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Sample records for cfa-induced pain hypersensitivity

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    Objective 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.Methods 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.Results 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.Conclusion 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.

  3. 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.

  4. Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.

    Science.gov (United States)

    Hernstadt, Hayley; Wang, Shuxing; Lim, Grewo; Mao, Jianren

    2009-08-25

    Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund's Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on Days 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral laminae I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Days 7 and 14. Moreover, TSPO was colocalized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.

  5. 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.

  6. Hypothalamic GPR40 Signaling Activated by Free Long Chain Fatty Acids Suppresses CFA-Induced Inflammatory Chronic Pain

    OpenAIRE

    Kazuo Nakamoto; Takashi Nishinaka; Naoya Sato; Mitsumasa Mankura; Yutaka Koyama; Fumiyo Kasuya; Shogo Tokuyama

    2013-01-01

    GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently inc...

  7. Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

    Science.gov (United States)

    Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

    2015-04-01

    Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

  8. Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

    Science.gov (United States)

    Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

    2013-01-01

    GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP), an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol), a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg) and GW9508 (1.0 µg), a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg), a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg) significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long chain fatty

  9. Hypothalamic GPR40 signaling activated by free long chain fatty acids suppresses CFA-induced inflammatory chronic pain.

    Directory of Open Access Journals (Sweden)

    Kazuo Nakamoto

    Full Text Available GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA. However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently increased at day 7, but not at days 1, 3 and 14, after CFA injection. GPR40 was co-localized with NeuN, a neuron marker, but not with glial fibrillary acidic protein (GFAP, an astrocyte marker. At day 1 after CFA injection, GFAP protein expression was markedly increased in the hypothalamus. These increases were significantly inhibited by the intracerebroventricular injection of flavopiridol (15 nmol, a cyclin-dependent kinase inhibitor, depending on the decreases in both the increment of GPR40 protein expression and the induction of mechanical allodynia and thermal hyperalgesia at day 7 after CFA injection. Furthermore, the level of DHA in the hypothalamus tissue was significantly increased in a flavopiridol reversible manner at day 1, but not at day 7, after CFA injection. The intracerebroventricular injection of DHA (50 µg and GW9508 (1.0 µg, a GPR40-selective agonist, significantly reduced mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects were inhibited by intracerebroventricular pretreatment with GW1100 (10 µg, a GPR40 antagonist. The protein expression of GPR40 was colocalized with that of β-endorphin and proopiomelanocortin, and a single intracerebroventricular injection of GW9508 (1.0 µg significantly increased the number of neurons double-stained for c-Fos and proopiomelanocortin in the arcuate nucleus of the hypothalamus. Our findings suggest that hypothalamic GPR40 activated by free long

  10. Intra-articular administration of an antibody against CSF-1 receptor reduces pain-related behaviors and inflammation in CFA-induced knee arthritis.

    Science.gov (United States)

    Alvarado-Vazquez, P A; Morado-Urbina, C E; Castañeda-Corral, G; Acosta-Gonzalez, R I; Kitaura, H; Kimura, K; Takano-Yamamoto, T; Jiménez-Andrade, J M

    2015-01-01

    Several studies have shown that blockade of colony stimulating factor-1 (CSF-1) or its receptor (CSF-1R) inhibits disease progression in rodent models of rheumatoid arthritis (RA); however, the role of the CSF-1/CSF-1R pathway in RA-induced pain and functional deficits has not been studied. Thus, we examined the effect of chronic intra-articular administration of a monoclonal anti-CSF-1R antibody (AFS98) on spontaneous pain, knee edema and functional disabilities in mice with arthritis. Unilateral arthritis was produced by multiple injections of complete Freund's adjuvant (CFA) into the right knee joint of adult male ICR mice. CFA-injected mice were then treated twice weekly from day 10 until day 25 with anti-CSF-1R antibody (3 and 10 μg/5 μL per joint), isotype control (rat IgG 10 μg/5 μL per joint) or PBS (5 μl/joint). Knee edema, spontaneous flinching, vertical rearing and horizontal exploratory activity were assessed at different days. Additionally, counts of peripheral leukocytes and body weight were measured to evaluate general health status. Intra-articular treatment with anti-CSF-1R antibody significantly increased horizontal exploratory activity and vertical rearing as well as reduced spontaneous flinching behavior and knee edema as compared to CFA-induced arthritis mice treated with PBS. Treatment with this antibody neither significantly affect mouse body weight nor the number of peripheral leukocytes. These results suggest that blockade of CSF-1R at the initial injury site (joint) could represent a therapeutic alternative for improving the functional disabilities and attenuating pain and inflammation in patients with RA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.

    Science.gov (United States)

    Asgar, J; Zhang, Y; Saloman, J L; Wang, S; Chung, M-K; Ro, J Y

    2015-12-03

    Transient receptor potential cation channel, subfamily A, member 1 (TRPA1) is expressed in muscle afferents and direct activation of these receptors induces acute mechanical hypersensitivity. However, the functional role of TRPA1 under pathological muscle pain conditions and mechanisms by which TRPA1 mediate muscle pain and hyperalgesia are not clearly understood. Two rodent behavioral models validated to assess craniofacial muscle pain conditions were used to study ATP- and N-Methyl-D-aspartate (NMDA)-induced acute mechanical hypersensitivity and complete Freund's adjuvant (CFA)-induced persistent mechanical hypersensitivity. The rat grimace scale (RGS) was utilized to assess inflammation-induced spontaneous muscle pain. Behavioral pharmacology experiments were performed to assess the effects of AP18, a selective TRPA1 antagonist under these conditions. TRPA1 expression levels in trigeminal ganglia (TG) were examined before and after CFA treatment in the rat masseter muscle. Pre-treatment of the muscle with AP18 dose-dependently blocked the development of acute mechanical hypersensitivity induced by NMDA and α,β-methylene adenosine triphosphate (αβmeATP), a specific agonist for NMDA and P2X3 receptor, respectively. CFA-induced mechanical hypersensitivity and spontaneous muscle pain responses were significantly reversed by post-treatment of the muscle with AP18 when CFA effects were most prominent. CFA-induced myositis was accompanied by significant up-regulation of TRPA1 expression in TG. Our findings showed that TRPA1 in muscle afferents plays an important role in the development of acute mechanical hypersensitivity and in the maintenance of persistent muscle pain and hypersensitivity. Our data suggested that TRPA1 may serve as a downstream target of pro-nociceptive ion channels, such as P2X3 and NMDA receptors in masseter afferents, and that increased TRPA1 expression under inflammatory conditions may contribute to the maintenance of persistent muscle pain

  12. Central hypersensitivity in chronic musculoskeletal pain.

    Science.gov (United States)

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-05-01

    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity.

  13. Central hypersensitivity in chronic musculoskeletal pain

    DEFF Research Database (Denmark)

    Curatolo, Michele; Arendt-Nielsen, Lars

    2015-01-01

    Clinical research has consistently detected alteration in central pain processing leading to hypersensitivity. Most methods used in humans are reliable and have face validity to detect widespread central hypersensitivity. However, construct validity is difficult to investigate due to lack of gold...... standards. Reference values in the pain-free population have been generated, but need replication. Research on pain biomarkers that reflect specific central hypersensitivity processes is warranted. Few studies have analyzed the prognostic value of central hypersensitivity. Most medications acting at central...... level and some non-pharmacological approaches, including psychological interventions, are likely to attenuate central hypersensitivity....

  14. Transcutaneous electrical nerve stimulation on Yongquan acupoint reduces CFA-induced thermal hyperalgesia of rats via down-regulation of ERK2 phosphorylation and c-Fos expression.

    Science.gov (United States)

    Yang, Lin; Yang, Lianxue; Gao, Xiulai

    2010-07-01

    Activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and its involvement in regulating gene expression in spinal dorsal horn, cortical and subcortical neurons by peripheral noxious stimulation contribute to pain hypersensitivity. Transcutaneous electrical nerve stimulation (TENS) is a treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. In this study, a total number of 114 rats were used for three experiments. Effects of complete Freund's adjuvant (CFA)-induced inflammatory pain hypersensitivity and TENS analgesia on ERK1/2 phosphorylation and c-Fos protein expression were examined by using behavioral test, Western blot, and immunostaining methods. We found that CFA injection caused an area of localized swelling, erythema, hypersensitivity to thermal stimuli, the decreased response time of hind paw licking (HPL), as well as upregulation of c-Fos protein expression and ERK2 phosphorylation in the ipsilateral spinal dorsal horn and the contralateral primary somatosensory area of cortex and the amygdala of rats. TENS on Yongquan acupoint for 20 min produced obvious analgesic effects as demonstrated with increased HPL to thermal stimuli of CFA-treated rats. In addition, TENS application suppressed the CFA-induced ERK2 activation and c-Fos protein expression. These results suggest that down-regulation of ERK2 phosphorylation and c-Fos expression were involved in TENS inhibition on CFA-induced thermal hyperalgesia of rats.

  15. Probing the Effects and Mechanisms of Electroacupuncture at Ipsilateral or Contralateral ST36-ST37 Acupoints on CFA-induced Inflammatory Pain.

    Science.gov (United States)

    Lu, Kung-Wen; Hsu, Chao-Kuei; Hsieh, Ching-Liang; Yang, Jun; Lin, Yi-Wen

    2016-02-24

    Transient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund's adjuvant (CFA), (2.14 ± 0.1, p CFA injection; this expression can be further attenuated significantly in EA treatment. TRPV1 and associated signaling pathways can be prevented in TRPV1 knockout mice, suggesting that TRPV1 knockout mice are resistant to inflammatory pain. Through this study, we have increased the understanding of the mechanism that both ipsilateral and contralateral EA might alter TRPV1 and associated signaling pathways to reduce inflammatory pain.

  16. 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

    2017-01-01

    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 N6-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. PMID:28211895

  17. 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.

  18. Anti-hyperalgesic activity of the aqueous and methanol extracts of the leaves of Pittosporum mannii Hook on CFA-induced persistent inflammatory pain.

    Science.gov (United States)

    Wandji, Bibiane Aimée; Bomba, Francis Desire Tatsinkou; Nkeng-Efouet, Pepin Alango; Piegang, Basile Nganmegne; Kamanyi, Albert; Nguelefack, Télesphore Benoît

    2017-08-29

    Previous study showed that aqueous (AEPM) and methanol (MEPM) extracts from the leaves of Pittosporum mannii have analgesic effects in acute pain models. The present study evaluates the acute and chronic anti-hypernociceptive and anti-inflammatory effects of AEPM and MEPM in a model of persistent inflammatory pain. The third day after induction of inflammatory pain by subplantar injection of 100 µL of CFA in Wistar rats, AEPM and MEPM were administered orally (75, 150 and 300 mg/kg/day) and their anti-hyperalgesic and anti-inflammatory effects were follow in acute (1-24 h) and chronic (for 14 days) treatments. At the end of the chronic treatment, oxidative stress and liver parameters were assessed. Effects of plant extracts were also evaluated on nociception induced by Phorbol 12-Myristate 13-Acetate (PMA) and 8-bromo 3',5'-cAMP (8-Br-cAMP) in mice. AEPM and MEPM significantly reversed the mechanical hyperalgesia caused by CFA in acute and chronic treatment. Moreover, AEPM and MEPM also significantly reduced the nociception caused by PMA (60%) and 8-Br-cAMP (87%). Nevertheless, AEPM and MEPM failed to inhibit the paw edema caused by CFA. Plant extracts significantly reduced the nitric oxide content in the spinal cord and the plasmatic concentration of alanine aminotransferase. MEPM also significantly increased the glutathione content in the spinal cord. AEPM and MEPM given orally are effective in inhibiting mechanical hyperalgesia in persistent inflammatory pain caused by CFA. Their mechanisms of action seem to involve an interaction with PKC, PKA and nitric oxide pathways. These extracts might be devoid of hepatotoxic effects.

  19. High-fat diet exacerbates pain-like behaviors and periarticular bone loss in mice with CFA-induced knee arthritis.

    Science.gov (United States)

    Loredo-Pérez, Aleyda A; Montalvo-Blanco, Carlos E; Hernández-González, Luis I; Anaya-Reyes, Maricruz; Fernández Del Valle-Laisequilla, Cecilia; Reyes-García, Juan G; Acosta-González, Rosa I; Martínez-Martínez, Arisai; Villarreal-Salcido, Jaira C; Vargas-Muñoz, Virginia M; Muñoz-Islas, Enriqueta; Ramírez-Rosas, Martha B; Jiménez-Andrade, Juan M

    2016-05-01

    Our aim was to quantify nociceptive spontaneous behaviors, knee edema, proinflammatory cytokines, bone density, and microarchitecture in high-fat diet (HFD)-fed mice with unilateral knee arthritis. ICR male mice were fed either standard diet (SD) or HFD starting at 3 weeks old. At 17 weeks, HFD and SD mice received intra-articular injections either with Complete Freund's Adjuvant (CFA) or saline into the right knee joint every 7 days for 4 weeks. Spontaneous pain-like behaviors and knee edema were assessed for 26 days. At day 26 post-first CFA injection, serum levels of IL-1β, IL-6, and RANKL were measured by ELISA, and microcomputed tomography analysis of knee joints was performed. HFD-fed mice injected with CFA showed greater spontaneous pain-like behaviors of the affected extremity as well as a decrease in the weight-bearing index compared to SD-fed mice injected with CFA. Knee edema was not significantly different between diets. HFD significantly exacerbated arthritis-induced bone loss at the distal femoral metaphysis but had no effect on femoral diaphyseal cortical bone. HFD did not modify serum levels of proinflammatory cytokines. HFD exacerbates pain-like behaviors and significantly increases the magnitude of periarticular trabecular bone loss in a murine model of unilateral arthritis. © 2016 The Obesity Society.

  20. Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner.

    Science.gov (United States)

    Fernandes, Elizabeth S; Russell, Fiona A; Alawi, Khadija M; Sand, Claire; Liang, Lihuan; Salamon, Robin; Bodkin, Jennifer V; Aubdool, Aisah A; Arno, Matthew; Gentry, Clive; Smillie, Sarah-Jane; Bevan, Stuart; Keeble, Julie E; Malcangio, Marzia; Brain, Susan D

    2016-01-11

    The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. Mono-arthritis was induced by unilateral intra-articular injection of complete Freund's adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK1) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP8-37). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints. We provide evidence that environmental

  1. Antinociceptive effects of systemic tanshinone IIA on visceral and somatic persistent nociception and pain hypersensitivity in rats.

    Science.gov (United States)

    Cao, Fa-Le; Su, Xue-Jia; Wang, Yan; Xu, Min; Shan, Liang

    2014-09-01

    Previous studies showed that tanshinone IIA (TIIA), an important lipophilic component of Danshen, has been well-established to exhibit various neuroprotective actions in the nervous system. Although we previously reported that TIIA had a significant anti-nociceptive effect in complete Freund's adjuvant (CFA)-induced pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA in animals and the appropriate indications for treatment of clinical pain remain unclear. Therefore, in the present study, by using both somatic and visceral pain models, the antinociceptive and antihyperalgesic effects of TIIA were evaluated by intraperitoneal administration in rats. In the bee venom (BV) test, when compared with saline controls, systemic pre- and post-treatment with TIIA resulted in an apparent antinociception against persistent spontaneous nociception (PSN) and primary heat and mechanical hypersensitivity, while for the mirror-image heat hypersensitivity, only pre-treatment was effective. Moreover, in the formalin test, the antinociception of TIIA was significant for both phases 1 and 2 in the pretreatment groups, but only effective for phase 2 in the post-treatment group. In the acetic acid writhing test, the number of writhes was effectively blocked by both pre- and post-treatment of TIIA. Taken together, these results provide a new line of evidence showing that TIIA is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity.

  2. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    Science.gov (United States)

    Farmer, A D; Aziz, Q

    2009-01-01

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

  3. UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: Comparison with the NMDA receptor antagonist MK-801

    DEFF Research Database (Denmark)

    Andreasen, Jesper T.; Bach, Anders; Gynther, Mikko

    2013-01-01

    's adjuvant (CFA) model of inflammatory pain. To examine side-effect profiles we also compared the effects of UCCB01-125 and MK-801 in tests of attention, long-term memory, and motor performance. When administered concurrently with CFA, both MK-801 and UCCB01-125 prevented the development of CFA......-induced mechanical hypersensitivity 1 and 24 h after treatment. Moreover, UCCB01-125 was found to reverse CFA-induced hypersensitivity when administered 24 h after CFA treatment, an effect lasting for at least 3 days. At the dose reducing hypersensitivity, MK-801 disrupted attention, long-term memory, and motor...

  4. Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Keizer, Ron; Munro, Gordon

    2016-01-01

    PURPOSE: Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA......-induced inflammatory hyperalgesia. METHODS: A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration...

  5. Ranolazine attenuation of CFA-induced mechanical hyperalgesia.

    Science.gov (United States)

    Casey, Gregory P; Roberts, Jomar S; Paul, Dennis; Diamond, Ivan; Gould, Harry J

    2010-01-01

    To determine whether ranolazine, a new anti-angina medication, could be an effective analgesic agent in complete Freund's adjuvant-induced inflammatory pain. Plantar injection of complete Freund's adjuvant (CFA) produces an extended period of hyperalgesia that is associated with a dramatic up-regulation of Na(v) 1.7 sodium channels in populations of large and small dorsal root ganglion neurons related to the injection site. Ranolazine appears to produce its anti-angina effect through blocking the late sodium current associated with the voltage-gated sodium channel, Na(v) 1.5. Because ranolazine also inhibits Na(v) 1.7, and 1.8, we sought to determine whether it could be an effective analgesic agent in CFA-induced inflammatory pain. Baseline determinations of withdrawal from thermal and mechanical stimulation were made in Sprague-Dawley rats ( approximately 300-350 x g). Following determination of baseline, one hindpaw in each group was injected with 0.1 mL of CFA. The contralateral paw received saline. Thermal and mechanical stimulation was repeated on the third day post-injection. Vehicle (0.9% isotonic saline; pH 3.0) or ranolazine was then administered in randomized and blinded doses either by intraperitoneal (ip) injection (0, 10, 20, and 50 mg/kg) or by oral gavage (po; 0, 20, 50, 100, and 200 mg/kg). Animals were again tested 30 minutes (ip) and 1 hour (po) after drug administration. Ranolazine produced dose-dependant analgesia on mechanical allodynia induced by CFA injection, but had no effect on thermal hyperalgesia. Ranolazine's potential as a new option for managing both angina and chronic inflammatory pain warrants further study.

  6. ERK MAP kinase activation in spinal cord regulates phosphorylation of Cdk5 at serine 159 and contributes to peripheral inflammation induced pain/hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Xiaoqin Zhang

    Full Text Available Cyclin-dependent kinase 5 is a proline-directed serine/threonine kinase and its activity participates in the regulation of nociceptive signaling. Like binding with the activators (P35 or P25, the phosphorylation of Cdk5 plays a critical role in Cdk5 activation. However, it is still unclear whether Cdk5 phosphorylation (p-Cdk5 contributes to pain hyperalgesia. The aim of our current study was to identify the roles of p-Cdk5 and its upstream regulator in response to peripheral inflammation. Complete Freund's adjuvant (CFA injection induced acute peripheral inflammation and heat hyperalgesia, which was accompanied by sustained increases in phospho-ERK1/2 (p-ERK1/2 and phospho-Cdk5(S159 (p-Cdk5(S159 in the spinal cord dorsal horn (SCDH. CFA-induced p-ERK primarily colocalized with p-Cdk5(S159 in superficial dorsal horn neurons. Levels in p-ERK and p-Cdk5 were also increased in the 2(nd phase of hyperalgesia induced by formalin injection, which can produce acute and tonic inflammatory pain. MAP kinase kinase inhibitor U0126 intrathecal delivery significantly suppressed the elevation of p-Cdk5(S159, Cdk5 activity and pain response behavior (Heat hyperalgesia, Spontaneous flinches induced by CFA or formalin injection. Cdk5 inhibitor roscovitine intrathecal administration also suppressed CFA-induced heat hyperalgesia and Cdk5 phosphorylation, but did not attenuate ERK activation. All these findings suggested that p-Cdk5(S159 regulated by ERK pathway activity may be a critical mechanism involved in the activation of Cdk5 in nociceptive spinal neurons contributes to peripheral inflammatory pain hypersensitivity.

