-01-01

    Abstract Background Hypersensitivity of the central nervous system is widely present in pain patients and recognized as one of the determinants of chronic pain and disability. Electronic pressure algometry is often used to explore aspects of central hypersensitivity. We hypothesized that a simple pain provocation test with a clothes peg provides information on pain sensitivity that compares meaningfully to that obtained by a well-established electronic pressure algometer. "Clinically meaningf...

  9. Infection or metal hypersensitivity? The diagnostic challenge of failure in metal-on-metal bearings.

    LENUS (Irish Health Repository)

    Galbraith, John G

    2011-04-01

    The use of second generation metal-on-metal hip articulations has gained favour in the past few years. A hypersensitivity reaction to the metal-on-metal bearing, although rare, is a reported complication and is a novel mode of failure of these implants. Differentiating failure secondary to infection from failure secondary to metal hypersensitivity represents a significant diagnostic challenge. A retrospective review of all cases of hip arthroplasty using metal-on-metal bearings over a 5-year period at a tertiary referral centre identified 3 cases of failure secondary to metal hypersensitivity. Clinical presentation, serological markers, radiological imaging and histological analysis of all cases identified were evaluated. Histological analysis of periprosthetic tissue in all 3 cases identified characteristic features such as perivascular lymphocytic aggregates and chronic inflammation consistent with aseptic lymphocytic vasculitis-associated lesions (ALVAL). This study highlights that failure secondary to metal hypersensitivity must be considered in patients presenting with the reappearance of persistent pain, marked joint effusion, and the development of early osteolysis in the absence of infection.

  10. ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

    Science.gov (United States)

    Miyazaki, Shingo; Diwan, Ashish D; Kato, Kenji; Cheng, Kevin; Bae, Won C; Sun, Yang; Yamada, Junichi; Muehleman, Carol; Lenz, Mary E; Inoue, Nozomu; Sah, Robert L; Kawakami, Mamoru; Masuda, Koichi

    2018-04-01

    To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

  11. Electroacupuncture Attenuates CFA-induced Inflammatory Pain by suppressing Nav1.8 through S100B, TRPV1, Opioid, and Adenosine Pathways in Mice.

    Science.gov (United States)

    Liao, Hsien-Yin; Hsieh, Ching-Liang; Huang, Chun-Ping; Lin, Yi-Wen

    2017-02-13

    Pain is associated with several conditions, such as inflammation, that result from altered peripheral nerve properties. Electroacupuncture (EA) is a common Chinese clinical medical technology used for pain management. Using an inflammatory pain mouse model, we investigated the effects of EA on the regulation of neurons, microglia, and related molecules. Complete Freund's adjuvant (CFA) injections produced a significant mechanical and thermal hyperalgesia that was reversed by EA or a transient receptor potential V1 (TRPV1) gene deletion. The expression of the astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, receptor for advanced glycation end-products (RAGE), TRPV1, and other related molecules was dramatically increased in the dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) of CFA-treated mice. This effect was reversed by EA and TRPV1 gene deletion. In addition, endomorphin (EM) and N 6 -cyclopentyladenosine (CPA) administration reliably reduced mechanical and thermal hyperalgesia, thereby suggesting the involvement of opioid and adenosine receptors. Furthermore, blocking of opioid and adenosine A1 receptors reversed the analgesic effects of EA. Our study illustrates the substantial therapeutic effects of EA against inflammatory pain and provides a novel and detailed mechanism underlying EA-mediated analgesia via neuronal and non-neuronal pathways.

  12. Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity ...

    African Journals Online (AJOL)

    Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity Reaction and Cellular Immune Responses. ... The tuberculin skin test (TST) and peripheral blood mono-nuclear cells (PBMCs) culture were conducted using PPD. The cytokines were measured using commercial kits. Results: The mean TST was 24.6 ±8.0 ...

  13. Severe Hyperacusis, Photophobia, and Skin Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Alessandra Barbara Fioretti

    2016-01-01

    Full Text Available We report a case of a patient with severe hyperacusis, photophobia, and skin hypersensitivity. The patient was initially treated with sound therapy and medical therapy for 4 months and successfully with a selective serotonin reuptake inhibitor (SSRI and cognitive behavioral therapy which improved her mood and the tolerance for sounds and light.

  14. Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats

    Science.gov (United States)

    Zhou, Yuan-Yuan; Wanner, Natalie J; Xiao, Ying; Shi, Xuan-Zheng; Jiang, Xing-Hong; Gu, Jian-Guo; Xu, Guang-Yin

    2012-01-01

    AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates. METHODS: Six to nine week-old male Sprague-Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 °C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (NLX) or NLX methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments. RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 ± 0.2, 1.3 ± 0.2, 1.9 ± 0.2 and 2.3 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 ± 0.1, 2.5 ± 0.1, 2.8 ± 0.2 and 3.5 ± 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 ± 0.2 vs 0.7 ± 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 ± 0.2 vs 1.5 ± 0.2, P

  15. Fasting mitigates immediate hypersensitivity: a pivotal role of endogenous D-beta-hydroxybutyrate.

    Science.gov (United States)

    Nakamura, Shigeru; Hisamura, Ryuji; Shimoda, Sachiko; Shibuya, Izumi; Tsubota, Kazuo

    2014-01-01

    Fasting is a rigorous type of dietary restriction that is associate with a number of health benefits. During fasting, ketone bodies significantly increase in blood and become major body fuels, thereby sparing glucose. In the present study, we investigated effects of fasting on hypersensitivity. In addition, we also investigated the possible role of D-beta-hydroxybutyrate provoked by fasting in the attenuation of immediate hypersensitivity by fasting. Effects of fasting on systemic anaphylaxis were examined using rat model of toluene 2, 4-diisocyanate induced nasal allergy. In addition to food restriction, a ketogenic high-fat and low-carbohydrate diet that accelerates fatty acid oxidation and systemic instillation of D-beta-hydroxybutyrate were employed to elevate internal D-beta-hydroxybutyrate concentration. We assessed relationship between degranulation of rat peritoneal mast cells and internal D-beta-hydroxybutyrate concentration in each treatment. Changes in [Ca(2+)]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Immediate hypersensitivity reaction was significantly suppressed by fasting. A significant reduction in mast cells degranulation, induced by mast cell activator compound 48/80, was observed in rat peritoneal mast cells delivered from the 24 hours fasting treatment. In addition, mast cells delivered from a ketogenic diet and D-beta-hydroxybutyrate infusion treatment also had reduced mast cell degranulation and systemic D-beta-hydroxybutyrate concentrations were elevated to similar extent as the fasting state. The peak increase in [Ca(2+)]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. The results of the present study demonstrates that fasting suppress hypersensitivity reaction, and indicate that increased level of D-beta-hydroxybutyrate by fasting plays an important role, via the stabilization of mast cells, in

  16. 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.

  17. Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in mice

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Nasser, Arafat; Falk, Sarah

    2012-01-01

    The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. However, the role of the ......X3 receptor in chronic cancer-induced bone pain is less known. Here we investigated the effect of systemic acute and chronic administration of the selective P2X3, P2X2/3 receptor antagonist (5-[[[(3-Phenoxyphenyl)methyl][(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl]-1...

  18. Attenuation of reserpine-induced pain/depression dyad by gentiopicroside through downregulation of GluN2B receptors in the amygdala of mice.

    Science.gov (United States)

    Liu, Shui-bing; Zhao, Rong; Li, Xu-sheng; Guo, Hong-ju; Tian, Zhen; Zhang, Nan; Gao, Guo-dong; Zhao, Ming-gao

    2014-06-01

    Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the reserpine-induced pain/depression dyad and its underlying mechanisms are unclear. Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong evidence that Gent inhibits reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala.

  19. An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UV(B)-inflamed and normal skin.

    Science.gov (United States)

    Schaffler, Klaus; Reeh, Peter; Duan, W Rachel; Best, Andrea E; Othman, Ahmed A; Faltynek, Connie R; Locke, Charles; Nothaft, Wolfram

    2013-02-01

    Laser (radiant-heat) evoked potentials (LEPs) from vertex-EEG peak-to-peak (PtP) amplitude were used to determine acute antinociceptive/antihyperalgesic efficacy of ABT-102, a novel TRPV1 antagonist efficacious in preclinical pain models, compared with active controls and placebo in normal and UV(B)-inflamed skin. This was a randomized, placebo- and active-controlled, double-blind, intra-individual, crossover trial. Twenty-four healthy subjects received six sequences of single doses of ABT-102 (0.5, 2, 6 mg), etoricoxib 90 mg, tramadol 100 mg and placebo. Painful stimuli were induced by CO(2) -laser on normal and UV(B) -inflamed skin. LEPs and visual analogue scale (VAS-pain) ratings were taken at baseline and hourly up to 8 h post-dose from both skin types. Compared with placebo, significant mean decreases in the primary variable of LEP PtP-amplitude from UV(B)-inflamed skin were observed with ABT-102 6 mg (P < 0.001), ABT-102 2 mg (P = 0.002), tramadol 100 mg (P < 0.001), and etoricoxib 90 mg (P = 0.001) over the 8 h period; ABT-102 0.5 mg was similar to placebo. ABT-102 6 mg was superior to active controls over the 8 h period (P < 0.05) whereas ABT-102 2 mg was comparable. Improvements in VAS scores compared with placebo were observed with ABT-102 6 mg (P < 0.001) and ABT-102 2 mg (P = 0.002). ABT-102 average plasma concentrations were 1.3, 4.4 and 9.4 ng ml(-1) for the 0.5, 2 and 6 mg doses, respectively. There were no clinically significant safety findings. TRPV-1 antagonism appears promising in the management of clinical pain, but requires further investigation. © 2012 Abbott. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  20. Patients With Knee Osteoarthritis Who Score Highly on the PainDETECT Questionnaire Present With Multimodality Hyperalgesia, Increased Pain, and Impaired Physical Function

    OpenAIRE

    Moss, Penny; Benson, Heather A.E.; Will, Rob; Wright, Anthony

    2017-01-01

    Objectives: PainDETECT is a self-report questionnaire that can be used to identify features of neuropathic pain. A proportion of patients with knee osteoarthritis (OA) score highly on the PainDETECT questionnaire. This study aimed to determine whether those with a higher “positive neuropathic” score on the PainDETECT questionnaire also had greater pain, hypersensitivity, and reduced function compared with individuals with knee OA with lower PainDETECT scores. Materials and Methods: In total, ...

  1. Treatment of Dentine Hypersensitivity by Diode Laser: A Clinical Study

    Directory of Open Access Journals (Sweden)

    Romeo Umberto

    2012-01-01

    Full Text Available Introduction. Dentine hypersensitivity (DH is characterized by pain after stimuli that usually provoke no symptoms. This study compared the effectiveness of GaAlAs diode laser alone and with topical sodium fluoride gel (NaF. Materials and Methods. The study was conducted on 10 patients (8 F/2 M, age 25–60 and 115 teeth with DH assessed by air and tactile stimuli measured by Numeric Rating Scale (NRS. Teeth were randomly divided into G1 (34 teeth treated by 1.25% NaF; G2 (33 teeth lased at 0.5 W PW (T on 100 m and T off 100 ms, fluence 62.2 J/cm2 in defocused mode with a 320 μ fiber. Each tooth received three 1′ applications; G3 (48 teeth received NaF gel plus laser at same G2 parameters. NRS was checked at each control. Results. Significant pain reduction was showed. The NRS reduction percentages were calculated, and there was a concrete decrease of DH above all in G3 than G2 and G1. Conclusion. Diode laser is a useful device for DH treatment if used alone and mainly if used with NaF gel.

  2. Attenuating effect of seeds of Adenanthera pavonina aqueous extract in neuropathic pain in streptozotocin-induced diabetic rats: an evidence of neuroprotective effects

    Directory of Open Access Journals (Sweden)

    Ramdas B Pandhare

    2012-04-01

    Full Text Available The aim of present study was to investigate the attenuating effects of Adenanthera pavonina L., Leguminosae-Mimosaceae seeds aqueous extract (APSAE, in streptozotocin (STZ-induced diabetic neuropathy in rats. APSAE (50, 100 and 200 mg/kg per day was given to diabetic rats for twelve weeks. Cold and hot water tail immersion tests, photoactometer and Rota-rod tests were performed to assess degree of colder, thermal, spontaneous motor activity and motor co-ordination changes respectively at different time intervals i.e., week 0, 4, 8 and 12. Tissue superoxide anion and total calcium levels were determined after twelve weeks to assess biochemical alterations. Histopathological evaluations of sciatic nerve were also performed to assess nerve damage. APSAE treatment increased tail flick latency significantly in diabetic rats. APSAE also reduced superoxide anion and total calcium levels. These results suggested that APSAE has attenuated development of diabetic neuropathy in streptozotocin-induced diabetic rats when compared with pregabalin (10 mg/kg, p.o. and could be beneficial in preventing the progression of diabetic nephropathy.

  3. Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

    Science.gov (United States)

    Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

    2013-01-01

    Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

  4. Dysmenorrhoea is associated with hypersensitivity in the sigmoid colon and rectum

    DEFF Research Database (Denmark)

    Brinkert, Willem; Dimcevski, Georg; Arendt-Nielsen, Lars

    2007-01-01

    if dysmenorrhoea is associated with hypersensitivity in the referred somatic skin area or in the large bowel, i.e., viscero-visceral hyperalgesia. We measured skin sensitivity in the referred area of the sigmoid colon as well as stimulus-response relationships in the sigmoid colon and rectum. The latter were...... measured using mechanical (balloon) distension applied via a Barostat in 11 dysmenorrhoea patients without gastro-intestinal complaints and 10 healthy and age matched women, again without gastrointestinal complaints. We found no skin hypersensitivity in the colonic referred area. In contrast, significantly...... lower distension volumes were seen at each threshold in dysmenorrhoea patients, particularly in the sigmoid colon. The mean reduction in colonic distension volume thresholds for dysmenorrhoea patients vs. controls was 57% at the detection threshold and 39% at the pain threshold. There were...

  5. Complex Regional Pain Syndrome (CRPS/RSD and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

    Directory of Open Access Journals (Sweden)

    Jennifer Yanow

    2008-01-01

    Full Text Available Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.

  6. Case of immediate hypersensitivity to beer.

    Science.gov (United States)

    Inoue, Tomoko; Yagami, Akiko; Shimojo, Naoshi; Hara, Kazuhiro; Nakamura, Masashi; Matsunaga, Kayoko

    2016-06-01

    We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. © 2015 Japanese Dermatological Association.

  7. 7th drug hypersensitivity meeting: part one

    OpenAIRE

    Carr, Daniel F.; Chung, Wen-Hung; Jenkiins, Rosalind E.; Chaponda, Mas; Nwikue, Gospel; Cornejo Castro, Elena M.; Antoine, Daniel J.; Pirmohamed, Munir; Wuillemin, Natascha; Dina, Dolores; Eriksson, Klara K.; Yerly, Daniel; Pavlos, Rebecca; Mckinnin, Elizabeth; Ostrov, David

    2016-01-01

    Table of contents Oral Abstracts O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture? Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly O3 Specific binding characteristics ...

  8. The role for decorin in delayed-type hypersensitivity

    Science.gov (United States)

    Seidler, Daniela G.; Mohamed, Negia A.; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V.; Zarbock, Alexander; Götte, Martin

    2016-01-01

    Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling and cell growth. As decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity, DTH) in decorin-deficient (Dcn−/−) and wild-type mice. Dcn−/− mice showed a reduced ear swelling 24 hours after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism as determined by 18FDG uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn−/− blood vessels were significantly increased, accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy, flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn−/− leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn−/− mice 24 hours after DTH elicitation, but only moderately increased in wild-type mice. Expression of the pro-inflammatory cytokine TNF-α was reduced, while syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn−/− mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn−/− mice. Collectively, these results implicate a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two non-mutually exclusive mechanisms that involve a direct anti-adhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID:22043007

  9. The Effect of Topical Local Anesthetics on Thermal Pain Sensitivity in Patients with Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    Anthony Rodrigues

    2012-01-01

    Full Text Available Generalized hypersensitivity that extends into somatic areas is common in patients with irritable bowel syndrome (IBS. The sensitized state, particularly assessed by experimental methods, is known to persist even during remissions of clinical pain. It was hypothesized that disease-related nociceptive activity in the gut maintains a systemic-sensitized state. The present study evaluated responses to prolonged thermal stimuli maintained at constant temperature or constant pain intensity during stimulation. The effect of topically applied rectal lidocaine on heat sensitivity was also evaluated. The question is whether silencing potential intestinal neural activity (which may not always lead to a conscious pain experience with lidocaine attenuates sensitization of somatic areas. Tests were also performed where lidocaine was applied orally to control for systemic or placebo effects of the drug. The IBS subjects exhibited a greater sensitivity to somatic heat stimuli compared to controls; however, lidocaine had no discernible effect on sensitization in this sample of IBS patients, where most of the individuals did not have clinical pain on the day of testing.

  10. Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain

    Directory of Open Access Journals (Sweden)

    Rachel D. Moloney

    2015-01-01

    Full Text Available Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8 are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need.

  11. Central sensitization: implications for the diagnosis and treatment of pain.

    Science.gov (United States)

    Woolf, Clifford J

    2011-03-01

    Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the

  12. Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice.

    Science.gov (United States)

    Zhang, Qian; Cao, De-Li; Zhang, Zhi-Jun; Jiang, Bao-Chun; Gao, Yong-Jing

    2016-07-11

    Trigeminal nerve damage-induced neuropathic pain is a severely debilitating chronic orofacial pain syndrome. Spinal chemokine CXCL13 and its receptor CXCR5 were recently demonstrated to play a pivotal role in the pathogenesis of spinal nerve ligation-induced neuropathic pain. Whether and how CXCL13/CXCR5 in the trigeminal ganglion (TG) mediates orofacial pain are unknown. The partial infraorbital nerve ligation (pIONL) was used to induce trigeminal neuropathic pain in mice. The expression of ATF3, CXCL13, CXCR5, and phosphorylated extracellular signal-regulated kinase (pERK) in the TG was detected by immunofluorescence staining and western blot. The effect of shRNA targeting on CXCL13 or CXCR5 on pain hypersensitivity was checked by behavioral testing. pIONL induced persistent mechanical allodynia and increased the expression of ATF3, CXCL13, and CXCR5 in the TG. Inhibition of CXCL13 or CXCR5 by shRNA lentivirus attenuated pIONL-induced mechanical allodynia. Additionally, pIONL-induced neuropathic pain and the activation of ERK in the TG were reduced in Cxcr5 (-/-) mice. Furthermore, MEK inhibitor (PD98059) attenuated mechanical allodynia and reduced TNF-α and IL-1β upregulation induced by pIONL. TNF-α inhibitor (Etanercept) and IL-1β inhibitor (Diacerein) attenuated pIONL-induced orofacial pain. Finally, intra-TG injection of CXCL13 induced mechanical allodynia, increased the activation of ERK and the production of TNF-α and IL-1β in the TG of WT mice, but not in Cxcr5 (-/-) mice. Pretreatment with PD98059, Etanercept, or Diacerein partially blocked CXCL13-induced mechanical allodynia, and PD98059 also reduced CXCL13-induced TNF-α and IL-1β upregulation. CXCL13 and CXCR5 contribute to orofacial pain via ERK-mediated proinflammatory cytokines production. Targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain.

  13. Peripheral and central P2X3 receptor contributions to colon mechanosensitivity and hypersensitivity in the mouse

    Science.gov (United States)

    Shinoda, Masamichi; Feng, Bin; Gebhart, G. F.

    2009-01-01

    Background & Aims Irritable bowel syndrome is characterized by altered sensory qualities, namely discomfort/pain and colorectal hypersensitivity. In mice, we examined the role of P2X3 receptors in colon mechanosensitivity and intracolonic zymosan-produced hypersensitivity, a model of persistent colon hypersensitivity without colon inflammation. Methods The visceromotor response (VMR) to colon distension (15 – 60 mmHg) was determined before and after intracolonic saline or zymosan (30 mg/mL, 0.1 mL, daily for 3 days) treatment. Colon pathology and intracolonic ATP release was assessed in parallel experiments. To examine P2X3 receptor contributions to colon mechanosensation and hypersensitivity, electrophysiological experiments were performed using an in vitro colon-pelvic nerve preparation. Results VMRs to distension were significantly reduced in P2X3+/−and P2X3−/− mice relative to wildtype mice. Colon hypersensitivity produced by zymosan was virtually absent in P2X3−/− relative to wildtype or P2X3+/− mice. Intralumenal release of the endogenous P2X receptor ligand ATP did not differ between wildtype and P2X3−/− mice or change after intracolonic zymosan treatment. Responses of muscular and muscular-mucosal pelvic nerve afferents to mechanical stretch did not differ between P2X3−/− and wildtype mice. Both muscular and muscular-mucosal afferents in wildtype mice sensitized to application of an inflammatory soup, whereas only muscular-mucosal afferents did so in P2X3−/− mice. Conclusions These results suggest differential roles for peripheral and central P2X3 receptors in colon mechanosensory transduction and hypersensitivity. PMID:19549524

  14. Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sagen J

    2016-06-01

    Full Text Available Jacqueline Sagen, Daniel A Castellanos,† Aldric T Hama The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA †Daniel A Castellanos passed away on April 14, 2010 Background: A consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain.Methods: The efficacy of topical anesthetics was evaluated in a preclinical rodent model of painful peripheral neuropathy induced by epineural administration of the HIV envelope protein gp120 delivered using saturated oxidized cellulose implanted around the sciatic nerve. Beginning at 2 weeks following gp120 administration, the effects of local anesthetics topically applied via gauze pads were tested on heat and mechanical hyperalgesia in the hind paw. Rats were tested using several concentrations of mepivacaine or lidocaine during the following 2 weeks.Results: By 2 weeks following epineural gp120 implantation, the ipsilateral hind paw developed significant hypersensitivity to noxious pressure and heat hyperalgesia. A short-lasting, concentration-dependent amelioration of pressure and heat hyperalgesia was observed following topical application of mepivacaine to the ipsilateral plantar hind paw. By contrast, topical lidocaine ameliorated heat hyperalgesia in a concentration-dependent manner but not pressure hyperalgesia. Equipotent concentrations of mepivacaine and lidocaine applied topically to the

  15. Development of mechanical hypersensitivity in rats during heroin and ethanol dependence: alleviation by CRF₁ receptor antagonism.

    Science.gov (United States)

    Edwards, Scott; Vendruscolo, Leandro F; Schlosburg, Joel E; Misra, Kaushik K; Wee, Sunmee; Park, Paula E; Schulteis, Gery; Koob, George F

    2012-02-01

    Animal models of drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often leads to the development of mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to heroin or cocaine self-administration, or in rats made dependent on ethanol via ethanol vapor exposure (ethanol-dependent group). In heroin self-administering animals, after transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to heroin LgA rats, ethanol-dependent rats also developed mechanical hypersensitivity after eight weeks of ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the hypersensitivity observed in rats dependent on heroin or ethanol. The emergence of mechanical hypersensitivity with heroin and ethanol dependence may thus represent one critical drug-associated negative emotional state driving dependence on these substances. These results also suggest a recruitment of CRF-regulated nociceptive pathways associated with escalation of intake and dependence. A greater understanding of relationships between chronic drug exposure and pain-related states may provide insight into mechanisms underlying the transition to drug addiction, as well as reveal new treatment opportunities. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

    Science.gov (United States)

    Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

    2014-01-01

    Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

  17. An unusual oral habit presenting as Dentin Hypersensitivity | Afolabi ...

    African Journals Online (AJOL)

    We present the case of a 30-year-old man with an unusual oral habit- office pin chewing and filing of the front tooth which resulted in dentine hypersensitivity. Clinical relevance: The role of daily oral habits and techniques of cessation were suggested in the management of dentine hypersensitivity. Keywords: Unusual oral ...

  18. Teenagers' experiences of living with food hypersensitivity: a qualitative study.

    Science.gov (United States)

    MacKenzie, Heather; Roberts, Graham; van Laar, Darren; Dean, Taraneh

    2010-06-01

    Teenagers are a high-risk group for food-hypersensitivity fatalities, engage in risk-taking behaviours and may experience impaired quality of life. Understanding their experience is important to inform their care. This study aimed to describe the lived experiences of teenagers with food hypersensitivity. Individual semi-structured interviews were conducted with 21 teenagers (13-18 yr) with food hypersensitivity to a variety of foods and analysed using a phenomenological approach. Teenagers described living with (or coming to know) food hypersensitivity (FHS) as a way of life but still found living with food hypersensitivity to be burdensome. A necessary part of living with food hypersensitivity was coping with associated burden; a variety of coping strategies were employed to this effect. Teenagers described ways in which the burden of living with food hypersensitivity was alleviated or exacerbated by others. Management of food hypersensitivity was based on an assessment of acceptable risk resulting in varying levels of precaution taking. Teenagers' understanding of their FHS and ability to cope with it needs to be regularly assessed. Educational support may be required to ensure they take an appropriate level of precautions to minimize the chance of future reactions while not over compromising their quality of life. Psychological support may be required to help them to utilize healthy adaptive strategies to cope with the stresses of living with FHS. This approach is also likely to facilitate the smooth handover of responsibility from parent to teenager.

  19. Clinical efficacy of toothpaste containing potassium citrate in treating dentin hypersensitivity

    Directory of Open Access Journals (Sweden)

    Shih-Ya Shen

    2009-12-01

    Conclusion: The prevalence of dentin hypersensitivity in this study was 38%. The use of desensitizing toothpaste containing potassium citrate with oral hygiene instruction can effectively reduce dentin hypersensitivity.

  20. Salmon and human thrombin differentially regulate radicular pain, glial-induced inflammation and spinal neuronal excitability through protease-activated receptor-1.

    Directory of Open Access Journals (Sweden)

    Jenell R Smith

    Full Text Available Chronic neck pain is a major problem with common causes including disc herniation and spondylosis that compress the spinal nerve roots. Cervical nerve root compression in the rat produces sustained behavioral hypersensitivity, due in part to the early upregulation of pro-inflammatory cytokines, the sustained hyperexcitability of neurons in the spinal cord and degeneration in the injured nerve root. Through its activation of the protease-activated receptor-1 (PAR1, mammalian thrombin can enhance pain and inflammation; yet at lower concentrations it is also capable of transiently attenuating pain which suggests that PAR1 activation rate may affect pain maintenance. Interestingly, salmon-derived fibrin, which contains salmon thrombin, attenuates nerve root-induced pain and inflammation, but the mechanisms of action leading to its analgesia are unknown. This study evaluates the effects of salmon thrombin on nerve root-mediated pain, axonal degeneration in the root, spinal neuronal hyperexcitability and inflammation compared to its human counterpart in the context of their enzymatic capabilities towards coagulation substrates and PAR1. Salmon thrombin significantly reduces behavioral sensitivity, preserves neuronal myelination, reduces macrophage infiltration in the injured nerve root and significantly decreases spinal neuronal hyperexcitability after painful root compression in the rat; whereas human thrombin has no effect. Unlike salmon thrombin, human thrombin upregulates the transcription of IL-1β and TNF-α and the secretion of IL-6 by cortical cultures. Salmon and human thrombins cleave human fibrinogen-derived peptides and form clots with fibrinogen with similar enzymatic activities, but salmon thrombin retains a higher enzymatic activity towards coagulation substrates in the presence of antithrombin III and hirudin compared to human thrombin. Conversely, salmon thrombin activates a PAR1-derived peptide more weakly than human thrombin. These

  1. Tunicate-Inspired Gallic Acid/Metal Ion Complex for Instant and Efficient Treatment of Dentin Hypersensitivity.

    Science.gov (United States)

    Prajatelistia, Ekavianty; Ju, Sung-Won; Sanandiya, Naresh D; Jun, Sang Ho; Ahn, Jin-Soo; Hwang, Dong Soo

    2016-04-20

    Dentin hypersensitivity is sharp and unpleasant pains caused by exposed dentinal tubules when enamel outside of the tooth wears away. The occlusion of dentinal tubules via in situ remineralization of hydroxyapatite is the best method to alleviate the symptoms caused by dentin hypersensitivity. Commercially available dental desensitizers are generally effective only on a specific area and are relatively toxic, and their performance usually depends on the skill of the clinician. Here, a facile and efficient dentin hypersensitivity treatment with remarkable aesthetic improvement inspired by the tunicate-self-healing process is reported. As pyrogallol groups in tunicate proteins conjugate with metal ions to heal the torn body armor of a tunicate, the ingenious mechanism by introducing gallic acid (GA) as a cheap, abundant, and edible alternative to the pyrogallol groups of the tunicate combined with a varied daily intake of metal ion sources is mimicked. In particular, the GA/Fe(3+) complex exhibits the most promising results, to the instant ≈52% blockage in tubules within 4 min and ≈87% after 7 d of immersion in artificial saliva. Overall, the GA/metal ion complex-mediated coating is facile, instant, and effective, and is suggested as an aesthetic solution for treating dentin hypersensitivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Effectiveness of a baking soda toothpaste delivering calcium and phosphate in reducing dentinal hypersensitivity.