  7. Visceral pain hypersensitivity in functional gastrointestinal disorders

    National Research Council Canada - National Science Library

    Farmer, A. D; Aziz, Q

    2009-01-01

    .... 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...

  8. 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...... and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. We also assessed detection thresholds for innocuous warmth and cold, and participants' attitude toward painful encounters in daily life. Our results show that, compared to sighted subjects...

  9. Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia.

    Science.gov (United States)

    Huang, Chun-Ping; Chen, Hsiang-Ni; Su, Hong-Lin; Hsieh, Ching-Liang; Chen, Wei-Hsin; Lai, Zhen-Rung; Lin, Yi-Wen

    2013-01-01

    Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

  10. Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia

    Directory of Open Access Journals (Sweden)

    Chun-Ping Huang

    2013-01-01

    Full Text Available Several voltage-gated sodium channels (Navs from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG. We injected carrageenan and complete Freund's adjuvant (CFA into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36 acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36 acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

  11. Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia

    OpenAIRE

    Chun-Ping Huang; Hsiang-Ni Chen; Hong-Lin Su; Ching-Liang Hsieh; Wei-Hsin Chen; Zhen-Rung Lai; Yi-Wen Lin

    2013-01-01

    Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST3...

  12. Amelioratory effect of flavonoids rich Pergularia daemia extract against CFA induced arthritic rats.

    Science.gov (United States)

    Ananth, Devanesan Arul; Rameshkumar, Angappan; Jeyadevi, Ramachandran; Aseervatham, G Smilin Bell; Sripriya, Jaganathan; Bose, Prabaharan Chandra; Sivasudha, Thilagar

    2016-05-01

    Pergularia daemia Forsk. (Asclepiadaceae) is a traditionally reported medicinal herb used to treat joint pain and arthritis. However, there are no scientific reports about anti-arthritic activity of P. daemia methanolic extract on rats as animal model. This study identifies bioactive compounds present in the P. daemia methanolic extract and evaluates its anti-arthritic potential in CFA induced arthritic rats. Phytoconstituents of P. daemia extract were examined using LC-ESI/MS method. Anti-arthritic activity of P. daemia extract was determined by various biochemical experiments (RF, ESR and CRP), ultrasonography and histological analysis. LC-ESI/MS analysis resulted in the identification of major flavonoids compounds such as formononetin, qurecetin, chrysoeriol, taxifolin and naringenin. Serum biomarker analysis, after the treatment with PDME (500mg/kg b.w.) revealed that the hemoglobin (11.84±0.42g/dL) and RBC (8.38±0.67million/mm(3)) levels were significantly increased whereas WBC (8.91±0.38thousands/mm(3)), RF (17.94±0.45IU/mL), ESR (7.91±0.12mm/h) and CRP (22.56±0.26mg/L) levels were decreased when compared with the CFA induced arthritic control group. Histology results revealed that treatment with PDME has resulted in significant prevention against bony destruction by decreasing soft tissue swelling and narrowing of joint spaces (250 and 500mg/kg b.w.). Anti-arthritic effect of P. daemia might be due to the presence of these bioactive flavonoids. These findings lend pharmacological support to the reported folkloric use of P. daemia in the treatment and management of painful, arthritic inflammatory conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. 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.

  14. Hypersensitivity and pain induced by operative procedures and the "cracked tooth" syndrome.

    Science.gov (United States)

    Seltzer, S; Boston, D

    1997-01-01

    Various dental conditions are responsible for tooth hypersensitivity and pain. They include hypersensitive dentin; the "cracked tooth" syndrome; pulp and periapical irritation, inflammation and/or degeneration; barodontalgia (aerodontalgia); and periodontal pathoses, particularly the pulpal-periodontal syndrome. Each operative condition is reviewed with respect to its etiology, symptomatology, and diagnosis. Some treatment recommendations are made to prevent or reduce symptoms.

  15. Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.

    Science.gov (United States)

    King, Tamara; Qu, Chaoling; Okun, Alec; Mercado, Ramon; Ren, Jiyang; Brion, Triza; Lai, Josephine; Porreca, Frank

    2011-09-01

    A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as burning. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain, allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of an experimental neuropathic pain model were explored. Desensitization of TRPV1-positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor-expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. After nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large-diameter fibers, and inactivation of the brainstem target of these fibers in the nucleus gracilis prevents tactile but not thermal hypersensitivity. Blockade of NPY signaling within the nucleus gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into nucleus gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1-positive fibers and spinal NK-1-positive ascending projections. In contrast, the large-diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. Because inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the nucleus gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect allodynia.

  16. Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    Clive H Wilder-Smith; Joan Robert-Yap

    2007-01-01

    AIM: To investigate the role of endogenous pain modulatory mechanisms in the central sensitization implicated by the visceral hypersensitivity demonstrated in patients with irritable bowel syndrome (IBS).Dysfunction of modulatory mechanisms would be expected to also result in changes of somatic sensory function.METHODS: Endogenous pain modulatory mechanisms were assessed using heterotopic stimulation and somatic and visceral sensory testing in IBS. Pain intensities (visual analogue scale, VAS 0-100) during suprathreshold rectal distension with a barostat, cold pressor stimulation of the foot and during both stimuli simultaneously (heterotopic stimulation) were recorded in 40 female patients with IBS and 20 female healthy controls.RESULTS: Rectal hypersensitivity (defined by 95% CI of controls) was seen in 21 (53%), somatic hypersensitivity in 22 (55%) and both rectal and somatic hypersensitivity in 14 of these IBS patients. Heterotopic stimulation decreased rectal pain intensity by 6 (-11 to -1) in controls, but increased rectal pain by 2 (-3 to +6) in all IBS patients (P<0.05) and by 8 (-2 to +19) in IBS patients with somatic and visceral hypersensitivity (P<0.02).CONCLUSION: A majority of IBS patients had abnormal endogenous pain modulation and somatic hypersensitivity as evidence of central sensitization.

  17. Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model.

    Science.gov (United States)

    Larsen, Malte Selch; Keizer, Ron; Munro, Gordon; Mørk, Arne; Holm, René; Savic, Rada; Kreilgaard, Mads

    2016-05-01

    Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA-induced inflammatory hyperalgesia. A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration of a range of gabapentin doses (oral and intravenous). The plasma/brain ECF concentration-time profiles of gabapentin were adequately described with a two-compartment plasma model with saturable intestinal absorption rate (K m  = 44.1 mg/kg, V max  = 41.9 mg/h∙kg) and dose-dependent oral bioavailability linked to brain ECF concentration through a transit compartment. Brain ECF concentration was directly linked to a sigmoid E max function describing reversal of hyperalgesia (EC 50, plasma  = 16.7 μg/mL, EC 50, brain  = 3.3 μg/mL). The proposed semi-mechanistic population-based PKPD model provides further knowledge into the understanding of gabapentin's non-linear pharmacokinetics and the link between plasma/brain disposition and anti-hyperalgesic effects. The model suggests that intestinal absorption is the primary source of non-linearity and that the investigated rat model provides reasonable predictions of clinically effective plasma concentrations for gabapentin.

  18. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

    Science.gov (United States)

    Wang, Bing; Chen, Li-Hua

    2016-01-01

    In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

  19. Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice.

    Science.gov (United States)

    Chen, Yong; Boettger, Michael K; Reif, Andreas; Schmitt, Angelika; Uçeyler, Nurcan; Sommer, Claudia

    2010-03-02

    Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1beta. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1beta, and IL-10 following CFA, overall corroborating the inhibitor data. These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

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

    DEFF Research Database (Denmark)

    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...

  1. Reduction of follistatin-like 1 in primary afferent neurons contributes to neuropathic pain hypersensitivity

    Institute of Scientific and Technical Information of China (English)

    Kai-Cheng Li; Feng Wang; Yan-Qing Zhong; Ying-Jin Lu; Qiong Wang; Fang-Xiong Zhang; Hua-Sheng Xiao; Lan Bao; Xu Zhang

    2011-01-01

    @@ Dear Editor, Nerve injury-induced neuropathic pain is difficult to treat in clinic.Lack of comprehensive understanding of the mechanism underlying such chronic pain hypersensitivity delays the development of more effective therapy.Accumulated evidence shows that peripheral nerve injury alters the expression of many neurotransmitters, receptors, ion channels and signaling molecules in the dorsal root ganglion (DRG) and the dorsal horn of spinal cord [1].Some of these molecular changes in the pain pathway are correlated with the current therapy for neuropathic pain.

  2. Mast cell degranulation distinctly activates trigemino-cervical and lumbosacral pain pathways and elicits widespread tactile pain hypersensitivity.

    Science.gov (United States)

    Levy, Dan; Kainz, Vanessa; Burstein, Rami; Strassman, Andrew M

    2012-02-01

    Mast cells (MCs) are tissue resident immune cells that participate in a variety of allergic and other inflammatory conditions. In most tissues, MCs are found in close proximity to nerve endings of primary afferent neurons that signal pain (i.e. nociceptors). Activation of MCs causes the release of a plethora of mediators that can activate these nociceptors and promote pain. Although MCs are ubiquitous, conditions associated with systemic MC activation give rise primarily to two major types of pain, headache and visceral pain. In this study we therefore examined the extent to which systemic MC degranulation induced by intraperitoneal administration of the MC secretagogue compound 48/80 activates pain pathways that originate in different parts of the body and studied whether this action can lead to development of behavioral pain hypersensitivity. Using c-fos expression as a marker of central nervous system neural activation, we found that intraperitoneal administration of 48/80 leads to the activation of dorsal horn neurons at two specific levels of the spinal cord; one responsible for processing cranial pain, at the medullary/C2 level, and one that processes pelvic visceral pain, at the caudal lumbar/rostral sacral level (L6-S2). Using behavioral sensory testing, we found that this nociceptive activation is associated with development of widespread tactile pain hypersensitivity within and outside the body regions corresponding to the activated spinal levels. Our data provide a neural basis for understanding the primacy of headache and visceral pain in conditions that involve systemic MC degranulation. Our data further suggest that MC activation may lead to widespread tactile pain hypersensitivity.

  3. Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients.

    Science.gov (United States)

    Neziri, Alban Y; Dickenmann, Martina; Scaramozzino, Pasquale; Andersen, Ole K; Arendt-Nielsen, Lars; Dickenson, Anthony H; Curatolo, Michele

    2012-02-01

    The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2mg, and tropisetron 5mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

  4. Upregulation of adrenomedullin in the spinal cord and dorsal root ganglia in the early phase of CFA-induced inflammation in rats.

    Science.gov (United States)

    Hong, Yanguo; Liu, Yushan; Chabot, Jean-Guy; Fournier, Alain; Quirion, Rémi

    2009-11-01

    Adrenomedullin (AM), a member of calcitonin gene-related peptide (CGRP) family, has been demonstrated to be a pronociceptive mediator [28]. This study was undertaken to investigate the role of AM in a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Injection of CFA, but not of saline, in the unilateral hindpaw produced an increase in the expression of AM-like immunoreactivity (AM-IR) in laminae I-II of the spinal cord as well as in small- and medium-sized dorsal root ganglion (DRG) neurons at 48 h. The content of AM in DRG on the side ipsilateral to CFA injection started to increase at 4 h and remained at high levels at 24 and 48 h. The selective antagonist of AM receptors, AM(22-52), administered intrathecally (i.t.) 24 h after CFA injection inhibited inflammation-associated hyperalgesia in a dose-dependent manner (2, 5 and 10 nmol). Impressively, this anti-hyperalgesic effect lasted for at least 24 h. I.t. administration of AM(22-52) (10 nmol) also reversed CFA-induced increase in AM-IR in the spinal dorsal horn and DRG. Furthermore, blockade of AM receptors abolished CFA-induced changes in the expression and content of CGRP-like immunoreactivity in these regions. Taken together, our results suggest that the upregulation of AM in DRG neurons contributes to the development of inflammatory pain, and this effect is mediated, at least in part, by enhancing the expression and release of CGRP. Blocking AM receptor downstream signaling effects using antagonists has the potential of relieving pain following the induction of inflammation.

  5. 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...... detection thresholds and summation threshold to intra-articular electrical stimulation, tactile and pin-prick sensitivity in the TMJ area, pressure-pain threshold and tolerance on the lateral side of the TMJ and on the finger. Persons with TMJ arthralgia had lower pain detection and summation thresholds (P...

  6. Dentin hypersensitivity-like tooth pain seen in patients receiving steroid therapy: An exploratory study.

    Science.gov (United States)

    Shoji, Noriaki; Endo, Yu; Iikubo, Masahiro; Ishii, Tomonori; Harigae, Hideo; Aida, Jun; Sakamoto, Maya; Sasano, Takashi

    2016-11-01

    To ascertain whether steroid therapy evokes dentin hypersensitivity (DH)-like tooth pain, we performed a study based on compelling evidence from patients receiving steroid therapy. An exploratory study was conducted using a questionnaire for 220 patients prescribed steroids who attended the Department of Hematology and Rheumatology of Tohoku University Hospital. Group comparisons between patients with and without steroid pulse therapy were analysed by statistical means. In this study, any DH-like tooth pain that commenced subsequent to steroid treatment was defined as steroid-derived (SD) tooth pain. The prevalence of SD tooth pain was 17.7% (39/220 patients). SD tooth pain was triggered in many vital teeth by cold and/or hot water (84.2% and 23.7%, respectively) with the pain characterised as continuous, in contrast to typical DH tooth pain. SD tooth pain was significantly more frequent in pulse therapy patients than in non-pulse therapy patients (p pain score (ρ = 0.642). Dose reduction or discontinuation of steroid therapy relieved SD tooth pain in all cases. Thus, steroid therapy can evoke DH-like tooth pain during treatment. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  7. Dentin hypersensitivity-like tooth pain seen in patients receiving steroid therapy: An exploratory study

    OpenAIRE

    Noriaki Shoji; Yu Endo; Masahiro Iikubo; Tomonori Ishii; Hideo Harigae; Jun Aida; Maya Sakamoto; Takashi Sasano

    2016-01-01

    To ascertain whether steroid therapy evokes dentin hypersensitivity (DH)-like tooth pain, we performed a study based on compelling evidence from patients receiving steroid therapy. An exploratory study was conducted using a questionnaire for 220 patients prescribed steroids who attended the Department of Hematology and Rheumatology of Tohoku University Hospital. Group comparisons between patients with and without steroid pulse therapy were analysed by statistical means. In this study, any DH-...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Transient inflammation-induced ongoing pain is driven by TRPV1 sensitive afferents

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    Mercado Ramon

    2011-01-01

    Full Text Available Abstract Background Tissue injury elicits both hypersensitivity to evoked stimuli and ongoing, stimulus-independent pain. We previously demonstrated that pain relief elicits reward in nerve-injured rats. This approach was used to evaluate the temporal and mechanistic features of inflammation-induced ongoing pain. Results Intraplantar Complete Freund's Adjuvant (CFA produced thermal hyperalgesia and guarding behavior that was reliably observed within 24 hrs and maintained, albeit diminished, 4 days post-administration. Spinal clonidine produced robust conditioned place preference (CPP in CFA treated rats 1 day, but not 4 days following CFA administration. However, spinal clonidine blocked CFA-induced thermal hyperalgesia at both post-CFA days 1 and 4, indicating different time-courses of ongoing and evoked pain. Peripheral nerve block by lidocaine administration into the popliteal fossa 1 day following intraplantar CFA produced a robust preference for the lidocaine paired chamber, indicating that injury-induced ongoing pain is driven by afferent fibers innervating the site of injury. Pretreatment with resiniferatoxin (RTX, an ultrapotent capsaicin analogue known to produce long-lasting desensitization of TRPV1 positive afferents, fully blocked CFA-induced thermal hypersensitivity and abolished the CPP elicited by administration of popliteal fossa lidocaine 24 hrs post-CFA. In addition, RTX pretreatment blocked guarding behavior observed 1 day following intraplantar CFA. In contrast, administration of the selective TRPV1 receptor antagonist, AMG9810, at a dose that reversed CFA-induced thermal hyperalgesia failed to reduce CFA-induced ongoing pain or guarding behavior. Conclusions These data demonstrate that inflammation induces both ongoing pain and evoked hypersensitivity that can be differentiated on the basis of time course. Ongoing pain (a is transient, (b driven by peripheral input resulting from the injury, (c dependent on TRPV1 positive

  10. Effects of active immunisation with myelin basic protein and myelin-derived altered peptide ligand on pain hypersensitivity and neuroinflammation.

    Science.gov (United States)

    Perera, Chamini J; Lees, Justin G; Duffy, Samuel S; Makker, Preet G S; Fivelman, Brett; Apostolopoulos, Vasso; Moalem-Taylor, Gila

    2015-09-15

    Neuropathic pain is a debilitating condition in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Specific myelin basic protein (MBP) peptides are encephalitogenic, and myelin-derived altered peptide ligands (APLs) are capable of preventing and ameliorating EAE. We investigated the effects of active immunisation with a weakly encephalitogenic epitope of MBP (MBP87-99) and its mutant APL (Cyclo-87-99[A(91),A(96)]MBP87-99) on pain hypersensitivity and neuroinflammation in Lewis rats. MBP-treated rats exhibited significant mechanical and thermal pain hypersensitivity associated with infiltration of T cells, MHC class II expression and microglia activation in the spinal cord, without developing clinical signs of paralysis. Co-immunisation with APL significantly decreased pain hypersensitivity and neuroinflammation emphasising the important role of neuroimmune crosstalk in neuropathic pain.

  11. 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.

  12. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson’s Disease

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    Lei-Fang Cao

    2016-01-01

    Full Text Available In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA into the bilateral striatum (CPu. PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4 aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE precursor droxidopa (L-DOPS or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE and 5-hydroxytryptamine (5-HT reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain.

  13. 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 measured...... thresholds and response times to selective C- and Aδ-fibre activation in congenitally blind, late blind and normally sighted participants. Ultrafast constant-temperature heat pulses were delivered to the hand with a CO2 laser using an interleaved adaptive double staircase procedure. Participants were...... instructed to respond as quickly as possible when detecting a laser-induced sensation. We used a 650 ms cut-off criterion to distinguish fast Aδ- from slow C-fibre–mediated sensations. Results Congenitally blind participants showed significantly faster reaction times to C- but not to Aδ...

  14. Altered sympathovagal balance and pain hypersensitivity in TNBS-induced colitis.

    Science.gov (United States)

    Ciesielczyk, Katarzyna; Furgała, Agata; Dobrek, Łukasz; Juszczak, Kajetan; Thor, Piotr

    2017-02-01

    Pain hypersensitivity, abnormal motility and autonomic dysfunction contribute to functional symptoms of inflammatory bowel disease (IBD). The aim of this study was to assess: nociceptive thresholds for mechanical allodynia (MA) and thermal hyperalgesia (TH), intestinal motility (distal colonic transit and emptying), and cardiac autonomic neuropathy (indices of heart rate variability - HRV) in male Wistar rats with experimental trinitrobenzene sulfonic acid (TNBS) induced colitis. To identify a potential vagal contribution the bilateral subdiaphragmatic vagotomy (SDV) was performed. Experimental colitis resulted in a significant decrease in pain threshold (MA 23.60 ±2.12, p vagal integrity presented with reduced gastrointestinal motility (39.8 ±25.1, p vagal balance on HRV testing (LFnu 28.25 ±14.66, p hormonal and inflammatory factors. This leads to dysregulation of the brain-gut interactions in the course of IBD. Sensitization and visceral-somatic convergence trigger pain hypersensitivity and autonomic sympathovagal imbalance. While integral vagal innervation impacts analgesic mechanisms via modulation of the immune response, SDV raises sympathetic activity and induces excessive hyperalgesia.

  15. Brain derived neurotrophic factor (BDNF contributes to the pain hypersensitivity following surgical incision in the rats

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    Zhang Jian-Yi

    2008-07-01

    Full Text Available Abstract Background The pathogenic role of brain derived neurotrophic factor (BDNF in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity. Methods A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG and spinal cords were removed at various postoperative times (1–72 h. Expression pattern of BDNF was determined by immunohistochemistry and double-labeling immunofluorescence. Lidocaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on BDNF expression in the DRG and spinal cord after incision. BDNF antibody was administered intrathecally (IT or intraperitoneal (IP to modulate the spinal BDNF or peripheral BDNF after incision. Results After hind-paw incision, the BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord whereas thoracic BDNF remained unchanged in response to incision. The upregulated BDNF was mainly expressed in the large-sized neurons in DRG and the neurons and the primary nerve terminals in the spinal cord. Sciatic nerve blockade prevented the increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody greatly inhibited the mechanical allodynia induced by incision whereas IP administration had only marginal effect. Conclusion The present study showed that incision induced the segmental upregulation of BDNF in the DRG and spinal cord through somatic afferent nerve transmission, and the upregulated BDNF contributed to the pain hypersensitivity induced by surgical incision.