    Science.gov (United States)

    Ghassemi, A; Hooper, W; Winston, A E; Sowinski, J; Bowman, J; Sharma, N

    2009-01-01

    The purpose of this controlled clinical trial was to determine the effectiveness and safety of a single-phase dentifrice that delivers calcium, phosphate, and fluoride to the tooth surface (Arm & Hammer Enamel Care for Sensitive Teeth toothpaste, United Kingdom) in reducing dentinal hypersensitivity. Two-hundred and eight qualifying subjects were randomly assigned to either the Enamel Care dentifrice group or a control dentifrice group, and brushed twice daily with their assigned dentifrice for eight weeks. Pain/discomfort in response to a thermal stimulus was assessed at baseline, week 4, and week 8 using a Visual Analogue Scale (VAS; primary outcome variable) and the Schiff Thermal Sensitivity Scale (STSS; secondary outcome variable). After eight weeks, volunteers from the Enamel Care group were switched to the control dentifrice and participated in a second eight-week study to determine the degree of persistence of pain reduction. Both groups had statistically significant VAS score reductions from baseline at weeks 4 and 8, with mean VAS scores in the Enamel Care group decreasing by 45.6% at week 4 and 61.1% at week 8 (p < 0.0001). Enamel Care was statistically significantly more effective than the control at weeks 4 and 8, with respective mean VAS reductions of 63% (p < 0.0001) and 33% (p = 0.0004) greater than the control. Consistent with the VAS score results, the Enamel Care group had respective statistically significant STSS score reductions of 77% and 58% greater than the control group (p < 0.0001). The reductions in dentinal hypersensitivity seen in the Enamel Care group at week 8 persisted for an additional eight weeks, during which the subjects discontinued use of Enamel Care and brushed with the control dentifrice. Enamel Care for Sensitive Teeth toothpaste (United Kingdom) is an effective dentifrice for the management of dentinal hypersensitivity, and its efficacy persists for a least eight weeks following discontinued product use.

  3. Dentin hypersensitivity clinical study comparing LILT and LEDT keeping the same irradiation parameters

    International Nuclear Information System (INIS)

    Lizarelli, R F Z; Miguel, F A C; Bagnato, V S; Freitas-Pontes, K M; Villa, G E P; Nunez, S C

    2010-01-01

    Dentin hypersensitivity is a common condition associated with high dental pain. A new LED-based (light emitting diode) light source has been used as an experimental tool in some studies. Purpose: The main objective was to compare these two light sources emitting in the same spectral band (red – from 625 to 660 nm) to promote pain relief. Material and methods: A total of 6 sessions were accomplished, being three irradiation sessions and three follow-up sessions. This single-blind study compared a control group (Placebo) and two other groups with different equipments: low laser intensity treatment (LILT) and a light emitting diode system treatment (LEDT). Results: The results showed that there is no statistical difference between LILT and LEDT groups, however, both were better than control group (p ≤ 0.01) in terms of treatment efficiency; there is no difference between the second and the third sessions for both treatment, it means that the third session was not necessary; finally, the improvement at the end of the entire research (follow up care of 30 days) was very expressive in comparison to pre-treatment situation for all teeth (p ≤ 0.01). Conclusion: LILT and LEDT were equally effective to treat dentine hypersensitivity, a 3rd treatment session was not necessary/two sessions are enough

  4. Respiratory hypersensitivity reactions to NSAIDs in Europe

    DEFF Research Database (Denmark)

    Makowska, J S; Burney, P; Jarvis, D

    2016-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper...... and lower respiratory tract disorders. METHODS: The GA(2) LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled...... prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants...

  5. Cold hypersensitivity increases with age in mice with sickle cell disease

    Science.gov (United States)

    Zappia, Katherine J.; Garrison, Sheldon R.; Hillery, Cheryl A.; Stucky, Cheryl L.

    2014-01-01

    Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. Additionally, both humans and mice with SCD experience heighted cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization, nor its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Further, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold-sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold-detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the Transient Receptor Potential Melastatin 8 (Trpm8) and TRP Ankyrin 1 (Trpa1) channels, as well as the two-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk4), and TRAAK (Kcnk10). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Sensory neurons from sickle cell disease mice are sensitized to cold, mirroring behavioral observations, and have increased expression of endothelin 1 and tachykinin receptor 1. PMID:24953902

  6. Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion.

    Science.gov (United States)

    Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

    2014-09-01

    Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. © 2014 Associated Professional Sleep Societies, LLC.

  7. Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Limsrivilai, Julajak; Charatcharoenwitthaya, Phunchai; Pausawasdi, Nonthalee; Leelakusolvong, Somchai

    2016-02-01

    Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.

  8. Plasticity in intact A delta- and C-fibers contributes to cold hypersensitivity in neuropathic rats.

    Science.gov (United States)

    Ji, G; Zhou, S; Kochukov, M Y; Westlund, K N; Carlton, S M

    2007-11-30

    Cold hypersensitivity is a common sensory abnormality accompanying peripheral neuropathies and is difficult to treat. Progress has been made in understanding peripheral mechanisms underlying neuropathic pain but little is known concerning peripheral mechanisms of cold hypersensitivity. The aim of this study was to analyze the contribution of uninjured primary afferents to the cold hypersensitivity that develops in neuropathic rats. Rats with a lumbar 5 (L5) and L6 spinal nerve ligation (SNL, Chung model) but not sham, developed mechanical allodynia, evidenced by decreased paw withdrawal thresholds and increased magnitude of response to von Frey stimulation. Cold hypersensitivity also developed in SNL but not sham rats, evidenced by enhanced nociceptive behaviors induced by placement on a cold plate (6 degrees C) or application of icilin (a transient receptor potential M8 (TRPM8)/transient receptor potential A1 (TRPA1) receptor agonist) to nerve-injured hind paws. Single fiber recordings demonstrated that the mean conduction velocities of intact L4 cutaneous A delta- and C-fibers were not different between naive and SNL rats; however, mechanical thresholds of the A delta- but not the C-fibers were significantly decreased in SNL compared with naive. There was a higher prevalence of C-mechanoheat-cold (CMHC) fibers in SNL compared with naive, but the overall percentage of cold-sensitive C-fibers was not significantly increased compared with naive. This was in contrast to the numerous changes in A delta-fibers: the percentage of L4 cold sensitive A delta-, but not C-fibers, was significantly increased, the percentage of L4 icilin-sensitive A delta-, but not C-fibers, was significantly increased, the icilin-induced activity of L4 A delta-, but not C-fibers, was significantly increased. Icilin-induced activity was blocked by the TRPA1 antagonist Ruthenium Red. The results indicate plasticity in both A delta- and C-uninjured fibers, but A delta fibers appear to provide a

  9. Dilemma in the Diagnosis of Povidone-Iodine Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Patil N

    2016-01-01

    Full Text Available Povidone-iodine is a commonly used antiseptic solution in surgical practice. Almost every patient who needs a minor or a major surgical procedure (sometimes, a medical procedure too gets exposed to this antiseptic. Even though the use of this antiseptic is widespread, the number of cases reporting hypersensitivity to it is meagre. This case report highlights a case of povidone-iodine – induced hypersensitivity, which presented a great difficulty in diagnosis, due to the usage of other drugs that could have been more likely causes for this hypersensitivity.

  10. Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

    Science.gov (United States)

    O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L

    2017-06-01

    Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Investigation of Seminal Plasma Hypersensitivity Reactions

    National Research Council Canada - National Science Library

    Bernstein, Jonathan

    1998-01-01

    Gulf War (GW)Veterans and/or their sexual partners have been-experiencing burning, pain and swelling of the urogenital tract after exposure to semen since returning from the Persian Gulf which has been...

  12. Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity.

    Science.gov (United States)

    Sideris, Alexandra; Piskoun, Boris; Russo, Lori; Norcini, Monica; Blanck, Thomas; Recio-Pinto, Esperanza

    2016-01-01

    The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R-/-) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. At baseline, CB1R-/- mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R-/- mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R-/- mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/-) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R-/- mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different among genotypes. Cold allodynia and

  13. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

    Science.gov (United States)

    Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

    2009-04-01

    Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

  14. Prevalence and potential factors associated with probable sleep or awake bruxism and dentin hypersensitivity in undergraduate students

    Directory of Open Access Journals (Sweden)

    Neusa Barros DANTAS-NETA

    Full Text Available OBJECTIVE: To measure the prevalence of probable sleep or awake bruxism and cervical dentin hypersensitivity of undergraduate students and to determine the symptoms associated with these conditions.METHODOLOGY: This was a cross-sectional study. A diagnosis of probable bruxism was reached when students reported clenching or grinding of the teeth during sleep and/or wakefulness, and when they also presented some of the signs and symptoms of bruxism and masseter muscle pain on palpation. Cervical dentinal hypersensitivity was diagnosed by testing for sensitivity to pain in the cervical region of the teeth. Pain was triggered either by touch (using a #5 probe or by an air jet spray. The sample consisted of 306 university students aged between 19 and 35 years old. The data were stored and analysed using SPSS software, version 15.0 for Windows.RESULT: The prevalence of probable bruxism was 34.3%, with no predominance regarding sex. Probable awake bruxism was more prevalent (61.9%, mostly occurring when the individual reported being in a state of mental concentration (63.1%. There was no association between probable sleep or awake bruxism and dentin hypersensitivity (p = 0.195. Individuals with probable sleep bruxism had increased odds of having muscular pain in the face upon waking (OR = 14.14, 95% CI 5.06-39.55, and those with probable awake bruxism had a increased odds of having facial muscle fatigue when chewing or talking for a long time (OR = 2.88, 95% CI 1.53-5.43 and muscular pain in the face upon waking (OR = 5.31, 95% CI 1.93-14.62.CONCLUSION: The prevalence of probable bruxism was 34.3% and that of HDC was 57.8%, with 22.2% of these subjects also showing probable bruxism. Individuals with probable bruxism tended to have a higher odds of facial pain when they awakened and when chewing or talking for long periods. There were no associations between probable sleep and awake bruxism and cervical dentin hypersensitivity.

  15. Comparative study of analgesic effect of the infrared low-intensity laser and 33% sodium fluoride paste in the treatment of dentinal hypersensitivity

    International Nuclear Information System (INIS)

    Oliveira, Glen Anderson Maia de

    2003-01-01

    Different desensitizing agents have been used in the treatment of dentinal hypersensitivity, however, some presented treatments are still frustrating. The purpose of this study was to evaluate the analgesic effect of the low-intensity GaAlAs laser (λ= 830 nm) in the treatment of dentinal hypersensitivity after mechanical and thermal stimuli, and compared it with the 33% sodium fluoride paste. Thirty two teeth with dentinal hypersensitivity were selected and randomly divided into two groups. For the laser group, each tooth was irradiated by a dose of 6 J/cm 2 during two minutes and half on the buccal side. The paste group was treated with a NaF/kaolin/glycerin (33:33:33) paste by burnishing the sensitive surface during four minutes. The sensitivity degree was measured before the beginning of the experiment, 24 h, 48 h, 72 h, 120 h, 15 days and 30 days after the first application. The results indicate that the dentinal hypersensitivity significantly diminished for the paste group after dental explorer. Regarding to air-blast, no significant differences were observed between the groups. Both of them were effective in reducing pain of the dentine hypersensitive after 120 h. (author)

  16. Visceral hypersensitivity is provoked by 2,4,6-trinitrobenzene sulfonic acid-induced ileitis in rats

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Shah

    2016-07-01

    Full Text Available Background and Aims: Crohn’s Disease (CD, a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn’s ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS-induced ileitis rats.Methods: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48, an equal volume of 30% Ethanol (n = 24 and Saline (n = 24, respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR to 20, 40, 60, 80 and 100 mmHg colorectal distension pressure (CRD at day 1, 3, 7, 14, 21 and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1β, IL-6, and dorsal root ganglia (T11 for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. Results: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05 VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05 in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats.Conclusions: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral

  17. Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

    Science.gov (United States)

    Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

    2012-09-01

    Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Progressive anticonvulsant hypersensitivity syndrome associated with change of drug product

    DEFF Research Database (Denmark)

    Sabroe, T.P.; Sabers, A.

    2008-01-01

    This report describes the laboratory and physical manifestations of lamotrigine-like toxicity in a young man with refractory epilepsy receiving lamotrigine presenting as anticonvulsant hypersensitivity syndrome (AHS) associated with an abrupt change of drug product Udgivelsesdato: 2008/6...

  19. The radiation hypersensitivity of cells at mitosis.

    Science.gov (United States)

    Stobbe, C C; Park, S J; Chapman, J D

    2002-12-01

    Mitotic cells are hypersensitive to ionizing radiation, exhibiting single-hit inactivation coefficients near to those of repair deficient cell lines and lymphocytes. To elucidate possible mechanisms for this hypersensitivity, the kinetics of oxygen radiosensitization, the proportion of indirect effect by OH radicals and the kinetics of radiation-induced DNA strand breakage in the chromatin of mitotic cells were investigated. Synchronized populations of >90% mitotic HT-29 cells were obtained by the mitotic shake-off method. Cells were irradiated at indirect effect of OH radicals was investigated with the radical scavenger, DMSO. DNA strand breakage was measured by the comet assay. Mitotic HT-29 cell inactivation is well described by a single-hit inactivation coefficient (alpha) of 1.14 +/- 0.06 Gy(-1). The oxygen enhancement ratio of mitotic cells (at 10% survival) was found to be approximately 2.0, significantly lower than the value of 2.8 measured for interphase (asynchronous) cells. More than 60% of mitotic cell killing was eliminated when the media contained 2 M DMSO, indicating that indirect effect is as important in the killing of mitotic cells as it is for interphase cells. The chromatin in mitotic cells was found to be ~2.8 times more sensitive to radiation-induced DNA single-strand breakage than the chromatin of interphase cells. The alpha-inactivation coefficient of mitotic HT-29 cells was ~30 times larger than that of interphase cells. Mitotic cell chromatin appears to contain intrinsic DNA breaks that are not lethal. In addition, chromatin in mitotic cells was found to be more susceptible to radiation-induced DNA strand-breakage than the dispersed chromatin of interphase cells. How the enhanced production of these simple DNA lesions (that are usually reparable) translates into the lethal (non-reparable) events associated with alpha-inactivation is not known. The compaction/dispersion status of DNA throughout the cell cycle appears to be an important

  20. A Rare Diabetic Autonomic Neuropathy: Carotid Sinus Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Ahmet Kaya

    2016-03-01

    Full Text Available Carotid sinus hypersensitivity is a common cause of fainting and falls in the elderly, and can be diagnosed by carotid sinus massage. We present a 67-year-old diabetic man who was admitted with hyperglycemia. During thyroid examination, clouding of consciousness occurred with unilateral palpation. Asystole was documented for 4.8 seconds and suspected for 7 seconds upon carotid sinus massage. A cardioverter defibrillator was implanted. Carotid sinus hypersensitivity should be kept in mind when examining diabetic patients.

  1. Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs: An Update

    OpenAIRE

    Sánchez-Borges, Mario; Caballero-Fonseca, Fernan; Capriles-Hulett, Arnaldo; González-Aveledo, Luis

    2010-01-01

    After beta lactam antibiotics, hypersensitivity reactions to nonsteroidal antiinflammatory drugs are the second cause of hypersensitivity to drugs. Acute manifestations affect the respiratory tract (aspirin exacerbated respiratory disease), the skin (urticaria and angioedema), or are generalized (anaphylaxis). Correct diagnosis and treatment in order to prevent unnecessary morbidity and the potential risk of death from these severe reactions, and to provide proper medical advice on future dru...

  2. Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model.

    Science.gov (United States)

    Prusator, D K; Greenwood-Van Meerveld, B

    2016-12-01

    Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific. Following ELA, adult stress was induced via a single exposure (acute) or repetitive daily exposure, 1 h/day for 7 days (chronic), to water avoidance stress (WAS). Acute WAS increased pain behaviors in all adult female rats, however, females that experienced unpredictable ELA exhibited significantly more pain behaviors compared to those exposed to predictable ELA or controls. Following chronic WAS, all adult females exhibited increased pain responses, however, an exaggerated response was observed in rats exposed to unpredictable or predictable ELA compared to controls. Similarly, in adult male rats exposure to acute or chronic WAS increased pain behaviors, however, there were no differences in pain behaviors between ELA groups. This study highlights a novel consequence of ELA on stress-induced visceral nociception in adulthood that is sex-specific. More importantly, our study suggests that ELA not only serves as a risk factor for development of chronic pain in adulthood, but also serves as a predisposition for worsening of visceral pain following adult stress in female rats. © 2016 John Wiley & Sons Ltd.

  3. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice

    International Nuclear Information System (INIS)

    Patterson, Rachel; Vega, Libia; Trouba, Kevin; Bortner, Carl; Germolec, Dori

    2004-01-01

    Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity

  4. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Chun-Bing Chen

    2018-01-01

    Full Text Available Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS/drug-induced hypersensitivity syndrome (DIHS, or Stevens–Johnson syndrome (SJS/toxic epidermal necrolysis (TEN. Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs. The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.

  5. An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity

    Science.gov (United States)

    Abe, Riichiro; Pan, Ren-You; Wang, Chuang-Wei

    2018-01-01

    Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity. PMID:29651444

  6. Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

    Science.gov (United States)

    Bonamichi-Santos, Rafael; Castells, Mariana

    2016-01-01

    Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Bilateral experimental neck pain reorganize axioscapular muscle coordination and pain sensitivity.

    Science.gov (United States)

    Christensen, S W; Hirata, R P; Graven-Nielsen, T

    2017-04-01

    Neck pain is a large clinical problem where reorganized trunk and axioscapular muscle activities have been hypothesised contributing to pain persistence and pain hypersensitivity. This study investigated the effects of bilateral experimental neck pain on trunk and axioscapular muscle function and pain sensitivity. In 25 healthy volunteers, bilateral experimental neck pain was induced in the splenius capitis muscles by hypertonic saline injections. Isotonic saline was used as control. In sitting, subjects performed slow, fast and slow-resisted unilateral arm movements before, during and after injections. Electromyography (EMG) was recorded from eight shoulder and trunk muscles bilaterally. Pressure pain thresholds (PPTs) were assessed bilaterally at the neck, head and arm. Data were normalized to the before-measures. Compared with control and post measurements, experimental neck pain caused (1) decreased EMG activity of the ipsilateral upper trapezius muscles during all but slow-resisted down movements (p neck pain reorganized axioscapular and trunk muscle activity together with local hyperalgesia and widespread hypoalgesia indicating that acute neck pain immediately affects trunk and axioscapular function which may affect both assessment and treatment. Bilateral clinical neck pain alters axioscapular muscle coordination but only effects of unilateral experimental neck pain has been investigated. Bilateral experimental neck pain causes task-dependent reorganized axioscapular and trunk muscle activity in addition to widespread decrease in pressure pain sensitivity. © 2016 European Pain Federation - EFIC®.

  8. Nonimmediate hypersensitivity reactions to iodinated contrast media.

    Science.gov (United States)

    Gómez, Enrique; Ariza, Adriana; Blanca-López, Natalia; Torres, Maria J

    2013-08-01

    To provide a detailed analysis of the latest findings on the mechanisms underlying the nonimmediate reactions to iodinated contrast media and comment on the recent advances in diagnosis, focusing on the roles of the skin test, drug provocation test (DPT), and lymphocyte transformation test (LTT). Several studies have reported new findings supporting an important role for T-lymphocytes in the nonimmediate reactions to iodinated contrast media. The LTT has been used as an in-vitro tool for diagnosis, but with variable results. However, the inclusion of autologous monocyte-derived dendritic cells as professional antigen-presenting cells has improved the sensitivity of this test. Regarding in-vivo diagnosis, although skin testing has been routine, it has now been shown that its sensitivity and negative predictive value are low. Recent studies have demonstrated that the DPT is a well tolerated and useful procedure that is necessary to confirm the diagnosis of nonimmediate hypersensitivity reactions to iodinated contrast media. Nonimmediate reactions to contrast media are usually T-cell mediated. Diagnosis is based on skin testing, although its sensitivity and negative predictive value are not optimal. Consequently, drug provocation testing is often needed to confirm the diagnosis and also to seek alternative contrast media that can be tolerated.

  9. Severe dapsone hypersensitivity syndrome in a child

    Directory of Open Access Journals (Sweden)

    So Yoon Choi

    2013-06-01

    Full Text Available Dapsone (4,4'-diaminodiphenylsulfone, DDS, a potent anti-inflammatory agent, is widely used in the treatment of leprosy and several chronic inflammatory skin diseases. Dapsone therapy rarely results in development of dapsone hypersensitivity syndrome, which is characterized by fever, hepatitis, generalized exfoliative dermatitis, and lymphadenopathy. Here, we describe the case of an 11-year-old Korean boy who initially presented with high fever, a morbilliform skin rash, generalized lymphadenopathy, hepatosplenomegaly, and leukopenia after 6 weeks of dapsone intake. Subsequently, he exhibited cholecystitis, gingivitis, colitis, sepsis, aseptic meningitis, disseminated intravascular coagulation, syndrome of inappropriate antidiuretic hormone secretion, pneumonia, pleural effusions, peritonitis, bronchiectatic changes, exfoliative dermatitis, and acute renal failure. After 2 months of supportive therapy, and prednisolone and antibiotic administration, most of the systemic symptoms resolved, with the exception of exfoliative dermatitis and erythema, which ameliorated over the following 4 months. Agranulocytosis, atypical lymphocytosis, aseptic meningitis, and bronchiectatic changes along with prolonged systemic symptoms with exfoliative dermatitis were the most peculiar features of the present case.

  10. Hazards of the 'hard cash': hypersensitivity pneumonitis.

    Science.gov (United States)

    Kupeli, Elif; Karnak, Demet; Sak, Serpil Dizbay; Kayacan, Oya

    2010-01-01

    Hypersensitivity pneumonitis (HP) is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors' knowledge, the present report is the first to describe 'hard cash HP', possibly caused by chipping dust or printing dye.

  11. 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.

  12. Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy

    Directory of Open Access Journals (Sweden)

    Ricardo A Gómez Tejada

    2017-12-01

    Full Text Available In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.

  13. The endogenous hydrogen sulfide producing enzyme cystathionine-β synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Chen Jiande DZ

    2009-08-01

    Full Text Available Abstract Background The pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS, remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-β-synthetase (CBS in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH. CVH was induced by colonic injection of 0.5% acetic acid (AA in 10-day-old rats and experiments were performed at 8–10 weeks of age. Dorsal root ganglion (DRG neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate into the colon wall. Results In rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H2S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation. Conclusion Our results suggest that upregulation of CBS expression in colonic DRG neurons and H2S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.

  14. Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia?

    Science.gov (United States)

    Bashashati, Mohammad; Hejazi, Reza A; Andrews, Christopher N; Storr, Martin A

    2014-01-01

    Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy. PMID:24719900

  15. Effect of DA-9701 on colorectal distension-induced visceral hypersensitivity in a rat model.

    Science.gov (United States)

    Kim, Eun Ran; Min, Byung-Hoon; Lee, Tae Ho; Son, Miwon; Rhee, Poong-Lyul

    2014-07-01

    DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Co-rydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.

  16. Hypersensitivity myocarditis associated with ephedra use.

    Science.gov (United States)

    Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B

    1999-01-01

    Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

  17. Hypersensitivity pneumonitis: a complex lung disease.

    Science.gov (United States)

    Riario Sforza, Gian Galeazzo; Marinou, Androula

    2017-01-01

    Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is a respiratory syndrome involving the lung parenchyma and specifically the alveoli, terminal bronchioli, and alveolar interstitium, due to a delayed allergic reaction. Such reaction is secondary to a repeated and prolonged inhalation of different types of organic dusts or other substances to which the patient is sensitized and hyper responsive, primarily consisting of organic dusts of animal or vegetable origin, more rarely from chemicals. The prevalence of HP is difficult to evaluate because of uncertainties in detection and misdiagnosis and lacking of widely accepted diagnostic criteria, and varies considerably depending on disease definition, diagnostic methods, exposure modalities, geographical conditions, agricultural and industrial practices, and host risk factors. HP can be caused by multiple agents that are present in work places and in the home, such as microbes, animal and plant proteins, organic and inorganic chemicals. The number of environment, settings and causative agents is increasing over time. From the clinical point of view HP can be divided in acute/subacute and chronic, depending on the intensity and frequency of exposure to causative antigens. The mainstay in managing HP is the avoidance of the causative antigen, though the complete removal is not always possible due to the difficulties to identify the agent or because its avoidance may lead to major changes in life style or occupational settings. HP is a complex syndrome that needs urgently for more stringent and selective diagnostic criteria and validation, including wider panels of IgG, and a closer collaboration with occupational physicians, as part of a multidisciplinary expertise.

  18. Contribution of the local and referred pain from active myofascial trigger points in fibromyalgia syndrome

    DEFF Research Database (Denmark)

    Ge, Hong-You; Nie, Hongling; Madeleine, Pascal

    2009-01-01

    The generalized hypersensitivity associated with fibromyalgia syndrome (FMS) may in part be driven by peripheral nociceptive sources. The aim of the study was to investigate whether local and referred pain from active myofascial trigger points (MTrPs) contributes to fibromyalgia pain. FMS patients...

  19. 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. ...

  20. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    International Nuclear Information System (INIS)

    Winocour, P.D.; Rand, M.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.