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

    OpenAIRE

    2011-01-01

    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, han...

  17. Altered sympathovagal balance and pain hypersensitivity in TNBS-induced colitis

    Science.gov (United States)

    Furgała, Agata; Dobrek, Łukasz; Juszczak, Kajetan; Thor, Piotr

    2016-01-01

    Introduction Pain hypersensitivity, abnormal motility and autonomic dysfunction contribute to functional symptoms of inflammatory bowel disease (IBD). Material and methods The aim of this study was to assess: nociceptive thresholds for mechanical allodynia (MA) and thermal hyperalgesia (TH), intestinal motility (distal colonic transit and emptying), and cardiac autonomic neuropathy (indices of heart rate variability – HRV) in male Wistar rats with experimental trinitrobenzene sulfonic acid (TNBS) induced colitis. To identify a potential vagal contribution the bilateral subdiaphragmatic vagotomy (SDV) was performed. Results Experimental colitis resulted in a significant decrease in pain threshold (MA 23.60 ±2.12, p rats with colitis showed the strongest nociceptive response (MA 22.46 ±3.02, p induces excessive hyperalgesia. PMID:28144278

  18. 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.

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

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    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.

  20. Colon distention induces persistent visceral hypersensitivity by mechanotranscription of pain mediators in colonic smooth muscle cells.

    Science.gov (United States)

    Lin, You-Min; Fu, Yu; Wu, Chester C; Xu, Guang-Yin; Huang, Li-Yen; Shi, Xuan-Zheng

    2015-03-01

    Abdominal pain and distention are major complaints in irritable bowel syndrome. Abdominal distention is mainly attributed to intraluminal retention of gas or solid contents, which may cause mechanical stress to the gut wall. Visceral hypersensitivity (VHS) may account for abdominal pain. We sought to determine whether tonic colon distention causes persistent VHS and if so whether mechanical stress-induced expression (mechanotranscription) of pain mediators in colonic smooth muscle cells (SMCs) plays a role in VHS. Human colonic SMCs were isolated and stretched in vitro to investigate whether mechanical stress upregulates expression of the pain mediator cyclooxygenase-2 (COX-2). Rat colon was distended with a 5-cm-long balloon, and gene expression of COX-2, visceromotor response (VMR), and sensory neuron excitability were determined. Static stretch of colonic SMCs induced marked expression of COX-2 mRNA and protein in a force- and time-dependent manner. Subnoxious tonic distention of the distal colon at ∼30-40 mmHg for 20 or 40 min induced COX-2 expression and PGE2 production in colonic smooth muscle, but not in the mucosa layer. Lumen distention also increased VMR in a force- and time-dependent manner. The increase of VMR persisted for at least 3 days. Patch-clamp experiments showed that the excitability of colon projecting sensory neurons in the dorsal root ganglia was markedly augmented, 24 h after lumen distention. Administration of COX-2 inhibitor NS-398 partially but significantly attenuated distention-induced VHS. In conclusion, tonic lumen distention upregulates expression of COX-2 in colonic SMC, and COX-2 contributes to persistent VHS.

  1. 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.

  2. 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.

  3. A time-dependent degeneration manner of condyle in rat CFA-induced inflamed TMJ.

    Science.gov (United States)

    Xu, Liqin; Guo, Huilin; Li, Cheng; Xu, Jie; Fang, Wei; Long, Xing

    2016-01-01

    Temporomandibular joint (TMJ) inflammation is a potential risk factor of osteoarthritis (OA) but the detailed degenerative changes in the inflamed TMJ remain unclear. In this study, we evaluated the changes of condylar cartilage and subchondral bone in rat inflamed TMJ induced by Freund's complete adjuvant (CFA). Articular cavity was injected with CFA and the TMJ samples were collected 1, 2, 3, and 4-week post-injection. Hematoxylin & Eosin (H&E) staining, toluidine blue (TB) staining, Safranin O (S.O) staining, Masson trichrome staining and micro-CT were used to assess TMJ degeneration during inflammation. Osteoclast and osteoblast activities were analyzed by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin (OCN) immunohistochemistry staining respectively. The expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in condylar cartilage and subchondral bone was also evaluated through immunohistochemistry and RANKL/OPG ratio was evaluated. Reduced cartilage thickness, decreased number of chondrocytes, and down-regulated proteoglycan expression were observed in the condylar cartilage in the inflamed TMJ. Enhanced osteoclast activity, and expanded bone marrow cavity were reached the peak in the 2-week after CFA-injection. Meanwhile the RANKL/OPG ratio in the cartilage and subchondral bone also increased in the 2-week CFA-injection. Immature, unmineralized new bones with irregular trabecular bone structure, atypical condylar shape, up-regulated OCN expression, and decreased bone mineral density (BMD) were found in the inflamed TMJ. The time-dependent degeneration manner of TMJ cartilage and subchondral bone was found in CFA-induced arthritis rat model. The degeneration in the TMJ with inflammation might be a risk factor and should be concerned.

  4. The alleviating pain effect of aqueous extract from tong-xie-yao-fang, on experimental visceral hypersensitivity and its mechanism.

    Science.gov (United States)

    Hu, Xu-Guang; Xu, Di; Zhao, Yue; Yang, Xiang-Bo; Meng, Jiang; Shen, Han; Guo, Jiao

    2009-06-01

    Tong-Xie-Yao-Fang (TXYF) is a prescription in traditional chinese medicine (TCM), used for relieving abdominal pain associated with irritable bowel syndrome. The aim of the present study was to investigate the effects and mechanism of TXYF on experimental visceral hypersensitivity (VH) models. TXYF affected the abdominal withdrawal reflex produced by colonic distention in maternal separation-induced visceral hypersensitivity rats, in a dosage-dependent manner. TXYF significantly decreased serotonin (5-HT) levels in serum and corticotrophin releasing factor (CRF) concentrations in the brain. Moreover, it was found that VH alleviation by TXYF was dependent on the substance P (SP) expression in the colon mucosa. These results suggest that TXYF attenuates behavioral hyperalgesia by regulating substance associated with the brain-gut axis, including decreasing the expression of 5-HT and SP in the periphery and that of CRF in the center.

  5. Mechanical and thermal hypersensitivities associated with orthodontic tooth movement: a behavioral rat model for orthodontic tooth movement-induced pain.

    Science.gov (United States)

    Sood, Mandeep; Bhatt, Poolak; Sessle, Barry J

    2015-01-01

    To test whether orofacial mechanical and thermal hypersensitivities occur in rats during orthodontic tooth movement (OTM). Sprague-Dawley rats (140 to 160 g) were divided into an experimental (E) group (n =7), with an active orthodontic spring placed in the right side of their mouth, and a sham (S) group (n = 7), with an inactive orthodontic spring. Mechanical sensitivity was tested preoperatively (1 day before attaching the orthodontic spring) and postoperatively (1 hour, 3 hours, 6 hours, days 1 to 7, day 14, day 21, and day 28 after orthodontic spring attachment) on the cheek, upper lip, and maxillary incisor labial gingiva bilaterally by recording the threshold for a head withdrawal response evoked by von Frey filaments. Thermal sensitivity was also tested preoperatively and postoperatively on the cheek bilaterally by applying a noxious thermal stimulus and measuring head withdrawal response duration, response score, and response percentile rate. Statistical analyses involved a mixed-model repeated-measures analysis of variance (MMRM ANOVA). The mechanical and thermal sensitivities at all bilateral sites were significantly increased (P pain model correlates with the time course of OTM-induced pain in humans and suggests that OTM-induced mechanical and thermal hypersensitivities may be useful measures of OTM-induced pain.

  6. Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Boesenbergia rotunda (L.) Mansf. inhibits CFA-induced rheumatoid arthritis in rats.

    Science.gov (United States)

    Voon, Fui-Ling; Sulaiman, Mohd Roslan; Akhtar, Muhammad Nadeem; Idris, Mohamad Fauzi; Akira, Ahmad; Perimal, Enoch Kumar; Israf, Daud Ahmad; Ming-Tatt, Lee

    2017-01-05

    Boesenbergia rotunda (L.) Mansf. had been traditionally used as herbs to treat pain and rheumatism. Cardamonin (2',4'-dihydroxy-6'-methoxychalcone) is a compound isolated from Boesenbergia rotunda (L.) Mansf.. Previous study had shown the potential of cardamonin in inhibiting the release of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. Thus, the possible therapeutic effect of cardamonin in the rheumatoid arthritis (RA) joints is postulated. This study was performed to investigate the anti-arthritic properties of cardamonin in rat model of induced RA, particularly on the inflammatory and pain response of RA. Rheumatoid arthritis paw inflammation was induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA) in Sprague Dawley rats. Using four doses of cardamonin (0.625, 1.25, 2.5, and 5.0mg/kg), anti-arthritic activity was evaluated through the paw edema, mechanical allodynia and thermal hyperalgesia responses. Enzyme-linked immunosorbent assay (ELISA) was carried out to evaluate the plasma level of TNF-α, IL-1β, and IL-6. Histological slides were prepared from the harvested rat paws to observe the arthritic changes in the joints. Behavioral, biochemical, and histological studies showed that cardamonin demonstrated significant inhibition on RA-induced inflammatory and pain responses as well as progression of joint destruction in rats. ELISA results showed that there was significant inhibition in TNF-α, IL-1β, and IL-6 levels in plasma of the cardamonin-treated RA rats. Overall, cardamonin possesses potential anti-arthritic properties in CFA-induced RA rat model. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity.

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    Tramullas, Mónica; Finger, Beate C; Dinan, Timothy G; Cryan, John F

    2016-01-01

    Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain. However, it remains unknown whether there is a functional interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present study we investigated the impact of long-term exposure to high-fat diet on visceral pain perception and on the levels of TLR4 and Cd11b (a microglial cell marker) protein expression in the prefrontal cortex (PFC) and hippocampus. Peripheral alterations in TLR4 were assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise, peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity present in pathologies associated to fat diet consumption.

  8. Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity.

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    Mónica Tramullas

    Full Text Available Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain. However, it remains unknown whether there is a functional interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present study we investigated the impact of long-term exposure to high-fat diet on visceral pain perception and on the levels of TLR4 and Cd11b (a microglial cell marker protein expression in the prefrontal cortex (PFC and hippocampus. Peripheral alterations in TLR4 were assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise, peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity present in pathologies associated to fat diet consumption.

  9. Effects of Virtual Walking Treatment on Spinal Cord Injury-Related Neuropathic Pain: Pilot Results and Trends Related to Location of Pain and at-level Neuronal Hypersensitivity.

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    Jordan, Melissa; Richardson, Elizabeth J

    2016-05-01

    Previous studies have shown that virtual walking to treat spinal cord injury-related neuropathic pain (SCI-NP) can be beneficial, although the type of SCI-NP that may benefit the most is unclear. This study's aims were to (1) determine the effect of location of SCI-NP on pain outcomes after virtual walking treatment and (2) examine the potential relationship between neuronal hyperexcitability, as measured by quantitative sensory testing, and pain reduction after virtual walking treatment. Participants were recruited from a larger ongoing trial examining the benefits of virtual walking in SCI-NP. Neuropathic pain was classified according to location of pain (at- or below-level). In addition, quantitative sensory testing was performed on a subset of individuals at a nonpainful area corresponding to the level of their injury before virtual walking treatment and was used to characterize treatment response. These pilot results suggest that when considered as a group, SCI-NP was responsive to treatment irrespective of the location of pain (F1, 44 = 4.82, P = 0.03), with a trend for the greatest reduction occurring in at-level SCI-NP (F1, 44 = 3.18, P = 0.08). These pilot results also potentially implicate cold, innocuous cool, and pressure hypersensitivity at the level of injury in attenuating the benefits of virtual walking to below-level pain, suggesting certain SCI-NP sensory profiles may be less responsive to virtual walking.

  10. Effect of Mas-related gene (Mrg) receptors on hyperalgesia in rats with CFA-induced inflammation via direct and indirect mechanisms.

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    Jiang, Jianping; Wang, Dongmei; Zhou, Xiaolong; Huo, Yuping; Chen, Tingjun; Hu, Fenjuan; Quirion, Rémi; Hong, Yanguo

    2013-11-01

    Mas oncogene-related gene (Mrg) receptors are exclusively distributed in small-sized neurons in trigeminal and dorsal root ganglia (DRG). We investigated the effects of MrgC receptor activation on inflammatory hyperalgesia and its mechanisms. A selective MrgC receptor agonist, bovine adrenal medulla peptide 8-22 (BAM8-22) or melanocyte-stimulating hormone (MSH) or the μ-opioid receptor (MOR) antagonist CTAP was administered intrathecally (i.t.) in rats injected with complete Freund's adjuvant (CFA) in one hindpaw. Thermal and mechanical nociceptive responses were assessed. Neurochemicals were measured by immunocytochemistry, Western blot, ELISA and RT-PCR. CFA injection increased mRNA for MrgC receptors in lumbar DRG. BAM8-22 or MSH, given i.t., generated instant short and delayed long-lasting attenuations of CFA-induced thermal hyperalgesia, but not mechanical allodynia. These effects were associated with decreased up-regulation of neuronal NOS (nNOS), CGRP and c-Fos expression in the spinal dorsal horn and/or DRG. However, i.t. administration of CTAP blocked the induction by BAM8-22 of delayed anti-hyperalgesia and inhibition of nNOS and CGRP expression in DRG. BAM8-22 also increased mRNA for MORs and pro-opiomelanocortin, along with β-endorphin content in the lumbar spinal cord and/or DRG. MrgC receptors and nNOS were co-localized in DRG neurons. Activation of MrgC receptors suppressed up-regulation of pronociceptive mediators and consequently inhibited inflammatory pain, because of the activation of up-regulated MrgC receptors and subsequent endogenous activity at MORs. The uniquely distributed MrgC receptors could be a novel target for relieving inflammatory pain. © 2013 The British Pharmacological Society.

  11. TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice

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    Marie-Claire Delfini

    2013-10-01

    Full Text Available C-low-threshold mechanoreceptors (C-LTMRs are unique among C-unmyelinated primary sensory neurons. These neurons convey two opposite aspects of touch sensation: a sensation of pleasantness, and a sensation of injury-induced mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs. Genetic labeling in combination with electrophysiological recordings show that TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury as well as increased excitability of spinal cord lamina IIi neurons, which could be reversed by intrathecal or bath application of recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity, suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and controls the threshold of somatic sensation.

  12. TAFA4, a chemokine-like protein, modulates injury-induced mechanical and chemical pain hypersensitivity in mice.

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    Delfini, Marie-Claire; Mantilleri, Annabelle; Gaillard, Stéphane; Hao, Jizhe; Reynders, Ana; Malapert, Pascale; Alonso, Serge; François, Amaury; Barrere, Christian; Seal, Rebecca; Landry, Marc; Eschallier, Alain; Alloui, Abdelkrim; Bourinet, Emmanuel; Delmas, Patrick; Le Feuvre, Yves; Moqrich, Aziz

    2013-10-31

    C-low-threshold mechanoreceptors (C-LTMRs) are unique among C-unmyelinated primary sensory neurons. These neurons convey two opposite aspects of touch sensation: a sensation of pleasantness, and a sensation of injury-induced mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs. Genetic labeling in combination with electrophysiological recordings show that TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury as well as increased excitability of spinal cord lamina IIi neurons, which could be reversed by intrathecal or bath application of recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity, suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and controls the threshold of somatic sensation.

  13. The effects of pressure on arthritic knees in a rat model of CFA-induced arthritis.

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    Koo, Sung Tae; Lee, Chang-Hyung; Choi, Hyeunseok; Shin, Yong Il; Ha, Ki Tae; Ye, Hanna; Shim, Hyun Bo

    2013-01-01

    Pain is influenced by weather changes under certain circumstances, and inflammatory pain in animal models is ameliorated by pressure, but the underlying mechanism of atmospheric pressure has not been clearly elucidated. To examine the effect of pressure on pain in an arthritic animal model. Controlled animal study. Laboratory animal study. Following an injection of complete Freund's adjuvant (CFA) into one side of a knee joint, 32 rats were assigned randomly to 2 groups and either placed under 1 or 2.5 atmospheres absolute (ATA) in a hyperbaric chamber for 5 hours. The pain levels were assessed daily for up to 2 weeks post-injection to determine the changes in weight bearing (WB) of the affected limbs. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. After arthritis induction, the rats in the 1 ATA group showed reduced WB of the affected limbs (CFA injection in the 1 ATA group. However, repetitive exposure to 2.5 ATA significantly reduced this ratio in the 2.5 ATA group. Although a sufficient number of samples were used to support the hypothesis that high atmospheric pressure improves a painful condition in this study, an additional larger-scale study will be needed to confirm these findings. Exposure to elevated pressures appears to relieve arthritic pain for extended periods by reducing the inflammatory process and should be considered as a possible alternative pain-reducing therapy.

  14. Women with dysmenorrhea are hypersensitive to experimental deep muscle pain across the menstrual cycle.

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    Iacovides, Stella; Baker, Fiona C; Avidon, Ingrid; Bentley, Alison

    2013-10-01

    Primary dysmenorrhea is a common painful condition in women that recurs every month across the reproductive years. The recurrent nociceptive input into the central nervous system that occurs during menstruation each month in women with dysmenorrhea is hypothesized to lead to increased sensitivity to painful stimuli. We investigated whether women with primary dysmenorrhea are hyperalgesic to deep muscle pain induced by a cleanly nociceptive method of hypertonic saline injection. Pain stimulation was applied both within an area of referred menstrual pain (lower back) and at a remote site outside of referred menstrual pain (forearm) in 12 healthy women with severe dysmenorrhea and 9 healthy women without dysmenorrhea, at 3 phases of the menstrual cycle: menstruation and follicular and luteal phases. Women rated their pain severity on a 100-mm visual analog scale every 30 seconds after injection until the pain subsided. In both groups of women, menstrual cycle phase had no effect on the reported intensity and duration of muscle pain. However, women with dysmenorrhea had increased sensitivity to experimental muscle pain both at the site of referred pain and at a remote nonpainful site, as assessed by peak pain severity visual analog scale rating, area under the visual analog scale curve, and pain duration, compared to women without dysmenorrhea. These data show that women with severe primary dysmenorrhea, who experience monthly menstrual pain, are hyperalgesic to deep muscle pain compared to women without dysmenorrhea. Our findings that dysmenorrheic women are hyperalgesic to a clinically relevant, deep muscle pain in areas within and outside of referred menstrual pain indicates lasting changes in pain sensitivity outside of the painful period during menstruation. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  15. Sleep Fragmentation Hypersensitizes Healthy Young Women to Deep and Superficial Experimental Pain.

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    Iacovides, Stella; George, Kezia; Kamerman, Peter; Baker, Fiona C

    2017-07-01

    The effect of sleep deprivation on pain sensitivity has typically been studied using total and partial sleep deprivation protocols. These protocols do not mimic the fragmented pattern of sleep disruption usually observed in individuals with clinical pain conditions. Therefore, we conducted a controlled experiment to investigate the effect of sleep fragmentation on pain perception (deep pain: forearm muscle ischemia, and superficial pain: graded pin pricks applied to the skin) in 11 healthy young women after 2 consecutive nights of sleep fragmentation, compared with a normal night of sleep. Compared with normal sleep, sleep fragmentation resulted in significantly poorer sleep quality, morning vigilance, and global mood. Pin prick threshold decreased significantly (increased sensitivity), as did habituation to ischemic muscle pain (increased sensitivity), over the course of the 2 nights of sleep fragmentation compared with the night of normal sleep. Sleep fragmentation did not increase the maximum pain intensity reported during muscle ischemia (no increase in gain), and nor did it increase the number of spontaneous pains reported by participants. Our data show that sleep fragmentation in healthy, young, pain-free women increases pain sensitivity in superficial and deep tissues, indicating a role for sleep disruption, through sleep fragmentation, in modulating pain perception. Our findings that pain-free, young women develop hyperalgesia to superficial and deep muscle pain after short-term sleep disruption highlight the need for effective sleep management strategies in patients with pain. Findings also suggest the possibility that short-term sleep disruption associated with recurrent acute pain could contribute to increased risk for future chronic pain conditions. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  16. Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model.

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    Gao, Yong-Jing; Cheng, Jen-Kun; Zeng, Qing; Xu, Zhen-Zhong; Decosterd, Isabelle; Xu, Xiaoyin; Ji, Ru-Rong

    2009-09-01

    Cancer pain significantly affects the quality of cancer patients, and current treatments for this pain are limited. C-Jun N-terminal kinase (JNK) has been implicated in tumor growth and neuropathic pain sensitization. We investigated the role of JNK in cancer pain and tumor growth in a skin cancer pain model. Injection of luciferase-transfected B16-Fluc melanoma cells into a hindpaw of mouse induced robust tumor growth, as indicated by increase in paw volume and fluorescence intensity. Pain hypersensitivity in this model developed rapidly (Tumor growth was associated with JNK activation in tumor mass, dorsal root ganglion (DRG), and spinal cord and a peripheral neuropathy, such as loss of nerve fibers in the hindpaw skin and induction of ATF-3 expression in DRG neurons. Repeated systemic injections of D-JNKI-1 (6 mg/kg, i.p.), a selective and cell-permeable peptide inhibitor of JNK, produced an accumulative inhibition of mechanical allodynia and heat hyperalgesia. A bolus spinal injection of D-JNKI-1 also inhibited mechanical allodynia. Further, JNK inhibition suppressed tumor growth in vivo and melanoma cell proliferation in vitro. In contrast, repeated injections of morphine (5 mg/kg), a commonly used analgesic for terminal cancer, produced analgesic tolerance after 1 day and did not inhibit tumor growth. Our data reveal a marked peripheral neuropathy in this skin cancer model and important roles of the JNK pathway in cancer pain development and tumor growth. JNK inhibitors such as D-JNKI-1 may be used to treat cancer pain.

  17. Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

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    Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

    2013-06-15

    Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1

  18. Long lasting pain hypersensitivity following ligation of the tendon of the masseter muscle in rats: A model of myogenic orofacial pain

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    Dubner Ronald

    2010-07-01

    Full Text Available Abstract Background A major subgroup of patients with temporomandibular joint (TMJ disorders have masticatory muscle hypersensitivity. To study myofacial temporomandibular pain, a number of preclinical models have been developed to induce myogenic pain of the masseter muscle, one of the four muscles involved in mastication. The currently used models, however, generate pain that decreases over time and only lasts from hours to weeks and hence are not suitable for studying chronicity of the myogenic pain in TMJ disorders. Here we report a model of constant myogenic orofacial pain that lasts for months. Results The model involves unilateral ligation of the tendon of the anterior superficial part of the rat masseter muscle (TASM. The ligation of the TASM was achieved with two chromic gut (4.0 ligatures via an intraoral approach. Nocifensive behavior of the rat was assessed by probing the skin site above the TASM with a series of von Frey filaments. The response frequencies were determined and an EF50 value, defined as the von Frey filament force that produces a 50% response frequency, was derived and used as a measure of mechanical sensitivity. Following TASM ligation, the EF50 of the injured side was significantly reduced and maintained throughout the 8-week observation period, suggesting the presence of mechanical hyperalgesia/allodynia. In sham-operated rats, the EF50 of the injured side was transiently reduced for about a week, likely due to injury produced by the surgery. Somatotopically relevant Fos protein expression was indentified in the subnucleus caudalis of the spinal trigeminal sensory complex. In the same region, persistent upregulation of NMDA receptor NR1 phosphorylation and protein expression and increased expression of glial markers glial fibrillary acidic protein (astroglia and CD11b (microglia were found. Morphine (0.4-8 mg/kg, s.c. and duloxetine (0.4-20 mg/kg, i.p., a selective serotonin-norepinephrine reuptake inhibitor

  19. Selective class I histone deacetylase inhibitors suppress persistent spontaneous nociception and thermal hypersensitivity in a rat model of bee venom-induced inflammatory pain.

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    Yang, Fan; Yang, Yan; Wang, Yan; Yang, Fei; Li, Chun-Li; Wang, Xiao-Liang; Li, Zhen; Chen, Jun

    2015-10-25

    To confirm whether class I histone deacetylase inhibitors (HDACIs) are effective in relief of peripheral inflammatory pain, the effects of two selective inhibitors, MS-275 and MGCD0103, were studied in rats inflamed by subcutaneous (s.c.) injection of bee venom (BV). The BV test is characterized by displaying both persistent spontaneous nociception (PSN) and primary hypersensitivity. Intrathecal (i.t.) pre-treatment of either MS-275 or MGCD0103 with a single dose of 60 nmol/20 μL resulted in profound suppression of both PSN and primary thermal hypersensitivity but without significant influence upon the primary mechanical hypersensitivity and mirror-image thermal hypersensitivity. Moreover, the up-regulation of both HDAC1 and HDAC2 induced by s.c. BV injection was completely suppressed by i.t. pre-treatment of MS-275. The present results provide with another new line of evidence showing involvement of epigenetic regulation of chromatin structure by HDAC1/2-mediated histone hypoacetylation in the BV-induced PSN and thermal hypersensitivity and demonstrate the beneficial effects of class I HDACIs in prevention of peripheral inflammatory pain from occurring.

  20. Can widespread hypersensitivity in carpal tunnel syndrome be substantiated if neck and arm pain are absent?

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    Schmid, A B; Soon, B T C; Wasner, G; Coppieters, M W

    2012-02-01

    Recent studies demonstrated that patients with carpal tunnel syndrome (CTS) have signs of thermal and mechanical hyperalgesia in extra-median territories suggesting an involvement of central pain mechanisms. As previous studies included patients with shoulder/arm symptoms or neck pain, a potential influence of these coexisting disorders cannot be excluded. This study therefore evaluated whether widespread sensory changes (hypoesthesia or hyperalgesia) are present in patients with unilateral CTS in the absence of coexisting disorders. Twenty-six patients with unilateral CTS with symptoms localised to their hand and 26 healthy controls participated in the study. A comprehensive quantitative sensory testing (QST) protocol including thermal and mechanical detection and pain thresholds was performed over the hands (median, ulnar and radial innervation area), lateral elbows, neck and tibialis anterior muscle. Patients with CTS demonstrated thermal and mechanical hypoesthesia in the hand but not at distant sites. Thermal or mechanical hyperalgesia was not identified at any location with traditional QST threshold testing. However, patients with CTS rated the pain during thermal pain testing significantly higher than healthy participants. This was especially apparent for heat pain ratings which were elevated not only in the affected hand but also in the neck and tibialis anterior muscle. In conclusion, CTS alone in the absence of coexisting neck and arm pain does not account for sensory changes outside the affected hand as determined by traditional QST threshold testing. Elevated pain ratings may however be an early indication of central pain mechanisms.

  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

    2016-08-01

    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. Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans.

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    Benson, Sven; Kattoor, Joswin; Wegner, Alexander; Hammes, Florian; Reidick, Daniel; Grigoleit, Jan-Sebastian; Engler, Harald; Oberbeck, Reiner; Schedlowski, Manfred; Elsenbruch, Sigrid

    2012-04-01

    Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean ± standard error of the mean age 26.6 ± 1.1 years) received an intravenous injection of either lipopolysaccharide (LPS; 0.4 ng/kg) or saline on 2 otherwise identical study days. Blood samples were collected 15 min before and 1, 2, 3, 4, and 6h after injection to characterize changes in immune parameters including proinflammatory cytokines. Rectal sensory and pain thresholds and subjective pain ratings were assessed with barostat rectal distensions 2h after injection. LPS administration induced an acute inflammatory response indicated by transient increases in tumor necrosis factor alpha, interleukin 6, and body temperature (all Pvisceral sensory and pain thresholds (both PVisceral stimuli were rated as more unpleasant (PPain thresholds correlated with interleukin 6 at +1h (r=0.60, Pvisceral sensory and pain thresholds and altered subjective pain ratings. Our results support the relevance of inflammatory processes in the pathophysiology of visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication pathways in gastrointestinal disorders. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

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    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.

  4. Nitrous Oxide Persistently Alleviates Pain Hypersensitivity in Neuropathic Rats: A Dose-Dependent Effect

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    Meric Ben Boujema

    2015-01-01

    Full Text Available BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR. The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury.

  5. Presynaptically localized cyclic GMP-dependent protein kinase 1 is a key determinant of spinal synaptic potentiation and pain hypersensitivity.

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    Ceng Luo

    Full Text Available Synaptic long-term potentiation (LTP at spinal neurons directly communicating pain-specific inputs from the periphery to the brain has been proposed to serve as a trigger for pain hypersensitivity in pathological states. Previous studies have functionally implicated the NMDA receptor-NO pathway and the downstream second messenger, cGMP, in these processes. Because cGMP can broadly influence diverse ion-channels, kinases, and phosphodiesterases, pre- as well as post-synaptically, the precise identity of cGMP targets mediating spinal LTP, their mechanisms of action, and their locus in the spinal circuitry are still unclear. Here, we found that Protein Kinase G1 (PKG-I localized presynaptically in nociceptor terminals plays an essential role in the expression of spinal LTP. Using the Cre-lox P system, we generated nociceptor-specific knockout mice lacking PKG-I specifically in presynaptic terminals of nociceptors in the spinal cord, but not in post-synaptic neurons or elsewhere (SNS-PKG-I(-/- mice. Patch clamp recordings showed that activity-induced LTP at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG was completely abolished in SNS-PKG-I(-/- mice, although basal synaptic transmission was not affected. Analyses of synaptic failure rates and paired-pulse ratios indicated a role for presynaptic PKG-I in regulating the probability of neurotransmitter release. Inositol 1,4,5-triphosphate receptor 1 and myosin light chain kinase were recruited as key phosphorylation targets of presynaptic PKG-I in nociceptive neurons. Finally, behavioural analyses in vivo showed marked defects in SNS-PKG-I(-/- mice in several models of activity-induced nociceptive hypersensitivity, and pharmacological studies identified a clear contribution of PKG-I expressed in spinal terminals of nociceptors. Our results thus indicate that presynaptic mechanisms involving an increase in release probability from nociceptors are

  6. Acquiring the optimal time for hyperbaric therapy in the rat model of CFA induced arthritis.

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    Koo, Sung Tae; Lee, Chang-Hyung; Shin, Yong Il; Ko, Hyun Yoon; Lee, Da Gyo; Jeong, Han-Sol

    2014-01-01

    We previously published an article about the pressure effect using a rheumatoid animal model. Hyperbaric therapy appears to be beneficial in treating rheumatoid arthritis (RA) by reducing the inflammatory process in an animal model. In this sense, acquiring the optimal pressure-treatment time parameter for RA is important and no optimal hyperbaric therapy time has been suggested up to now. The purpose of our study was to acquire the optimal time for hyperbaric therapy in the RA rat model. Controlled animal study. Following injection of complete Freund's adjuvant (CFA) into one side of the knee joint, 32 rats were randomly assigned to 3 different time groups (1, 3, 5 hours a day) under 1.5 atmospheres absolute (ATA) hyperbaric chamber for 12 days. The pain levels were assessed daily for 2 weeks by weight bearing force (WBF) of the affected limb. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. The reduction of WBF was high at 2 days after injection and then it was spontaneously increased up to 14 days in all 3 groups. There were significant differences of WBF between 5 hours and control during the third through twelfth days, between 3 hours and control during the third through fifth and tenth through twelfth days, and between 3 hours and 5 hours during the third through seventh days (P CFA injection in all groups compared to the initial findings, however, the 3 hour group showed a smaller MMP-9/MMP-2 ratio than the control group. Although enough samples were used for the study to support our hypothesis, more samples will be needed to raise the validity and reliability. The effect of hyperbaric treatment appears to be dependent upon the elevated therapy time under 1.5 ATA pressure for a short period of time; however, the long-term effects were similar in all pressure groups. Further study will be needed to acquire the optimal pressure-treatment parameter relationship in various conditions for

  7. 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

  8. Effect of new polyherbal formulations DF1911, DF2112 and DF2813 on CFA induced inflammation in rat model.

    Science.gov (United States)

    Nagarkar, Bhagyashri; Jagtap, Suresh

    2017-04-04

    Aim of the present study was to evaluate anti-inflammatory activity of newly developed polyherbal formulations DF1911, DF2112 and DF2813. These newly developed formulations are modifications of Dashamoola, a well known Ayurvedic formulation, along with addition of new plants. Complete Freund's adjuvant (CFA) induced inflammation in rat was used as an experimental model. Effects of the treatment in rats were monitored by physiological and biochemical parameters, histopathology and through gene expression studies. Diclofenac sodium showed maximum percentage inhibition (56.8 ± 3.5%) of paw edema followed by Dashamoola Kwatha (19.9 ± 1.8%). Among test formulations treated groups, DF1911 at 250 mg/kg bw (48.2 ± 5.4%, p CFA rats were normalized after treatment with test formulations. Results of serum markers and histopathological observations also supported the activity of formulations. Increased MDA levels in liver tissue of CFA injected animals significantly (p < 0.05) decreased by Diclofenac sodium and test formulation treated groups. DF1911, DF2112 and DF2813 showed down-regulation of IL1-β (~6.4-fold, ~5.2-fold and ~7.6-fold), IL-6 (~1.1-fold, ~1.6-fold and ~1.9-fold), TNF-α (~2.0-fold, ~4.6-fold and ~3.5-fold), and iNOS (~1.2-fold, ~1.8-fold and ~1.1-fold) in inflamed paw tissue compared to negative control group, respectively. The anti-inflammatory effects of DF1911 and DF2112 in rats were significantly higher than the Dashamoola Kwatha and are comparable to Diclofenac sodium.

  9. 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.

  10. 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...

  11. Involvement of PKA-dependent upregulation of nNOS-CGRP in adrenomedullin-initiated mechanistic pathway underlying CFA-induced response in rats.

    Science.gov (United States)

    Wang, Dongmei; Ruan, Liqin; Hong, Yanguo; Chabot, Jean-Guy; Quirion, Rémi

    2013-01-01

    We have previously shown that intrathecal administration of the adrenomedullin (AM) receptor antagonist AM(22-52) produces a long-lasting anti-hyperalgesia effect. This study examined the hypothesis that AM recruits other pronociceptive mediators in complete Freund's adjuvant (CFA)-induced inflammation. Injection of CFA in the hindpaw of rat produced an increase in the expression of nNOS in dorsal root ganglion (DRG) and the spinal dorsal horn. An intrathecal administration of AM(22-52), but not the CGRP antagonist BIBN4096BS, abolished the CFA-induced increase of nNOS. Moreover, AM-induced increase of CGRP was inhibited by the nNOS inhibitors L-NAME and 7-nitroindazole in cultured ganglion explants. Addition of AM to ganglion cultures induced an increase in nNOS protein, which was attenuated by the PKA inhibitor H-89. Treatment with AM also concentration-dependently increased cAMP content and pPKA protein level, but not its non-phosphorylated form, in cultured ganglia. In addition, nNOS was shown to be co-localized with the AM receptor components calcitonin receptor-like receptor and receptor activity-modifying protein 2- and 3 in DRG neurons. The present study suggests that the enhanced activity of nitric oxide (NO) mediates the biological action of AM at the spinal level and that AM recruits NO-CGRP via cAMP/PKA signaling in a mechanistic pathway underlying CFA-induced hyperalgesia. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Antisense-mediated knockdown of Na(V1.8, but not Na(V1.9, generates inhibitory effects on complete Freund's adjuvant-induced inflammatory pain in rat.

    Directory of Open Access Journals (Sweden)

    Yao-Qing Yu

    Full Text Available Tetrodotoxin-resistant (TTX-R sodium channels Na(V1.8 and Na(V1.9 in sensory neurons were known as key pain modulators. Comparing with the widely reported Na(V1.8, roles of Na(V1.9 on inflammatory pain are poorly studied by antisense-induced specific gene knockdown. Here, we used molecular, electrophysiological and behavioral methods to examine the effects of antisense oligodeoxynucleotide (AS ODN targeting Na(V1.8 and Na(V1.9 on inflammatory pain. Following complete Freund's adjuvant (CFA inflammation treatment, Na(V1.8 and Na(V1.9 in rat dorsal root ganglion (DRG up-regulated mRNA and protein expressions and increased sodium current densities. Immunohistochemical data demonstrated that Na(V1.8 mainly localized in medium and small-sized DRG neurons, whereas Na(V1.9 only expressed in small-sized DRG neurons. Intrathecal (i.t. delivery of AS ODN was used to down-regulate Na(V1.8 or Na(V1.9 expressions confirmed by immunohistochemistry and western blot. Unexpectedly, behavioral tests showed that only Na(V1.8 AS ODN, but not Na(V1.9 AS ODN could reverse CFA-induced heat and mechanical hypersensitivity. Our data indicated that TTX-R sodium channels Na(V1.8 and Na(V1.9 in primary sensory neurons played distinct roles in CFA-induced inflammatory pain and suggested that antisense oligodeoxynucleotide-mediated blocking of key pain modulator might point toward a potential treatment strategy against certain types of inflammatory pain.

  13. KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Warfvinge, K; Kruse, L S

    2016-01-01

    modify the neurogenic inflammatory response in the trigeminal ganglion. METHODS: Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were...... investigated using immunohistochemistry and Western blot. FINDINGS: Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. CONCLUSIONS...

  14. Activation of the RAGE/STAT3 Pathway in the Dorsal Root Ganglion Contributes to the Persistent Pain Hypersensitivity Induced by Lumbar Disc Herniation.

    Science.gov (United States)

    Zhang, Xin-Sheng; Li, Xiao; Luo, Hai-Jie; Huang, Zhu-Xi; Liu, Cui-Cui; Wan, Qing; Xu, Shu-Wei; Wu, Shao-Ling; Ke, Song-Jian; Ma, Chao

    2017-07-01

    Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy. The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH. Controlled animal study. University laboratory. After LDH induced by implantation of autologous nucleus pulposus (NP, harvested from animal tail) on the left L5 nerve root was established, mechanical thresholds and electrophysiological tests were conducted at relevant time points during an observation period of 28 days. Protein levels and localization of RAGE and p-STAT3 were performed by using Western blotting and immunohistochemistry, respectively. LDH induced persistent pain hypersensitivity, increased excitability of DRG neurons, and upregulated the expression of RAGE and p-STAT3 in the DRG. Consecutive injection of both RAGE antagonist FPS-ZM1 (i.t.) and STAT3 activity inhibitor S3I-201 (i.t.) inhibited the enhanced excitability of DRG neurons and mechanical allodynia induced by NP implantation. Furthermore, local knockdown of STAT3 by intrathecal injection of AAV-Cre-GFP into STAT3flox/flox mice markedly alleviated NP implantation-induced mechanical allodynia in mice. Importantly, the expression of p-STAT3 was colocalized with that of RAGE in the DRG and inhibition of RAGE with FPS-ZM1 prevented NP implantation-induced STAT3 activation. More underlying mechanism(s) of the role of the RAGE/STAT3 pathway on the formation and development of persistent pain hypersensitivity induced by LDH will be needed to be explored in future research. These findings suggest activation of the RAGE/STAT3 pathway plays a critical role in persistent pain induced by LDH, and this pathway may represent novel therapeutic targets for the treatment of LDH

  15. Extracellular signal-regulated protein kinase activation in spinal cord contributes to pain hypersensitivity in a mouse model of type 2 diabetes.