    1986-01-01

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with 14 C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A 2 (TXA 2 ) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more 14 C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p 14 C release: 1.5 +/- 0.5%, p 2 formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of 125 I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA 2 formation, the action of released ADP or increased thrombin binding

  1. NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity.

    Science.gov (United States)

    Norcini, Monica; Sideris, Alexandra; Adler, Samantha M; Hernandez, Lourdes A M; Zhang, Jin; Blanck, Thomas J J; Recio-Pinto, Esperanza

    2016-01-01

    Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma's plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23

  2. Asthma and chemical hypersensitivity: prevalence, etiology, and age of onset.

    Science.gov (United States)

    Caress, S M; Steinemann, A C

    2009-02-01

    This study investigates asthma's national prevalence and potential overlap with chemical hypersensitivity. It also examines asthma's etiology, age of onset, and demographic characteristics. Data were collected from a geographically weighted random sample of the continental U.S. (1058 cases), in four seasonal cohorts (2005-2006). The study found that 12.9% of the sample report asthma, 11.6% report chemical hypersensitivity, and 31.4% of those with asthma report chemical hypersensitivity. Among asthmatics, 38% report irritation from scented products, 37.2% report health problems from air fresheners, and 13.6% report their asthma was caused by toxic exposure. Asthma cases affected each racial/ethic group in roughly the same proportion, with nearly 50% classified as childhood onset.

  3. Multinational experience with hypersensitivity drug reactions in Latin America.

    Science.gov (United States)

    Jares, Edgardo José; Sánchez-Borges, Mario; Cardona-Villa, Ricardo; Ensina, Luis Felipe; Arias-Cruz, Alfredo; Gómez, Maximiliano; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos D; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Cherrez-Ojeda, Iván

    2014-09-01

    Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. FOOD HYPERSENSITIVITY AND PRODUCTS OF ANIMAL ORIGIN RESOURCES

    Directory of Open Access Journals (Sweden)

    A. B. Lisitsyn

    2017-01-01

    Full Text Available The number of people with food hypersensitivity, namely food intolerance and food allergies, grows every year. Food intolerance is classified into following types: enzymopathy; leaky gut syndrome; psychogenic food intolerance; detoxification insufficiency and true food intolerance. Food allergens mainly are glycoproteins, haptensor polypeptides. Most cases of food allergy are IgE-mediated allergic reactions. Recent discoveries in medicine, detailing and classification of food hypersensitivity require further researches to develop modern techniques and product recipes with specified propertiesfor consumers with food hypersensitivity. Existing technologies are based on the elimination and or reduction of the content of the allergenic substance in food. The article provides an overview of causes of food intolerance and food allergy, legislative background, a list of food allergens and methods of control, market profile of hypoallergenic produce and scientific approaches to creating hypoallergenic food products based on raw materials of animal origin.

  5. [Adaptive desensitization for acetylsalicylic acid hypersensitivity: A success story?].

    Science.gov (United States)

    Mühlmeier, G; Hausch, R; Maier, H

    2015-10-01

    Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.

  6. Efficacy of two commercially available dentifrices in reducing dentinal hypersensitivity

    Directory of Open Access Journals (Sweden)

    Prasad KVV

    2010-01-01

    Full Text Available Objective: A parallel design clinical study evaluated reduction in hypersensitivity after brushing for 12 weeks with Anchor toothpaste (containing potassium citrate, zinc citrate, triclosan and sodium monofluorophosphate (test and Colgate Total (sodium fluoride, silica, triclosan and copolymer (control dentifrices. Materials and Methods: Sixty adults with sensitivity to hot and cold stimulus in at least two tooth surfaces were stratified at the baseline examination by tactile, hot and cold stimuli scores in two balanced groups. Subjects were randomly allocated the test and control dentifrices and evaluated after 6 and 12 weeks of dentifrice use for hypersensitivity. Results: The two teeth that were selected in each patient were designated as two different sets. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the test group showed a reduction in tooth hypersensitivity by 36.67% (P < 0.01, 20.35% (P < 0.01 and 53.64 % (P < 0.01, respectively, in the first set of teeth and 43.75% (P < 0.01, 24.48% (P < 0.01 and 59.78% (P < 0.01, respectively, in the second set of teeth. The 12 th -week scores as compared to baseline scores for tactile, heat and cold tests in the control group showed a reduction in tooth hypersensitivity by 42.86% (P < 0.01, 13.02% (P < 0.01 and 45.14% (P < 0.01, respectively, in the first set of teeth and 40% (P < 0.01, 16.59% (P < 0.01 and 44.16% (P < 0.01, respectively, in the second set of teeth. Conclusions: Both the products reduced dentinal hypersensitivity in the study subjects at the end of the 12-week period. However, there was no statistically significant difference in reduction in hypersensitivity between the two products.

  7. Corticosteroid hypersensitivity studies in a skin allergy clinic.

    Science.gov (United States)

    Berbegal, L; DeLeon, F J; Silvestre, J F

    2015-12-01

    Corticosteroids can cause hypersensitivity reactions, particularly delayed-type allergic reactions. A new classification system for testing hypersensitivity to corticosteroids distributes the drugs into 3 groups according to molecular structure; patients are classified according to whether they are allergic to agents in 1 or more of the groups. We aimed to describe the clinical characteristics of corticosteroid-allergic patients treated at our clinic and apply the new classification system to them; we also compared these patients' characteristics to those of others treated at our clinic. Retrospective study of cases of delayed-type corticosteroid hypersensitivity treated in the skin allergy clinic of a tertiary level hospital over an 11-year period. We reviewed the records of 2857 patients, finding 33 with at least one positive patch test result showing corticosteroid hypersensitivity. Atopic dermatitis and hand involvement were less common in our corticosteroid-allergic patients. All were allergic to a group 1 corticosteroid (most often, budesonide, the culprit in 87.9%). Testing with a specific corticosteroid series revealed that 14 (42.4%) were also allergic to corticosteroids in group 2 and/or group 3. None were allergic exclusively to group 2 or group 3 agents. Twenty-one patients were exposed to a corticosteroid cream from a group their patch test results indicated allergy to; 13 of them (61.9%) did not develop a hypersensitivity reaction. The Spanish standard series only contains group 1 corticosteroids. In the interest of improving allergy management, we recommend testing with a specific corticosteroid series and a patient's own creams whenever patch testing with a standard series reveals a hypersensitivity reaction to corticosteroids. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  8. Low heat pain thresholds in migraineurs between attacks.

    Science.gov (United States)

    Schwedt, Todd J; Zuniga, Leslie; Chong, Catherine D

    2015-06-01

    Between attacks, migraine is associated with hypersensitivities to sensory stimuli. The objective of this study was to investigate hypersensitivity to pain in migraineurs between attacks. Cutaneous heat pain thresholds were measured in 112 migraineurs, migraine free for ≥ 48 hours, and 75 healthy controls. Pain thresholds at the head and at the arm were compared between migraineurs and controls using two-tailed t-tests. Among migraineurs, correlations between heat pain thresholds and headache frequency, allodynia symptom severity, and time interval until next headache were calculated. Migraineurs had lower pain thresholds than controls at the head (43.9 ℃ ± 3.2 ℃ vs. 45.1 ℃ ± 3.0 ℃, p = 0.015) and arm (43.2 ℃ ± 3.4 ℃ vs. 44.8 ℃ ± 3.3 ℃, p pain thresholds and headache frequency or allodynia symptom severity. For the 41 migraineurs for whom time to next headache was known, there were positive correlations between time to next headache and pain thresholds at the head (r = 0.352, p = 0.024) and arm (r = 0.312, p = 0.047). This study provides evidence that migraineurs have low heat pain thresholds between migraine attacks. Mechanisms underlying these lower pain thresholds could also predispose migraineurs to their next migraine attack, a hypothesis supported by finding positive correlations between pain thresholds and time to next migraine attack. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  9. Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs)

    DEFF Research Database (Denmark)

    Nissen, Christoffer V; Bindslev-Jensen, Carsten; Mørtz, Charlotte G

    2015-01-01

    BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the second most common cause of drug hypersensitivity. In 2011, experts from the EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID hypersensitivity. The aim of this study was to classify...... responders reacted to non-pyrazolone drugs. Only one patient could not be classified according to the EAACI/ENDA system. An overlap between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients. CONCLUSIONS: All but one of our patients could be classified according to the EAACI...

  10. Functional dyspepsia: The role of visceral hypersensitivity in its pathogenesis

    Institute of Scientific and Technical Information of China (English)

    John Keohane; Eamonn M M Quigley

    2006-01-01

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists.It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process.The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review,we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  11. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

    LENUS (Irish Health Repository)

    Keohane, John

    2012-02-03

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  12. Association of HLA genotypes with phenobarbital hypersensitivity in children.

    Science.gov (United States)

    Manuyakorn, Wiparat; Mahasirimongkol, Surakameth; Likkasittipan, Plernpit; Kamchaisatian, Wasu; Wattanapokayakit, Sukanya; Inunchot, Wimala; Visudtibhan, Anannit; Wichukchinda, Nuanjun; Benjaponpitak, Suwat

    2016-10-01

    Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children

  13. Childhood Adversity and Pain Sensitization.

    Science.gov (United States)

    You, Dokyoung Sophia; Meagher, Mary W

    Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

  14. Genome-wide association study of insect bite hypersensitivity in two horse populations in the Netherlands

    NARCIS (Netherlands)

    Schurink, A.; Wolc, A.; Ducro, B.J.; Frankena, K.; Garrick, D.J.; Dekkers, J.C.M.; Arendonk, van J.A.M.

    2012-01-01

    Background: Insect bite hypersensitivity is a common allergic disease in horse populations worldwide. Insect bite hypersensitivity is affected by both environmental and genetic factors. However, little is known about genes contributing to the genetic variance associated with insect bite

  15. Anti-inflammatory and anti-hypersensitive effects of the crude extract, fractions and triterpenes obtained from Chrysophyllum cainito leaves in mice.

    Science.gov (United States)

    Meira, Nicole Anzanelo; Klein, Luiz Carlos; Rocha, Lilian W; Quintal, Zhelmy Martin; Monache, Franco Delle; Cechinel Filho, Valdir; Quintão, Nara Lins Meira

    2014-02-03

    properties against inflammatory pain in mice. The mechanisms through which Chrysophyllum cainito exerts its anti-hypersensitive actions are still unclear, and require further investigation; however, this could well constitute a new and attractive alternative for the management of persistent inflammatory and neuropathic pain in humans. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Applicability of visual-analogue scale in patients with orofacial pain

    Directory of Open Access Journals (Sweden)

    Lončar Jovana

    2013-01-01

    Full Text Available Introduction. Orofacial pain occurs in various disorders of the orofacial region. Objective. The aim of this study was to examine applicability of the visual-analogue scale (VAS in patients with orofacial pain (model of acute and chronic pain. Methods. The study involved 60 patients, aged 18-70 years. The first group consisted of patients with dentin hypersensitivity, and the second group of patients with chronic rhinosinusitis. All patients were asked to fill-in a pain questionnaire and to rate pain intensity on the modified visual analogue scale (VAS; 0-10. Air indexing method was performed in the patients with dentin hypersensitivity in order to provoke pain, while the patients with chronic rhinosinusitis underwent CT imaging of paranasal sinuses. Wilcoxon’s test and Pearson’s correlation coefficient were used for statistical analysis. Results. In patients with dentin hypersensitivity provocation increased subjective feeling of pain, but without statistical significance (t=164.5; p>0.05. In patients with chronic rhinosinusitis a significant statistical correlation (r=0.53; p<0.05 was found between subjective pain assessment of VAS and CT findings. Conclusion. Applying VAS in the evaluation of acute and chronic pain can indicate progression or regression of pathological state under clinical conditions. This study showed that VAS, as a method for follow-up of pathological state, is more applicable and efficient when applied in chronic pain evaluation.

  17. Agrobacterium -induced hypersensitive necrotic reaction in plant cells

    African Journals Online (AJOL)

    High necrosis and poor survival rate of target plant tissues are some of the major factors that affect the efficiency of Agrobacterium-mediated T-DNA transfer into plant cells. These factors may be the result of, or linked to, hypersensitive defense reaction in plants to Agrobacterium infection, which may involve the recognition ...

  18. Incidence of abacavir hypersensitivity reactions in euroSIDA

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Friis-Møller, Nina; Mocroft, Amanda

    2008-01-01

    BACKGROUND: The aim of the study was to investigate the incidence of abacavir-related hypersensitivity reaction (HSR) and associated deaths in EuroSIDA HIV-1-infected patients. METHODS: Poisson regression models were developed to compare incidence of abacavir discontinuation according to the line...

  19. Auditory Hypersensitivity in Children with Autism Spectrum Disorders

    Science.gov (United States)

    Lucker, Jay R.

    2013-01-01

    A review of records was completed to determine whether children with auditory hypersensitivities have difficulty tolerating loud sounds due to auditory-system factors or some other factors not directly involving the auditory system. Records of 150 children identified as not meeting autism spectrum disorders (ASD) criteria and another 50 meeting…

  20. Culicoides species attracted to horses with and without insect hypersensitivity

    NARCIS (Netherlands)

    Rijt, van der R.; Boom, van den R.; Jongema, Y.; Sloet van Oldruitenborgh-Oosterbaan, M.M.

    2008-01-01

    The aims of this study were to determine (1) which species of Culicoides is most commonly attracted to horses, (2) whether horses suffering insect hypersensitivity attract more Culicoides spp. than unaffected horses, and (3) the times when Culicoides spp. are most active. Horses affected by insect

  1. Trichloroethylene hypersensitivity syndrome: a disease of fatal outcome.

    Science.gov (United States)

    Jung, Hyun Gul; Kim, Hyung Hun; Song, Bong Gun; Kim, Eun Jin

    2012-01-01

    Trichloroethylene is commonly used as an industrial solvent and degreasing agent. The clinical features of acute and chronic intoxication with trichloroethylene are well-known and have been described in many reports, but hypersensitivity syndrome caused by trichloroethylene is rarely encountered. For managing patients with trichloroethylene hypersensitivity syndrome, avoiding trichloroethylene and initiating glucocorticoid have been generally accepted. Generally, glucocorticoid had been tapered as trichloroethylene hypersensitivity syndrome had ameliorated. However, we encountered a typical case of trichloroethylene hypersensitivity syndrome refractory to high dose glucocorticoid treatment. A 54-year-old Korean man developed jaundice, fever, red sore eyes, and generalized erythematous maculopapular rashes. A detailed history revealed occupational exposure to trichloroethylene. After starting intravenous methylprednisolone, his clinical condition improved remarkably, but we could not reduce prednisolone because his liver enzyme and total bilirubin began to rise within 2 days after reducing prednisolone under 60 mg/day. We recommended an extended admission for complete recovery, but the patient decided to leave the hospital against medical advice. The patient visited the emergency department due to pneumonia and developed asystole, which did not respond to resuscitation.

  2. Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis.

    Science.gov (United States)

    Nguyen, Yvonne; Bradford, Jennifer; Fischer, Gayle

    2018-02-01

    Oestrogen hypersensitivity vulvovaginitis is a rare chronic cyclical vulvovaginitis responsive to oestrogen suppression or antagonism. We present a case series of 16 patients with refractory cyclical vulvovaginitis, all of whom responded to oestrogen suppression with cyproterone acetate. © 2017 The Australasian College of Dermatologists.

  3. Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis.

    Directory of Open Access Journals (Sweden)

    Masahiro Ishizuka

    Full Text Available Hypersensitivity pneumonitis (HP is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif ligand 5 (CXCL5 in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.

  4. 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...

  5. Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

    Directory of Open Access Journals (Sweden)

    L. D. Wang

    2016-01-01

    Full Text Available Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25 and Shangjuxu (ST37 acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25 and Shangjuxu (ST37 acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

  6. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  7. Hypersensitivity Reaction and Acute Respiratory Distress Syndrome in Pyrethroid Poisoning and Role of Steroid Therapy

    Directory of Open Access Journals (Sweden)

    Jisa George

    2015-06-01

    Full Text Available Background: Pyrethroids are generally of low toxicity to humans, but in suicidal poisonings which are usually associated with ingestion of high doses, they lead to severe systemic effects. Case Report: A 30-year old woman presented to emergency department with a history of intentional ingestion of about 15 mL of prallethrin around 3 days earlier. She complained of shortness of breath along with chest pain for the last 2 days. She reported no vomiting or stomach pain prior to presentation to hospital. On chest auscultation, breath sounds were mildly decreased in bilateral infrascapular areas with generalized crepitation. Arterial blood gas analysis revealed respiratory alkalosis. Chest X ray and computed tomography of thorax revealed widespread confluent areas of consolidation with interlobular septal thickening involving bilateral parahilar regions suggestive of acute respiratory distress syndrome (ARDS. The patient did not respond to broad spectrum antibiotic coverage, diuretics and oxygen inhalation. Intravenous methylprednisolone (2 mg/kg/day divided 6 hourly was started and slowly tapered off during the next days. The patient discharged after 3 weeks in good health. Discussion: As pyrethroids can affect sodium channels, the osmotic gradient of alveolar epithelium probably disrupts and therefore, alveolar infiltrations gradually spread over lungs. In addition, there is a possibility of hypersensitivity reactions to pyrethroids, which can cause progressive inflammation and involve respiratory tract in severe cases. Conclusion: Pyrethroid poisoning can lead to ARDS. Steroid therapy may help such patients tide over the pulmonary crisis.

  8. Evaluation of reward from pain relief

    Science.gov (United States)

    Navratilova, Edita; Xie, Jennifer Yanhua; King, Tamara; Porreca, Frank

    2014-01-01

    The human experience of pain is multidimensional and comprises sensory, affective, and cognitive dimensions. Preclinical assessment of pain has been largely focused on the sensory features that contribute to nociception. The affective (aversive) qualities of pain are clinically significant but have received relatively less mechanistic investigation in preclinical models. Recently, operant behaviors such as conditioned place preference, avoidance, escape from noxious stimulus, and analgesic drug self-administration have been used in rodents to evaluate affective aspects of pain. An important advance of such operant behaviors is that these approaches may allow the detection and mechanistic investigation of spontaneous neuropathic or ongoing inflammatory/nociceptive (i.e., nonevoked) pain that is otherwise difficult to assess in nonverbal animals. Operant measures may allow the identification of mechanisms that contribute differentially to reflexive hypersensitivity or to pain affect and may inform the decision to progress novel mechanisms to clinical trials for pain therapy. Additionally, operant behaviors may allow investigation of the poorly understood mechanisms and neural circuits underlying motivational aspects of pain and the reward of pain relief. PMID:23496247

  9. Pain in fibromyalgia and related conditions

    Directory of Open Access Journals (Sweden)

    G. Cassisi

    2014-06-01

    Full Text Available Pain is the hallmark symptom of fibromyalgia (FM and other related syndromes, but quite different from that of other rheumatic diseases, which depends on the degree of damage or inflammation in peripheral tissues. Sufferers are often defined as patients with chronic pain without an underlying mechanistic cause, and these syndromes and their symptoms are most appropriately described as “central pain”, “neuropathic pain”, “nonnociceptive pain” or “central sensitivity syndromes”. The pain is particular, regional or widespread, and mainly relates to the musculoskeletal system; hyperalgesia or allodynia are typical. Its origin is currently considered to be distorted pain or sensory processing, rather than a local or regional abnormality. FM is probably the most important and extensively described central pain syndrome, but the characteristics and features of FM-related pain are similar in other disorders of particular interest for rheumatologists, such as myofascial pain syndromes and temporo-mandibular joint disorders, and there is also an intriguing overlap between FM and benign joint hypermobility syndrome. This suggests that the distinctive aspects of pain in these idiopathic or functional conditions is caused by central nervous system hypersensitivity and abnormalities. Pharmacological and non-pharmacological therapies have been suggested for the treatment of these conditions, but a multidisciplinary approach is required in order to reduce the abnormal cycle of pain amplification and the related maladaptive and self-limiting behaviours.

  10. The Effect of Calcium Sodium Phosphosilicate on Dentin Hypersensitivity: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Mengjiao Zhu

    Full Text Available To investigate the effect of calcium sodium phosphosilicate (CSPS in treating dentin hypersensitivity (DH and to compare this effect to that of a negative (placebo control.Several databases, including Medline, EMBASE, Web of Science, The Cochrane Library, and the Chinese Biomedical Literature Database, were searched to identify relevant articles published through January 2015; grey literature (i.e., academic literature that is not formally published was also searched. Two authors performed data extraction independently and jointly using data collection forms. The primary outcome was the DH pain response to routine activities or to thermal, tactile, evaporative, or electrical stimuli, and the secondary outcome was the side effects of CSPS use. Each study was evaluated using the Cochrane Collaboration tool for assessing risk bias. Meta-analysis of studies with the same participant demographics, interventions, controls, assessment methods and follow-up periods was performed. The Grading of Recommendations Assessment Development and Evaluation System was used to assess the quality of the evidence and the risk of bias across studies.Meta-analysis demonstrated that toothpaste containing 5% CSPS was more effective than the negative control at relieving dentin sensitivity, with the level of evidence classified as "moderate". In addition, prophylaxis paste containing 15% calcium sodium phosphosilicate was favored over the negative control at reducing post-periodontal therapy hypersensitivity, with the level of evidence categorized as "low". Only two studies reported side effects of CSPS use.The majority of studies found that calcium sodium phosphosilicate was more effective than the negative control at alleviating DH. Because strong evidence is scarce, high-quality, well-designed clinical trials are required in the future before definitive recommendations can be made.

  11. 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.

  12. Cow's milk protein allergy and other food hypersensitivities in infants.

    Science.gov (United States)

    Venter, Carina

    2009-01-01

    Food hypersensitivity (FHS) is the umbrella term used to describe both food allergy, which involves the immune system, and food intolerances, which do not. It is therefore important that the diagnosis is made by a specialist health care professional such as a paediatrician or allergist. Some experienced dietitians and health visitors may be able to assist in making a diagnosis. The diagnostic work-up includes a medical history and blood tests/skin tests (where applicable). A food and symptom diary followed by a special test diet to identify the foods causing the infant's symptoms may also be needed. Once a diagnosis is made, dietary advice should be given to eliminate or reduce the intake of the offending foods. For cow's milk hypersensitivity in infants, this will include choosing the most appropriate specialised infant formula.

  13. ATM status of the clinically radio-hypersensitive

    International Nuclear Information System (INIS)

    Clarke, R. A.; Hasnain, H.; Goozee, G.; Alvandi, R.; Miller, A.; Kearsley, J.H.; Farrell, A.; Bittell, G.; Chen, P.; Lavin, M.

    1996-01-01

    The aim of this study was to characterise the response to ionising radiation of normal tissues from patients that display early and acute hypersensitivity to radiotherapy. Methods include cell proliferation assay using MTT, induced chromosomal aberration testing, cell cycle response to radiation via FACs, mutation analysis of Ataxia Telangiectasia (AT) gene, p53 and AT Western analysis. It is now well appreciated that standard clinical doses (1.8-2 Gy per fraction per day) produce predictable acute and late toxicity in most patients. Occasionally, however, the standard clinical dose produces acute and late toxicity which can exceed the norm both in their extent and timing. The study confirmed the innate cellular radiosensitivity of the clinically radio-hypersensitive patients. No indication of AT gene mutations was found

  14. Hypersensitivity to mosquito bite manifested as Skeeter syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Pérez-Vanzzini

    2015-02-01

    Full Text Available The reactions to mosquito bites are immunological reactions with involvement of IgE, IgG and T cells mediated hypersensitivity. These reactions are common and range from small local reactions, large local reactions to systemic allergic reactions. Skeeter syndrome is defined as a large local induced inflammatory reaction to mosquito bite and sometimes accompanied by systemic symptoms such as fever and vomiting. Diagnosis is based on clinical history and physical examination, supported by the identification of specific IgE by skin testing. Treatment includes prevention, antihistamines and steroids in some cases. Specific immunotherapy still requires further study. This paper reports two cases of patients with hypersensitivity reactions to mosquito bites, which were evaluated in our center presenting positive skin tests.

  15. The Prevalence of food hypersensitivity in young adults

    DEFF Research Database (Denmark)

    Østerballe, Morten; Mørtz, Charlotte G; Hansen, Tine Kjær

    2009-01-01

    by questionnaire, skin prick test (SPT) and histamin release (HR) followed by oral challenge to the most common allergenic foods. FHS was divided into primary and secondary FHS. Primary FHS was defined as being independent of pollen sensitization, whereas secondary FHS was defined as reactions to pollen related......Osterballe M, Mortz CG, Hansen TK, Andersen KE, Bindslev-Jensen C. The Prevalence of food hypersensitivity in young adults. Pediatr Allergy Immunol 2009. (c) 2009 The Authors Journal compilation (c) 2009 John Wiley & Sons A/SA rising prevalence of food hypersensitivity (FHS) and severe allergic...... reactions to foods have been reported in the last decade. However, little is known on the prevalence in young adults. This study estimated the prevalence of FHS to the most common allergenic foods in an unselected population of young adults. We investigated a cohort of 1272 young adults 22 years of age...

  16. Old, new and hidden causes of perioperative hypersensitivity

    DEFF Research Database (Denmark)

    Garvey, Lene Heise

    2016-01-01

    intravenously such as neuromuscular blocking agents (NMBA), induction agents and antibiotics have traditionally been reported to be implicated most commonly. It has recently become apparent that there are geographical differences in sensitization patterns related to variation in exposures, referral patterns...... and performance and interpretation of investigations. Differences in sensitization to NMBAs are partly explained by cross sensitization to pholcodine, an ingredient in cough-medicines available in some countries. While NMBAs are the most common causes of perioperative hypersensitivity in some countries, this may...... in causes of perioperative hypersensitivity emerging over time and to increase awareness about the “hidden allergens” in the perioperative setting. Some practical advice on how to approach the patient testing negative on all initial investigations is also included....

  17. [Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab].

    Science.gov (United States)

    Boin, C; Lambert, S; Thomann, P; Aujoulat, O; Kieffer, P

    2016-06-01

    Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative. We report a 49-year-old patient who presented with a hypersensitivity reaction following an infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome. After a clinical flare (splenomegaly, adenopathies) despite treatment with tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was decided, according to the rapid desensitization protocol. Four full dose desensitizations were successfully performed allowing immediate clinical improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial regression) and biological (negativation of HHV8 viral load, and disappearance of neutropenia, anemia and thrombocytopenia). Rapid desensitization is a promising method for the pursuit of rituximab therapy after a hypersensitivity reaction and should be considered in patients with no acceptable therapeutic alternative. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  18. Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.

    Science.gov (United States)

    Böhm, Ruwen; Cascorbi, Ingolf

    2016-01-01

    Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.

  19. Differential pain modulation in patients with peripheral neuropathic pain and fibromyalgia.

    Science.gov (United States)

    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

  20. A haemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis.

    Science.gov (United States)

    Oliveira, Rudolf K F; Pereira, Carlos A C; Ramos, Roberta P; Ferreira, Eloara V M; Messina, Carolina M S; Kuranishi, Lilian T; Gimenez, Andrea; Campos, Orlando; Silva, Célia M C; Ota-Arakaki, Jaquelina S

    2014-08-01

    Chronic hypersensitivity pneumonitis is a common fibrotic interstitial lung disease. The prevalence of pulmonary hypertension diagnosed by right heart catheterisation and its cardiopulmonary function findings in patients with chronic hypersensitivity pneumonitis are unknown. Consecutive symptomatic patients with chronic hypersensitivity pneumonitis were prospectively evaluated. All patients were submitted to right heart catheterisation, pulmonary function testing, a 6-min walk test, echocardiography, blood gas determination and N-terminal pro-brain natriuretic peptide analyses. Nonhypoxaemic patients also underwent incremental cardiopulmonary exercise testing. 50 patients underwent right heart catheterisation; 25 (50%) of these had pulmonary hypertension and 22 (44%) had a pre-capillary haemodynamic pattern. The patients with pre-capillary pulmonary hypertension had lower forced vital capacity (mean ± sd 50 ± 17% versus 69 ± 22% predicted, p<0.01), carbon monoxide diffusing capacity (37 ± 12% versus 47 ± 14% predicted, p<0.01), arterial oxygen tension (median (interquartile range) 59.0 (47.8-69.3) versus 73.0 (62.2-78.5) mmHg, p<0.01) and saturation after the 6-min walk test (78 ± 8% versus 86 ± 7%, p<0.01). In pre-capillary pulmonary hypertension, oxygen uptake was also lower at the anaerobic threshold (41 ± 11% versus 50 ± 8% predicted, p=0.04) and at peak exercise (12.8 ± 1.6 versus 15.0 ± 2.5 mL · kg(-1) · min(-1), p=0.02). Pre-capillary pulmonary hypertension is common in symptomatic chronic hypersensitivity pneumonitis and is related to interstitial lung disease severity. Additionally, pulmonary hypertension is more prevalent in hypoxaemic patients with impaired lung function and exercise capacity. ©ERS 2014.