    Science.gov (United States)

    Xu, Xiang; Chen, Hui; Ling, Bing-Yu; Xu, Lan; Cao, Hong; Zhang, Yu-Qiu

    2014-02-01

    Painful peripheral neuropathy is a common complication of diabetes mellitus. The symptom of pain can become a major factor that decreases the quality of life of patients with diabetes, while effective treatment is lacking. In the present study, we aimed to investigate the changes of pain threshold in the early stage of diabetes in db/db mice, an animal model of type 2 diabetes mellitus, and the underlying molecular mechanisms. We found that (1) db/db mice (with a leptin receptor-null mutation and characterized by obesity and hyperglycemia) showed hypersensitivity to mechanical and thermal stimuli at the early stage of diabetes; (2) phosphorylated extracellular signal-regulated kinase (pERK), but not total ERK in the spinal cord and dorsal root ganglia in db/db mice significantly increased compared with wild-type mice. The increased pERK immunoreactivity occurred in both NeuN-expressing neurons and GFAP-expressing astrocytes, but not in Iba-1-expressing microglia; (3) both single and consecutive (for 5 days) intrathecal injections of U0126 (2 nmol per day), a selective MEK (an ERK kinase) inhibitor beginning at 8 weeks of age, attenuated the bilateral mechanical allodynia in the von-Frey test and heat hyperalgesia in Hargreave's test; and (4) db/db mice also displayed increased nocifensive behavior during the formalin test, and this was blocked by intrathecal injection of U0126. Also, the expression of pERK1 and pERK2 was upregulated following the formalin injection. Our results suggested that the activation of ERK in spinal neurons and astrocytes is correlated with pain hypersensitivity of the type 2 diabetes animal model. Inhibiting the ERK pathway may provide a new therapy for pain control in type 2 diabetes.

  16. Widespread Pressure Pain Hypersensitivity Is Similar in Women With Frequent Episodic and Chronic Tension-Type Headache: A Blinded Case-Control Study.

    Science.gov (United States)

    Palacios Ceña, María; Castaldo, Matteo; Kelun Wang; Torelli, Paola; Pillastrini, Paolo; Fernández-de-Las-Peñas, César; Arendt-Nielsen, Lars

    2017-02-01

    To investigate differences in widespread pressure pain hyperalgesia in the trigemino-cervical and extra-trigeminal (distant pain-free) regions in women with frequent episodic (FETTH) and chronic (CTTH) tension-type headache. It seems that people with tension-type headache exhibit central sensitization. No study has investigated differences between FETTH and CTTH in terms of widespread pressure pain hypersensitivity. Forty-three women with FETTH, 42 with CTTH, and 45 women without headache diagnosis were recruited. Pressure pain thresholds (PPTs) were bilaterally assessed over trigeminal area (ie, temporalis muscle), extra-trigeminal (ie, C5/C6 zygapophyseal joint), and two distant points (ie, second metacarpal and tibialis anterior muscle) by a blinded assessor. Clinical features of the headache were collected with a 4-week headache diary. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). The ANCOVA revealed that PPTs were significantly decreased bilaterally over trigeminal (mean differences ranging from 97.5 to 101.5 kPa), extra-trigeminal (from 94.3 to 114.5 kPa), and distant points (from 99.4 to 208.6 kPa) in both FETTH and CTTH groups compared with controls (all, P  .217). Anxiety (all, P > .803) or depression (P > .206) did not influence pressure pain hyperalgesia. No associations between widespread pressure hypersensitivity and headache features were observed (all, P > .110). Current results suggest the presence of similar local and widespread pressure hyperalgesia, not associated with anxiety or depression, in women with FETTH and CTTH supporting that localized and central manifestations are involved in both the episodic and chronic forms of tension-type headache. © 2016 American Headache Society.

  17. 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.

  18. Effects of a non-selective TRPC channel blocker, SKF-96365, on melittin-induced spontaneous persistent nociception and inflammatory pain hypersensitivity

    Institute of Scientific and Technical Information of China (English)

    Jing Ding; Jia-Rui Zhang; Yan Wang; Chun-Li Li; Dan Lu; Su-Min Guan; Jun Chen

    2012-01-01

    Objective Melittin is the main peptide in bee venom and causes both persistent spontaneous nociception and pain hypersensitivity.Our recent studies indicated that both transient receptor potential (TRP) vanilloid receptor 1 (TRPV1) and canonical TRPs (TRPCs) are involved in mediating the melittin-induced activation of different subpopulations of primary nociceptive cells.Here,we further determined whether TRPC channels are involved in melittin-induced inflammatory nociceptive responses in behavioral assays.Methods The anti-nociceptive and anti-hyperalgesic effects of localized peripheral administration of three doses of the non-selective TRPC antagonist,SKF-96365 (1-{β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenyl}-1H-imidazole hydrochloride),were evaluated in melittin tests.Pain-related behaviors were rated by counting the number of paw flinches,and measuring paw withdrawal thermal latency (s) and paw withdrawl mechanical threshold (g),over a 1-h time-course.Results Localized peripheral SKF-96365 given before melittin prevented,and given after melittin significantly suppressed,the melittin-evoked persistent spontaneous nociception.Pre-blockade and post-suppression of activation of primary nociceptive activity resulted in decreased hypersensitivity to both thermal and mechanical stimuli applied to the primary injury site of the ipsilateral hindpaw,despite dose-effect differences between thermal and mechanical hyperalgesia.However,local administration of SKF-96365 into the contralateral hindpaw had no significant effect on any pain-associated behaviors.In addition,SKF-96365 had no effect on baseline threshold for either thermal or mechanical sensitivity under normal conditions.Conclusion Besides TRPV1,SKF-96365-sensitive TRPC channels might also be involved in the pathophysiological processing of melittin-induced inflammatory pain and hypersensitivity.Therapeutically,SKF-96365 is equally effective in preventing primary thermal and mechanical hyperalgesia as well as

  19. 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.

  20. CXCL12/CXCR4 chemokine signaling in spinal glia induces pain hypersensitivity through MAPKs-mediated neuroinflammation in bone cancer rats.

    Science.gov (United States)

    Hu, Xue-Ming; Liu, Yan-Nan; Zhang, Hai-Long; Cao, Shou-Bin; Zhang, Ting; Chen, Li-Ping; Shen, Wen

    2015-02-01

    The activation of MAPK pathways in spinal cord and subsequent production of proinflammatory cytokines in glial cells contribute to the development of spinal central sensitization, the basic mechanism underlying bone cancer pain (BCP). Our previous study showed that spinal CXCL12 from astrocytes mediates BCP generation by binding to CXCR4 in both astrocyters and microglia. Here, we verified that CXCL12/CXCR4 signaling contributed to BCP through a MAPK-mediated mechanism. In naïve rats, a single intrathecal administration of CXCL12 considerably induced pain hyperalgesia and phosphorylation expression of spinal MAPK members (including extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase), which could be partially prevented by pre-treatment with CXCR4 inhibitor AMD3100. This CXCL12-induced hyperalgesia was also reduced by MAPK inhibitors. In bone cancer rats, tumor cell inoculation into the tibial cavity caused prominent and persistent pain hyperalgesia, and associated with up-regulation of CXCL12 and CXCR4, activation of glial cells, phosphorylation of MAPKs, and production of proinflammatory cytokines in the spinal cord. These tumor cell inoculation-induced behavioral and neurochemical alterations were all suppressed by blocking CXCL12/CXCR4 signaling or MAPK pathways. Taken together, these results demonstrate that spinal MAPK pathways mediated CXCL12/CXCR4-induced pain hypersensitivity in bone cancer rats, which could be druggable targets for alleviating BCP and glia-derived neuroinflammation. Following tumor cell inoculation, chemokine CXCL12 from astrocytes spreads around the spinal environment, resulting in functional activation of CXCR4-expressing astrocytes and microglia. Once glia are activated, they may initiate MAPK (mitogen-activated protein kinase) pathways, and subsequently produce proinflammatory cytokines and chemokines. Among them, CXCL12 could reinforce the astrocytic and microglial activation in autocrine and paracrine manners

  1. HCN1 and HCN2 in Rat DRG neurons: levels in nociceptors and non-nociceptors, NT3-dependence and influence of CFA-induced skin inflammation on HCN2 and NT3 expression.

    Science.gov (United States)

    Acosta, Cristian; McMullan, Simon; Djouhri, Laiche; Gao, Linlin; Watkins, Roger; Berry, Carol; Dempsey, Katherine; Lawson, Sally N

    2012-01-01

    cutaneous inflammation (CFA-induced) and recovered by 4 days. This could contribute to acute inflammatory pain. HCN2-immunostaining in large neurons decreased 4 days after CFA, when NT3 was decreased in the DRG. Thus HCN2-expression control differs between large and small neurons.

  2. 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.

  3. Intra-articular injection of Botulinum toxin A reduces neurogenic inflammation in CFA-induced arthritic rat model.

    Science.gov (United States)

    Wang, Lin; Wang, Kaile; Chu, Xiao; Li, Tieshan; Shen, Nana; Fan, Chenglei; Niu, Zhenyuan; Zhang, Xiaochen; Hu, Luoman

    2017-02-01

    Currently, administration of Botulinum toxin Type A (BoNT/A) to treat arthritic pain has promising efficacy in clinical research. However, the mechanisms underlying anti-neurogenic inflammation mediated by BoNT/A remains unclear. The aim of this study was to demonstrate the effectiveness in macro and micro levels and to explore the causal mechanism of BoNT/A. Wistar rats (n = 60) were injected with 50ul complete Freund's adjuvant (CFA) in the left ankle joint capsule to establish a model of chronic monoarthritis. Pain behaviour (Evoked pain assessment) and infrared thermal imaging testing were performed at the macroscopic level to assess the effectiveness of analgesia and anti-inflammation. Western blotting and immunofluorescence staining were used at the microscopic level in an attempt to determine the mechanisms of anti-nociceptive or anti-inflammatory effects of BoNT/A. Additionally, hematoxylin-eosin staining was also used to visualise the cartilage and the synovial degenerative conditions of arthritis. By comparing the outcome of the evoked pain test and immunofluorescence staining, there was a significant improvement in BoNT/A compared with the normal saline (NS) injected control group. In addition, thermal variations showed that the temperature of ipsilateral ankle joint increased between 1 and 2 weeks following injection of CFA, but decreased after 3 weeks (still above the contralateral side). However, the temperature showed no difference between the BoNT/A group and NS group after treatment. The expression of IL-1β or TNF-α in the ankle synovial tissue was significantly decreased in the BoNT/A group compared to the NS group (p < 0.05). Based on the HE assessment, cartilage degeneration and infiltration of inflammatory cells in the BoNT/A group was alleviated compared to the NS group after treatment. In conclusion, we proposed the hypothesis that intra-articular BoNT/A administration does play an important role in anti-neurogenic inflammation. The

  4. Curcumin attenuates CFA induced thermal hyperalgesia by modulation of antioxidant enzymes and down regulation of TNF-α, IL-1β and IL-6.

    Science.gov (United States)

    Singh, Ajeet Kumar; Vinayak, Manjula

    2015-03-01

    Reactive oxygen species are signaling mediators of nociceptive pathways. Exogenous administrations of antioxidants show anti-hyperalgesic effect. However, very little is known about the role of endogenous antioxidant defense system in pain pathology. Curcumin is a dietary antioxidant which shows ameliorative effect on thermal hypersensitivity, however detailed study is lacking. Present study was aimed to analyze the changes in oxidative stress, modulation of antioxidant enzymes and pro-inflammatory cytokines in complete Freund's adjuvant induced inflammatory hyperalgesia and the effect of curcumin on antioxidant defense system and pro-inflammatory cytokines. Anti-hyperalgesic activity of curcumin was evidenced after 6 h of treatment. Oxidative stress was evidenced in paw skin and spinal cord of hyperalgesic rats by high level of lipid peroxidation. A decrease in activity of antioxidant enzymes like catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and an increase in level of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in paw skin was observed as compared to normal rats. However, activity of antioxidant enzymes was enhanced in spinal cord. The changes were brought towards normal level after curcumin treatment. The results suggest that modulation of antioxidant defense system is early event in initiation of inflammatory hyperalgesia which might lead to initiation of other signaling pathways mediated by lipid peroxide, TNF-α, IL-1β and IL-6. Decrease in oxidative stress and down regulation of these cytokines by curcumin is suggested to be involved in its anti-hyperalgesic effect.

  5. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na⁺ channels.

    Science.gov (United States)

    Abbas, Najwa; Gaudioso-Tyzra, Christelle; Bonnet, Caroline; Gabriac, Mélanie; Amsalem, Muriel; Lonigro, Aurélie; Padilla, Françoise; Crest, Marcel; Martin-Eauclaire, Marie-France; Delmas, Patrick

    2013-08-01

    Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins' effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5 nM and 1 μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8 nM and 1.76 μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. Suppression of KCNQ/M (Kv7) potassium channels in the spinal cord contributes to the sensitization of dorsal horn WDR neurons and pain hypersensitivity in a rat model of bone cancer pain.

    Science.gov (United States)

    Cai, Jie; Fang, Dong; Liu, Xiao-Dan; Li, Song; Ren, Juan; Xing, Guo-Gang

    2015-03-01

    Primary and metastatic cancers that affect bones are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. In the present study, we investigated whether inhibition of KCNQ/M (Kv7) potassium channels in the spinal cord contributes to the development of bone cancer pain via sensitization of dorsal horn wide dynamic range (WDR) neurons. Using a rat model of bone cancer pain based on intratibial injection of MRMT-1 tumor cells, we observed a significant increase in C-fiber responses of dorsal horn WDR neurons in the MRMT-1 injected rats, indicating sensitization of spinal WDR neurons in bone cancer rats. Furthermore, we discovered that blockade of KCNQ/M channels in the spinal cord by local administration of XE-991, a specific KCNQ/M channel blocker, caused a robust increase in excitability of dorsal horn WDR neurons, while, producing obvious pain hypersensitivity in normal rats. On the contrary, activation of spinal KCNQ/M channels by retigabine, a selective KCNQ/M channel opener, not only inhibited the bone cancer‑induced hyperexcitability of dorsal horn WDR neurons, but also alleviated mechanical allodynia and thermal hyperalgesia in the bone cancer rats, while all of these effects of retigabine could be blocked by KCNQ/M-channel antagonist XE-991. All things considered, these results suggest that suppression of KCNQ/M channels in the spinal cord likely contributes to the development of bone cancer pain via sensitization of dorsal horn WDR neurons in rats following tumor cell inoculation.

  7. KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion.

    Science.gov (United States)

    Lukács, M; Warfvinge, K; Kruse, L S; Tajti, J; Fülöp, F; Toldi, J; Vécsei, L; Edvinsson, L

    2016-12-01

    Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.

  8. 雷莫司琼降低幼鼠内脏痛觉敏感性%Ramosetron decrease visceral pain hypersensitivity in young rats

    Institute of Scientific and Technical Information of China (English)

    林希; 杨帆; 吴斌; 张晓燕; 林春

    2012-01-01

    AIM: To explore the effects of 5-HT3 receptor antagonist ramosetron on young rats of visceral hypersensitivity by the methods of behavior and electrophysiology research. METHODS: Colorectal irritation (CD stimulation in neonatal period was used to establish the model of visceral hypersensitivity in young rats. 32 neonatal rats were divided into four groups by 2×2 factorial design with each 8. Group A, B1 was imposed on CI at neonatal period and imposed on ramosetron intraperitoneal injection in 15-21 day; Group A1B2 was imposed on CI at neonatal period and not imposed on ramosetron intraperitoneal injection; Group A2B1 was not imposed on CI at neonatal period and imposed on ramosetron intraperitoneal injection; Group A2B2 was not imposed on CI at neonatal period and not imposed on ramosetron intraperitoneal injection. Then, conventionally breeding till the young period (6-week age), abdonminal withdrawal reflex (AWR) , pain thresholds and spike external oblique muscle of abdomen (EOMA) were used to evaluate visceral pain hypersensitivity. RESULTS: he pain thresholds in young rats were affected both by CI at neonatal period and using ramosetron in 15-21 days. In group A1B2 which imposed on CI at neonatal period, the pain thresholds decreased 11. 56 mm Hg. In group A1B1 which imposed on CI at neonatal period and imposed on ramosetron in 15-21 day, the pain thresholds increased 9.06 mm Hg, while the AWR scores and EOMA were decreased. Future more, there are interaction effects between the two factors. There were a significant main effect for AWR scores at different pressures and a significant main effect for EOMA at different pressures. CONCLUSION: 5-HT3 receptor antagonist ramosetron can decrease visceral hypersensitivity in young rats.%目的:采用行为学和电生理学评价方法,探讨应用5-羟色胺3 (5-HT3)受体拮抗剂雷莫司琼对幼鼠内脏痛觉敏感性影响.方法:新生期反复结直肠刺激(colorectal irritation,CI)建立幼鼠

  9. Copper hypersensitivity.

    Science.gov (United States)

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

    2014-10-01

    The world production of copper is steadily increasing. Although humans are widely exposed to copper-containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper 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. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions.

  10. 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....

  11. NR2B phosphorylation at tyrosine 1472 in spinal dorsal horn contributed to N-methyl-D-aspartate-induced pain hypersensitivity in mice.

    Science.gov (United States)

    Li, Shuai; Cao, Jing; Yang, Xian; Suo, Zhan-Wei; Shi, Lei; Liu, Yan-Ni; Yang, Hong-Bin; Hu, Xiao-Dong

    2011-11-01

    Calcium influx via N-methyl-D-aspartate (NMDA)-subtype glutamate receptors (NMDARs) regulates the intracellular trafficking of NMDARs, leading to long-lasting modification of NMDAR-mediated synaptic transmission that is involved in development, learning, and synaptic plasticity. The present study investigated the contribution of such NMDAR-dependent synaptic trafficking in spinal dorsal horn to the induction of pain hypersensitivity. Our data showed that direct activation of NMDARs by intrathecal NMDA application elicited pronounced mechanical allodynia in intact mice, which was concurrent with a specific increase in the abundance of NMDAR subunits NR1 and NR2B at the postsynaptic density (PSD)-enriched fraction. Selective inhibition of NR2B-containing NMDARs (NR2BR) by ifenprodil dose dependently attenuated the mechanical allodynia in NMDA-injected mice, suggesting the importance of NR2BR synaptic accumulation in NMDA-induced pain sensitization. The NR2BR redistribution at synapses after NMDA challenge was associated with a significant increase in NR2B phosphorylation at Tyr1472, a catalytic site by Src family protein tyrosine kinases (SFKs) that has been shown to prevent NR2B endocytosis. Intrathecal injection of a specific SFKs inhibitor, PP2, to block NR2B tyrosine phosphorylation eliminated NMDA-induced NR2BR synaptic expression and also attenuated the mechanical allodynia. These data suggested that activation of spinal NMDARs was able to accumulate NR2BR at synapses via SFK signaling, which might exaggerate NMDAR-dependent nociceptive transmission and contribute to NMDA-induced nociceptive behavioral hyperresponsiveness.

  12. 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

    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......, whereas locomotor activity was unaffected. A significant, albeit modest, reduction in saccharin preference was observed. PEAP responses showed no significant correlations with any other behavioural measure. Comparison with Existing Method and Conclusions The PEAP results suggest that this paradigm might...

  13. Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

    Science.gov (United States)

    Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

    2011-01-01

    Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14(th) and 21(st) days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

  14. Avocado hypersensitivity.

    Science.gov (United States)

    Blanco, C; Carrillo, T; Castillo, R; Quiralte, J; Cuevas, M

    1994-07-01

    The avocado (Av) is a fruit that belongs to the Lauraceae family. We report 17 patients with immediate hypersensitivity to avocado. Clinical manifestations in relation to avocado ingestion were as follows: systemic anaphylaxis in seven patients, angioedema/urticaria in six, vomiting in two, bronchial asthma in one, and rhinoconjunctivitis in one. Skin prick test (SPT) with fresh avocado was positive in all patients with the Strong avocado variety (SAv) and in 14 patients with the Hass avocado variety (HAv). Our patient-associated sensitizations were as follows: 10 to latex, eight to chestnut, eight to banana, four to kiwi, and four to walnut. Avocado-sensitized patients with latex allergy were typically middle-aged women, professionally exposed to latex, who also exhibited frequent associated sensitizations to chestnut, banana, and other fruits. Specific IgE against avocado was demonstrated in 11 of our patients, by both commercial CAP and RAST with avocado extract coupled to nitrocellulose disks. Despite its lower protein content, SAv seems to be more allergenic than HAv, both in vivo and in vitro. On incubating a pool of sera from our patients with avocado, latex, chestnut, and banana extracts, a progressive RAST inhibition was obtained, with SAv- and chestnut-marked disks. This suggests the existence of common antigenic determinants among these allergens.