  1. Induction of Hypozincemia and Hepatic Metallothionein Synthesis in Hypersensitivity Reactions.

    Science.gov (United States)

    1978-06-19

    cells to produce endogenous pyrogen (EP), the mediator of febrile response. Controversial evidence exists, however , concerning the differentiation of LEM...hypersensitivity reactions, Kampschmid t and Pulliam (1) proposed that leukocytic endogenous mediator (LEN) is released from phagocytic cells after... endogenous mediator(s) such as LEN, no conclusive evidence is available to indicate a mRNA requirement for the production of potential mediator(s

  2. Nickel-induced hypersensitivity: etiology, immune reactions, prevention and therapy.

    Science.gov (United States)

    Hostýnek, Jurij J

    2002-08-01

    As a contact allergen causing type I and type IV hypersensitivity, mediated by reagins and allergen-specific T lymphocytes, expressed in a wide range of cutaneous eruptions following dermal or systemic exposure, nickel has acquired the distinction of being among the most frequent causes of hypersensitivity, occupationally as well as among the general population. In synoptic form the many effects that nickel has on the organism are presented, to provide a comprehensive picture of the aspects of that metal with many biologically noxious, but metallurgically indispensable characteristics. This paper reviews the epidemiology, the prognosis for occupational and non-occupational nickel allergic hypersensitivity (NAH), the many types of exposure and the resulting immune responses, immunotoxicity and rate of diffusion through the skin. Alternatives towards prevention and remediation, topical and systemic, for this pervasive and increasing form of morbidity resulting from multiple types of exposure are discussed. Merits and limitations of preventive measures in industry and private life are considered, as well as the effectiveness of topical and systemic therapy in treating NAH.

  3. Cracking the egg: An insight into egg hypersensitivity.

    Science.gov (United States)

    Dhanapala, Pathum; De Silva, Chamika; Doran, Tim; Suphioglu, Cenk

    2015-08-01

    Hypersensitivity to the chicken egg is a widespread disorder mainly affecting 1-2% of children worldwide. It is the second most common food allergy in children, next to cow's milk allergy. Egg allergy is mainly caused by hypersensitivity to four allergens found in the egg white; ovomucoid, ovalbumin, ovotransferrin and lysozyme. However, some research suggests the involvement of allergens exclusively found in the egg yolk such as chicken serum albumin and YGP42, which may play a crucial role in the overall reaction. In egg allergic individuals, these allergens cause conditions such as itching, atopic dermatitis, bronchial asthma, vomiting, rhinitis, conjunctivitis, laryngeal oedema and chronic urticaria, and anaphylaxis. Currently there is no permanent cure for egg allergy. Upon positive diagnosis for egg allergy, strict dietary avoidance of eggs and products containing traces of eggs is the most effective way of avoiding future hypersensitivity reactions. However, it is difficult to fully avoid eggs since they are found in a range of processed food products. An understanding of the mechanisms of allergic reactions, egg allergens and their prevalence, egg allergy diagnosis and current treatment strategies are important for future studies. This review addresses these topics and discusses both egg white and egg yolk allergy as a whole. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Suspected zonisamide-related anticonvulsant hypersensitivity syndrome in a cat.

    Science.gov (United States)

    Collinet, Audrey; Sammut, Veronique

    2017-12-15

    CASE DESCRIPTION A 2-year-old neutered male domestic shorthair cat was evaluated for sudden onset of cluster seizures. CLINICAL FINDINGS At an emergency clinic, the cat had hyperimmunoglobulinemia and thrombocytopenia. On referral, treatment with levetiracetam, zonisamide, and phenobarbital initially provided good control of cluster seizure activity (attributable to epilepsy of unknow origin). Two weeks later, assessments revealed that serum phenobarbital concentration was within the ideal range but serum zonisamide concentration exceeded the recommended therapeutic range. The dosage of zonisamide was therefore decreased. Four days after dosage reduction, the cat developed generalized lymphadenopathy. Cytologic analysis of lymph node aspirate samples revealed a heterogeneous population of well-differentiated lymphocytes, interpreted as marked reactivity. Although neoplasia could not be ruled out, hypersensitivity to phenobarbital was suspected, and this treatment was discontinued. TREATMENT AND OUTCOME Despite cessation of phenobarbital administration, generalized peripheral lymphadenopathy progressed and hyperglobulinemia and cytopenias developed. These abnormalities resolved after discontinuation of zonisamide administration. The cat remained seizure free with no recurrence of the aforementioned concerns after reinstitution of phenobarbital treatment. CLINICAL RELEVANCE To the authors' knowledge, this is the first reported case of zonisamide-related lymphadenopathy, hyperglobulinemia, and cytopenias in a cat. Anticonvulsant hypersensitivity syndrome is well documented in human medicine, but little information has been published in the veterinary medical literature. Although the effects of anticonvulsant hypersensitivity syndrome in this cat were serious, these effects were reversible with treatment discontinuation.

  5. Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children

    Directory of Open Access Journals (Sweden)

    Kidon Mona

    2007-12-01

    Full Text Available Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.

  6. Linezolid desensitization for a patient with multiple medication hypersensitivity reactions.

    Science.gov (United States)

    Bagwell, Autumn D; Stollings, Joanna L; White, Katie D; Fadugba, Olajumoke O; Choi, Jane J

    2013-01-01

    To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions. A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol. Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols. Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.

  7. [Anorectal pain in children: rare or rarely recognised?].

    Science.gov (United States)

    Sonneveld, Laura J H; Engelberts, Adèle C; van den Elzen, Annette P M

    2016-01-01

    Anorectal pain is a common symptom, often as part of functional gastrointestinal disorders. Children seldom present with this complaint. Proctalgia fugax and chronic proctalgia are both anorectal pain syndromes but differ in duration and frequency of episodes and in pain characteristics. No research has been conducted on anorectal pain syndromes in children. We present two patients. Firstly, an 8-year-old girl who suffered from anorectal cramps. We found no underlying cause apart from constipation. The symptoms disappeared spontaneously. The second concerned an 8-year-old boy who presented with recurrent anorectal cramps. He was diagnosed with celiac disease. Anorectal dysfunction and visceral hypersensitivity have been described in adult celiac patients. Symptoms of anorectal pain in children are rare probably because it often remains unrecognised. Noninvasive diagnostic methods and interventions are preferred in paediatric medicine. Screening for celiac disease in children with anorectal pain episodes should be considered.

  8. Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury.

    Science.gov (United States)

    Park, Jonghyuck; Zheng, Lingxing; Acosta, Glen; Vega-Alvarez, Sasha; Chen, Zhe; Muratori, Breanne; Cao, Peng; Shi, Riyi

    2015-12-01

    Acrolein, an endogenous aldehyde, has been shown to be involved in sensory hypersensitivity after rat spinal cord injury (SCI), for which the pathogenesis is unclear. Acrolein can directly activate a pro-algesic transient receptor protein ankyrin 1 (TRPA1) channel that exists in sensory neurons. Both acrolein and TRPA1 mRNA are elevated post SCI, which contributes to the activation of TRPA1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post-SCI elevation of TRPA1 mRNA exists not only in dorsal root ganglias but also in both peripheral (paw skin) and central endings of primary afferent nerves (dorsal horn of spinal cord). This is the first indication that pain signaling can be over-amplified in the peripheral skin by elevated expressions of TRPA1 following SCI, in addition over-amplification previously seen in the spinal cord and dorsal root ganglia. Furthermore, we show that acrolein alone, in the absence of physical trauma, could lead to the elevation of TRPA1 mRNA at various locations when injected to the spinal cord. In addition, post-SCI elevation of TRPA1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA1 expression through gene regulation. Taken together, these data indicate that acrolein is likely a critical causal factor in heightening pain sensation post-SCI, through both the direct binding of TRPA1 receptor, and also by boosting the expression of TRPA1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI. We propose that the trauma-mediated elevation of acrolein causes neuropathic pain through at least two mechanisms: acrolein stimulates the production of transient receptor protein ankyrin 1 (TRPA1) in both central and peripheral locations, and it activates TRPA1 channels directly. Therefore, acrolein appears to be a critical

  9. CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Piekarz Andrew D

    2012-07-01

    Full Text Available Abstract Background The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2 to bind to N-type voltage-activated calcium channels (CaV2.2 [Brittain et al. Nature Medicine 17:822–829 (2011]. Results and discussion Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP release compared to vehicle control. Conclusions Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of

  10. Sympathetically maintained pain presenting first as temporomandibular disorder, then as parotid dysfunction.

    Science.gov (United States)

    Giri, Subha; Nixdorf, Donald

    2007-03-01

    Complex regional pain syndrome (CRPS) is a chronic condition characterized by intense pain, swelling, redness, hypersensitivity and additional sudomotor effects. In all 13 cases of CRPS in the head and neck region reported in the literature, nerve injury was identified as the etiology for pain initiation. In this article, we present the case of a 30-year-old female patient with sympathetically maintained pain without apparent nerve injury. Her main symptoms--left-side preauricular pain and inability to open her mouth wide--mimicked temporomandibular joint arthralgia and myofascial pain of the masticatory muscles. Later, symptoms of intermittent preauricular pain and swelling developed, along with hyposalivation, which mimicked parotitis. After an extensive diagnostic process, no definitive underlying pathology could be identified and a diagnosis of neuropathic pain with a prominent sympathetic component was made. Two years after the onset of symptoms and initiation of care, treatment with repeated stellate ganglion blocks and enteral clonidine pharmacotherapy provided adequate pain relief.

  11. 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.

  12. Long non-coding RNA CCAT1 modulates neuropathic pain progression through sponging miR-155

    OpenAIRE

    Dou, Lidong; Lin, Hongqi; Wang, Kaiwei; Zhu, Guosong; Zou, Xuli; Chang, Enqiang; Zhu, Yongfeng

    2017-01-01

    Neuropathic pain is caused by dysfunction or primary injury of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) play important roles in the development of neuropathic pain. However, the effects of lncRNA colon cancer associated transcript-1 (CCAT1) in neuropathic pain have not been reported. The model of bilateral sciatic nerve chronic constriction injuries (bCCI) is regarded as long-lasting mechanical hypersensitivity and cold allodynia, which is the representative symptom in ...

  13. Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model.

    Science.gov (United States)

    Chaloner, Aaron; Greenwood-Van Meerveld, Beverley

    2013-03-01

    Visceral pain is the hallmark feature of irritable bowel syndrome (IBS), a gastrointestinal disorder, which is more commonly diagnosed in women. Female IBS patients frequently report a history of early life adversity (ELA); however, sex differences in ELA-induced visceral pain and the role of ovarian hormones have yet to be investigated. Therefore, we tested the hypothesis that ELA induces visceral hypersensitivity through a sexually dimorphic mechanism mediated via estradiol. As a model of ELA, neonatal rats were exposed to different pairings of an odor and shock to control for trauma predictability. In adulthood, visceral sensitivity was assessed via a visceromotor response to colorectal distension. Following ovariectomy and estradiol replacement in a separate group of rats, the visceral sensitivity was quantified. We found that females that received unpredictable odor-shock developed visceral hypersensitivity in adulthood. In contrast, visceral sensitivity was not significantly different following ELA in adult males. Ovariectomy reversed visceral hypersensitivity following unpredictable ELA, whereas estradiol replacement reestablished visceral hypersensitivity in the unpredictable group. This study is the first to show sex-related differences in visceral sensitivity following unpredictable ELA. Our data highlight the activational effect of estradiol as a pivotal mechanism in maintaining visceral hypersensitivity. This article directly implicates a critical role for ovarian hormones in maintaining visceral hypersensitivity following ELA, specifically identifying the activational effect of estradiol as a key modulator of visceral sensitivity. These data suggest that ELA induces persistent functional abdominal pain in female IBS patients through an estrogen-dependent mechanism. Copyright © 2013 American Pain Society. All rights reserved.

  14. Pelvic Pain

    Science.gov (United States)

    ... OLPP) Office of Science Policy, Reporting, and Program Analysis (OSPRA) Division of Extramural Research (DER) Extramural Scientific ... treat my pain? Can pelvic pain affect my emotional well-being? How can I cope with long- ...

  15. Neck pain

    Science.gov (United States)

    ... cause of neck pain is muscle strain or tension. Most often, everyday activities are to blame. Such ... of a heart attack , such as shortness of breath, sweating, nausea, vomiting, or arm or jaw pain. ...

  16. Carboplatin hypersensitivity in children with glial tumors: a report of two cases

    Directory of Open Access Journals (Sweden)

    Tugce Kazgan

    2016-12-01

    Full Text Available Carboplatin, commonly used chemotherapeutic agent in treatment of pediatric cancers, can cause life-threatening hypersensitivty reactions. Carboplatin hypersensitivity is protocol-specific and associated with repeated doses and prolonged use of the drug. Vincristin and carboplatin combination is used efficiently in treatment of pediatric low-grade gliomas. However, hypersensitivity reactions are frequently observed during usage of this protocol. Desensitization strategies with variable success rates were reported. Failure of these strategies may lead to cessation of carboplatin Here, we report two cases with carboplatin hypersensitivity treated with epinephrine administration, in whom carboplatin was discontinued after hypersensitivity reaction. [Cukurova Med J 2016; 41(4.000: 796-798

  17. Patellofemoral Pain.

    Science.gov (United States)

    Dutton, Rebecca A; Khadavi, Michael J; Fredericson, Michael

    2016-02-01

    Patellofemoral pain is characterized by insidious onset anterior knee pain that is exaggerated under conditions of increased patellofemoral joint stress. A variety of risk factors may contribute to the development of patellofemoral pain. It is critical that the history and physical examination elucidate those risk factors specific to an individual in order to prescribe an appropriate and customized treatment plan. This article aims to review the epidemiology, risk factors, diagnosis, and management of patellofemoral pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. [Sexual pain disorders in females and males].

    Science.gov (United States)

    Monforte, M; Mimoun, S; Droupy, S

    2013-07-01

    The occurrence of pain during sex is one of the most common complaints in gynecological and sexological practice but nonetheless one of the most difficult problems to deal with and treat effectively. A literature review was conducted on Medline considering the articles listed until January 2012 dealing with sexual pain in women and men. The different descriptions of painful intercourse (dyspareunia, vestibulo-vulvodynies, vaginismus) are not separate entities but the result of the interaction of many factors including genital pain, emotional and behavioral responses to penetration, caresses, desire and excitement, in a context of possible organic pathology (infection, endometriosis, inflammatory or dermatological disease, morphological or pelvic abnormality, hormonal deficiency) sometimes associated with chronic pain phenomena self-sustained by neurogenic inflammation. The clinical expression of sexual pain is as variable as its causes are many. The etiological investigation is essential but should not omit the sexological context and the need for appropriate management. The neurogenic inflammation and hypersensitivity impose an algological approach associated to etiological and sexological treatment. Chronic sexual pains, whether they are superficial or deep, can be the sign of organic or psycho-sexual (primary or secondary) disorders. The development of a "therapeutic program" helps patients, allows them to restore self-confidence and leads to the disappearance of the symptom in more than half cases. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Phantom Pain

    Science.gov (United States)

    ... Because this is yet another version of tangled sensory wires, the result can be pain. A number of other factors are believed to contribute to phantom pain, including damaged nerve endings, scar tissue at the site of the amputation and the physical memory of pre-amputation pain in the affected area. ...

  20. 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

  1. 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

  2. Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zhang Zhi-Jun

    2012-07-01

    Full Text Available Abstract Background Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2-chemokine C-C motif receptor 2 (CCR2 signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. Methods The inferior alveolar nerve and mental nerve transection (IAMNT was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP, and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing. Results IAMNT induced persistent (>21 days heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg significantly attenuated IAMNT-induced heat hyperalgesia. Conclusion The data suggest that CCL2-CCR

  3. Accuracy of a Computer Assisted Program for ’Classic’ Presentations of Dental Pain

    Science.gov (United States)

    1989-04-11

    diagnosis of trauma and non-trauma related dental pain. Abscess /infection/cellulitis Acute apical abscess Acute apical periodontitis Acute...spasms Necrotizing ulcerative gingivitis Neurologic injury Osseous sequestrum Occlusal trauma Periodontal abscess Periocoronitis/erupting tooth...Acute apical abscess Acute apical periodontitis Acute gingivitis Carious lesion (decay) Dentin hypersensitivity Defective restoration

  4. Involvement of transient receptor potential vanilloid 2 in intra-oral incisional pain.

    Science.gov (United States)

    Urata, K; Shinoda, M; Ikutame, D; Iinuma, T; Iwata, K

    2018-03-05

    To examine whether transient receptor potential vanilloid 2 (TRPV2) contributes to the changes in intra-oral thermal and mechanical sensitivity following the incision of buccal mucosa. Buccal mucosal pain threshold was measured after the incision. Changes in the number of TRPV2-immunoreactive (IR) trigeminal ganglion (TG) neurons which innervate the whisker pad skin and buccal mucosa, changes in the number of isolectin B4-negative/isolectin B4-positive TRPV2-IR TG neurons which innervate the whisker pad skin and the buccal mucosa, and the effect of peripheral TRPV2 antagonism on the pain threshold of incisional whisker pad skin and buccal mucosa were examined after these injuries. Buccal mucosal pain hypersensitivities were induced on day 3 following the incision. The total number of TRPV2-IR TG neurons and the number of isolectin B4-negative TRPV2-IR TG neurons which innervate the whisker pad skin and buccal mucosa were increased. Buccal mucosal TRPV2 antagonism completely suppressed the heat and mechanical hypersensitivities, but not cold hypersensitivity. TRPV2 antagonist administration to the incisional whisker pad skin only partially suppressed pain hypersensitivities. The increased expression of TRPV2 in peptidergic TG neurons innervating the incisional buccal mucosa is predominantly involved in buccal mucosal heat hyperalgesia and mechanical allodynia following buccal mucosal incision. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  5. Effects of the dimeric PSD-95 inhibitor UCCB01-144 in mouse models of pain, cognition and motor function

    DEFF Research Database (Denmark)

    Andreasen, Jesper T; Nasser, Arafat; Caballero-Puntiverio, Maitane

    2016-01-01

    NOS interaction has therefore been proposed as an alternative analgesic mechanism. We recently reported that UCCB01-125, a dimeric PSD-95 inhibitor with limited blood-brain-barrier permeability, reduced mechanical hypersensitivity in the complete Freund's adjuvant (CFA) inflammatory pain model, without disrupting...... of neuropathic pain. Potential cognitive effects of UCCB01-144 were examined using the social transmission of food preference (STFP) test and the V-maze test, and motor coordination was assessed with the rotarod test. UCCB01-144 (10mg/kg) reversed CFA-induced mechanical hypersensitivity after 1h, and completely...

  6. Bay11-7082 attenuates neuropathic pain via inhibition of nuclear factor-kappa B and nucleotide-binding domain-like receptor protein 3 inflammasome activation in dorsal root ganglions in a rat model of lumbar disc herniation

    Directory of Open Access Journals (Sweden)

    Zhang AL

    2017-02-01

    Full Text Available Ailiang Zhang, Kun Wang, Lianghua Ding, Xinnan Bao, Xuan Wang, Xubin Qiu, Jinbo Liu Spine Surgery, Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China Abstract: Lumbar disc herniation (LDH is an important cause of radiculopathy, but the underlying mechanisms are incompletely understood. Many studies suggested that local inflammation, rather than mechanical compression, results in radiculopathy induced by LDH. On the molecular and cellular level, nuclear factor-kappa B (NF-κB and nucleotide-binding domain-like receptor protein 3 (NLRP3 inflammasome have been implicated in the regulation of neuroinflammation formation and progression. In this study, the autologous nucleus pulposus (NP was implanted in the left L5 dorsal root ganglion (DRG to mimic LDH in rats. We investigated the expression of NF-κB and the components of NLRP3 inflammasome in the DRG neurons in rats. Western blotting and immunofluorescence for the related molecules, including NLRP3, apoptosis-associated speck-like protein containing caspase-1 activator domain (ASC, caspase-1, interleukin (IL-1β, IL-18, IκBα, p-IκBα, p65, p-p65, and calcitonin gene-related peptide (CGRP were examined. In the NP-treated group, the activations of NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 in DRG neurons in rats were elevated at 1 day after surgery, and the peak occurred at 7 days. Treatment with Bay11-7082, an inhibitor of the actions of IKK-β, was able to inhibit expression and activation of the molecules (NLRP3, ASC, caspase-1, IL-1β, IL-18, p-IκBα, and p-p65 and relieve the pain in rats. Our study shows that NF-κB and NLRP3 inflammasome are involved in the maintenance of NP-induced pain, and that Bay11-7082 could alleviate mechanical allodynia and thermal hyperalgesia by inhibiting NF-κB and NLRP3 inflammasome activation. Keywords: pain, NLRP3, NF-κB, dorsal root ganglion, nucleus pulposus

  7. Evaluation of basophil activation test in suspected food hypersensitivity.

    Science.gov (United States)

    Pignatti, Patrizia; Yacoub, Mona-Rita; Testoni, Claudia; Pala, Gianni; Corsetti, Maura; Colombo, Giselda; Meriggi, Antonio; Moscato, Gianna

    2017-07-01

    Food hypersensitivity is characterized by a wide range of symptoms. The relationship between symptoms and food is more frequently suspected than objectively proven. Basophil activation test (BAT) is based on the evaluation of activation markers on blood basophils in vitro stimulated with drugs or allergens. The aim of the study was to evaluate the usefulness of BAT when introduced in the routine work-up of suspected food hypersensitivity. BAT was requested in subjects with food adverse reactions when a discrepancy existed among history and skin prick test (SPT) and/or specific IgE. Data from 150 subjects were analysed using CD63 as basophil activation marker. Thirty controls were evaluated for cut-offs. Immunoblots was performed with the sera of representative subjects positive for BAT and negative for SPT and sIgE. 1,024 BAT were carried out, the agreement (positive/positive and negative/negative) was 78.5% for BAT vs. SPT and 78.3% for BAT vs. IgE. Atopic patients, but not atopic controls, more frequently had a positive BAT than non-atopic patients (P tested food) and both negative sIgE and SPT. Immunoblots revealed the presence of sIgE for the tested foods in representative patients with positive BAT, negative SPT and sIgE. Introduction of BAT in routine of food hypersensitivity, limited to subjects with a discrepancy between history and traditional tests, might be useful particularly when total IgE are low. © 2015 International Clinical Cytometry Society. © 2015 International Clinical Cytometry Society.

  8. Models of Inflammation: Carrageenan- or Complete Freund's Adjuvant (CFA)-Induced Edema and Hypersensitivity in the Rat.

    Science.gov (United States)

    McCarson, Kenneth E

    2015-09-01

    Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this unit are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). Copyright © 2015 John Wiley & Sons, Inc.

  9. Effects of vicarious pain on self-pain perception: investigating the role of awareness

    Science.gov (United States)

    Terrighena, Esslin L; Lu, Ge; Yuen, Wai Ping; Lee, Tatia MC; Keuper, Kati

    2017-01-01

    The observation of pain in others may enhance or reduce self-pain, yet the boundary conditions and factors that determine the direction of such effects are poorly understood. The current study set out to show that visual stimulus awareness plays a crucial role in determining whether vicarious pain primarily activates behavioral defense systems that enhance pain sensitivity and stimulate withdrawal or appetitive systems that attenuate pain sensitivity and stimulate approach. We employed a mixed factorial design with the between-subject factors exposure time (subliminal vs optimal) and vicarious pain (pain vs no pain images), and the within-subject factor session (baseline vs trial) to investigate how visual awareness of vicarious pain images affects subsequent self-pain in the cold-pressor test. Self-pain tolerance, intensity and unpleasantness were evaluated in a sample of 77 healthy participants. Results revealed significant interactions of exposure time and vicarious pain in all three dependent measures. In the presence of visual awareness (optimal condition), vicarious pain compared to no-pain elicited overall enhanced self-pain sensitivity, indexed by reduced pain tolerance and enhanced ratings of pain intensity and unpleasantness. Conversely, in the absence of visual awareness (subliminal condition), vicarious pain evoked decreased self-pain intensity and unpleasantness while pain tolerance remained unaffected. These findings suggest that the activation of defense mechanisms by vicarious pain depends on relatively elaborate cognitive processes, while – strikingly – the appetitive system is activated in highly automatic manner independent from stimulus awareness. Such mechanisms may have evolved to facilitate empathic, protective approach responses toward suffering individuals, ensuring survival of the protective social group. PMID:28831270

  10. Attenuation correction for SPECT

    International Nuclear Information System (INIS)

    Hosoba, Minoru

    1986-01-01

    Attenuation correction is required for the reconstruction of a quantitative SPECT image. A new method for detecting body contours, which are important for the correction of tissue attenuation, is presented. The effect of body contours, detected by the newly developed method, on the reconstructed images was evaluated using various techniques for attenuation correction. The count rates in the specified region of interest in the phantom image by the Radial Post Correction (RPC) method, the Weighted Back Projection (WBP) method, Chang's method were strongly affected by the accuracy of the contours, as compared to those by Sorenson's method. To evaluate the effect of non-uniform attenuators on the cardiac SPECT, computer simulation experiments were performed using two types of models, the uniform attenuator model (UAM) and the non-uniform attenuator model (NUAM). The RPC method showed the lowest relative percent error (%ERROR) in UAM (11 %). However, 20 to 30 percent increase in %ERROR was observed for NUAM reconstructed with the RPC, WBP, and Chang's methods. Introducing an average attenuation coefficient (0.12/cm for Tc-99m and 0.14/cm for Tl-201) in the RPC method decreased %ERROR to the levels for UAM. Finally, a comparison between images, which were obtained by 180 deg and 360 deg scans and reconstructed from the RPC method, showed that the degree of the distortion of the contour of the simulated ventricles in the 180 deg scan was 15 % higher than that in the 360 deg scan. (Namekawa, K.)