  15. Oral Hypersensitivity Reactions

    Science.gov (United States)

    ... food, food additives, drugs, oral hygiene products, and dental materials. Q: Are there any specific foods that are ... dental treatment trigger a hypersensitivity reaction? A: Some dental materials used by the dentist can cause a hypersensitivity ...

  16. Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats

    OpenAIRE

    Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

    2013-01-01

    Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund’s Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extr...

  17. Ibuprofen-induced hypersensitivity syndrome.

    Science.gov (United States)

    Nanau, Radu M; Neuman, Manuela G

    2010-06-01

    Ibuprofen is a widely used antipyretic and analgesic nonsteroidal antiinflammatory drug (NSAID). With the aging of the population, there will be a significant increase in the prevalence of painful degenerative and inflammatory rheumatic conditions. This increase likely will lead to a parallel increase in the use of NSAIDs, including ibuprofen. The primary effect of the NSAIDs is to inhibit cyclooxygenase (prostaglandin synthase), thereby impairing the ultimate transformation of arachidonic acid to prostaglandins, prostacyclin, and thromboxanes. Although in the majority of cases it is safe, this NSAID, ibuprofen, can produce an unpredictable, idiosyncratic, type B reaction that may pose a major concern in clinical practice. Type B reactions are known to occur in susceptible individuals. The true hypersensitivity reaction (HSR) is a systemic disease defined by the triad of fever, rash, and internal organ involvement that starts 1 day to 12 weeks after the initiation of therapy. HSR has limited the therapeutic use of many drugs, including ibuprofen. Hypersensitivity syndrome associated with ibuprofen is a host-dependent drug reaction that is idiosyncratic in nature. This reaction likely is caused by a combination of metabolic and immunologic factors. Immune mediated components, such as T-cell and their products cytokines and chemokines, can exacerbate cellular responses and create complex pathways that lead to a variety of clinical manifestations. Our review presents an ibuprofen-induced clinical manifestation of hypersensitivity syndrome and the necessity of wisely monitoring the patients clinically and by laboratory investigations when prescribing this drug.

  18. Measurement of CFA-induced hyperalgesia and morphine-induced analgesia in rats: dorsal vs plantar mechanical stimulation of the hindpaw.

    Science.gov (United States)

    Soignier, R Denis; Taylor, Bradley K; Baiamonte, Brandon A; Lee, Frank A; Paul, Dennis; Gould, Harry J

    2011-03-01

    To compare the sensitivity of stimulating the plantar and dorsal hindpaw surfaces in the detection of mechanical allodynia and morphine analgesia. Several approaches are used to assess nociceptive reactivity to mechanical stimulation in animal models of pain. Although certain techniques seem to be favored for studying specific nociceptive conditions, the differences between techniques have not been directly compared and characterized. We chose to compare methods employing stimulation applied to the dorsum of the paw with stimulation of the plantar surface to demonstrate the utility of each approach in determining baseline nociceptive thresholds, changes in those thresholds after injury, and analgesic efficacy. Withdrawal thresholds from mechanical stimulation applied to the dorsal and plantar surface of the hindpaw were measured in rats treated with morphine after receiving subcutaneous injections of complete Freund's adjuvant (CFA) using Semmes-Weinstein (S-W) monofilaments and electro von Frey (EVF) stimulation. In contrast to stimulation of the dorsal surface, plantar hindpaw stimulation seldom elicited an aversive withdrawal response. Differences in withdrawal response from baseline were only detectable within the first 5 hours post-CFA and only with EVF stimulation. No significant differences in stimulation techniques were observed after the initial 5-hour window. Effective dose 50 (ED(50)) for analgesic efficacy was consistently lower using dorsal stimulation. Stimulation of the plantar surface of the paw is superior for detecting small changes in paw sensitivity at very low stimulus intensities, whereas stimulation of the dorsal surface is superior for delineating baseline pain thresholds and for detecting robust analgesia. Reliable and sensitive assessment of animal pain behaviors is critical to translational pain research. This study demonstrates the importance of using proper test protocols in animal studies and its implication in preclinical screening of

  19. Immediate hypersensitivity to chlorhexidine.

    Science.gov (United States)

    Vu, Mi; Rajgopal Bala, Harini; Cahill, Jennifer; Toholka, Ryan; Nixon, Rosemary

    2017-06-07

    Chlorhexidine is a widely used and effective antiseptic agent. Although skin contact is usually well tolerated, it may cause both immediate and delayed hypersensitivity reactions. We report a case of immediate hypersensitivity to chlorhexidine causing both skin and respiratory symptoms following occupational exposure to chlorhexidine in a health-care worker. © 2017 The Australasian College of Dermatologists.

  20. Visceral hypersensitivity in irritable bowel syndrome.

    Science.gov (United States)

    Kanazawa, Motoyori; Hongo, Michio; Fukudo, Shin

    2011-04-01

    Altered central processing, abnormal gastrointestinal motility and visceral hypersensitivity may be possible major pathophysiology of irritable bowel syndrome (IBS). These factors affect each other and are probably associated with development of IBS symptoms. It has been confirmed that lower pain threshold to colonic distention was observed in most of patients with IBS than healthy subjects. We have investigated pain perception of the descending colon among different subtypes of IBS. There was no difference in pain threshold to colonic distention between IBS with diarrhea and constipation. Some brain regions such as the anterior cingulate cortex (ACC) may play a major role for generating pain and/or pain-related emotion in humans. IBS patients showed greater activation in the perigenual ACC during painful rectal distention compared with healthy subjects. Inflammation, stress and the combination of both stimuli can induce significant increase in visceral sensitivity in animal models. Serotonin (5-HT) can modulate visceral perception. It has been thought that 5-HT(3) receptors may play an important role for conveying visceral sensation from the gut. Corticotropin-releasing hormone (CRH) may also modulate visceral pain hypersensitivity in IBS. CRH receptor-1 antagonist significantly prevented an increase in gut sensitivity in rats. It has been demonstrated that non-specific CRH receptor antagonist α-helical CRH significantly reduced abdominal pain score during gut stimulus in patients with IBS. In conclusion, visceral hypersensitivity is common in IBS patients and probably plays a major role in development of the symptoms and both central and peripheral factors may enhance the pain sensitivity.

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

    DEFF Research Database (Denmark)

    Christensen, Steffan Wittrup; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

    2017-01-01

    BACKGROUND: 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 ...

  2. The α5 subunit containing GABAA receptors contribute to chronic pain.

    Science.gov (United States)

    Bravo-Hernández, Mariana; Corleto, José A; Barragán-Iglesias, Paulino; González-Ramírez, Ricardo; Pineda-Farias, Jorge B; Felix, Ricardo; Calcutt, Nigel A; Delgado-Lezama, Rodolfo; Marsala, Martin; Granados-Soto, Vinicio

    2016-03-01

    It has been recently proposed that α5-subunit containing GABAA receptors (α5-GABAA receptors) that mediate tonic inhibition might be involved in pain. The purpose of this study was to investigate the contribution of α5-GABAA receptors in the loss of GABAergic inhibition and in formalin-induced, complete Freund's adjuvant (CFA)-induced and L5 and L6 spinal nerve ligation-induced long-lasting hypersensitivity. Formalin or CFA injection and L5 and L6 spinal nerve ligation produced long-lasting allodynia and hyperalgesia. Moreover, formalin injection impaired the rate-dependent depression of the Hofmann reflex. Peripheral and intrathecal pretreatment or post-treatment with the α5-GABAA receptor antagonist, L-655,708 (0.15-15 nmol), prevented and reversed, respectively, these long-lasting behaviors. Formalin injection increased α5-GABAA receptor mRNA expression in the spinal cord and dorsal root ganglia (DRG) mainly at 3 days. The α5-GABAA receptors were localized in the dorsal spinal cord and DRG colabeling with NeuN, CGRP, and IB4 which suggests their presence in peptidergic and nonpeptidergic neurons. These receptors were found mainly in small and medium sized neurons. Formalin injection enhanced α5-GABAA receptor fluorescence intensity in spinal cord and DRG at 3 and 6 days. Intrathecal administration of L-655,708 (15 nmol) prevented and reversed formalin-induced impairment of rate-dependent depression. These results suggest that α5-GABAA receptors play a role in the loss of GABAergic inhibition and contribute to long-lasting secondary allodynia and hyperalgesia.

  3. Platinum hypersensitivity and desensitization.

    Science.gov (United States)

    Miyamoto, Shingo; Okada, Rika; Ando, Kazumichi

    2015-09-01

    Platinum agents are drugs used for various types of cancer. With increased frequency of administration of platinum agents, hypersensitivity reactions appear more frequently, occurring in over 25% of cases from the seventh cycle or second line onward. It then becomes difficult to conduct treatment using these agents. Various approaches have been investigated to address hypersensitivity reactions to platinum agents. Desensitization, which gradually increases the concentration of the anticancer drug considered to be the antigen until the target dosage, has been reported as being particularly effective, with a success rate of 80-100%. The aims of this paper are to present the current findings regarding hypersensitivity reactions to platinum agents and to discuss attempts of using desensitization against hypersensitivity reactions worldwide. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Neural manual vs. robotic assisted mobilization to improve motion and reduce pain hypersensitivity in hand osteoarthritis: study protocol for a randomized controlled trial

    OpenAIRE

    Villafa?e, Jorge Hugo; Valdes, Kristin; Imperio, Grace; Borboni, Alberto; Cantero-T?llez, Raquel; Galeri, Silvia; Negrini, Stefano

    2017-01-01

    [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 (...

  5. Carmine hypersensitivity masquerading as azithromycin hypersensitivity.

    Science.gov (United States)

    Greenhawt, Matthew; McMorris, Marc; Baldwin, James

    2009-01-01

    Macrolide hypersensitivity is a rarely reported event. However, carmine dye has become increasingly important as a provocative agent. We present a case of a woman with documented carmine hypersensitivity, who reported anaphylaxis 90 minutes after ingestion of a generic azithromycin. Our investigations revealed that this was an allergy to the carmine dye in the tablet's coating rather than to the antibiotic. Seven extracts were prepared including carmine dye, crushed dried female cochineal insects, crushed tablets of Zithromax (Pfizer Inc.) and generic azithromycin (Teva Pharmaceuticals), and the crushed colored coatings from both tablets. These were suspended in preservative-free normal saline, and then applied as a skin-prick test and read at 30 minutes. The skin-prick skin test results were 4+ to histamine and carmine dye, but negative to cochineal insect extract, Pfizer crushed tablets, and negative control. The patient was 1+ to the Teva crushed tablet, but was 4+ to the Teva brand coating and negative to the Pfizer brand coating, which did not contain carmine. The patient subsequently ingested Pfizer Zithromax without any sequelae. To our knowledge, this is the first reported case of carmine anaphylaxis attributed to carmine-containing medication. Careful history and skin-prick testing to the appropriate agents allowed elucidation of the subtlety of the true offending agent without unnecessary avoidance of the medication class. Patients with a carmine hypersensitivity should actively check with their pharmacy or prescribing physician to verify their medications are free of this offending agent.

  6. Mechanisms underlying visceral hypersensitivity in irritable bowel syndrome.

    Science.gov (United States)

    Barbara, Giovanni; Cremon, Cesare; De Giorgio, Roberto; Dothel, Giovanni; Zecchi, Lisa; Bellacosa, Lara; Carini, Giovanni; Stanghellini, Vincenzo; Corinaldesi, Roberto

    2011-08-01

    Visceral hypersensitivity is currently considered a key pathophysiological mechanism involved in pain perception in large subgroups of patients with functional gastrointestinal disorders, including irritable bowel syndrome (IBS). In IBS, visceral hypersensitivity has been described in 20%-90% of patients. The contribution of the central nervous system and psychological factors to visceral hypersensitivity in patients with IBS may be significant, although still debated. Peripheral factors have gained increasing attention following the recognition that infectious enteritis may trigger the development of persistent IBS symptoms, and the identification of mucosal immune, neural, endocrine, microbiological, and intestinal permeability abnormalities. Growing evidence suggests that these factors play an important role in pain transmission from the periphery to the brain via sensory nerve pathways in large subsets of patients with IBS. In this review, we will report on recent data on mechanisms involved in visceral hypersensitivity in IBS, with particular attention paid to peripheral mechanisms.

  7. Multi-factoriality of dentine hypersensitivity

    OpenAIRE

    Stojšin Ivana; Petrović Ljubomir; Stojanac Igor; Drobac Milan

    2008-01-01

    Introduction. Dentine hypersensitivity has been defined as a sharp, short pain arising from exposed dentin in response to stimuli typically thermal, evaporative tactile, osmoticor, chemical and which cannot be ascribed to any other form of dental defect or pathology. Prevalence. The most affected patients range in age from 20 to 40. The following teeth tend to be most sensitive: cuspids, premolars and incisors, location-concentrated on the facial surface. Morphological bases of dentine hypers...

  8. Association between Severity of Tooth Wear and Dentinal Hypersensitivity

    Directory of Open Access Journals (Sweden)

    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.

  9. Multi-factoriality of dentine hypersensitivity

    Directory of Open Access Journals (Sweden)

    Stojšin Ivana

    2008-01-01

    Full Text Available Introduction. Dentine hypersensitivity has been defined as a sharp, short pain arising from exposed dentin in response to stimuli typically thermal, evaporative tactile, osmoticor, chemical and which cannot be ascribed to any other form of dental defect or pathology. Prevalence. The most affected patients range in age from 20 to 40. The following teeth tend to be most sensitive: cuspids, premolars and incisors, location-concentrated on the facial surface. Morphological bases of dentine hypersensitivity Sensitive teeth have much greater numbers of open tubules per unit area and the average diameter of tubules is almost 2 times greater than tubules in nonsensitive teeth. Mechanisms of dentine hypersensitivity. The most widely accepted theory of how the pain occurs is Brannstroms theory. Etiology Dentine hypersensitivity represents a condition of presumable multifactorial pathology. Two processes are essential for its development: (1 dentin must be exposed through either genetic disturbance, enamel defect (lamellae, tufts and spindles, loss of enamel (erosion, abrasion, attrition, abfraction, gingival recession with rapid loss of cementum and (2 the dentin tubules must be open to both the oral cavity and the pulp. Diagnosis. Diagnostic protocol for this condition consisted of Medical, Dental Dietary, Oral Hygiene History and Intra-oral examinations with air indexing method. Differential Diagnosis: We must take into consideration a number of variables such as: dental caries, cracked tooth, restorative sensitivity, medication sensitivity, bleaching sensitivity and abscessed or non-vital tooth. Conclusion. Dentin hypersensitivity is a problem that bothes many patients. Many conditions share the symptoms of tooth sensitivity so differential diagnosis is essential for suitable treatment or preventive measures.

  10. Efficacy and gastrointestinal tolerability of ML3403, a selective inhibitor of p38 MAP kinase and CBS-3595, a dual inhibitor of p38 MAP kinase and phosphodiesterase 4 in CFA-induced arthritis in rats.

    Science.gov (United States)

    Koch, Diana A; Silva, Rodrigo B M; de Souza, Alessandra H; Leite, Carlos E; Nicoletti, Natália F; Campos, Maria M; Laufer, Stefan; Morrone, Fernanda B

    2014-03-01

    Mitogen-activated protein kinase (MAPK) p38 inhibitors have entered the clinical phase, although many of them have failed due to high toxicity and lack of efficacy. In the present study we compared the effects of the selective p38 inhibitor ML3403 and the dual p38-PDE4 inhibitor CBS-3595, on inflammatory and nociceptive parameters in a model of polyarthritis in rats. Male Wistar rats (180-200 g) were used for the complete Freund's adjuvant (CFA)-induced arthritis model and they were evaluated at 14-21 days. We also analysed the effects of these pharmacological tools on liver and gastrointestinal toxicity and on cytokine levels. Repeated CBS-3595 (3 mg/kg) or ML3403 (10 mg/kg) administration produced significant anti-inflammatory actions in the chronic arthritis model induced by CFA. CBS-3595 and ML3403 treatment also markedly reduced the production of the proinflammatory cytokine IL-6 in the paw tissue, whereas it widely increased the levels of the anti-inflammatory cytokine IL-10. Moreover, CBS-3595 produced partial anti-allodynic effects in the CFA model at 4 and 8 days after treatment. Notably, ML3403 and CBS-3595 did not show marked signs of hepatoxicity, as supported by unaltered histological observations in the liver sections. Finally, both compounds were safe in the gastrointestinal tract, according to evaluation of intestinal biopsies. CBS-3595 displayed a superior profile regarding its anti-inflammatory effects. Thus p38 MAPK/PDE4 blocking might well constitute a relevant strategy for the treatment of RA.

  11. Effectiveness of Lasers in the Treatment of Dentin Hypersensitivity

    Science.gov (United States)

    Asnaashari, Mohammad; Moeini, Masoumeh

    2013-01-01

    Dentin hypersensitivity (DH) is a relatively common painful condition among dental problems. Although many studies have been performed regarding the diagnosis and treatment of DH, dental practitioners are still confused about the definite diagnosis and treatment.The use of lasers as a treatment for dentin hypersensitivity was first introduced in 1985.Laser treatment in dentin hypersensitivity is an interesting and controversial issue and many investigations have been done on its mechanism of action, advantages, and unclear points.The present literature review tries to go over the definition, diagnosis, etiology , predisposing factors, various laser types in the treatment of DH alone or in combination with topical desensitizing agents. Since a certain treatment has not yet introduced for dentin hypersensitivity, a combination of laser therapy and topical desensitizing factors ,can increase the success of the treatment compared with either treatments alone. PMID:25606300

  12. An unexpected positive hypersensitive reaction to eugenol.

    Science.gov (United States)

    Tammannavar, Praveen; Pushpalatha, C; Jain, Shrenik; Sowmya, S V

    2013-09-18

    Eugenol is an active, principal aromatic liquid responsible for several pharmacological activities. It is widely used in dental practice to relieve pain arising from various sources, such as pulpitis and dentinal hypersensitivity. As a primary irritant and sensitiser, it is known to cause contact urticaria as well as chronic urticaria. However, eugenol causes allergic contact dermatitis, possibly because it can react directly with proteins to form conjugate and reactive haptens. It is found that eugenol in various dental preparations-especially in the case of some zinc oxide-contains preparations such as periodontal dressings and root canal cements. This can cause hypersensitivity when it comes in contact with gingiva or teeth. This article presents a case of immediate allergic contact urticaria to eugenol during dental treatment.

  13. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Blichfeldt-Eckhardt, Morten Rune; Ording, Helle; Andersen, Claus

    2014-01-01

    , and 3, 6, and 12months postoperatively for pain, psychological factors, and signs of hypersensitivity. Overall pain, incisional pain (somatic pain component), deep abdominal pain (visceral pain component), and shoulder pain (referred pain component) were registered on a 100-mm visual analogue scale...... during the first postoperative week. Nine patients developed chronic unexplained pain 12months postoperatively. In a multivariate analysis model, cumulated visceral pain during the first week and number of preoperative biliary pain attacks were identified as independent risk factors for unexplained......, but significantly related to the visceral pain response during the first postoperative week....

  14. Hypersensitivity to Suture Anchors

    Directory of Open Access Journals (Sweden)

    Masafumi Goto

    2013-01-01

    Full Text Available Hypersensitivity to suture anchor is extremely rare. Herein, we present a case in which hypersensitivity to suture anchor was strongly suspected. The right rotator cuff of a 50-year-old woman was repaired with a metal suture anchor. Three weeks after the surgery, she developed erythema around her face, trunk, and hands, accompanied by itching. Infection was unlikely because no abnormalities were detected by blood testing or by medical examination. Suspicious of a metallic allergy, a dermatologist performed a patch testing 6 months after the first surgery. The patient had negative reactions to tests for titanium, aluminum, and vanadium, which were the principal components of the suture anchor. The anchor was removed 7 months after the first surgery, and the erythema disappeared immediately. When allergic symptoms occur and persist after the use of a metal anchor, removal should be considered as a treatment option even if the patch test result is negative.