  11. Considerations on the electromagnetic hypersensitivity and idiopathic environmental intolerances

    International Nuclear Information System (INIS)

    Perrin, Anne

    2017-01-01

    After having noticed that environmental and health concerns are an important matter of concern in our society, and that always more pathologies are blamed on the environment, the author more particularly addresses electromagnetic hypersensitivity (EHS) which is considered by the WHO as a part of idiopathic environmental intolerances (IEI). He more particularly discusses the various conditions of emergence of these syndromes as they have been noticed, analysed and identified in different countries and in different studies. He discusses the possible definition to be given to these syndromes and their possible meaning

  12. Hypersensitive transition spectrum of f-element and coordination structure

    International Nuclear Information System (INIS)

    Cao Xuan; Song Chongli; Zhu Youngjun

    1992-10-01

    Some f-f transitions of Ln(An) metallic ions have particular super-sensitivity to the change of coordination environments. This is called super-sensitive transitions. Based on the irreducible tensor operator method, a computation model and corresponding computer program for calculating the hypersensitive transition spectrum of f-element were developed. By comparing the theoretical spectra of all possible coordination structures with experimental one, the possible coordination structures of complex can be determined. The coordination structures of Nd 3+ , Er 3 + hydrate and their extraction complex with H(DEHP) were successfully determined by this method, and the experimental spectra were also assigned

  13. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines

    DEFF Research Database (Denmark)

    Salik, Elaha; Løvik, Ida; Andersen, Klaus E

    2016-01-01

    There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year...... period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons...... treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations....

  14. Electromagnetic hypersensitivity: The opinion of an observer neurologist

    Science.gov (United States)

    Marc-Vergnes, Jean-Pierre

    2010-11-01

    Electromagnetic hypersensitivity (EHS) is a recent, uncertain and somehow confusing concept. It is now widely agreed that people claiming to be EHS really experience symptoms. However, no evidence for a causal link between the symptoms and electromagnetic fields (EMF) has been reported. Thus, we have to wonder whether EHS constitutes truly a relevant entity. Most of the previous studies suffer from methodological flaws. Owing to the quantification of symptoms, the interdisciplinary assessment of patients, and the use of personal exposimeters, the recent studies are of better quality. A set of convergent associated signs suggests that individual neuropsychic factors take a prominent, but maybe not unique, part in this condition.

  15. Interpersonal sensitivity and persistent attenuated psychotic symptoms in adolescence.

    Science.gov (United States)

    Masillo, Alice; Brandizzi, M; Valmaggia, L R; Saba, R; Lo Cascio, N; Lindau, J F; Telesforo, L; Venturini, P; Montanaro, D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

    2018-03-01

    Interpersonal sensitivity defines feelings of inner-fragility in the presence of others due to the expectation of criticism or rejection. Interpersonal sensitivity was found to be related to attenuated positive psychotic symptom during the prodromal phase of psychosis. The aims of this study were to examine if high level of interpersonal sensitivity at baseline are associated with the persistence of attenuated positive psychotic symptoms and general psychopathology at 18-month follow-up. A sample of 85 help-seeking individuals (mean age = 16.6, SD = 5.05) referred an Italian early detection project, completed the interpersonal sensitivity measure and the structured interview for prodromal symptoms (SIPS) at baseline and were assessed at 18-month follow-up using the SIPS. Results showed that individuals with high level of interpersonal sensitivity at baseline reported high level of attenuated positive psychotic symptoms (i.e., unusual thought content) and general symptoms (i.e., depression, irritability and low tolerance to daily stress) at follow-up. This study suggests that being "hypersensitive" to interpersonal interactions is a psychological feature associated with attenuated positive psychotic symptoms and general symptoms, such as depression and irritability, at 18-month follow-up. Assessing and treating inner-self fragilities may be an important step of early detection program to avoid the persistence of subtle but very distressing long-terms symptoms.

  16. TRPA1 in the spinal dorsal horn is involved in post-inflammatory visceral hypersensitivity: in vivo study using TNBS-treated rat model

    Directory of Open Access Journals (Sweden)

    Li Q

    2016-12-01

    Full Text Available Qian Li,1,* Cheng-Hao Guo,2,* Mohammed Ali Chowdhury,1 Tao-Li Dai,1 Wei Han,1,3 1Department of Gastroenterology, Qilu Hospital of Shandong University, 2Department of Pathology, Medical School of Shandong University, 3Laboratory of Translational Gastroenterology, Shandong University, Qilu Hospital, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Introduction: The transient receptor potential ankyrin-1 (TRPA1 channel, a pain transducer and amplifier, is drawing increasing attention in the field of visceral hypersensitivity, commonly seen in irritable bowel syndrome and inflammatory bowel disease. However, the role of TRPA1 in visceral nociception during post-inflammatory states is not well defined. Here, we explore the correlation between TRPA1 expression in the spinal dorsal horn (SDH and persistent post-inflammatory visceral hypersensitivity.Methods: We injected rats intracolonically with 2,4,6-trinitrobenzene sulfonic acid (TNBS or vehicle (n=12 per group. Post-inflammatory visceral hypersensitivity was assessed by recording the electromyographic activity of the external oblique muscle in response to colorectal distension. TRPA1 expression and distribution in the spinal cord and colon were examined by Western blotting and immunohistochemistry.Results: Animals exposed to TNBS had more abdominal contractions than vehicle-injected controls (P<0.05, which corresponded to a lower nociceptive threshold. Expression of TRPA1 in the SDH (especially in the substantia gelatinosa and the colon was significantly greater in the TNBS-treated group than in controls (P<0.05. In the SDH, the number of TRPA1-immunopositive neurons was 25.75±5.12 in the control group and 34.25±7.89 in the TNBS-treated group (P=0.023, and integrated optical density values of TRPA1 in the control and TNBS-treated groups were 14,544.63±6,525.54 and 22,532.75±7,608.11, respectively (P=0.041.Conclusion: Our results indicate

  17. Increased auditory startle reflex in children with functional abdominal pain.

    Science.gov (United States)

    Bakker, Mirte J; Boer, Frits; Benninga, Marc A; Koelman, Johannes H T M; Tijssen, Marina A J

    2010-02-01

    To test the hypothesis that children with abdominal pain-related functional gastrointestinal disorders have a general hypersensitivity for sensory stimuli. Auditory startle reflexes were assessed in 20 children classified according to Rome III classifications of abdominal pain-related functional gastrointestinal disorders (13 irritable bowel syndrome [IBS], 7 functional abdominal pain syndrome; mean age, 12.4 years; 15 girls) and 23 control subjects (14 girls; mean age, 12.3 years) using a case-control design. The activity of 6 left-sided muscles and the sympathetic skin response were obtained by an electromyogram. We presented sudden loud noises to the subjects through headphones. Both the combined response of 6 muscles and the blink response proved to be significantly increased in patients with abdominal pain compared with control subjects. A significant increase of the sympathetic skin response was not found. Comorbid anxiety disorders (8 patients with abdominal pain) or Rome III subclassification did not significantly affect these results. This study demonstrates an objective hyperresponsivity to nongastrointestinal stimuli. Children with abdominal pain-related functional gastrointestinal disorders may have a generalized hypersensitivity of the central nervous system. Copyright 2010 Mosby, Inc. All rights reserved.

  18. Mechanisms of, and Adjuvants for, Bone Pain.

    Science.gov (United States)

    Figura, Nicholas; Smith, Joshua; Yu, Hsiang-Hsuan Michael

    2018-06-01

    Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Landing gear noise attenuation

    Science.gov (United States)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  20. Pain and anxiety control: an online study guide.

    Science.gov (United States)

    2008-05-01

    The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section will cover pain theories and dentin hypersensitivity, referred pain, oral pain not of dental origin, barodontalgia, local anesthetics, long-acting local anesthetics, intrapulpal anesthesia, intraligamentary anesthesia, intraosseous anesthesia, inferior alveolar nerve block anesthesia, Gow-Gates anesthesia technique, Vazirani-Akinosi anesthesia technique, second-division block anesthesia technique, endodontic postoperative pain, effect of occlusal adjustment on endodontic pain, paresthesia associated with periradicular pathosis, analgesics, sedation, and endodontic flare-ups.

  1. 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

  2. Oral 2-hydroxyoleic acid inhibits reflex hypersensitivity and open-field-induced anxiety after spared nerve injury.

    Science.gov (United States)

    Avila-Martin, G; Galan-Arriero, I; Ferrer-Donato, A; Busquets, X; Gomez-Soriano, J; Escribá, P V; Taylor, J

    2015-01-01

    Recently, fatty acids have been shown to modulate sensory function in animal models of neuropathic pain. In this study, the antinociceptive effect of 2-hydroxyoleic acid (2-OHOA) was assessed following spared nerve injury (SNI) with reflex and cerebrally mediated behavioural responses. Initial antinociceptive behavioural screening of daily administration of 2-OHOA (400 mg/kg, p.o.) was assessed in Wistar rats by measuring hindlimb reflex hypersensitivity to von Frey and thermal plate stimulation up to 7 days after SNI, while its modulatory effect on lumbar spinal dorsal horn microglia reactivity was assessed with OX-42 immunohistochemistry. In vitro the effect of 2-OHOA (120 μM) on cyclooxygenase protein expression (COX-2/COX-1 ratio) in lipopolysaccharide-activated macrophage cells was tested with Western blot analysis. Finally, the effects of 2-OHOA treatment on the place escape aversion paradigm (PEAP) and the open-field-induced anxiety test were tested at 21 days following nerve injury compared with vehicle-treated sham and pregabalin-SNI (30 mg/kg, p.o.) control groups. Oral 2-OHOA significantly reduced ipsilateral mechanical and thermal hypersensitivity up to 7 days after SNI. Additionally 2-OHOA decreased the COX-2/COX-1 ratio in lipopolysaccharide-activated macrophage cells and OX-42 expression within the ipsilateral lumbar spinal dorsal horn 7 days after SNI. 2-OHOA significantly restored inner-zone exploration in the open-field test compared with the vehicle-treated sham group at 21 days after SNI. Oral administration of the modified omega 9 fatty acid, 2-OHOA, mediates antinociception and prevents open-field-induced anxiety in the SNI model in Wistar rats, which is mediated by an inhibition of spinal dorsal horn microglia activation. © 2014 European Pain Federation - EFIC®

  3. Slack channels expressed in sensory neurons control neuropathic pain in mice.

    Science.gov (United States)

    Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

    2015-01-21

    Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

  4. Effect of mesenchymal stromal cells (MSC) on chronic visceral hypersensitivity in a radio-induced colonic ulceration model in the rat

    International Nuclear Information System (INIS)

    Durand, Christelle

    2014-01-01

    Patients who undergo pelvic radiotherapy may develop significant incidence of undesirable chronic gastrointestinal complications resulting from radiation-induced damages around the tumour. Chronic visceral pain is one of the radiation-induced side effects that greatly affects the quality of life of 'cancer survivors'. The lack of effective analgesic treatment highlights the importance of novel and effective therapeutic strategies. In our laboratory, mesenchymal stromal cell (MSC) based approach showed beneficial immunomodulatory and regenerative effects in a rat model of irreversible radiationinduced colonic ulcers. The goal of my work was to assess the relevance of this model to study radiation-induced visceral persistent hypersensitivity and its modulation by MSC treatment. We first demonstrated that this model is associated with long-lasting visceral hypersensitivity and central neuronal sensitization. In this context we showed then that mast cells (MC) are involved in the mechanism of peripheral sensitization. Moreover, we suggested the implication of the neuro-mediator NO . in the pathophysiology of persistent radiation-induced visceral hypersensitivity. We also suggested that MSC treatment reversed radiation-induced hypersensitivity by a mechanism that in part may involve the modulation of MC activation and/or the decrease in the number of MC and nerve fiber interactions. In addition, MSC treatment reduced the percentage of nitrinergic neurons, increased after irradiation, and restored colonic muscular contractibility. Such processes may promote the therapeutic benefit of MSC observed in our study. In conclusion, this work provided new insights on the therapeutic benefit of MSC in our study model and a new argument in favour of their use in a future clinical trial to cure abdomino-pelvic radiotherapy side effects. (author) [fr

  5. Rice hypersensitive induced reaction protein 1 (OsHIR1) associates with plasma membrane and triggers hypersensitive cell death.

    Science.gov (United States)

    Zhou, Liang; Cheung, Ming-Yan; Li, Man-Wah; Fu, Yaping; Sun, Zongxiu; Sun, Sai-Ming; Lam, Hon-Ming

    2010-12-30

    In plants, HIR (Hypersensitive Induced Reaction) proteins, members of the PID (Proliferation, Ion and Death) superfamily, have been shown to play a part in the development of spontaneous hypersensitive response lesions in leaves, in reaction to pathogen attacks. The levels of HIR proteins were shown to correlate with localized host cell deaths and defense responses in maize and barley. However, not much was known about the HIR proteins in rice. Since rice is an important cereal crop consumed by more than 50% of the populations in Asia and Africa, it is crucial to understand the mechanisms of disease responses in this plant. We previously identified the rice HIR1 (OsHIR1) as an interacting partner of the OsLRR1 (rice Leucine-Rich Repeat protein 1). Here we show that OsHIR1 triggers hypersensitive cell death and its localization to the plasma membrane is enhanced by OsLRR1. Through electron microscopy studies using wild type rice plants, OsHIR1 was found to mainly localize to the plasma membrane, with a minor portion localized to the tonoplast. Moreover, the plasma membrane localization of OsHIR1 was enhanced in transgenic rice plants overexpressing its interacting protein partner, OsLRR1. Co-localization of OsHIR1 and OsLRR1 to the plasma membrane was confirmed by double-labeling electron microscopy. Pathogen inoculation studies using transgenic Arabidopsis thaliana expressing either OsHIR1 or OsLRR1 showed that both transgenic lines exhibited increased resistance toward the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. However, OsHIR1 transgenic plants produced more extensive spontaneous hypersensitive response lesions and contained lower titers of the invading pathogen, when compared to OsLRR1 transgenic plants. The OsHIR1 protein is mainly localized to the plasma membrane, and its subcellular localization in that compartment is enhanced by OsLRR1. The expression of OsHIR1 may sensitize the plant so that it is more prone to HR and hence can react more

  6. CT findings associated with survival in chronic hypersensitivity pneumonitis

    International Nuclear Information System (INIS)

    Chung, Jonathan H.; Montner, Steven M.; Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E.; Oldham, Justin M.; Husain, Aliya N.

    2017-01-01

    To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)

  7. The Role of Esophageal Hypersensitivity in Functional Heartburn.

    Science.gov (United States)

    Kondo, Takashi; Miwa, Hiroto

    2017-08-01

    Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.

  8. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

    Directory of Open Access Journals (Sweden)

    Najeeba Riyaz

    2012-01-01

    Full Text Available A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6. Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

  9. CT findings associated with survival in chronic hypersensitivity pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jonathan H.; Montner, Steven M. [University of Chicago Medical Center, Department of Radiology, Chicago, IL (United States); Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E. [University of Chicago Medical Center, Section of Pulmonary/Critical Care, Department of Medicine, Chicago, IL (United States); Oldham, Justin M. [University of California at Davis, Section of Pulmonary/Critical Care, Department of Medicine, Sacramento, CA (United States); Husain, Aliya N. [University of Chicago Medical Center, Department of Pathology, Chicago, IL (United States)

    2017-12-15

    To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)

  10. Metalworking fluid-associated hypersensitivity pneumonitis: a workshop summary.

    Science.gov (United States)

    Kreiss, K; Cox-Ganser, J

    1997-10-01

    A workshop discussing eight clusters of hypersensitivity pneumonitis in the automotive industry among metalworking fluid-exposed workers concluded that a risk exists for this granulomatous lung disease where water-based fluids are used and unusual microbial contaminants predominate. Strong candidates for microbial etiology are nontuberculous mycobacteria and fungi. Cases of hypersensitivity pneumonitis occur among cases with other work-related respiratory symptoms and chest diseases. Reversibility of disease has occurred in many cases with exposure cessation, allowing return to work to jobs without metalworking fluid exposures or, in some situations, to jobs without the same metalworking fluid exposures. Cases have been recognized with metalworking fluid exposures generally less than 0.5 mg/m3. The workshop participants identified knowledge gaps regarding risk factors, exposure-response relationships, intervention efficacy, and natural history, as well as surveillance needs to define the extent of the problem in this industry. In the absence of answers to these questions, guidance for prevention is necessarily limited.

  11. Perioperative Ketamine Administration for Thoracotomy Pain.

    Science.gov (United States)

    Moyse, Daniel W; Kaye, Alan D; Diaz, James H; Qadri, Muhammad Y; Lindsay, David; Pyati, Srinivas

    2017-03-01

    Of all the postsurgical pain conditions, thoracotomy pain poses a particular therapeutic challenge in terms of its prevalence, severity, and ensuing postoperative morbidity. Multiple pain generators contribute to the severity of post-thoracotomy pain, and therefore a multimodal analgesic therapy is considered to be a necessary strategy. Along with opioids, thoracic epidural analgesia, and paravertebral blocks, N-Methyl-D-Aspartate (NMDA) receptor antagonists such as ketamine have been used as adjuvants to improve analgesia. We reviewed the evidence for the efficacy of intravenous and epidural administration of ketamine in acute post-thoracotomy pain management, and its effectiveness in reducing chronic post-thoracotomy pain. Systematic literature review and an analytic study of a data subset were performed. We searched PubMed, Embase, and Cochrane reviews using the key terms "ketamine," "neuropathic pain," "postoperative," and "post-thoracotomy pain syndrome." The search was limited to human trials and included all studies published before January 2015. Data from animal studies, abstracts, and letters were excluded. All studies not available in the English language were excluded. The manuscript bibliographies were reviewed for additional related articles. We included randomized controlled trials and retrospective studies, while excluding individual case reports. This systematic literature search yielded 15 randomized control trials evaluating the efficacy of ketamine in the treatment of acute post-thoracotomy pain; fewer studies assessed its effect on attenuating chronic post-thoracotomy pain. The majority of reviewed studies demonstrated that ketamine has efficacy in reduction of acute pain, but the evidence is limited on the long-term benefits of ketamine to prevent post-thoracotomy pain syndrome, regardless of the route of administration. A nested analytical study found there is a statistically significant reduction in acute post-thoracotomy pain with IV or

  12. Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

    Science.gov (United States)

    Hatch, R J; Jennings, E A; Ivanusic, J J

    2013-08-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. © 2012 European Federation of International Association for the Study of Pain Chapters.

  13. Operant conditioning of enhanced pain sensitivity by heat-pain titration.

    Science.gov (United States)

    Becker, Susanne; Kleinböhl, Dieter; Klossika, Iris; Hölzl, Rupert

    2008-11-15

    Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. This study replicates and extends our previous demonstration that enhanced pain sensitivity to prolonged heat-pain stimulation could be learned in healthy participants through intrinsic reinforcement (contingent changes in nociceptive input) independent of verbal pain reports. In addition, we examine whether different magnitudes of reinforcement differentially enhance pain sensitivity using an operant heat-pain titration paradigm. It is based on the previously developed non-verbal behavioral discrimination task for the assessment of sensitization, which uses discriminative down- or up-regulation of stimulus temperatures in response to changes in subjective intensity. In operant heat-pain titration, this discriminative behavior and not verbal pain report was contingently reinforced or punished by acute decreases or increases in heat-pain intensity. The magnitude of reinforcement was varied between three groups: low (N1=13), medium (N2=11) and high reinforcement (N3=12). Continuous reinforcement was applied to acquire and train the operant behavior, followed by partial reinforcement to analyze the underlying learning mechanisms. Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic.

  14. 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.

  15. Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants

    DEFF Research Database (Denmark)

    Schalock, Peter C; Thyssen, Jacob P

    2013-01-01

    Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated.......Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated....

  16. Genome-wide association study of insect bite hypersensitivity in swedish-born icelandic horses

    NARCIS (Netherlands)

    Shrestha, M.; Eriksson, S.; Schurink, A.; Andersson, L.S.; Sundquist, M.; Frey, R.; Brostrom, H.; Bergstrom, T.; Ducro, B.J.; lindgren, G.

    2015-01-01

    Insect bite hypersensitivity (IBH) is the most common allergic skin disease in horses and is caused by biting midges, mainly of the genus Culicoides. The disease predominantly comprises a type I hypersensitivity reaction, causing severe itching and discomfort that reduce the welfare and commercial

  17. Baroreflex Sensitivity And Autonomic Nervous System Function In Carotid Sinus Hypersensitivity

    DEFF Research Database (Denmark)

    Brinth, Louise Schouborg; Pors, Kirsten; Theibel, Ann Cathrine

    2015-01-01

    hypersensitivity ranging from reduced to increased sensitivity compared to controls. We wanted to establish whether measures of baroreflex sensitivity and autonomic function differed between patients diagnosed with carotid sinus hypersensitivity and age matched controls. We included 36 patients (12 women; 74 +/-10...... sensitivity may not follow the same neuronal pathways as those responding to the crude external pressures applied during carotid sinus massage...

  18. Successful desensitization protocol for hypersensitivity reaction probably caused by dabrafenib in a patient with metastatic melanoma.

    Science.gov (United States)

    Bar-Sela, Gil; Abu-Amna, Mahmoud; Hadad, Salim; Haim, Nissim; Shahar, Eduardo

    2015-09-01

    Vemurafenib and dabrafenib are both orally bioavailable small molecule agents that block mitogen activated protein kinase signalling in patients with melanoma and BRAF(V600E) mutation. Generalized hypersensitivity reactions to vemurafenib or dabrafenib have not been described. Continuing vemurafenib or dabrafenib therapy despite hypersensitivity reaction is especially important in patients with melanoma and BRAF(V600E) mutation, in whom this mutation plays a critical role in tumour growth. Desensitization protocols to overcome hypersensitivity reactions by gradual reintroduction of small amounts of the offending drug up to full therapeutic doses are available for many anti-cancer agents, including vemurafenib but, to the best of our knowledge, have not been reported for dabrafenib. We describe a patient with metastatic melanoma who developed Type I hypersensitivity reaction to vemurafenib and to subsequent treatment with dabrafenib, and who was successfully treated by drug desensitization which allowed safe prolonged continuation of dabrafenib. The development of hypersensitivity reactions for both dabrafenib and vemurafinib in the current case could be because these drugs have a similar chemical structure and cause a cross-reactivity. However, hypersensitivity reaction to a non-medicinal ingredient shared by the two drugs is also possible. Oral desensitization appears to be an option for patients with hypersensitivity Type I to dabrafenib. This approach may permit clinicians to safely administer dabrafenib to patients who experience hypersensitivity reactions to this life-prolonging medication. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Hypersensitive cell death in plants : its mechanisms and role in plant defense against pathogens

    NARCIS (Netherlands)

    Iakimova, E.T.; Michalczuk, L.; Woltering, E.J.

    2005-01-01

    This review is a recent update in the understanding of the hypersensitive response (HR) of plants with special consideration to the physiological and biochemical determinants in different model systems. Hypersensitive response is reviewed as a form of programmed cell death (PCD) representing one of

  20. Detective quantum efficiency gains compared with speed gains for hypersensitized astronomical plates

    International Nuclear Information System (INIS)

    Kaye, A.L.

    1977-01-01

    It is reasonable to assume that gains in detective quantum efficiency (DQE) are far better criteria for assessing the performance of hypersensitizing techniques than gains in speed. It is shown here that gains in speed can be misleading, for some methods of hypersensitization give plates of increased speed but reduced detective quantum efficiency. (author)

  1. [Pain and its pathways. A study for therapeutic action].

    Science.gov (United States)

    Barbin, J Y; Robert, R; Fresche, F; Lajat, J; Menegalli-Boggelli, D

    1992-01-01

    Pain is as old as mankind. It has a threshold beyond which nobody can escape it. Pain is a biological and physiological phenomenon, an integrated part of our body and ego. Will all our efforts eventually make it disappear? Is its disappearance desirable? Pain is one of the major expressions of sensation. It is integrated by the central structures and expressed as a behavior of avoidance or attenuation of the effects produced by the cause of pain. The study of this behavior and of the transmission of the pain message corresponds to the study of how to fight against this message, which means that it should logically lead to the treatment of pain.

  2. Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats.

    Science.gov (United States)

    Botschuijver, Sara; Roeselers, Guus; Levin, Evgeni; Jonkers, Daisy M; Welting, Olaf; Heinsbroek, Sigrid E M; de Weerd, Heleen H; Boekhout, Teun; Fornai, Matteo; Masclee, Ad A; Schuren, Frank H J; de Jonge, Wouter J; Seppen, Jurgen; van den Wijngaard, René M

    2017-10-01

    Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity. We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble β-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1. α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal

  3. National prevalence of asthma and chemical hypersensitivity: an examination of potential overlap.

    Science.gov (United States)

    Caress, Stanley M; Steinemann, Anne C

    2005-05-01

    The objective of this study was to investigate the linkage between asthma and chemical hypersensitivity. The authors conducted a population study with a random sample of 1057 geographically weighted cases to determine the prevalence of both asthma and chemical hypersensitivity in the American population and to explore their co-occurrence. A total of 14.1% of the respondents reported being diagnosed with asthma and 11.2% reported a hypersensitivity to chemicals. Of those with asthma, 27.2% also reported being hypersensitive to chemicals and 7.4% reported also being diagnosed with multiple chemical sensitivities (MCS). Of those diagnosed with MCS, 42% reported also being diagnosed with asthma. Additionally, 29.7% of those with asthma said air fresheners caused breathing difficulties, and 37.2% found scented products irritating. The results indicate that there is significant overlap between some forms of asthma and chemical hypersensitivity.

  4. Linking Anxiety and Insistence on Sameness in Autistic Children: The Role of Sensory Hypersensitivity.

    Science.gov (United States)

    Black, Karen R; Stevenson, Ryan A; Segers, Magali; Ncube, Busiswe L; Sun, Sol Z; Philipp-Muller, Aviva; Bebko, James M; Barense, Morgan D; Ferber, Susanne

    2017-08-01

    Sensory hypersensitivity and insistence on sameness (I/S) are common, co-occurring features of autism, yet the relationship between them is poorly understood. This study assessed the impact of sensory hypersensitivity on the clinical symptoms of specific phobia, separation anxiety, social anxiety and I/S for autistic and typically developing (TD) children. Parents of 79 children completed questionnaires on their child's difficulties related to sensory processing, I/S, and anxiety. Results demonstrated that sensory hypersensitivity mediated 67% of the relationship between symptoms of specific phobia and I/S and 57% of the relationship between separation anxiety and I/S. No relationship was observed between sensory hypersensitivity and social anxiety. These mediation effects of sensory hypersensitivity were found only in autistic children, not in TD children.

  5. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  6. Comparative evaluation of Type 1 latex hypersensitivity in patients with chronic urticaria, rubber factory workers and healthy control subjects

    NARCIS (Netherlands)

    Piskin, Gamze; Akyol, Aynur; Uzar, Hatice; Tulek, Necla; Boyvat, Ayse; Gurgey, Erbak

    2003-01-01

    Latex hypersensitivity manifests itself most commonly with contact urticaria. In this study, we investigated the frequency of latex hypersensitivity as a possible aetiological factor in patients with chronic urticaria (CU) and compared latex hypersensitivity of CU patients (n = 50) with that of

  7. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Arjun eMuralidharan

    2016-05-01

    Full Text Available Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤450g of gravel on any two days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund’s complete adjuvant (FCA or saline, or underwent unilateral chronic constriction injury (CCI of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA- and CCI-rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

  8. Childhood hypersensitivity pneumonitis associated with fungal contamination of indoor hydroponics.

    Science.gov (United States)

    Engelhart, Steffen; Rietschel, Ernst; Exner, Martin; Lange, Lars

    2009-01-01

    Childhood hypersensitivity pneumonitis (HP) is often associated with exposure to antigens in the home environment. We describe a case of HP associated with indoor hydroponics in a 14-year-old girl. Water samples from hydroponics revealed Aureobasidium pullulans as the dominant fungal micro-organism (10(4)CFU/ml). The diagnosis is supported by the existence of serum precipitating antibodies against A. pullulans, lymphocytic alveolitis on bronchoalveolar lavage (BAL) fluid, a corresponding reaction on a lung biopsy, and the sustained absence of clinical symptoms following the removal of hydroponics from the home. We conclude that hydroponics should be considered as potential sources of fungal contaminants when checking for indoor health complaints.

  9. Adrenergic receptors are a fallible index of adrenergic denervation hypersensitivity

    DEFF Research Database (Denmark)

    Dejgaard, Anders; Liggett, S B; Christensen, N J

    1991-01-01

    In view of evidence that neither interindividual nor induced intra-individual variations of adrenergic receptor status are related to metabolic or haemodynamic sensitivity to adrenaline in vivo, we took an alternative approach to assessment of the relevance of adrenergic receptor measurement...... by measuring these in a group of subjects with well-documented adrenergic denervation hypersensitivity, patients with diabetic autonomic neuropathy. Mononuclear leukocyte beta 2-adrenergic receptor densities (and binding affinities), measured with 125I-labelled pindolol, and isoproterenol-stimulated cyclic AMP...... accumulation, in samples from patients with insulin-dependent diabetes mellitus (IDDM) with diabetic autonomic neuropathy (n = 8), were no different from those in samples from patients with IDDM without neuropathy (n = 8), or from non-diabetic subjects (n = 8). In addition, platelet alpha 2-adrenergic receptor...

  10. Immediate and delayed contact hypersensitivity to verbena plants

    DEFF Research Database (Denmark)

    Potter, P C; Mather, S; Lockey, P

    1995-01-01

    Plants from the Verbenaceae family may cause contact dermatitis of unknown nature. This report describes 2 cases of allergic reactions to the Verbena species. A teenage boy developed an anaphylactic allergic response following contact with the leaves of Verbena hybrida. Characterization...... of the patient's specific IgE response to Verbena hybrida, using Western blots and autoradiography, identified the specific 62000 Dalton allergen present in the verbena leaves to which the patient reacted. This is the first report of an IgE-mediated immediate contact hypersensitivity reaction to Verbena hybrida......, a common perennial in South African gardens. The other case was a 23-year-old female gardener who developed immediate and delayed-type contact dermatitis from Verbena elegans 'Cleopatra' produced in a Danish nursery. Prick tests to plant material were considered positive and of an allergic nature....

  11. Allopurinol-induced Severe Hypersensitivity with Acute Renal Failure

    Directory of Open Access Journals (Sweden)

    I-Hung Chen

    2005-05-01

    Full Text Available A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS. Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.

  12. Autophagic components contribute to hypersensitive cell death in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Schultz-Larsen, Torsten; Joensen, Jan

    2009-01-01

    Autophagy has been implicated as a prosurvival mechanism to restrict programmed cell death (PCD) associated with the pathogen-triggered hypersensitive response (HR) during plant innate immunity. This model is based on the observation that HR lesions spread in plants with reduced autophagy gene...... expression. Here, we examined receptor-mediated HR PCD responses in autophagy-deficient Arabidopsis knockout mutants (atg), and show that infection-induced lesions are contained in atg mutants. We also provide evidence that HR cell death initiated via Toll/Interleukin-1 (TIR)-type immune receptors through...... the defense regulator EDS1 is suppressed in atg mutants. Furthermore, we demonstrate that PCD triggered by coiled-coil (CC)-type immune receptors via NDR1 is either autophagy-independent or engages autophagic components with cathepsins and other unidentified cell death mediators. Thus, autophagic cell death...

  13. Persistent Skin Reactions and Aluminium Hypersensitivity Induced by Childhood Vaccines.

    Science.gov (United States)

    Salik, Elaha; Løvik, Ida; Andersen, Klaus E; Bygum, Anette

    2016-11-02

    There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons. Two patients had skin biopsies performed from their skin lesions, and 2 patients had the nodules surgically removed. Forty-two children had a patch-test performed with 2% aluminium chloride hexahydrate in petrolatum and 39 of them (92%) had a positive reaction. The persistent skin reactions were treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations.

  14. Desensitization of delayed-type hypersensitivity in mice: suppressive environment

    Directory of Open Access Journals (Sweden)

    Takashi Katsura

    1993-01-01

    Full Text Available The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2 activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.

  15. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat.

    Science.gov (United States)

    Seluanov, Andrei; Hine, Christopher; Azpurua, Jorge; Feigenson, Marina; Bozzella, Michael; Mao, Zhiyong; Catania, Kenneth C; Gorbunova, Vera

    2009-11-17

    The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, naked mole-rats have an extraordinary resistance to cancer as tumors have never been observed in these rodents. Furthermore, we show that a combination of activated Ras and SV40 LT fails to induce robust anchorage-independent growth in naked mole-rat cells, while it readily transforms mouse fibroblasts. The mechanisms responsible for the cancer resistance of naked mole-rats were unknown. Here we show that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed "early contact inhibition." Contact inhibition is a key anticancer mechanism that arrests cell division when cells reach a high density. In cell culture, naked mole-rat fibroblasts arrest at a much lower density than those from a mouse. We demonstrate that early contact inhibition requires the activity of p53 and pRb tumor suppressor pathways. Inactivation of both p53 and pRb attenuates early contact inhibition. Contact inhibition in human and mouse is triggered by the induction of p27(Kip1). In contrast, early contact inhibition in naked mole-rat is associated with the induction of p16(Ink4a). Furthermore, we show that the roles of p16(Ink4a) and p27(Kip1) in the control of contact inhibition became temporally separated in this species: the early contact inhibition is controlled by p16(Ink4a), and regular contact inhibition is controlled by p27(Kip1). We propose that the additional layer of protection conferred by two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole-rat.

  16. Ejaculatory pain

    DEFF Research Database (Denmark)

    Aasvang, Eske K; Møhl, Bo; Kehlet, Henrik

    2007-01-01

    . The psychosexual interview revealed no major psychosexual disturbances and concluded that the pain was of somatic origin. All patients with ejaculatory pain had experienced major negative life changes and deterioration in their overall quality of life and sexual function as a result of the hernia operation...

  17. Breast Pain

    Science.gov (United States)

    ... result in the development of breast cysts. Breast trauma, prior breast surgery or other factors localized to the breast can lead to breast pain. Breast pain may also start outside the breast — in the chest wall, muscles, joints or heart, for example — and ...

  18. Neuropathic pain

    Directory of Open Access Journals (Sweden)

    Giuseppe Re

    2009-02-01

    Full Text Available Neuropathic pain is the expression of a dysfunction or primary lesion of a nerve in the peripheral or central nervous system, or both, rather than the biological signal transmitted by the nerve following peripheral nociceptor activation. It represents about 20% of all painful syndromes, with an estimated prevalence of 1.5%, however is actual incidence is hard to pinpoint due to the difficulties encountered in distinguishing it from chronic pain, of which it represents a significant percentage, on account of the not infrequent concurrence of conditions. It is crucial to recognise the variety of symptoms with which it can present: these can be negative and positive and, in turn, motor, sensitive and autonomic. In public health terms, it is important to emphasise that the diagnosis of neuropathic pain does not in most cases require sophisticated procedures and does not therefore weigh on health expenditure. In clinical practice, a validated scale (the LANSS is mentioned is useful for identifying patients presenting neuropathic pain symptoms. Therapy is based on three categories of medication: tricyclic antidepressants, anti-epileptics and opioids at high doses: neuropathic pain has a bad reputation for often resisting common therapeutic approaches and responding less well that nociceptor pain to monotherapy. Therapeutic strategies are all the more adequate the more they are based on symptoms and therefore on the pain generation mechanisms, although the recommendations are dictated more by expert opinions that double-blind randomised trials.

  19. Painful shoulder

    Directory of Open Access Journals (Sweden)

    Benno Ejnismann

    2008-03-01

    Full Text Available Many factors can be involved in the painful shoulder. Beyond articularcauses other pathologies such as artrosis, periarticular diseases as rotadorcuff tears, long head of the biceps tendinitis, adhesive capsulitis, calcifyingtendinitis, degenerative arthritis of the acromioclavicular joint, cervicalradiculopathy and nervous injuries can cause pain in the shoulder.

  20. Orofacial Pain

    Science.gov (United States)

    ... aligned teeth can have trouble because the muscles work harder to bring the teeth together, causing strain. Pain also can be caused by clenching or grinding teeth, trauma to the head and neck or poor ergonomics. ; Some people may experience pain in the ears, ...

  1. Neck Pain

    Science.gov (United States)

    ... Vomiting Nausea and Vomiting in Infants and Children Neck Pain Neck Swelling Shortness of Breath Shortness of Breath ... worse or doesn’t get better. Start OverDiagnosisYour pain may be from DEGENERATIVE CERVICAL ARTHRITIS, a disorder that affects the bones and ...

  2. Radiofrequency attenuator and method

    Science.gov (United States)

    Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

    2009-01-20

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  3. Attenuation coefficients of soils

    International Nuclear Information System (INIS)

    Martini, E.; Naziry, M.J.

    1989-01-01

    As a prerequisite to the interpretation of gamma-spectrometric in situ measurements of activity concentrations of soil radionuclides the attenuation of 60 to 1332 keV gamma radiation by soil samples varying in water content and density has been investigated. A useful empirical equation could be set up to describe the dependence of the mass attenuation coefficient upon photon energy for soil with a mean water content of 10%, with the results comparing well with data in the literature. The mean density of soil in the GDR was estimated at 1.6 g/cm 3 . This value was used to derive the linear attenuation coefficients, their range of variation being 10%. 7 figs., 5 tabs. (author)

  4. On the phenomenon of electromagnetic hypersensitivity; Das Phaenomen der Elektrosensibilitaet

    Energy Technology Data Exchange (ETDEWEB)

    David, E.; Reissenweber, J.; Wojtysiak, A.; Pfotenhauer, M. [Witten-Herdecke Univ., Witten (Germany). Inst. fuer Normale und Pathologische Physiologie; Witten-Herdecke Univ., Witten (Germany). Zentrum fuer Elektropathologie

    2002-07-01

    For more than fifteen years electromagnetic fields (EMFs) are intensively discussed in connection with health hazards in mass media as well as questions of standard setting by the authorities. The present elaboration gives an extended overview over the actual situation of the special electromagnetic hypersensitivity issue in relation to electromagnetic field research in the international scientific community. There are parallels and analogies between the symptoms of electromagnetic hypersensitivity and those of the Multiple-Chemical-Sensitivity-Syndrome and other environmental diseases. The first part deals with the biophysical fundamental knowledge of interactions between electromagnetic fields and biological systems such as man or animal including threshold values and threshold philosophy. Then hypothetical mechanisms of action of EMF are demonstrated, with a special focus on the melatonin hypothesis, which has not been proved in all its parts up to now. Additionally, in the context of our biomedical research into disorders of well-being we conducted an analysis of written and telephone questions about the EMF issue which are sent to our center. The results are of scientific and political interest and are demonstrated in detail. (orig.) [German] Das Phaenomen der Elektrosensibilitaet gewinnt zunehmend an Bedeutung innerhalb der Diskussion um die medizinisch-biologischen Wirkungen elektromagnetischer Felder. Es konnte bisher nicht nachgewiesen werden, dass die Elektrosensibilitaet/Magnetosensibilitaet als eigenstaendige Krankheitseinheit (Krankheitsentitaet) existiert. Es handelt sich dabei um ein Phaenomen, das vor etwa 15 Jahren benannt und zunaechst nicht ernst genommen wurde. Im Rahmen des relativ jungen medizinisch-biologischen Fachgebietes Elektropathologie scheinen weitere Untersuchungen erforderlich, um die teilweise auch widerspruechlichen Befunde aufzuklaeren und zu erfahren, ob Felder Befindlichkeitsstoerungen ausloesen koennen, die in aehnlicher Form

  5. Computer-controlled attenuator.

    Science.gov (United States)

    Mitov, D; Grozev, Z

    1991-01-01

    Various possibilities for applying electronic computer-controlled attenuators for the automation of physiological experiments are considered. A detailed description is given of the design of a 4-channel computer-controlled attenuator, in two of the channels of which the output signal can change by a linear step, in the other two channels--by a logarithmic step. This, together with the existence of additional programmable timers, allows to automate a wide range of studies in different spheres of physiology and psychophysics, including vision and hearing.

  6. Clinical Presentation of Acute Gastroenteritis in Children With Functional Abdominal Pain Disorders.

    Science.gov (United States)

    Saps, Miguel; Mintjens, Stijn; Pusatcioglu, Cenk K; Cohen, Daniel M; Sternberg, Petra

    2017-08-01

    Visceral hypersensitivity and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with visceral hypersensitivity would report more pain if their gut is acutely inflamed. The aim of the study was to compare clinical symptoms and somatization of children with and without FAPDs at time of an episode of acute gastroenteritis. Seventy children with acute gastroenteritis and their parents completed the Rome III Diagnostic Questionnaire for Pediatric Functional GI Disorders and the Children's Somatization Inventory. Twenty-one percent of children were diagnosed with an FAPD. Children with FAPDs showed significantly more nongastrointestinal somatic symptoms than children without FAPDs. There were no significant differences in abdominal pain, nausea, vomiting, or school absenteeism between both groups at time of consultation.

  7. Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.

    Science.gov (United States)

    Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang

    2017-01-01

    We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease ( P Kruskal-Wallis test), serous and mixed histological types ( P = 0.003, Kruskal-Wallis test), malignant ascites ( P = 0.009, chi-square test), and history of other drug allergy ( P test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P test) and dose (6,816 vs. 3,844 mg, P test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

  8. Cervical dentin hypersensitivity: a cross-sectional investigation in Athens, Greece.

    Science.gov (United States)

    Rahiotis, C; Polychronopoulou, A; Tsiklakis, K; Kakaboura, A

    2013-12-01

    The purpose of this study was to identify the prevalence of cervical dentin hypersensitivity in a cross-sectional investigation of Greek adults. Seven hundred and sixty-seven subjects were examined. Participants were patients processed for first examination in the Clinic of Oral Diagnosis and Radiology at the Faculty of Dentistry, University of Athens. The evaluation of hypersensitivity was performed using two methods: for each tooth, the response to a) tactile stimulus and b) air-blast stimulus was measured. Additional factors such as smoking habits, oral health behaviour, consumption of acidic foods, type of toothbrush, daily use of fluoride solution and of desensitising toothpaste, gingival recession and non-carious cervical lesions were recorded and evaluated as causative factors. Descriptive statistics on the demographics of the study sample, of oral health behaviour characteristics and of oral examination findings were performed. Comparisons of these characteristics in the presence or absence of hypersensitivity were conducted with the chi-square test. Data were further analysed using multiple logistic regression modelling. Among study participants, 21·3% had at least one cervical dentin hypersensitivity reaction to the tactile stimulus, and 38·6%, to the air-blast stimulus. Multivariate analysis detected association of the hypersensitivity in tactile or air-blast stimulus with the non-carious lesions and with the gingival recessions. Additionally, a relation between hypersensitivity and air-blast stimulus with gender (female) was found. There was no association between the hypersensitivity in both of the stimuli and the level of education, smoking, consumption of acidic foods, type of toothbrush and daily use of fluoride solution or desensitising toothpaste. The overall prevalence of cervical dentin hypersensitivity in the adult population in Athens ranged from 21·3% to 38·6% depending on the type of stimuli. Cervical non-carious lesions and gingival

  9. Sigma-1 receptor and inflammatory pain.

    Science.gov (United States)

    Gris, Georgia; Cobos, Enrique José; Zamanillo, Daniel; Portillo-Salido, Enrique

    2015-06-01

    The sigma-1 receptor (Sig-1R) is a unique ligand-regulated molecular chaperone that interacts with several protein targets such as G protein-coupled receptors and ion channels to modulate their activity. Sig-1R is located in areas of the central and peripheral nervous system that are key to pain control. Previous preclinical studies have suggested a potential therapeutic use of Sig-1R antagonists for the management of neuropathic pain. Recent studies using pharmacological and genetic tools have explored the role of Sig-1R in inflammatory pain conditions. Mice lacking the Sig-1R have shown different patterns of phenotypic responses to inflammatory injury. Systemic or peripheral administration of several Sig-1R antagonists, including the selective Sig-1R antagonist S1RA, inhibited both mechanical and thermal hypersensitivity in several preclinical models of inflammatory pain. These recent studies are summarized in the present commentary. Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain.

  10. What do monoamines do in pain modulation?

    Science.gov (United States)

    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. 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®.

  12. Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

    Directory of Open Access Journals (Sweden)

    Coderre Terence J

    2009-09-01

    Full Text Available Abstract Background During the chronic stage of Complex Regional Pain Syndrome (CRPS, impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS. Discussion The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin. Summary The origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patient's report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients.

  13. Orofacial complex regional pain syndrome: pathophysiologic mechanisms and functional MRI.

    Science.gov (United States)

    Lee, Yeon-Hee; Lee, Kyung Mi; Kim, Hyug-Gi; Kang, Soo-Kyung; Auh, Q-Schick; Hong, Jyung-Pyo; Chun, Yang-Hyun

    2017-08-01

    Complex regional pain syndrome (CRPS) is one of the most challenging chronic pain conditions and is characterized by burning pain, allodynia, hyperalgesia, autonomic changes, trophic changes, edema, and functional loss involving mainly the extremities. Until recently, very few reports have been published concerning CRPS involving the orofacial area. We report on a 50-year-old female patient who presented with unbearable pain in all of her teeth and hypersensitivity of the facial skin. She also reported intractable pain in both extremities accompanied by temperature changes and orofacial pain that increased when the other pains were aggravated. In the case of CRPS with trigeminal neuropathic pain, protocols for proper diagnosis and prompt treatment have yet to be established in academia or in the clinical field. We performed functional magnetic resonance imaging for a thorough analysis of the cortical representation of the affected orofacial area immediately before and immediately after isolated light stimulus of the affected hand and foot and concluded that CRPS can be correlated with trigeminal neuropathy in the orofacial area. Furthermore, the patient was treated with carbamazepine administration and stellate ganglion block, which can result in a rapid improvement of pain in the trigeminal region. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms

    NARCIS (Netherlands)

    Kerckhoffs, A.P.M.

    2009-01-01

    Irritable Bowel Syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with a disordered defecation. No unique pathophysiological mechanism has been identified. It is most likely a multifactorial disease involving alterations in intestinal microbiota

  15. Natural attenuation of herbicides

    DEFF Research Database (Denmark)

    Tuxen, Nina; Højberg, Anker Lajer; Broholm, Mette Martina

    2002-01-01

    A field injection experiment in a sandy, aerobic aquifer showed that two phenoxy acids MCPP (mecoprop) and dichlorprop were degraded within I in downgradient of the injection wells after an apparent lag period. The plume development and microbial measurements indicated that microbial growth gover....... The observations may be important for application of natural attenuation as a remedy in field scale systems....

  16. Measured attenuation correction methods

    International Nuclear Information System (INIS)

    Ostertag, H.; Kuebler, W.K.; Doll, J.; Lorenz, W.J.

    1989-01-01

    Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4-5 in brain studies to 50-100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide 68 Ge/ 68 Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: Transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible. (orig.)

  17. Critical appraisal of Rome IV criteria: hypersensitive esophagus does belong to gastroesophageal reflux disease spectrum

    Science.gov (United States)

    Frazzoni, Leonardo; Frazzoni, Marzio; de Bortoli, Nicola; Tolone, Salvatore; Martinucci, Irene; Fuccio, Lorenzo; Savarino, Vincenzo; Savarino, Edoardo

    2018-01-01

    The Rome IV Committee introduced a major change in the classification of functional gastrointestinal disorders, proposing a more restrictive definition of gastroesophageal reflux disease (GERD). It was suggested that hypersensitive esophagus (HE) may sit more firmly within the functional realm. It was suggested that GERD diagnosis should be based upon abnormal acid exposure time (AET) only, implying no advantage of impedance-pH over pH monitoring. Symptom association probability (SAP), symptom index (SI) and heartburn relief with proton pump inhibitor (PPI) therapy were regarded as unreliable, whereas a lack of response to PPI was considered as evidence of functional heartburn. These assumptions are contradicted by numerous studies showing the clinical relevance of weakly acidic refluxes and the diagnostic utility of SAP, SI and new impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI). The PSPW index and MNBI provide significant diagnostic advantage, particularly in patients with normal AET who can be classified as HE when both parameters are abnormal, even though SAP and SI are negative. Visceral pain modulators are recommended by the Rome IV Committee despite scanty evidence of efficacy, but a positive outcome with medical or surgical anti-reflux treatment has been reported by several studies of HE patients. Therefore, we believe that patients with endoscopy-negative heartburn should be investigated by means of impedance-pH monitoring with analysis of PSPW index and MNBI: such an approach provides accurate identification of HE cases, who remain, in our opinion, within the realm of GERD and should be treated accordingly. PMID:29333061

  18. Chronic Osteoporotic Pain in Mice: Cutaneous and Deep Musculoskeletal Pain Are Partially Independent of Bone Resorption and Differentially Sensitive to Pharmacological Interventions

    Directory of Open Access Journals (Sweden)

    Miyako Suzuki

    2017-01-01

    Full Text Available Although the pathological changes in osteoporotic bones are well established, the characterization of the osteoporotic pain and its appropriate treatment are not fully elucidated. We investigated the behavioral signs of cutaneous and deep musculoskeletal pain and physical function; time-dependent changes in bone mineral density (BMD and the emergence of the behavioral phenotype; and the effects of pharmacological interventions having different mechanisms of action (chronic intraperitoneal administration of pamidronate [0.25 mg/kg, 5x/week for 5 weeks] versus acute treatment with intraperitoneal morphine [10 mg/kg] and pregabalin [100 mg/kg] in a mouse model of ovariectomized or sham-operated mice 6 months following surgery. We observed reduced BMD associated with weight gain, referred cutaneous hypersensitivity, and deep musculoskeletal pain that persisted for 6 months. Chronic bisphosphonate treatment, 6 months after ovariectomy, reversed bone loss and hypersensitivity to cold, but other behavioral indices of osteoporotic pain were unchanged. While the efficacy of acute morphine on cutaneous pain was weak, pregabalin was highly effective; deep musculoskeletal pain was intractable. In conclusion, the reversal of bone loss alone is insufficient to manage pain in chronic osteoporosis. Additional treatments, both pharmacological and nonpharmacological, should be implemented to improve quality of life for osteoporosis patients.

  19. Increased pain sensitivity is not associated with electrodiagnostic findings in women with carpal tunnel syndrome.

    Science.gov (United States)

    de la Llave-Rincón, Ana Isabel; Fernández-de-las-Peñas, César; Laguarta-Val, Sofia; Alonso-Blanco, Cristina; Martínez-Perez, Almudena; Arendt-Nielsen, Lars; Pareja, Juan A

    2011-01-01

    To determine the differences in widespread pressure pain and thermal hypersensitivity in women with minimal, moderate, and severe carpal tunnel syndrome (CTS) and healthy controls. A total of 72 women with CTS (19 with minimal, 18 with moderate, and 35 with severe) and 19 healthy age-matched women participated. Pressure pain thresholds were bilaterally assessed over the median, ulnar, and radial nerves, the C5 to C6 zygapophyseal joint, the carpal tunnel, and the tibialis anterior muscle. In addition, warm and cold detection thresholds and heat and cold pain thresholds were bilaterally assessed over the carpal tunnel and the thenar eminence. All outcome parameters were assessed by an assessor blinded to the participant's condition. No significant differences in pain parameters among patients with minimal, moderate, and severe CTS were found. The results showed that PPT were significantly decreased bilaterally over the median, ulnar, and radial nerve trunks, the carpal tunnel, C5 to C6 zygapophyseal joint, and the tibialis anterior muscle in patients with minimal, moderate, or severe CTS as compared with healthy controls (all, P<0.001). In addition, patients with CTS also showed lower heat pain threshold and reduced cold pain threshold compared with controls (P<0.001). No significant sensory differences between minimal, moderate, or severe CTS were found. The similar widespread pressure and thermal hypersensitivity in patients with minimal, moderate, or severe CTS and pain intensity suggests that increased pain sensitivity is not related to electrodiagnostic findings.

  20. How Is Pain Managed?

    Science.gov (United States)

    ... Detection- Goggins Lab Sol Goldman Center Discussion Board Pain Management Pain is a very common symptom in patients ... of pain. Pain Assessment The first step in pain management is a thorough assessment. Your healthcare provider will ...

  1. Pain Management

    Science.gov (United States)

    ... Funding Funding Opportunities (NIH Guide) Forms and Deadlines Electronic Research Admin (eRA) Grants Policy OER News About ... remains the most commonly used pain reliever. The French physician, Dr. Albert Schweitzer, proclaimed in 1931 that, “ ...

  2. Back Pain

    Science.gov (United States)

    ... addition, there doesn't appear to be one type of mattress that's best for people with back pain. It's probably a ... of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization ...

  3. Ankle Pain

    Science.gov (United States)

    ... home remedies for a while. Seek immediate medical attention if you: Have severe pain or swelling Have ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  4. Abdominal Pain

    Science.gov (United States)

    ... or pain in your chest Seek immediate medical attention Have someone drive you to urgent care or ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  5. Testicle Pain

    Science.gov (United States)

    ... is more common in adolescents. Seek immediate medical attention if you have: Sudden, severe testicle pain Testicle ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  6. Gastric pain

    African Journals Online (AJOL)

    drugs and drug classes are also linked to a range of mechanisms through which the drugs ... meal, occurring several times per ... Burning or distressing pain, relieved by food ..... antimicrobial agents, and several other drug interactions are.

  7. Penis pain

    Science.gov (United States)

    Pain - penis ... Bites, either human or insect Cancer of the penis Erection that does not go away (priapism) Genital herpes Infected hair follicles Infected prosthesis of the penis Infection under the foreskin of uncircumcised men ( balanitis ) ...

  8. Joint pain

    Science.gov (United States)

    ... or conditions. It may be linked to arthritis , bursitis , and muscle pain . No matter what causes it, ... Autoimmune diseases such as rheumatoid arthritis and lupus Bursitis Chondromalacia patellae Crystals in the joint: Gout (especially ...

  9. Elbow pain

    Science.gov (United States)

    ... the cause, but may involve: Antibiotics Corticosteroid shots Manipulation Pain medicine Physical therapy Surgery (last resort) Alternative ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  10. Knee pain

    Science.gov (United States)

    ... Fracture of the kneecap or other bones. Iliotibial band syndrome . Injury to the thick band that runs from your hip to the outside ... of your knee pain. When to Contact a Medical Professional Call your provider if: You cannot bear ...

  11. Abdominal Pain

    Science.gov (United States)

    ... I find more information and related topics? Functional Abdominal Pain (English, French or Spanish)—from The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). Gastro Kids , a ...

  12. Flank pain

    Science.gov (United States)

    ... how to do these exercises at home. Nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy may be prescribed for flank pain caused by spinal arthritis. Antibiotics are used to treat most kidney infections. You ...

  13. Elbow Pain

    Science.gov (United States)

    ... tear damage than are many other joints. Seek emergency care if you have: An obvious deformity in ... http://www.mayoclinic.org/symptoms/elbow-pain/basics/definition/SYM-20050874 . Mayo Clinic Footer Legal Conditions and ...

  14. Arm Pain

    Science.gov (United States)

    ... be a sign of a heart attack. Seek emergency treatment if you have: Arm, shoulder or back ... http://www.mayoclinic.org/symptoms/arm-pain/basics/definition/SYM-20050870 . Mayo Clinic Footer Legal Conditions and ...