  15. Ofloxacin induced hypersensitivity reaction

    Directory of Open Access Journals (Sweden)

    Hari Babu Ramineni

    2015-01-01

    Full Text Available Ofloxacin is a commonly used antimicrobial agent to combat various infections. The adverse profile of quinolones includes gastrointestinal symptoms, which are the most frequent, neuropsychiatric symptoms, hematologic abnormalities are less common. We report a rare case of ofloxacin induced hypersensitivity reaction in a 57 year old female patient with complaints of rashes over the axilla, upper limb and back, abdomen, thorax associated with exfoliation of skin all over the axilla associated with severe itching. Based on history and clinical examination patient was diagnosed as ofloxacin induced hypersensitivity reaction and was successfully treated with antihistamines and corticosteroids. Pharmacovigilance should be a part of patient care in order to reduce occurrence of adverse drug reaction and also encourage practitioners in reporting so as to gather more and more data regarding adverse drug reactions. [Int J Res Med Sci 2015; 3(1.000: 349-351

  16. TRPA1 contributes to cold hypersensitivity.

    Science.gov (United States)

    del Camino, Donato; Murphy, Sarah; Heiry, Melissa; Barrett, Lee B; Earley, Taryn J; Cook, Colby A; Petrus, Matt J; Zhao, Michael; D'Amours, Marc; Deering, Nate; Brenner, Gary J; Costigan, Michael; Hayward, Neil J; Chong, Jayhong A; Fanger, Christopher M; Woolf, Clifford J; Patapoutian, Ardem; Moran, Magdalene M

    2010-11-10

    TRPA1 is a nonselective cation channel expressed by nociceptors. Although it is widely accepted that TRPA1 serves as a broad irritancy receptor for a variety of reactive chemicals, its role in cold sensation remains controversial. Here, we demonstrate that mild cooling markedly increases agonist-evoked rat TRPA1 currents. In the absence of an agonist, even noxious cold only increases current amplitude slightly. These results suggest that TRPA1 is a key mediator of cold hypersensitivity in pathological conditions in which reactive oxygen species and proinflammatory activators of the channel are present, but likely plays a comparatively minor role in acute cold sensation. Supporting this, cold hypersensitivity can be induced in wild-type but not Trpa1(-/-) mice by subcutaneous administration of a TRPA1 agonist. Furthermore, the selective TRPA1 antagonist HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide] reduces cold hypersensitivity in rodent models of inflammatory and neuropathic pain.

  17. Laryngeal hypersensitivity in chronic cough.

    Science.gov (United States)

    Hull, J H; Menon, A

    2015-12-01

    Patients with chronic cough often report symptoms arising in the throat, in response to non-specific stimuli. Accordingly, the concept of a 'hypersensitivity' of the larynx in chronic cough has evolved over the past ten years. Patients with cough and laryngeal hypersensitivity frequently report features that overlap other laryngeal dysfunction syndromes, including a tendency for the vocal cords to inappropriately adduct. The mechanisms underlying laryngeal hypersensitivity in chronic cough are currently unclear, however recent studies provide new clinical and physiological techniques to aid detection and monitoring of laryngeal hypersensitivity. This review provides an overview of the current state of knowledge in this field.

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

    Science.gov (United States)

    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.

  19. Sulphasalazine Induced Hypersensitivity Syndrome

    Directory of Open Access Journals (Sweden)

    Hatice Şanlı

    2013-05-01

    Full Text Available Drug-induced hypersensitivity syndrome (DIHS is one of the most dangerous drug reactions. Mortality and morbidity is increased by consequent systemic organ involvement. Maculopapular eruptions are the most common lesions accompanying DIHS, however, the morphology of skin lesions may vary. The most common cause of DIHS is the use of aromatic anticonvulsant drugs. However, one must not forget that other drugs may also cause DIHS. Early recognition of the condition is the most important step in the treatment. Herein, we present a case of DIHS triggered by sulphasalazine and associated with pustular eruption and maculopapular eruption.

  20. Chronic hypersensitivity pneumonitis

    Science.gov (United States)

    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. PMID:27703382

  1. Hypersensitivity to antihistamines.

    Science.gov (United States)

    Shakouri, Alireza A; Bahna, Sami L

    2013-01-01

    Antihistamines are the cornerstone of allergy therapy and are not expected to cause hypersensitivity reactions. We describe two cases, one had urticaria to multiple anti-H1-preparations and the other had anaphylaxis to hydroxyzine. We also provide a review of the English literature on reported reactions regarding causative preparations and manifestations. The latter showed a wide range; most commonly urticaria/angioedema, contact dermatitis, anaphylaxis, and fixed drug eruption (FDE). Most reported cases were young to middle age adults, with apparent predilection to female subjects. The onset of reactions varied from a few minutes for anaphylaxis and urticaria/angioedema, several hours for maculopapular rashes, or longer for contact dermatitis and FDE. Almost all antihistamines have been reported as causing reactions; cetirizine was the most common oral preparation followed by its parent drug, hydroxyzine. Doxepin cream was the most commonly implicated topical preparation in causing contact dermatitis. A causal relationship is often difficult to recognize because the reaction may be similar to the disease being treated with that antihistamine preparation. Reactions to one preparation are likely to occur, but not always, to other members of the same class. Diagnosis is based on clinical suspicion and may be verified by challenge testing. Except for patch testing in contact dermatitis or fixed eruption, other tests have not shown optimal reliability. In most cases, challenge testing with multiple preparations would identify one or more preparations that can be tolerated. Although hypersensitivity to antihistamines seems to be very rare, awareness of the problem would reduce its misdiagnosis.

  2. 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.

  3. 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

  4. STUDIES ON HYPERSENSITIVITY

    Science.gov (United States)

    Gell, P. G. H.; Benacerraf, B.

    1961-01-01

    In earlier observations with the picryl system, it was concluded that contact sensitivity was a form of delayed (cellular) hypersensitivity to conjugates of sensitizer with autologous proteins indistinguishable in its immunological mechanism from other classical forms of delayed hypersensitivity to proteins. This conclusion has been confirmed and extended with the picryl and chlorbenzoyl chloride systems. 1. It is shown that to induce a state of contact sensitivity, the minimal necessary amounts of hapten are of the same order of magnitude, whether this hapten is conjugated with protein or the free reactive chemical itself. From this, it is evident that contamination of conjugates with small amounts of unreacted sensitizer plays no part in the induction of contact reactivity by the conjugate. With the dinitrophenyl system, no contact sensitivity could be induced by the conjugates used; possible reasons for this discrepancy are discussed. 2. Animals sensitized to contact by homologous conjugate can be completely desensitized by injections of such a conjugate in large amount; a similar injection schedule has no effect on the contact sensitivity of animals sensitized with the free reactive sensitizer. 3. The capacity of heterologous (ovalbumin) conjugates to evoke anti-hapten antibodies is shown to be greater than that of homologous (guinea pig seralbumin) conjugates: the reverse is true of their capacity to induce delayed reactivity. 4. Evidence is brought forward to suggest that in animals sensitized with homologous albumin conjugates, the specificity of the delayed reaction involves more than the hapten alone, even though the carrier protein is non-antigenic on its own. The contrast with the apparent lesser specificity of the antibodies later produced is discussed. PMID:13704282

  5. 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

  6. Absolute eosinophilia as dapsone hypersensitivity

    Directory of Open Access Journals (Sweden)

    Somani V

    1994-01-01

    Full Text Available A case of lepromatous leprosy (LL on multibacillary multidrug therapy (MBMDT presented with oedema of the acral parts and marked eosinophilia. The case is being reported because of this extremely rare manifestation of dapsone hypersensitivity.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Haryono Utomo

    2006-12-01

    Full Text Available In daily dental practice, the majority of patients’ main complaints are related to pain. Most patients assume that all pains inside the oral cavity originated from the tooth. One particular case is thermal sensitivity; sometimes patients were being able to point the site of pain, although there is neither visible caries nor secondary caries in dental radiograph. In this case, gingival recession and dentin hypersensitivity are first to be treated to eliminate the pain. If these treatments failed, pain may misdiagnose as pulpal inflammation and lead to unnecessary root canal treatment. Study in pain during periodontal instrumentation of plaque-related periodontitis revealed that the majority of patients feel pain and discomfort during probing and scaling. It seems obvious because an inflammation, either acute or chronic is related to a lowered pain threshold. However, in contrast, in this case report, patient suffered from chronic gingivitis and thermal sensitivity experienced a relative pain-free sensation during probing and scaling. Lowered pain threshold which accompanied by a blunted pain perception upon periodontal instrumentation is proposed to be termed as the periodontal pain paradox. The objective of this study is to reveal the possibility of certain factors in periodontal inflammation which may involved in the periodontal pain paradox hypothesis. Patient with thermal hypersensitivity who was conducted probing and scaling, after the relative pain-free instrumentation, thermal hypersensitivity rapidly disappeared. Based on the successful periodontal treatment, it is concluded that chronic gingivitis may modulate periodontal pain perception which termed as periodontal pain paradox

  9. Mechanisms of chronic pain from whiplash injury.

    Science.gov (United States)

    Davis, Charles G

    2013-02-01

    This article is to provide insights into the mechanisms underlying chronic pain from whiplash injury. Studies show that injury produces plasticity changes of different neuronal structures that are responsible for amplification of nociception and exaggerated pain responses. There is consistent evidence for hypersensitivity of the central nervous system to sensory stimulation in chronic pain after whiplash injury. Tissue damage, detected or not by the available diagnostic methods, is probably the main determinant of central hypersensitivity. Different mechanisms underlie and co-exist in the chronic whiplash condition. Spinal cord hyperexcitability in patients with chronic pain after whiplash injury can cause exaggerated pain following low intensity nociceptive or innocuous peripheral stimulation. Spinal hypersensitivity may explain pain in the absence of detectable tissue damage. Whiplash is a heterogeneous condition with some individuals showing features suggestive of neuropathic pain. A predominantly neuropathic pain component is related to a higher pain/disability level.

  10. Type I hypersensitivity reaction as a complication of lepa

    OpenAIRE

    Janthli, Deepa Manjunath; Chaturvedi, Ashutosh; Somashekar, Shruthi; Lohith, B. A.

    2015-01-01

    Adverse drug reaction is defined as response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological functions. Type I hypersensitivity reaction is known as anaphylactic reaction which is due to immediate immunoglobulin E-mediated reaction. It is characterized by symptoms such as fever nausea, back pain, angiodema, rash, flushing, etc. Lepa generally refers to the a...

  11. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy.

    Science.gov (United States)

    Blichfeldt-Eckhardt, Morten Rune; Ording, Helle; Andersen, Claus; Licht, Peter B; Toft, Palle

    2014-11-01

    Chronic pain after laparoscopic cholecystectomy is related to postoperative pain during the first postoperative week, but it is unknown which components of the early pain response is important. In this prospective study, 100 consecutive patients were examined preoperatively, 1 week postoperatively, and 3, 6, and 12 months postoperatively for pain, psychological factors, and signs of hypersensitivity. Overall pain, incisional pain (somatic pain component), deep abdominal pain (visceral pain component), and shoulder pain (referred pain component) were registered on a 100-mm visual analogue scale during the first postoperative week. Nine patients developed chronic unexplained pain 12 months postoperatively. In a multivariate analysis model, cumulated visceral pain during the first week and number of preoperative biliary pain attacks were identified as independent risk factors for unexplained chronic pain 12 months postoperatively. There were no consistent signs of hypersensitivity in the referred pain area either pre- or postoperatively. There were no significant associations to any other variables examined. The risk of chronic pain after laparoscopic cholecystectomy is relatively low, but significantly related to the visceral pain response during the first postoperative week. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. Confirmation of efficacy in providing relief from the pain of dentin hypersensitivity of an anhydrous dentifrice containing 0.454% with or without stannous fluoride in an 8-week randomized clinical trial.

    Science.gov (United States)

    Parkinson, Charles R; Jeffery, Peter; Milleman, Jeffery L; Milleman, Kimberly R; Mason, Stephen

    2015-08-01

    To compare the efficacy of an anhydrous dentifrice containing 0.454% w/w stannous fluoride and a negative control dentifrice containing 1,000 ppm fluoride, as sodium monofluorophosphate, at reducing dentin hypersensitivity over 8 weeks with twice-daily brushing. This was a randomized, examiner-blind, parallel, two treatment group, stratified (by maximum baseline Schiff sensitivity score), 8-week clinical study carried out at a single site in 119 healthy subjects with at least two sensitive teeth, who met all study criteria at the screening and baseline visits. Clinical assessments of sensitivity to evaporative (air) [with Schiff sensitivity score and visual analogue scale (VAS)] and tactile (Yeaple probe) stimuli were employed to compare the efficacy of the test dentifrice containing 0.454% w/w stannous fluoride to the negative control dentifrice at reducing sensitivity after 4 and 8 weeks treatment. Of the 119 subjects randomized to study treatment, 113 completed the study. At 4 and 8 weeks, between treatment analyses found the test dentifrice to be significantly better than the negative control dentifrice in relieving dentin hypersensitivity for all measures (Schiff: P < 0.0001 at 4 and 8 weeks; VAS score: P = 0.0003 at 4 weeks, P < 0.0001 at 8 weeks; tactile threshold: P = 0.0138 at 4 weeks, P < 0.0001 at 8 weeks).

  13. Eosinophilic leukemoid reaction associated with carbamazepine hypersensitivity

    Directory of Open Access Journals (Sweden)

    Laad Gaurish

    2005-01-01

    Full Text Available Carbamazepine is widely used in the treatment of epilepsy, neuralgic pain, and bipolar affective disorders. Several adverse drug reactions have been described during the course of carbamazepine administration, including exanthemata and hematological reactions. Carbamazepine is one of the common drugs that have been implicated in the etiology of drug hypersensitivity syndrome. A 50-year-old male presented with generalized erythroderma following 10 weeks of ingestion of carbamazepine 200 mg daily for idiopathic epilepsy. His systemic examination was within normal limits. Blood counts revealed marked eosinophilia of 52% (absolute eosinophil count of 10,400 per mm3. Bone marrow aspiration revealed a moderate increase in the eosinophilic series with cells showing normal morphology. The eosinophil counts returned to normal after 2 weeks of oral prednisolone therapy. This case is reported because of its rarity in the Indian medical literature.

  14. Biomarkers for visceral hypersensitivity identified by classification of electroencephalographic frequency alterations

    Science.gov (United States)

    Graversen, Carina; Brock, Christina; Mohr Drewes, Asbjørn; Farina, Dario

    2011-10-01

    Abdominal pain is frequently related to visceral hypersensitivity. This is associated with increased neuronal excitability in the central nervous system (CNS), which can be manifested as discrete electroencephalographic (EEG) alterations. In the current placebo-controlled study, visceral hypersensitivity was evoked by chemical irritation of the esophagus with acid and capsaicin perfusion. The resulting hyperexcitability of the CNS was evaluated by evoked brain potentials following painful electrical stimulations of a remote organ—the rectosigmoid colon. Alterations in individual EEG power distributions between baseline and after perfusion were quantified by extracting features from the evoked brain potentials using an optimized discrete wavelet transform. Visceral hypersensitivity was identified as increased EEG power in the delta, theta and alpha frequency bands. By applying a support vector machine in regression mode, the individual baseline corrected alterations after sensitization were discriminated from alterations caused by placebo perfusions. An accuracy of 91.7% was obtained (P pain physiology and pharmacological interventions.

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

    OpenAIRE

    2006-01-01

    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 fail...

  16. Drug hypersensitivity reactions involving skin.

    Science.gov (United States)

    Hausmann, Oliver; Schnyder, Benno; Pichler, Werner J

    2010-01-01

    Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit

  17. Gelofen Induced Hypersensitivity: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    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

  18. Application of Diode Laser in the Treatment of Dentine Hypersensitivity

    Science.gov (United States)

    Gojkov-Vukelic, Mirjana; Hadzic, Sanja; Zukanovic, Amila; Pasic, Enes; Pavlic, Veriva

    2016-01-01

    Introduction: Dentine hypersensitivity is characterized by acute, sharp pain arising from the exposed dentine, most commonly in response to thermal, tactile, or chemical stimuli, and which cannot be linked to any other pathological changes in the tooth or the environment. Therapy uses various impregnating agents in the form of solutions or gels and, in more recent times, laser. Aim: The aim of this research was to examine the effects of treatment of hypersensitive dental cervix with diode laser. Materials and Methods: The study included 18 patients with 82 sensitive teeth. The degree of dentine hypersensitivity was evaluated by visual analogue scale (VAS), and the treatment was carried out by application of low-power diode laser over the span of three visits, which depended on the initial sensitivity. Results: There is a significant difference in VAS values measured at the onset of treatment (baseline) and immediately after the first laser treatment (t=9.275; p=0.000), after 7 days, after the second laser treatment (14 days) (t=7.085, p=0.000), as well as after 14 days and the third laser treatment (t=5.517, p=0.000), which confirms the effectiveness of this therapeutic procedure. The results showed a reduction of hypersensitivity in response to tactile stimulus with a probe after the third treatment, even with teeth whose value on the VAS was very high at the beginning of treatment (baseline). Conclusion: Within the scope of the conducted study, laser therapy has provided extremely safe and effective results in the treatment of cervical dentine hypersensitivity.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Blockade of metabotropic glutamate receptor 5 activation inhibits mechanical hypersensitivity following abdominal surgery.

    Science.gov (United States)

    Dolan, Sharron; Nolan, Andrea Mary

    2007-08-01

    This study used the metabotropic glutamate 5 (mGlu5) receptor subtype-selective antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) to characterise the contribution of mGlu5 receptor activity to pain and hypersensitivity in an animal model of post-surgical pain. Adult female Wistar rats (200-250g) were anaesthetised with isoflurane (2%) and underwent a midline laparotomy with gentle manipulation of the viscera, and the effects of pre- (30min) or post- (5h) operative treatment with MPEP (1, 3 or 10mgkg(-1); i.p.) or drug-vehicle on hindpaw withdrawal latency (in seconds) to thermal stimulation (Hargreave's Test) and response threshold (in grams) to mechanical stimulation (using a dynamic plantar aesthesiometer) were measured. Animals that underwent surgery displayed significant hypersensitivity to mechanical stimulation of the hindpaws. Hypersensitivity was maximum at 6h post-surgery (44.5+/-2.4% decrease; p<0.01 vs. anaesthesia only controls) and persisted for 48h. Surgery had no effect on thermal withdrawal latency. Both pre-operative and post-operative administration of 10mgkg(-1)MPEP blocked mechanical hypersensitivity induced by surgery (p<0.01 vs. vehicle treatment). MPEP had no effect on acute nociceptive thresholds in naïve animals. These data suggest that activity at mGlu5 receptors contributes to development of pain and hypersensitivity following surgery.

  2. Food hypersensitivity in a cat.

    Science.gov (United States)

    Medleau, L; Latimer, K S; Duncan, J R

    1986-09-15

    Food hypersensitivity was diagnosed in a 4-year-old Siamese cat. Clinical signs included intense erythema, with alopecia, excoriations, erosions, and crusts involving the ventral portion of the abdomen, inguinal region, medial aspect of each thigh, and cranial and lateral aspects of all 4 limbs. The cat was intensely pruritic. Histologically, there was cutaneous mast cell hyperplasia and diffuse infiltration of eosinophils in the dermis. Blood eosinophilia also was found. Clinical signs resolved after exclusive feeding of a hypoallergenic diet.

  3. Carbamazepine induced anticonvulsant hypersensitivity syndrome

    OpenAIRE

    Shwetha Shivamurthy; Ravishankar Manchukonda

    2015-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a potentially fatal drug-induced, multi-organ syndrome. The syndrome has been reported with anticonvulsants such as carbamazepine, phenytoin, phenobarbitone, and lamotrigine. A 17-year-old female who presented with papules and desquamation all over was diagnosed with AHS. She gave a history of fever, earache, peripheral edema, and erythematous papular eruptions 3 days prior. She gave a history of carbamazepine treatment since 15 days for gener...