  15. Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain

    Directory of Open Access Journals (Sweden)

    Shih Ming-Hung

    2008-12-01

    Full Text Available Abstract Spinal cord α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs mediate acute spinal processing of nociceptive and non-nociceptive information, but whether and how their activation contributes to the central sensitization that underlies persistent inflammatory pain are still unclear. Here, we examined the role of spinal AMPARs in the development and maintenance of complete Freund's adjuvant (CFA-induced persistent inflammatory pain. Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2 (25 and 50 μg and GYKI 52466 (50 μg, significantly attenuated mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24 h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral basal responses to thermal and mechanical stimuli. Locomotor activity was not altered in any of the drug-treated animals. CFA-induced inflammation did not change total expression or distribution of AMPAR subunits GluR1 and GluR2 in dorsal horn but did alter their subcellular distribution. The amount of GluR2 was markedly increased in the crude cytosolic fraction and decreased in the crude membrane fraction from the ipsilateral L4–5 dorsal horn at 24 h (but not at 2 h post-CFA injection. Conversely, the level of GluR1 was significantly decreased in the crude cytosolic fraction and increased in the crude membrane fraction from the ipsilateral L4–5 dorsal horn at 24 h (but not at 2 h post-CFA injection. These findings suggest that spinal AMPARs might participate in the central spinal mechanism of persistent inflammatory pain.

  16. Comparative study of analgesic effect of the infrared low-intensity laser and 33% sodium fluoride paste in the treatment of dentinal hypersensitivity; Estudo comparativo do efeito analgesico do laser em baixa intensidade de emissao infravermelha e da pasta de fluoreto de sodio a 33% no tratamento da hipersensibilidade dentinaria

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Glen Anderson Maia de

    2003-07-01

    Different desensitizing agents have been used in the treatment of dentinal hypersensitivity, however, some presented treatments are still frustrating. The purpose of this study was to evaluate the analgesic effect of the low-intensity GaAlAs laser ({lambda}= 830 nm) in the treatment of dentinal hypersensitivity after mechanical and thermal stimuli, and compared it with the 33% sodium fluoride paste. Thirty two teeth with dentinal hypersensitivity were selected and randomly divided into two groups. For the laser group, each tooth was irradiated by a dose of 6 J/cm{sup 2} during two minutes and half on the buccal side. The paste group was treated with a NaF/kaolin/glycerin (33:33:33) paste by burnishing the sensitive surface during four minutes. The sensitivity degree was measured before the beginning of the experiment, 24 h, 48 h, 72 h, 120 h, 15 days and 30 days after the first application. The results indicate that the dentinal hypersensitivity significantly diminished for the paste group after dental explorer. Regarding to air-blast, no significant differences were observed between the groups. Both of them were effective in reducing pain of the dentine hypersensitive after 120 h. (author)

  17. Neonatal pain

    Science.gov (United States)

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  18. Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain

    Science.gov (United States)

    2013-01-01

    Background GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a “pain-protective” (PP) haplotype of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH1 gene results in decreased basal GCH1 expression, and is associated with DOPA-responsive dystonia (DRD). So far it is unknown if such mutations affect acute and inflammatory pain. Results In the current study, we examined the involvement of the GCH1 gene in pain models using the hyperphenylalaninemia 1 (hph-1) mouse, a genetic model for DRD, with only 10% basal GTP-CH1 activity compared to wild type mice. The study included assays for determination of acute nociception as well as models for pain after sensitisation. Pain behavioural analysis of the hph-1 mice showed reduced pain-like responses following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in naïve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms. Conclusions In this study, we demonstrate novel evidence that genetic mutations in the GCH1 gene modulate pain-like hypersensitivity. Together, the present data suggest that BH4 is not important for basal heat and mechanical pain, but they support the hypothesis that BH4 plays a role in inflammation-induced hypersensitivity. Our studies suggest that the BH4 pathway could be a therapeutic target for the treatment of inflammatory pain conditions. Moreover, the hph-1 mice provide a valid model to

  19. Photon attenuation by intensifying screens

    International Nuclear Information System (INIS)

    Holje, G.

    1983-01-01

    The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

  20. electro-hypersensitivity: survey among general practitioners, occupational physicians and hygienist from the Netherlands

    International Nuclear Information System (INIS)

    Bonnet-Belfais, Monique; Salines, Georges

    2017-01-01

    From October 2013 through January 2014, Dutch and Swiss researchers conducted a survey in the Netherlands on electro-hypersensitive (EHS) people among the health care providers likely to be consulted for primary care and prevention. (author)

  1. Hypersensitivity reactions to metallic implants-diagnostic algorithm and suggested patch test series for clinical use

    DEFF Research Database (Denmark)

    Schalock, Peter C; Menné, Torkil; Johansen, Jeanne D

    2011-01-01

    Cutaneous and systemic hypersensitivity reactions to implanted metals are challenging to evaluate and treat. Although they are uncommon, they do exist, and require appropriate and complete evaluation. This review summarizes the evidence regarding evaluation tools, especially patch and lymphocyte...... transformation tests, for hypersensitivity reactions to implanted metal devices. Patch test evaluation is the gold standard for metal hypersensitivity, although the results may be subjective. Regarding pre-implant testing, those patients with a reported history of metal dermatitis should be evaluated by patch...... testing. Those without a history of dermatitis should not be tested unless considerable concern exists. Regarding post-implant testing, a subset of patients with metal hypersensitivity may develop cutaneous or systemic reactions to implanted metals following implant. For symptomatic patients, a diagnostic...

  2. Nickel in nails, hair and plasma from nickel-hypersensitive women

    DEFF Research Database (Denmark)

    Gammelgaard, Bente; Veien, Niels

    1990-01-01

    The concentrations of nickel in finger-nails, toe-nails, hair and plasma from 71 nickel-hypersensitive women and 20 non-hypersensitive women were determined. Nickel concentrations in finger-nails were significantly higher than in toe-nails in both the nickel-hypersensitive group and the control...... group. Nickel-sensitive women had significantly higher levels of nickel in toe-nails, hair and plasma than had control subjects, whereas there was no significant difference in nickel concentration in finger-nails between the two groups. No correlation could be demonstrated between nickel levels in any...... combination of nails, hair and plasma in the nickel-hypersensitive or in the control group....

  3. Health-related quality of life in food hypersensitive schoolchildren and their families: parents' perceptions

    Directory of Open Access Journals (Sweden)

    Marklund Birgitta

    2006-08-01

    Full Text Available Abstract Background About 20% of schoolchildren and adolescents in Sweden suffer from perceived food hypersensitivity (e.g. allergy or intolerance. Our knowledge of how child food hypersensitivity affects parents HRQL and what aspects of the hypersensitivity condition relate to HRQL deterioration in the family is limited. Thus the aim of this study was to investigate the parent-reported HRQL in families with a schoolchild considered to be food hypersensitive. The allergy-associated parameters we operated with were number of offending food items, adverse food reactions, additional hypersensitivity, allergic diseases and additional family members with food hypersensitivity. These parameters, along with age and gender were assessed in relation to child, parent and family HRQL. Methods In May 2004, a postal questionnaire was distributed to parents of 220 schoolchildren with parent-reported food hypersensitivity (response rate 74%. Two questionnaires were used: CHQ-PF28 and a study-specific questionnaire including questions on allergy-associated parameters. In order to find factors that predict impact on HRQL, stepwise multiple linear regression analyses were carried out. Results An important predictor of low HRQL was allergic disease (i.e. asthma, eczema, rhino conjunctivitis in addition to food hypersensitivity. The higher the number of allergic diseases, the lower the physical HRQL for the child, the lower the parental HRQL and the more disruption in family activities. Male gender predicted lower physical HRQL than female gender. If the child had sibling(s with food hypersensitivity this predicted lower psychosocial HRQL for the child and lower parental HRQL. Food-induced gastro-intestinal symptoms predicted lower parental HRQL while food-induced breathing difficulties predicted higher psychosocial HRQL for the child and enhanced HRQL with regards to the family's ability to get along. Conclusion The variance in the child's physical HRQL was to a

  4. 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.

  5. Mitogen activated protein kinase phosphatase-1 prevents the development of tactile sensitivity in a rodent model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ndong Christian

    2012-04-01

    Full Text Available Abstract Background Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. Results We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide. Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced pro-inflammatory cytokines and chemokines and the phosphorylated form of p38. Conclusions Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.

  6. Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

    Directory of Open Access Journals (Sweden)

    Chen Zhao

    2018-01-01

    Full Text Available Background. Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1 is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs and the role of CHT1 in visceral hypersensitivity. Methods. Repetitive water avoidance stress (WAS was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD was determined, and the abdominal withdrawal reflex (AWR and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3, the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results. Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion. Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.

  7. Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

    Science.gov (United States)

    2018-01-01

    Background Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity. PMID:29849603

  8. Expression of antibacterial resistance at the site of a delayed hypersensitivity reaction.

    OpenAIRE

    Patel, P J

    1980-01-01

    The site of a delayed hypersensitivity reaction to tuberculin or bovine serum ablumin was shown to contain mechanisms that expressed increased antibacterial activity, as evidenced by restricted growth of a local inoculum of Listeria monocytogenes. As was the case with a delayed hypersensitivity reaction, the local generation of antibacterial activity was antigen specific and T-cell dependent. Antibacterial resistance was always expressed at the site of injection of specific antigen in sensiti...

  9. Mindfulness meditation-related pain relief: Evidence for unique brain mechanisms in the regulation of pain

    Science.gov (United States)

    Zeidan, F.; Grant, J.A.; Brown, C.A.; McHaffie, J.G.; Coghill, R.C.

    2013-01-01

    The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain. PMID:22487846

  10. Enhanced Attenuation: Chlorinated Organics

    Science.gov (United States)

    2008-04-01

    attenuation capacity of the aquifer downgradient from the source (e.g., permeable reactive barriers or phytoremediation ) Selection of EA remedies should be...prevalence and/or mobility of nitrate and sulfate compounds and/or metals such as iron, manganese, chromium, copper, and arsenic . Furthermore, in...ranging from very aggressive source destruction and removal methods to less energy-intensive methods, such as phytoremediation . In many cases, it

  11. A Review of Select Centralized Pain Syndromes

    Directory of Open Access Journals (Sweden)

    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.

  12. Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Jarmila Čelakovská

    2014-01-01

    Full Text Available Background: Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods have been reported, but the data are scarce. Aims and Objectives: Evaluation of food hypersensitivity reactions in patients suffering from atopic dermatitis. Materials and Methods: The dermatological examination was performed in patients of age 14 years and above and the detailed history was taken concerning the food hypersensitivity. Results: A total of 228 patients were examined-72 men, 156 women, average age 26.2 (SD 9.5 years. The food hypersensitivity reactions were recorded in 196 patients from 228 (86%, no reactions were recorded in 32 patients (24%. Foods with the most often recorded reactions are: Nuts (in 35% of patients, tomatoes (in 20%, and kiwi (in 17, 5%, apples and spices (in 16%, tangerines and oranges (in 15%, capsicum (in 13%, fishes (in 12%, celery (in 9%, and chocolate (in 7%. Conclusion: Food hypersensitivity reactions are recorded in 86% of patients suffering from atopic dermatitis. Nuts, tomatoes, and pollen-associated foods play a role in the majority of patients suffering from atopic dermatitis.

  13. Food hypersensitivity in patients over 14 years of age suffering from atopic dermatitis.

    Science.gov (United States)

    Celakovská, Jarmila; Ettler, K; Ettlerová, K; Vaněčková, J

    2014-05-01

    Patients suffering from atopic dermatitis often describe food hypersensitivity. Rising prevalence of food hypersensitivity and severe allergic reactions to foods have been reported, but the data are scarce. Evaluation of food hypersensitivity reactions in patients suffering from atopic dermatitis. The dermatological examination was performed in patients of age 14 years and above and the detailed history was taken concerning the food hypersensitivity. A total of 228 patients were examined-72 men, 156 women, average age 26.2 (SD 9.5) years. The food hypersensitivity reactions were recorded in 196 patients from 228 (86%), no reactions were recorded in 32 patients (24%). Foods with the most often recorded reactions are: Nuts (in 35% of patients), tomatoes (in 20%), and kiwi (in 17, 5%), apples and spices (in 16%), tangerines and oranges (in 15%), capsicum (in 13%), fishes (in 12%), celery (in 9%), and chocolate (in 7%). Food hypersensitivity reactions are recorded in 86% of patients suffering from atopic dermatitis. Nuts, tomatoes, and pollen-associated foods play a role in the majority of patients suffering from atopic dermatitis.

  14. Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group.

    Science.gov (United States)

    Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J

    2013-07-01

    Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Increased Evoked Potentials and Behavioral Indices in Response to Pain Among Individuals with Intellectual Disability.

    Science.gov (United States)

    Benromano, Tali; Pick, Chaim G; Granovsky, Yelena; Defrin, Ruth

    2017-09-01

    Previous studies on the sensitivity and reactivity to pain of individuals with intellectual disability (ID) are inconsistent. The inconsistency may result from the reliance on self-reports and facial expressions of pain that are subject to internal and external biases. The aim was therefore to evaluate the reactivity to pain of individuals with ID by recording pain-evoked potentials (EPs), here for the first time, and testing their association with behavioral pain indices. Forty-one healthy adults, 16 with mild-moderate ID and 25 controls. Subjects received series of phasic heat stimuli and rated their pain on self-report scales. Changes in facial expressions and in pain EPs were recorded and analyzed offline. Pain self-reports, facial expressions, and the N2P2 amplitudes of the EPs exhibited stimulus-response relationship with stimulation intensity in both groups. The facial expressions and N2P2 amplitudes of individuals with ID were increased and N2P2 latency prolonged compared with controls. N2P2 amplitudes correlated with self-reports only in controls. Individuals with ID are hypersensitive/reactive to pain, a finding bearing clinical implications. Although pain EPs may reflect a somewhat different aspect of pain than the behavioral indices do, there is evidence to support their use to record pain in noncommunicative individuals, pending further validation. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  16. The Pain System in Oesophageal Disorders: Mechanisms, Clinical Characteristics, and Treatment

    Directory of Open Access Journals (Sweden)

    Christian Lottrup

    2011-01-01

    Full Text Available Pain is common in gastroenterology. This review aims at giving an overview of pain mechanisms, clinical features, and treatment options in oesophageal disorders. The oesophagus has sensory receptors specific for different stimuli. Painful stimuli are encoded by nociceptors and communicated via afferent nerves to the central nervous system. The pain stimulus is further processed and modulated in specific pain centres in the brain, which may undergo plastic alterations. Hence, tissue inflammation and long-term exposure to pain can cause sensitisation and hypersensitivity. Oesophageal sensitivity can be evaluated ,for example, with the oesophageal multimodal probe. Treatment should target the cause of the patient's symptoms. In gastro-oesophageal reflux diseases, proton pump inhibitors are the primary treatment option, surgery being reserved for patients with severe disease resistant to drug therapy. Functional oesophageal disorders are treated with analgesics, antidepressants, and psychological therapy. Lifestyle changes are another option with less documentation.

  17. Sustained Elevated Adenosine via ADORA2B Promotes Chronic Pain through Neuro-immune Interaction

    Directory of Open Access Journals (Sweden)

    Xia Hu

    2016-06-01

    Full Text Available The molecular mechanisms of chronic pain are poorly understood and effective mechanism-based treatments are lacking. Here, we report that mice lacking adenosine deaminase (ADA, an enzyme necessary for the breakdown of adenosine, displayed unexpected chronic mechanical and thermal hypersensitivity due to sustained elevated circulating adenosine. Extending from Ada−/− mice, we further discovered that prolonged elevated adenosine contributed to chronic pain behaviors in two additional independent animal models: sickle cell disease mice, a model of severe pain with limited treatment, and complete Freund’s adjuvant paw-injected mice, a well-accepted inflammatory model of chronic pain. Mechanistically, we revealed that activation of adenosine A2B receptors on myeloid cells caused nociceptor hyperexcitability and promoted chronic pain via soluble IL-6 receptor trans-signaling, and our findings determined that prolonged accumulated circulating adenosine contributes to chronic pain by promoting immune-neuronal interaction and revealed multiple therapeutic targets.

  18. Napping reverses increased pain sensitivity due to sleep restriction.

    Science.gov (United States)

    Faraut, Brice; Léger, Damien; Medkour, Terkia; Dubois, Alexandre; Bayon, Virginie; Chennaoui, Mounir; Perrot, Serge

    2015-01-01

    To investigate pain sensitivity after sleep restriction and the restorative effect of napping. A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed. Laboratory-based study. 11 healthy male volunteers. Volunteers attended two three-day sessions: "sleep restriction" alone and "sleep restriction and nap". Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the "sleep restriction and nap" session, volunteers took two 30-minute naps, one in the morning and one in the afternoon. Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area. Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status.

  19. Napping reverses increased pain sensitivity due to sleep restriction.

    Directory of Open Access Journals (Sweden)

    Brice Faraut

    Full Text Available To investigate pain sensitivity after sleep restriction and the restorative effect of napping.A strictly controlled randomized crossover study with continuous polysomnography monitoring was performed.Laboratory-based study.11 healthy male volunteers.Volunteers attended two three-day sessions: "sleep restriction" alone and "sleep restriction and nap". Each session involved a baseline night of normal sleep, a night of sleep deprivation and a night of free recovery sleep. Participants were allowed to sleep only from 02:00 to 04:00 during the sleep deprivation night. During the "sleep restriction and nap" session, volunteers took two 30-minute naps, one in the morning and one in the afternoon.Quantitative sensory testing was performed with heat, cold and pressure, at 10:00 and 16:00, on three areas: the supraspinatus, lower back and thigh. After sleep restriction, quantitative sensory testing revealed differential changes in pain stimuli thresholds, but not in thermal threshold detection: lower back heat pain threshold decreased, pressure pain threshold increased in the supraspinatus area and no change was observed for the thigh. Napping restored responses to heat pain stimuli in the lower back and to pressure stimuli in the supraspinatus area.Sleep restriction induces different types of hypersensitivity to pain stimuli in different body areas, consistent with multilevel mechanisms, these changes being reversed by napping. The napping restorative effect on pain thresholds result principally from effects on pain mechanisms, since it was independent of vigilance status.

  20. The Relationship between Grandiose and Vulnerable (Hypersensitive Narcissism

    Directory of Open Access Journals (Sweden)

    Emanuel Jauk

    2017-09-01

    Full Text Available Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1 controlling for intro-/extraversion might reveal a “common core” of grandiose and vulnerable narcissism, and if (2 the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006. Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10% of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological narcissism.

  1. The Relationship between Grandiose and Vulnerable (Hypersensitive) Narcissism

    Science.gov (United States)

    Jauk, Emanuel; Weigle, Elena; Lehmann, Konrad; Benedek, Mathias; Neubauer, Aljoscha C.

    2017-01-01

    Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1) controlling for intro-/extraversion might reveal a “common core” of grandiose and vulnerable narcissism, and if (2) the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006). Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10%) of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological) narcissism. PMID:28955288

  2. Exploring Some Aspects Associated with Dentine Hypersensitivity in Children

    Directory of Open Access Journals (Sweden)

    Caleb Shitsuka

    2015-01-01

    Full Text Available Background. The etiology of dentine hypersensitivity (DH is still inconclusive and there are few studies concerning it in children. Aim. To evaluate clinical, dietary, and salivary variables in children with DH complaints. Design. Forty-eight children were asked about DH. Data regarding dietary habits were collected from the children’s parents and an examination was performed to determine dental erosion. Dental biofilm was estimated by oral hygiene status, according to Greene and Vermillion’s Simplified Oral Hygiene Index (OHI-S. Whole saliva was collected under mechanical stimulation and evaluated salivary flow rate, initial pH, buffer capacity, and calcium and phosphate concentrations. The temperature of soft drinks, drinking method, sense of bitter taste, and other variables were also determined. Possible factors associated with DH were analyzed by univariate and multiple Poisson regression analyses. The prevalence ratio (PR values and 95% confidence intervals (95% CI were calculated. Results. DH was associated with the presence of dental erosion (PR; 95% CI = 2.23; 1.05 to 4.71 and salivary flow rate (2.49; 1.05 to 5.91. When the presence of erosion was not included, other variables were retained as follows: bitter taste (2.36; 1.38 to 4.03, OHI-S (0.47; 0.23 to 0.97. Conclusion. DH in children is associated with factors related to dental erosion.

  3. A Case of Immediate Hypersensitivity Reaction to Maltitol

    Directory of Open Access Journals (Sweden)

    Ana Rodríguez Trabado

    2017-01-01

    Full Text Available Background. Maltitol is a sugar alcohol that is frequently used as a noncaloric sweetener, although it is also used as an excipient, a plasticizer in gelatin capsules, and an emollient. It has not been previously described as an agent involved in immediate hypersensitivity reactions. Methods. We report on an anaphylactoid reaction with pharyngeal occlusion suffered by a 60-year-old man after ingestion of a candy containing maltitol syrup. A prick-to-prick test was performed with the candy and maltitol powder. Other allergens were excluded as causative agents of the adverse reaction, although the patient refused to undergo an oral challenge test with the candy. A basophil activation test (BAT was performed with maltitol powder, and a dose-response curve was generated. The test was also performed in 3 healthy controls. Results. Both prick-to-prick tests were negative. The result of the BAT was positive at all the concentrations tested in the patient’s blood and negative in all the controls. Conclusions. The BAT can help to clarify the agents implicated in an adverse reaction and can reduce the risk involved in diagnosis. The BAT can also prove useful in the study of reactions caused by low-molecular-weight antigens, for which routine diagnostic tests are not feasible.

  4. Hypersensitivity pneumonitis with Mycobacterium avium complex among spa workers.

    Science.gov (United States)

    Moraga-McHaley, Stephanie Ann; Landen, Michael; Krapfl, Heidi; Sewell, C Mack

    2013-01-01

    The New Mexico Department of Health (NMDOH) investigated the cause of two cases of hypersensitivity pneumonitis (HP) in spa maintenance workers with laboratory confirmed Mycobacterium avium complex (MAC). The investigation occurred in tandem with worker protection and swimming pool regulatory investigations by the New Mexico Environment Department at the spa where the workers were employed. The investigation was conducted in order to identify unreported cases, exposure source(s), and to prevent further worker exposure. NMDOH surveyed 57 spa employees about symptoms and exposures, categorized jobs according to self-reported exposure to water, and computed odds ratios for symptom reporting by exposure category. Environmental isolates from spa water and filter swabs were cultured and compared to patient isolates by the Environmental and Applied Microbiology Team, Centers for Disease Control and Prevention (CDC). Workers with the highest exposure reported more HP-like symptoms (OR = 9.6), as did intermediate exposure workers (OR = 6.5), compared to workers with no aerosolized water exposure. Two of 13 environmental isolates were closely related to one of the patient isolates. Workers were likely exposed during spray cleaning of cartridge filters in a poorly ventilated work space. Recommendations include inhibiting organism growth in spa systems, assuring the use of respiratory protection, and adequately ventilating work spaces where filters and equipment are cleaned.

  5. Evaluation of the hypersensitivity potential of alternative butter flavorings

    Science.gov (United States)

    Anderson, Stacey E.; Franko, Jennifer; Wells, J.R.; Lukomska, Ewa; Meade, B. Jean

    2015-01-01

    Concern has been raised over the association of diacetyl with lung disease clinically resembling bronchiolitis obliterans in food manufacturing workers. This has resulted in the need for identification of alternative chemicals to be used in the manufacturing process. Structurally similar chemicals, 2,3-pentanedione, 2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione, used as constituents of synthetic flavoring agents have been suggested as potential alternatives for diacetyl, however, immunotoxicity data on these chemicals are limited. The present study evaluated the dermal irritation and sensitization potential of diacetyl alternatives using a murine model. None of the chemicals were identified as dermal irritants when tested at concentrations up to 50%. Similar to diacetyl (EC3 = 17.9%), concentration-dependent increases in lymphocyte proliferation were observed following exposure to all four chemicals, with calculated EC3 values of 15.4% (2,3-pentanedione), 18.2% (2,3-hexanedione), 15.5% (3,4-hexanedione) and 14.1% (2,3-heptanedione). No biologically significant elevations in local or total serum IgE were identified after exposure to 25–50% concentrations of these chemicals. These results demonstrate the potential for development of hypersensitivity responses to these proposed alternative butter flavorings and raise concern about the use of structurally similar replacement chemicals. Additionally, a contaminant with strong sensitization potential was found in varying concentrations in diacetyl obtained from different producers. PMID:24007741

  6. Presumed hydrochlorothiazide-associated immunologic-hypersensitivity-induced pericardial effusion

    Directory of Open Access Journals (Sweden)

    Michael J Chaskes

    2013-08-01

    Full Text Available A 50-year-old Caucasian female presented for a second opinion regarding a newly diagnosed pericardial effusion. Seven months previously, hydrochlorothiazide was introduced into her pharmacologic regimen to aid in the management of her hypertension. A routine echocardiogram indicated a large pericardial effusion with signs of early cardiac tamponade. The patient subsequently underwent successful pericardiocentesis with complete drainage of the pericardial effusion. The effusion was empirically attributed to a viral etiology. Repeat echocardiograms showed recurrence of the pericardial effusion. Prior to undergoing a second pericardiocentesis with pericardial biopsy, as her physicians recommended, the patient sought a second opinion. While obtaining the patient’s history, an allergy to sulfa was elicited. The possibility that the pericardial effusion may be secondary to an immunologic-hypersensitivity reaction was considered. It was recommended the patient discontinue the use of hydrochlorothiazide. Nine days following discontinuation of hydrochlorothiazide and without any other intervention, an echocardiogram was reported to show the size of the pericardial effusion had subsided substantially. Nine weeks following discontinuation, almost complete resolution of the pericardial effusion was reported. It is hypothesized that when treated with hydrochlorothiazide, the patient had an immune response leading to the pericardial effusion.

  7. Hazards of the ‘Hard Cash’: Hypersensitivity Pneumonitis

    Directory of Open Access Journals (Sweden)

    Elif Kupeli

    2010-01-01

    Full Text Available Hypersensitivity pneumonitis (HP is a nonimmunoglobulin E-related immune-mediated parenchymal lung disease. A 45-year-old woman who was a lifelong nonsmoker with a six-month history of frequent episodes of cough and dyspnea was admitted to hospital. She had been working as a money counter for 20 years at a central bank. Bibasilar crackles on lung auscultation, ground-glass opacities and a mosaic pattern on high-resolution computed tomography, restrictive abnormality on pulmonary function tests and mild hypoxemia were the prominent findings. Bronchoalveolar lavage fluid analysis revealed a predominance of CD4-positive T cells, and she tested positive on her natural challenge test. She was diagnosed with subacute HP based on established criteria. She was advised to discontinue counting fresh banknotes. Prednisolone was commenced, then tapered to discontinue in the ensuing six months. Clinical and radiological improvement was achieved within two months. To the authors’ knowledge, the present report is the first to describe ‘hard cash HP’, possibly caused by chipping dust or printing dye.

  8. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    Ayodeji Adegunsoye

    2017-08-01

    Full Text Available In chronic hypersensitivity pneumonitis (CHP, lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA, 93 (71% received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04 and 66% less frequent with mycophenolate mofetil (p=0.002. FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed.

  9. Change in FVC and survival in chronic fibrotic hypersensitivity pneumonitis.

    Science.gov (United States)

    Gimenez, Andrea; Storrer, Karin; Kuranishi, Lilian; Soares, Maria Raquel; Ferreira, Rimarcs Gomes; Pereira, Carlos A C

    2018-04-01

    The predictive value of the decline in FVC by ≥10% on survival in patients with fibrotic hypersensitivity pneumonitis is unknown. Of 112 patients included, 66 (59%) had surgical lung biopsies. Patients with ≥10% decline in predicted FVC after 6-12 months had a significantly increased risk of all-cause mortality (median survival 53 months, 95% CI 37 to 69 vs 139 months, 95% CI 66 to 212 months, p=0.007). On multivariate analysis remained associated with increasing mortality: decline in FVC by ≥10% (HR 4.13, 95% CI 1.96 to 8.70, p=0.005), lower FVC% (HR 1.03, 95% CI 1.01 to 1.05, p=0.003) and with decreasing mortality improvement with antigen avoidance (HR 0.18, 95% CI 0.04 to 0.77, p=0.021). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Hypersensitive Reaction to Tattoos: A Growing Menace in Rural India.

    Science.gov (United States)

    Shashikumar, B M; Harish, M R; Shwetha, B; Kavya, M; Deepadarshan, K; Phani, H N

    2017-01-01

    Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%), black (33.3%), green (5.1%), and multicolor (7.7%). Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction.

  11. Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.

    Science.gov (United States)

    Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R

    2000-09-01

    Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.

  12. Mindfulness meditation–based pain relief: a mechanistic account

    Science.gov (United States)

    Zeidan, Fadel; Vago, David

    2016-01-01

    Pain is a multidimensional experience that involves sensory, cognitive, and affective factors. The constellation of interactions between these factors renders the treatment of chronic pain challenging and financially burdensome. Further, the widespread use of opioids to treat chronic pain has led to an opioid epidemic characterized by exponential growth in opioid misuse and addiction. The staggering statistics related to opioid use highlight the importance of developing, testing, and validating fast-acting nonpharmacological approaches to treat pain. Mindfulness meditation is a technique that has been found to significantly reduce pain in experimental and clinical settings. The present review delineates findings from recent studies demonstrating that mindfulness meditation significantly attenuates pain through multiple, unique mechanisms—an important consideration for the millions of chronic pain patients seeking narcotic-free, self-facilitated pain therapy. PMID:27398643

  13. Pain and emotion: a biopsychosocial review of recent research.

    Science.gov (United States)

    Lumley, Mark A; Cohen, Jay L; Borszcz, George S; Cano, Annmarie; Radcliffe, Alison M; Porter, Laura S; Schubiner, Howard; Keefe, Francis J

    2011-09-01

    Research on emotion and pain has burgeoned. We review the last decade's literature, focusing on links between emotional processes and persistent pain. Neurobiological research documents the neural processes that distinguish affective from sensory pain dimensions, link emotion and pain, and generate central nervous system pain sensitization. Psychological research demonstrates that greater pain is related to emotional stress and limited emotional awareness, expression, and processing. Social research shows the potential importance of emotional communication, empathy, attachment, and rejection. Emotions are integral to the conceptualization, assessment, and treatment of persistent pain. Research should clarify when to eliminate or attenuate negative emotions, and when to access, experience, and express them. Theory and practice should integrate emotion into cognitive-behavioral models of persistent pain. © 2011 Wiley Periodicals, Inc.

  14. Effects of vicarious pain on self-pain perception: investigating the role of awareness

    Directory of Open Access Journals (Sweden)

    Terrighena EL

    2017-07-01

    Full Text Available Esslin L Terrighena,1,2 Ge Lu,1 Wai Ping Yuen,1 Tatia M C Lee,1–4 Kati Keuper1,2,5 1Department of Psychology, Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong; 2Laboratory of Social Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong; 3The State Key Laboratory of Brain and Cognitive Sciences, Hong Kong; 4Institute of Clinical Neuropsychology, The University of Hong Kong, Hong Kong; 5Institute for Biomagnetism and Biosignalanalysis, University of Münster, Münster, Germany Abstract: The observation of pain in others may enhance or reduce self-pain, yet the boundary conditions and factors that determine the direction of such effects are poorly understood. The current study set out to show that visual stimulus awareness plays a crucial role in ­determining whether vicarious pain primarily activates behavioral defense systems that enhance pain sensitivity and stimulate withdrawal or appetitive systems that attenuate pain sensitivity and stimulate approach. We employed a mixed factorial design with the between-subject factors exposure time (subliminal vs optimal and vicarious pain (pain vs no pain images, and the within-subject factor session (baseline vs trial to investigate how visual awareness of vicarious pain images affects subsequent self-pain in the cold-pressor test. Self-pain tolerance, intensity and unpleasantness were evaluated in a sample of 77 healthy participants. Results revealed ­significant interactions of exposure time and vicarious pain in all three dependent measures. In the presence of visual awareness (optimal condition, vicarious pain compared to no-pain elicited overall enhanced self-pain sensitivity, indexed by reduced pain tolerance and enhanced ratings of pain intensity and unpleasantness. Conversely, in the absence of visual awareness (subliminal condition, vicarious pain evoked decreased self-pain intensity and unpleasantness while pain tolerance remained unaffected. These

  15. Control algorithms for dynamic attenuators

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

    2014-06-15

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  16. Control algorithms for dynamic attenuators

    International Nuclear Information System (INIS)

    Hsieh, Scott S.; Pelc, Norbert J.

    2014-01-01

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  17. Control algorithms for dynamic attenuators.

    Science.gov (United States)

    Hsieh, Scott S; Pelc, Norbert J

    2014-06-01

    The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

  18. Low back pain - acute

    Science.gov (United States)

    Backache; Low back pain; Lumbar pain; Pain - back; Acute back pain; Back pain - new; Back pain - short-term; Back strain - new ... lower back supports most of your body's weight. Low back pain is the number two reason that Americans see ...

  19. Evoked potentials after painful cutaneous electrical stimulation depict pain relief during a conditioned pain modulation.

    Science.gov (United States)

    Höffken, Oliver; Özgül, Özüm S; Enax-Krumova, Elena K; Tegenthoff, Martin; Maier, Christoph

    2017-08-29

    Conditioned pain modulation (CPM) evaluates the pain modulating effect of a noxious conditioning stimulus (CS) on another noxious test stimulus (TS), mostly based solely on subjective pain ratings. We used painful cutaneous electrical stimulation (PCES) to induce TS in a novel CPM-model. Additionally, to evaluate a more objective parameter, we recorded the corresponding changes of cortical evoked potentials (PCES-EP). We examined the CPM-effect in 17 healthy subjects in a randomized controlled cross-over design during immersion of the non-dominant hand into 10 °C or 24 °C cold water (CS). Using three custom-built concentric surface electrodes, electrical stimuli were applied on the dominant hand, inducing pain of 40-60 on NRS 0-100 (TS). At baseline, during and after CS we assessed the electrically induced pain intensity and electrically evoked potentials recorded over the central electrode (Cz). Only in the 10 °C-condition, both pain (52.6 ± 4.4 (baseline) vs. 30.3 ± 12.5 (during CS)) and amplitudes of PCES-EP (42.1 ± 13.4 μV (baseline) vs. 28.7 ± 10.5 μV (during CS)) attenuated during CS and recovered there after (all p pain ratings during electrical stimulation and amplitudes of PCES-EP correlated significantly with each other (r = 0.5) and with CS pain intensity (r = 0.5). PCES-EPs are a quantitative measure of pain relief, as changes in the electrophysiological response are paralleled by a consistent decrease in subjective pain ratings. This novel CPM paradigm is a feasible method, which could help to evaluate the function of the endogenous pain modulation processes. German Clinical Trials Register DRKS-ID: DRKS00012779 , retrospectively registered on 24 July 2017.

  20. A selective role for α3 subunit glycine receptors in inflammatory pain

    Directory of Open Access Journals (Sweden)

    Victoria L Harvey

    2009-11-01

    Full Text Available GlyR α3 has previously been found to play a critical role in pain hypersensitivity following spinal PGE2 injection, complete Freund’s adjuvant (CFA and zymosan induced peripheral inflammation. In this study, although all models displayed typical phenotypic behaviours, no significant differences were observed when comparing the pain behaviours of Glra3-/- and wild-type littermates following the injection of capsaicin, carrageenan, kaolin/ carrageenan or monosodium iodoacetate, models of rheumatoid and osteoarthritis, respectively. However, clear differences were observed following CFA injection (p < 0.01. No significant differences were observed in the pain behaviours of Glra3-/- and wild-type littermates following experimentally induced neuropathic pain (partial sciatic nerve ligation. Similarly, Glra3-/- and wild-type littermates displayed indistinguishable visceromotor responses to colorectal distension (a model of visceral pain and in vivo spinal cord dorsal horn electrophysiology revealed no differences in responses to multimodal suprathreshold stimuli, intensities which equate to higher pain scores such as those reported in the clinic. These data suggest that apart from its clear role in CFA- and zymosan-induced pain sensitisation, hypersensitivity associated with other models of inflammation, neuropathy and visceral disturbances involves mechanisms other than the EP2 receptor - GlyR α3 pathway.

  1. Algometry with a clothes peg compared to an electronic pressure algometer: a randomized cross-sectional study in pain patients.

    Science.gov (United States)

    Egloff, Niklaus; Klingler, Nicole; von Känel, Roland; Cámara, Rafael J A; Curatolo, Michele; Wegmann, Barbara; Marti, Elizabeth; Ferrari, Marie-Louise Gander

    2011-07-25

    Hypersensitivity of the central nervous system is widely present in pain patients and recognized as one of the determinants of chronic pain and disability. Electronic pressure algometry is often used to explore aspects of central hypersensitivity. We hypothesized that a simple pain provocation test with a clothes peg provides information on pain sensitivity that compares meaningfully to that obtained by a well-established electronic pressure algometer. "Clinically meaningful" was defined as a medium (r = 0.3-0.5) or high (r > 0.5) correlation coefficient according to Cohen's conventions. We tested 157 in-patients with different pain types. A calibrated clothes peg was applied for 10 seconds and patients rated the pain intensity on a 0 to 10 numerical rating scale. Pressure pain detection threshold (PPdt) and pressure pain tolerance threshold (PPtt) were measured with a standard electronic algometer. Both methods were performed on both middle fingers and ear lobes. In a subgroup of 47 patients repeatability (test-retest reliability) was calculated. Clothes peg values correlated with PPdt values for finger testing with r = -0.54 and for earlobe testing with r = -0.55 (all p-values testing with r = -0.55 (p Test-retest reliability (repeatability) showed equally stable results for clothes peg algometry and the electronic algometer (all r-values > 0.89, all p-values pain sensitivity provided by a calibrated clothes peg and an established algometer correlate at a clinically meaningful level.

  2. Algometry with a clothes peg compared to an electronic pressure algometer: a randomized cross-sectional study in pain patients

    Directory of Open Access Journals (Sweden)

    Marti Elizabeth

    2011-07-01

    Full Text Available Abstract Background Hypersensitivity of the central nervous system is widely present in pain patients and recognized as one of the determinants of chronic pain and disability. Electronic pressure algometry is often used to explore aspects of central hypersensitivity. We hypothesized that a simple pain provocation test with a clothes peg provides information on pain sensitivity that compares meaningfully to that obtained by a well-established electronic pressure algometer. "Clinically meaningful" was defined as a medium (r = 0.3-0.5 or high (r > 0.5 correlation coefficient according to Cohen's conventions. Methods We tested 157 in-patients with different pain types. A calibrated clothes peg was applied for 10 seconds and patients rated the pain intensity on a 0 to 10 numerical rating scale. Pressure pain detection threshold (PPdt and pressure pain tolerance threshold (PPtt were measured with a standard electronic algometer. Both methods were performed on both middle fingers and ear lobes. In a subgroup of 47 patients repeatability (test-retest reliability was calculated. Results Clothes peg values correlated with PPdt values for finger testing with r = -0.54 and for earlobe testing with r = -0.55 (all p-values 0.89, all p-values Conclusions Information on pain sensitivity provided by a calibrated clothes peg and an established algometer correlate at a clinically meaningful level.

  3. Painful menstrual periods

    Science.gov (United States)

    Menstruation - painful; Dysmenorrhea; Periods - painful; Cramps - menstrual; Menstrual cramps ... into two groups, depending on the cause: Primary dysmenorrhea Secondary dysmenorrhea Primary dysmenorrhea is menstrual pain that ...

  4. Alternative medicine - pain relief

    Science.gov (United States)

    Acupuncture - pain relief; Hypnosis - pain relief; Guided imagery - pain relief ... neck, shoulder, knee, or elbow) Osteoarthritis Rheumatoid arthritis Hypnosis is a focused state of concentration. With self- ...

  5. Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain.

    Science.gov (United States)

    Shurman, Joseph; Koob, George F; Gutstein, Howard B

    2010-07-01

    Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek "katifeia" for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). Repeated engagement of opponent processes without time for the brain's emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

  6. Mast cell-derived histamine mediates cystitis pain.

    Directory of Open Access Journals (Sweden)

    Charles N Rudick

    2008-05-01

    Full Text Available Mast cells trigger inflammation that is associated with local pain, but the mechanisms mediating pain are unclear. Interstitial cystitis (IC is a bladder disease that causes debilitating pelvic pain of unknown origin and without consistent inflammation, but IC symptoms correlate with elevated bladder lamina propria mast cell counts. We hypothesized that mast cells mediate pelvic pain directly and examined pain behavior using a murine model that recapitulates key aspects of IC.Infection of mice with pseudorabies virus (PRV induces a neurogenic cystitis associated with lamina propria mast cell accumulation dependent upon tumor necrosis factor alpha (TNF, TNF-mediated bladder barrier dysfunction, and pelvic pain behavior, but the molecular basis for pelvic pain is unknown. In this study, both PRV-induced pelvic pain and bladder pathophysiology were abrogated in mast cell-deficient mice but were restored by reconstitution with wild type bone marrow. Pelvic pain developed normally in TNF- and TNF receptor-deficient mice, while bladder pathophysiology was abrogated. Conversely, genetic or pharmacologic disruption of histamine receptor H1R or H2R attenuated pelvic pain without altering pathophysiology.These data demonstrate that mast cells promote cystitis pain and bladder pathophysiology through the separable actions of histamine and TNF, respectively. Therefore, pain is independent of pathology and inflammation, and histamine receptors represent direct therapeutic targets for pain in IC and other chronic pain conditions.

  7. Chest pain

    International Nuclear Information System (INIS)

    Martinez A, Juan Carlos; Saenz M, Oscar; Martinez M, Camilo; Gonzales A Francisco; Nicolas R, Jose; Vergara V, Erika P; Pereira G, Alberto M

    2010-01-01

    In emergency departments, chest pain is one of the leading motives of consultation. We thus consider it important to review aspects such as its classification, causes, and clinical profiles. Initial assessment should include a full clinical history comprising thorough anamnesis and physical examination. Adequate interpretation of auxiliary tests, ordered in accordance with suspected clinical conditions, should lead to accurate diagnosis. We highlight certain symptoms and clinical signs, ECG and X-ray findings, cardiac bio markers, arterial blood gases, and CT-scanning. Scores of severity and prognosis such as TIMI are assessed. Optimal treatment of the clinical conditions leading to chest pain depends on adequate initial approach and assessment.

  8. CD14-159C/T polymorphism in the development of delayed skin hypersensitivity to tuberculin.

    Directory of Open Access Journals (Sweden)

    Magdalena Druszczynska

    Full Text Available The skin tuberculin test (TST, an example of a delayed-type hypersensitivity (DTH reaction, is based on measuring the extent of skin induration to mycobacterial tuberculin (PPD. Little is known about the genetic basis of TST reactivity, widely used for diagnosing TB infection. The study investigated the relationship of the single base change polymorphic variants in CD14 gene (CD14(-159C/T with the development of DTH to PPD in BCG-vaccinated Polish Caucasian individuals. We found persistent lack of TST reactivity in about 40% of healthy subjects despite receiving more than one dose of BCG. The TST size was negatively correlated with the number of BCG inoculations. The distribution of C/T genotype was significantly more frequent among TST-negative compared with TST-positive individuals. The concentration of serum sCD14 was positively associated with mCD14 expression, but not with the TST status or CD14(-159C/T polymorphism. A significant increase in mCD14 expression and serum sCD14 levels was found in TB group. We hypothesize that CD14(-159C/T polymorphic variants might be one of genetic components in the response to attenuated M. bovis BCG bacilli.

  9. Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases.

    Science.gov (United States)

    Matyszak, M K; Perry, V H

    1996-09-01

    We have studied the effect of an inhibitor of matrix metalloproleinases, BB-1101, on a delayed-type hypersensitivity (DTH) response in the CNS. We used a recently described model in which heat-killed bacillus Calmette-Guérin (BCG) sequestered behind the blood-brain barrier (BBB) is targeted by a T-cell mediated response after subcutaneous injection of BCG (Matyszak and Perry, 1995). The DTH lesions are characterised by breakdown of the BBB, macrophage and lymphocyte infiltration and tissue damage including myelin loss. Treatment with BB-1101, which is not only a potent inhibitor of matrix metalloproteinases but also strongly inhibits TNF-alpha release, dramatically attenuated the CNS lesions. Breakdown of the BBB and the recruitment of T-cells into the site of the lesion were significantly reduced. There were many fewer inflammatory macrophages in DTH lesions than in comparable lesions from untreated animals. There was also significantly less myelin damage (assessed by staining with anti-MBP antibody). The DTH response in animals treated with dexamethasone was also reduced, but to a lesser degree. No significant effect was seen after administration of pentoxifylline, a phosphodiesterase inhibitor with effects including the inhibition of TNF-alpha production. Our results suggest that inhibitors of matrix metalloproteinases may be of considerable therapeutic benefit in neuroinflammatory diseases.

  10. The stress regulator FKBP51: a novel and promising druggable target for the treatment of persistent pain states across sexes.

    Science.gov (United States)

    Maiarù, Maria; Morgan, Oakley B; Mao, Tianqi; Breitsamer, Michaela; Bamber, Harry; Pöhlmann, Max; Schmidt, Mathias V; Winter, Gerhard; Hausch, Felix; Géranton, Sandrine M

    2018-03-12

    It is well established that FKBP51 regulates the stress system by modulating the sensitivity of the glucocorticoid receptor to stress hormones. Recently, we have demonstrated that FKBP51 also drives long-term inflammatory pain states in male mice by modulating glucocorticoid signalling at spinal cord level. Here, we explored the potential of FKBP51 as a new pharmacological target for the treatment of persistent pain across the sexes. First, we demonstrated that FKBP51 regulates long-term pain states of different aetiologies independently of sex. Deletion of FKBP51 reduced the mechanical hypersensitivity seen in joint inflammatory and neuropathic pain states in female and male mice. Furthermore, FKBP51 deletion also reduced the hypersensitivity seen in a translational model of chemotherapy-induced pain. Interestingly, these 3 pain states were associated with changes in glucocorticoid signalling, as indicated by the increased expression, at spinal cord level, of the glucocorticoid receptor isoform associated with glucocorticoid resistance, GRβ, and increased levels of plasma corticosterone. These pain states were also accompanied by an upregulation of interleukin-6 in the spinal cord. Crucially, we were able to pharmacologically reduce the severity of the mechanical hypersensitivity seen in these 3 models of persistent pain with the unique FKBP51 ligand SAFit2. When SAFit2 was combined with a state-of-the-art vesicular phospholipid gel formulation for slow release, a single injection of SAFit2 offered pain relief for at least 7 days. We therefore propose the pharmacological blockade of FKBP51 as a new approach for the treatment of persistent pain across sexes, likely in humans as well as rodents.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  11. Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty

    Directory of Open Access Journals (Sweden)

    Andrew J. Mitchelson

    2015-01-01

    Full Text Available The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected.

  12. Acute hypersensitivity reaction to Crotalidae polyvalent immune Fab (CroFab) as initial presentation of galactose-α-1,3-galactose (α-gal) allergy.

    Science.gov (United States)

    Rizer, Justin; Brill, Kaitlin; Charlton, Nathan; King, Joshua

    2017-08-01

    Crotalidae polyvalent immune Fab antivenom (CroFab), commonly used for the treatment of clinically significant North American crotalinae envenomation, is generally well-tolerated. A novel form of anaphylaxis due to an IgE antibody response to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) has been established following red-meat consumption as well as IV administration of cetuximab, which contain the α-gal epitope. We present a case of α-gal allergy discovered after acute hypersensitivity reaction to FabAV. A 61-year-old healthy female was bitten on her left ankle by Agkistrodon contortrix. Given the patient's rapid progression of pain and swelling, she was given FabAV. During infusion of FabAV, she developed diffuse hives over her entire body and itching, but denied respiratory or gastrointestinal symptoms and her vital signs remained stable. The FabAV was immediately discontinued and she received intravenous diphenhydramine and famotidine with gradual resolution of symptoms. On further discussion, she denied a history of α-gal or papaya allergy but rarely ate red meat and endorsed sustaining frequent tick bites. Subsequent antibody testing was significant for an α-1,3-galactose IgE concentration of 45,000 U/L (normal allergy. To our knowledge, this is the first report of FabAV hypersensitivity associated with an underlying α-gal allergy.

  13. Diclofenac hypersensitivity: antibody responses to the parent drug and relevant metabolites.

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    Andrea Harrer

    2010-10-01

    Full Text Available Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs like diclofenac (DF can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug- and/or metabolite-specific antibodies in selective DF hypersensitivity.DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14% displayed drug/metabolite-specific IgG.We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded.

  14. Association of tinnitus and electromagnetic hypersensitivity: hints for a shared pathophysiology?

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    Michael Landgrebe

    Full Text Available BACKGROUND: Tinnitus is a frequent condition with high morbidity and impairment in quality of life. The pathophysiology is still incompletely understood. Electromagnetic fields are discussed to be involved in the multi-factorial pathogenesis of tinnitus, but data proofing this relationship are very limited. Potential health hazards of electromagnetic fields (EMF have been under discussion for long. Especially, individuals claiming themselves to be electromagnetic hypersensitive suffer from a variety of unspecific symptoms, which they attribute to EMF-exposure. The aim of the study was to elucidate the relationship between EMF-exposure, electromagnetic hypersensitivity and tinnitus using a case-control design. METHODOLOGY: Tinnitus occurrence and tinnitus severity were assessed by questionnaires in 89 electromagnetic hypersensitive patients and 107 controls matched for age-, gender, living surroundings and workplace. Using a logistic regression approach, potential risk factors for the development of tinnitus were evaluated. FINDINGS: Tinnitus was significantly more frequent in the electromagnetic hypersensitive group (50.72% vs. 17.5% whereas tinnitus duration and severity did not differ between groups. Electromagnetic hypersensitivity and tinnitus were independent risk factors for sleep disturbances. However, measures of individual EMF-exposure like e.g. cell phone use did not show any association with tinnitus. CONCLUSIONS: Our data indicate that tinnitus is associated with subjective electromagnetic hypersensitivity. An individual vulnerability probably due to an over activated cortical distress network seems to be responsible for, both, electromagnetic hypersensitivity and tinnitus. Hence, therapeutic efforts should focus on treatment strategies (e.g. cognitive behavioral therapy aiming at normalizing this dysfunctional distress network.

  15. Blast cells transfer experimental hypersensitivity pneumonitis in guinea pigs

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    Schuyler, M.; Cook, C.; Listrom, M.; Fengolio-Preiser, C.

    1988-01-01

    We previously demonstrated that experimental hypersensitivity pneumonitis (HP) can be transferred by lymph node cells (LNC) cultured in vitro with antigen. The purpose of this study was to identify the cells responsible for transfer and to determine if pulmonary cells can transfer HP. We cultured LNC from sensitized Strain 2 guinea pigs with a soluble extract of Micropolyspora faeni for 72 h, separated lymphoblasts from small lymphocytes, and transferred both subpopulations intravenously to syngeneic recipients. We also transferred irradiated lymphoblasts (1,500 rads), macrophage-depleted, lymphoblast-enriched populations, and pulmonary cells either without culture or after culture with M. faeni. Control animals received an equal volume of medium. All recipient animals were challenged intratracheally (i.t.) with M. faeni 48 h after the cell transfer, and they were killed 4 days after i.t. challenge. Randomly selected microscopic fields of the lung (250/animal) were judged to be normal or abnormal without knowledge of treatment. This measurement was reproducible (r = 0.95 for duplicate measurements, n = 55). All guinea pigs were maintained in HEPA-filtered air. There was a low level of pulmonary response to an i.t. challenge of M. faeni in animals that received medium. Animals that received pulmonary cells, either cultured or noncultured, did not differ from those in the control group. There was a substantial increase (p less than 0.01) in the extent of pulmonary abnormalities in the recipients of the lymphoblast population, with significant correlation (r = 0.87, p less than 0.01) between the number of lymphoblasts transferred and the extent of pulmonary abnormalities

  16. Hypersensitive reaction to tattoos: A growing menace in rural India

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    B M Shashikumar

    2017-01-01

    Full Text Available Background: Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions. Objective: The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district. Materials and Methods: An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction. Results: Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%, black (33.3%, green (5.1%, and multicolor (7.7%. Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction. Conclusion: Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction.

  17. Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents

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    Seki, J.T.; Sakurai, N.; Lam, W.; Reece, D.E.

    2017-01-01

    Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient’s advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient’s safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure. PMID:28874903

  18. Association of anticonvulsant hypersensitivity syndrome with Herpesvirus 6, 7.

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    Oskay, Tuğba; Karademir, Asli; Ertürk, Ozcan I

    2006-07-01

    Anticonvulsant hypersensitivity syndrome (AHS) is one of the most severe forms of drug eruption with potentially lethal, and multiorgan involvement. Recently, it has been suggested that Human Herpesvirus (HHV) infection has been involved in this syndrome, although the pathogenesis of this syndrome remains still unclear. The objective of this study was to determine the clinical characteristics of AHS and the possible role of viral infection as a co-factor. We prospectively analyzed clinical, laboratory and virological findings for 23 cases of AHS. A viral study including viral serology and a polymerase chain reaction (PCR) was performed. The most common anticonvulsant was carbamazepine (12) followed by phenytoin (6), phenobarbital (4) and gabapentin (1). All patients met fulfill the clinical criteria of AHS. Even though internal organ involvement such as liver (52%), kidney (34%), and lung (13%) has been observed, involvement of heart, lung, thyroid, muscle, pancreas, spleen, and brain was less frequent. We also noted two patients who died due to multiorgan failure. No association with viral infection including HSV, VZV, HHV-8, CMV, EBV, measles, rubella and parvovirus B19 was detected in the current series. Increased serum anti-HHV-6 IgG and HHV-7 titers and presence of HHV-6 and -7 DNA in serum, revealed by PCR analysis, suggested reactivation of HHV-6. In contrast to the control groups, DNA for HHV-6 was detected in serum in 5 out of the 23 patients while HHV-7 was seen in two patients. We found an evidence to link reactivation of HHV-6 or HHV-7 in the development of only carbamazepine-induced AHS. We propose that some cases of AHS are accompanied by reactivation of not only HHV-6 but also HHV-7. HHV infection may contribute to the severity, prolongation, or relapse of AHS and may possibly have fatal consequences in some susceptible individuals receiving the anticonvulsants.

  19. Pain Control After Surgery: Pain Medicines

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    ... 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: ...

  20. Breast pain

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    ... that reducing the amount of fat, caffeine, or chocolate in your diet helps reduce breast pain. Vitamin ... harmful, but most studies have not shown any benefit. Talk to your provider before starting any medicine or ... Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA. Review provided by ...