  4. Climate hypersensitivity to solar forcing?

    Directory of Open Access Journals (Sweden)

    W. Soon

    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

  5. Toll-Like Receptor 4 in Paraventricular Nucleus Mediates Visceral Hypersensitivity Induced by Maternal Separation

    Directory of Open Access Journals (Sweden)

    Hui-Li Tang

    2017-05-01

    Full Text Available Neonatal maternal separation (MS is a major early life stress that increases the risk of emotional disorders, visceral pain perception and other brain dysfunction. Elevation of toll-like receptor 4 (TLR4 signaling in the paraventricular nucleus (PVN precipitates early life colorectal distension (CRD-induced visceral hypersensitivity and pain in adulthood. The present study aimed to investigate the role of TLR4 signaling in the pathogenesis of postnatal MS-induced visceral hypersensitivity and pain during adulthood. The TLR4 gene was selectively knocked out in C57BL/10ScSn mice (Tlr4-/-. MS was developed by housing the offspring alone for 6 h daily from postnatal day 2 to day 15. Visceral hypersensitivity and pain were assessed in adulthood. Tlr4+/+, but not Tlr4-/-, mice that had experienced neonatal MS showed chronic visceral hypersensitivity and pain. TLR4 immunoreactivity was observed predominately in microglia in the PVN, and MS was associated with an increase in the expression of protein and/or mRNA levels of TLR4, corticotropin-releasing factor (CRF, CRF receptor 1 (CRFR1, tumor necrosis factor-α, and interleukin-1β in Tlr4+/+ mice. These alterations were not observed in Tlr4-/- mice. Local administration of lipopolysaccharide, a TLR4 agonist, into the lateral cerebral ventricle elicited visceral hypersensitivity and TLR4 mRNA expression in the PVN, which could be prevented by NBI-35965, an antagonist to CRFR1. The present results indicate that neonatal MS induces a sensitization and upregulation of microglial TLR4 signaling activity, which facilitates the neighboring CRF neuronal activity and, eventually, precipitates visceral hypersensitivity in adulthood.Highlights(1Neonatal MS does not induce chronic visceral hypersensitivity and pain in Tlr4-/- mice.(2Neonatal MS increases the expression of TLR4 mRNA, CRF protein and mRNA, CRFR1 protein, TNF-α protein, and IL-1β protein in Tlr4+/+ mice.(3TLR4 agonist LPS (i.c.v. elicits visceral

  6. Thermal hypersensitivity in a subset of irritable bowel syndrome patients

    Institute of Scientific and Technical Information of China (English)

    QiQi Zhou; Roger B Fillingim; Joseph L Riley III; G Nicholas Verne

    2009-01-01

    AIM: To characterize thermal hypersensitivity in patients with constipation- and diarrhea-predominant irritable bowel syndrome (IBS). METHODS: Thermal pain sensitivity was tested among patients with diarrhea-predominant IBS (D-IBS) and constipation-predominant IBS (C-IBS) compared to healthy subjects. A total of 42 patients (29 female and patients (16 female and eight male; mean age 32.5participated in the study. Thermal stimuli were delivered using a Medoc Thermal Sensory Analyzer with a 3 cm heat pain tolerance (HPTo) were assessed on the left ventral forearm and left calf using an ascending method of limits. The Functional Bowel Disease Severity Index (FBDSI) was also obtained for all subjects. RESULTS: Controls were less sensitive than C-IBS and D-IBS (both at P < 0.001) with no differences between C-IBS and D-IBS for HPTh and HPTo. Thermal hyperalgesia was present in both groups of IBS patients relative to controls, with IBS patients reporting significantly lower pain threshold and pain tolerance at both test sites. Cluster analysis revealed the presence of subgroups of IBS patients based on thermal hyperalgesia. One cluster (17% of the sample) showed a profile of heat pain sensitivity very similar to that of healthy controls; a second cluster (47% of the sample) showed moderate heat pain sensitivity; and a third cluster (36% of the sample) showed a very high degree of thermal hyperalgesia.CONCLUSION: A subset of IBS patients had thermal hypersensitivity compared to controls, who reported significantly lower HPTh and HPTo. All IBS patients had a higher score on the FBDSI than controls. Interestingly, the subset of IBS patients with high thermal sensitivity (36%) had the highest FBDSI score compared to the other two groups of IBS patients.

  7. Role of spinal 5-HT receptors in cutaneous hypersensitivity induced by REM sleep deprivation.

    Science.gov (United States)

    Wei, Hong; Ma, Ainiu; Wang, Yong-Xiang; Pertovaara, Antti

    2008-06-01

    Previous studies indicate that rapid eye movement (REM) sleep deprivation facilitates pain sensitivity. Since serotoninergic raphe neurons are involved both in regulation of sleep and descending pain modulation, we studied whether spinal 5-HT receptors have a role in sleep deprivation-induced facilitation of pain-related behavior. REM sleep deprivation of 48h was induced by the flower pot method in the rat. The pain modulatory influence of various serotoninergic compounds administered intrathecally was assessed by determining limb withdrawal response to monofilaments. REM sleep deprivation produced a marked hypersensitivity. Sleep deprivation-induced hypersensitivity and normal sensitivity in controls were reduced both by a 5-HT(1A) receptor antagonist (WAY-100635) and a 5-HT(2C) receptor antagonist (RS-102221). An antagonist of the 5-HT(3) receptor (LY-278584) failed to modulate hypersensitivity in sleep-deprived or control animals. Paradoxically, sensitivity in sleep-deprived and control animals was reduced not only by a 5-HT(1A) receptor antagonist but also by a 5-HT(1A) receptor agonist (8-OHDPAT). The results indicate that serotoninergic receptors in the spinal cord have a complex role in the control of sleep-deprivation induced cutaneous hypersensitivity as well as baseline sensitivity in control conditions. While endogenous serotonin acting on 5-HT(1A) and 5-HT(2C) receptors may facilitate mechanical sensitivity in animals with a sleep deprivation-induced hypersensitivity as well as in controls, increased activation of spinal 5-HT(1A) receptors by an exogenous agonist leads to suppression of mechanical sensitivity in both conditions. Spinal 5-HT(3) receptors do not contribute to cutaneous hypersensitivity induced by sleep deprivation.

  8. Dentin hypersensitivity: from diagnosis to a breakthrough therapy for everyday sensitivity relief.

    Science.gov (United States)

    Cummins, Diane

    2009-01-01

    This paper provides an overview of the current knowledge of diagnosis, epidemiology, etiology, and clinical management of dentin hypersensitivity. It summarizes technical approaches to relieve sensitivity in professional and home-use products, with emphasis on the clinical evidence for the efficacy of desensitizing toothpaste, and introduces a new innovative dentifrice technology containing 8% arginine, calcium carbonate, and 1450 ppm fluoride. Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to external stimuli which cannot be ascribed to any other form of dental defect or disease. The hydrodynamic theory proposes that pain-producing stimuli cause a change in dentin fluid flow that activates intra-dental nerve fibers, via a mechanoreceptor response, to cause pain. To be hypersensitive, dentin must be exposed and dentin tubules must be open to external stimuli and patent at the pulp. Gingival recession is the primary cause of dentin exposure, and a major predisposing factor for dentin hypersensitivity. Dentin hypersensitivity is a prevalent condition. It has been reported to afflict 15-20% of the adult population, typically 20 to 50-year-olds, with peak incidence between 30 and 39 years. Some studies have reported higher prevalence levels of up to 57%. The incidence of dentin hypersensitivity is expected to rise with changing diets, and as caries and periodontal disease prevention result in improved oral health status, and retention and functionality of the dentition. Treatments to relieve dentin hypersensitivity are based on interruption of the neural response to pain stimuli or occlusion of open tubules to block the hydrodynamic mechanism. Effective and robust dentin occlusion offers the greatest prospect for instant and lasting relief of dentin hypersensitivity. In particular, materials which can coat exposed dentin surfaces, in addition to plugging and sealing open dentin tubules, offer the intriguing

  9. Possible role for TRPV1 in neomycin-induced inhibition of visceral hypersensitivity in rat

    NARCIS (Netherlands)

    R.M. van den Wijngaard; O. Welting; D.C. Bulmer; M.M. Wouters; K. Lee; W.J. de Jonge; G.E. Boeckxstaens

    2009-01-01

    Transient receptor ion channel 1 (TRPV1) is a nociceptor involved in visceral hypersensitivity. Aminoglycosides like neomycin are not only potent antibiotics but in vitro data suggest that neomycin also acts as a TRPV1-antagonist and alleviates somatic pain responses. To what extent neomycin reduces

  10. How valid and applicable are current diagnostic criteria and assessment methods for dentin hypersensitivity? An overview.

    Science.gov (United States)

    Gernhardt, Christian R

    2013-03-01

    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 several different external stimuli, it is often inadequately understood. The purpose of this paper is to discuss different available diagnostic approaches and assessment methods used in order to suggest a basis to diagnose, monitor, and measure these challenging painful conditions related to dentin hypersensitivity in daily practice and scientific projects properly. A PubMed literature search strategy including the following MeSH terms were used as follows: "dentin sensitivity"[MeSH Terms] OR "dentin"[All Fields] AND "sensitivity"[All Fields] OR "dentin sensitivity"[All Fields] OR "dentin"[All Fields] AND "hypersensitivity"[All Fields] OR "dentin hypersensitivity"[All Fields] AND "diagnosis"[Subheading] OR "diagnosis"[All Fields] OR "diagnosis"[MeSH Terms] AND "assessment"[All Fields] AND ("methods"[Subheading] OR "methods"[All Fields] OR "methods"[MeSH Terms]. Furthermore, alternative terms such as "validity," "reliability," "root," "cervical," "diagnostic criteria," and "hypersensitivities" were additionally evaluated. The literature search, also including the alternative terms and journals, revealed only a small number of specific papers related to valid diagnosis, diagnostic criteria, and assessment methods of dentin hypersensitivity. Outcomes from these publications showed that the response to different stimuli varies substantially from one person to another and is, due to individual factors, often difficult to assess correctly. Furthermore, the cause of the reported pain can vary, and the patient's description of the history, symptoms, and discomfort might be different from one to another, not allowing a reliable and valid diagnosis. The dental practitioner, using a variety of diagnostic and measurement techniques each day, will often have difficulties in differentiating dentin hypersensitivity from

  11. Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015.

    Science.gov (United States)

    Homma, Yukio; Ueda, Tomohiro; Tomoe, Hikaru; Lin, Alex Tl; Kuo, Hann-Chorng; Lee, Ming-Huei; Oh, Seung-June; Kim, Joon Chul; Lee, Kyu-Sung

    2016-07-01

    Clinical guidelines for interstitial cystitis and hypersensitive bladder have been updated as of 2015. The guidelines define interstitial cystitis by the presence of hypersensitive bladder symptoms (discomfort, pressure or pain in the bladder usually associated with urinary frequency and nocturia) and bladder pathology, after excluding other diseases explaining symptoms. Interstitial cystitis is further classified by bladder pathology; either Hunner type interstitial cystitis with Hunner lesions or non-Hunner type interstitial cystitis with mucosal bleeding after distension in the absence of Hunner lesions. Hypersensitive bladder refers to a condition, where hypersensitive bladder symptoms are present, but bladder pathology or other explainable diseases are unproven. Interstitial cystitis and hypersensitive bladder severely affect patients' quality of life as a result of disabling symptoms and/or comorbidities. Reported prevalence suggestive of these disorders varies greatly from 0.01% to >6%. Pathophysiology would be an interaction of multiple factors including urothelial dysfunction, inflammation, neural hyperactivity, exogenous substances and extrabladder disorders. Definite diagnosis of interstitial cystitis and hypersensitive bladder requires cystoscopy with or without hydrodistension. Most of the therapeutic options lack a high level of evidence, leaving a few as recommended therapeutic options.

  12. Increased anxiety-like behaviors in rats experiencing chronic inflammatory pain.

    Science.gov (United States)

    Parent, Alexandre J; Beaudet, Nicolas; Beaudry, Hélène; Bergeron, Jenny; Bérubé, Patrick; Drolet, Guy; Sarret, Philippe; Gendron, Louis

    2012-04-01

    For many patients, chronic pain is often accompanied, and sometimes amplified, by co-morbidities such as anxiety and depression. Although it represents important challenges, the establishment of appropriate preclinical behavioral models contributes to drug development for treating chronic inflammatory pain and associated psychopathologies. In this study, we investigated whether rats experiencing persistent inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) developed anxiety-like behaviors, and whether clinically used analgesic and anxiolytic drugs were able to reverse CFA-induced anxiety-related phenotypes. These behaviors were evaluated over 28 days in both CFA- and saline-treated groups with a variety of behavioral tests. CFA-induced mechanical allodynia resulted in increased anxiety-like behaviors as evidenced by: (1) a significant decrease in percentage of time spent and number of entries in open arms of the elevated-plus maze (EPM), (2) a decrease in number of central squares visited in the open field (OF), and (3) a reduction in active social interactions in the social interaction test (SI). The number of entries in closed arms in the EPM and the distance traveled in the OF used as indicators of locomotor performance did not differ between treatments. Our results also reveal that in CFA-treated rats, acute administration of morphine (3mg/kg, s.c.) abolished tactile allodynia and anxiety-like behaviors, whereas acute administration of diazepam (1mg/kg, s.c) solely reversed anxiety-like behaviors. Therefore, pharmacological treatment of anxiety-like behaviors induced by chronic inflammatory pain can be objectively evaluated using multiple behavioral tests. Such a model could help identify/validate alternative potential targets that influence pain and cognitive dimensions of anxiety.

  13. 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.

  14. 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.

  15. Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    John; M; Rosen; Jose; T; Cocjin; Jennifer; V; Schurman; Jennifer; M; Colombo; Craig; A; Friesen

    2014-01-01

    Functional gastrointestinal disorders(FGID) are common clinical syndromes diagnosed in the absence of biochemical,structural,or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age,geography,and culture. Etiology of abdominal pain associated FGIDs,including functional dyspepsia(FD),remains incompletely understood,but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD,with focus on pediatric data when available,and provides a summary of potential therapeutic targets.

  16. 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

  17. Experimental evidence for alleviating nociceptive hypersensitivity by single application of capsaicin.

    Science.gov (United States)

    Ma, Xiao-Li; Zhang, Fang-Xiong; Dong, Fei; Bao, Lan; Zhang, Xu

    2015-04-22

    The single application of high-concentration of capsaicin has been used as an analgesic therapy of persistent pain. However, its effectiveness and underlying mechanisms remain to be further evaluated with experimental approaches. The present study provided evidence showing that the single application of capsaicin dose-dependently alleviated nociceptive hypersensitivity, and reduced the action potential firing in small-diameter neurons of the dorsal root ganglia (DRG) in rats and mice. Pre-treatment with capsaicin reduced formalin-induced acute nocifensive behavior after a brief hyperalgesia in rats and mice. The inhibitory effects of capsaicin were calcium-dependent, and mediated by the capsaicin receptor (transient receptor potential vanilloid type-1). We further found that capsaicin exerted inhibitory effects on the persistent nociceptive hypersensitivity induced by peripheral inflammation and nerve injury. Thus, these results support the long-lasting and inhibitory effects of topical capsaicin on persistent pain, and the clinic use of capsaicin as a pain therapy.

  18. Contact hypersensitivity after tongue piercing

    Directory of Open Access Journals (Sweden)

    Ananta Herachakri P

    2010-09-01

    Full Text Available Background: Recently tongue piercing has become increasingly popular in the society. Several case reports have presented various complications of tongue piercing. However, there is no scientific evidence about contact hypersensitivity to tongue piercing. Purpose: The aim of this study was to investigate the contact hypersensitivity after using tongue piercing. Methods: Nineteen male Rattus norvegicus were divided into three groups: group A treated with vaseline on the back and dorsum tongue (control group, group B (I treated with HgCl2 10% cream on the tongue dorsum, group B (II treated with tongue piercing for 10 days and group C with HgCl 2 10% cream on the back, ear lobe, and tongue, then re-exposure with same materials on ear, back and tongue for 24 and 48 hours. Before and after 24 and 48 hours applications, ear width was measured with sliding caliper. At the end of treatments, the rats were sacrificed. All tissue specimens were made for Hematoylin Eosine (H&E staining examination. The number of mononuclear cells was counted under light microscope Data was analyzed with One-Way ANOVA followed by LSD (p<0.05. Results: The result of this study showed that there were a significant difference of the thickness of ear lobe and the number of mononuclear cells (lymphocyte and monocyte among all groups. Conclusion: It is concluded that tongue piercing induce contact hypersensitivity.Latar belakang: Saat ini pemakaian tongue piercing sangat popular di masyarakat. Beberapa laporan kasus menunjukkan bahwa tongue piercing menimbulkan beberapa komplikasi. Namun, belum ada bukti ilmiah mengenai reaksi hipesensitivitas tongue piercing. Tujuan: Untuk mengetahui reaksi hipersensitivitas setelah menggunakan tongue piercing. Metode: Sembilan belas tikus jantan Rattus novergicus yang dibagi dalam tiga kemlompok yaitu: grup A diberi perlakuan dengan vaselin pada punggung dan dorsum lidah, grup B (I diberi perlakuan dengan krim HgCl2 10% pada dorsum lidah dan B

  19. Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity.

    Science.gov (United States)

    Brenchat, Alex; Nadal, Xavier; Romero, Luz; Ovalle, Sergio; Muro, Asunción; Sánchez-Arroyos, Ricard; Portillo-Salido, Enrique; Pujol, Marta; Montero, Ana; Codony, Xavier; Burgueño, Javier; Zamanillo, Daniel; Hamon, Michel; Maldonado, Rafael; Vela, José Miguel

    2010-06-01

    The involvement of the 5-HT(7) receptor in nociception and pain, particularly chronic pain (i.e., neuropathic pain), has been poorly investigated. In the present study, we examined whether the 5-HT(7) receptor participates in some modulatory control of nerve injury-evoked mechanical hypersensitivity and thermal (heat) hyperalgesia in mice. Activation of 5-HT(7) receptors by systemic administration of the selective 5-HT(7) receptor agonist AS-19 (1 and 10mg/kg) exerted a clear-cut reduction of mechanical and thermal hypersensitivities that were reversed by co-administering the selective 5-HT(7) receptor antagonist SB-258719. Interestingly, blocking of 5-HT(7) receptors with SB-258719 (2.5 and 10mg/kg) enhanced mechanical (but not thermal) hypersensitivity in nerve-injured mice and induced mechanical hypersensitivity in sham-operated mice. Effectiveness of the treatment with a 5-HT(7) receptor agonist was maintained after repeated systemic administration: no tolerance to the antiallodynic and antihyperalgesic effects was developed following treatment with the selective 5-HT(7) receptor agonist E-57431 (10mg/kg) twice daily for 11 days. The 5-HT(7) receptor co-localized with GABAergic cells in the dorsal horn of the spinal cord, suggesting that the activation of spinal inhibitory GABAergic interneurons could contribute to the analgesic effects of 5-HT(7) receptor agonists. In addition, a significant increase of 5-HT(7) receptors was found by immunohistochemistry in the ipsilateral dorsal horn of the spinal cord after nerve injury, suggesting a "pain"-triggered regulation of receptor expression. These results support the idea that the 5-HT(7) receptor subtype is involved in the control of pain and point to a new potential use of 5-HT(7) receptor agonists for the treatment of neuropathic pain.

  20. [Hypersensitivity Pneumonitis (extrinsic allergic alveolitis)].

    Science.gov (United States)

    Cebollero, P; Echechipía, S; Echegoyen, A; Lorente, M P; Fanlo, P

    2005-01-01

    Farmer's lung was first described in 1932. We can define hypersensitivity pneumonitis as a pulmonary and systemic disease that is accompanied by dyspnoea and coughing; it is caused by an immunological type of inflammation of the alveolar walls and the terminal airways and it is secondary to the repeated inhalation of a variety of antigens by a susceptible host. It can be said that it is an underdiagnosed disease and only a high degree of clinical manifestations and a detailed history of exposure can lead to an early diagnosis and satisfactory treatment. A combination among clinical-radiological, functional, cytological or pathological findings leads in some cases to a diagnosis. Treatment is based on avoiding further exposure to the causal agent and in the more serious cases the administration of systemic corticoid treatment.

  1. Abolishment of TNBS-induced visceral hypersensitivity in mast cell deficient rats.

    Science.gov (United States)

    Ohashi, Katsuyo; Sato, Yasushi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2008-02-13

    Mucosal mast cells are implicated in visceral hypersensitivity associated with irritable bowel syndrome (IBS). In this study, we investigated the role of mast cells in the development of visceral hypersensitivity by using mast cell deficient (Ws/Ws) rats and their control (W+/W+). In W+/W+ rats, an injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the proximal colon produced a significant decrease in pain threshold of the distal colon. Severe mucosal necrosis and inflammatory cell infiltration with concomitant increase in tissue myeloperoxidase activity were observed in the proximal colon that was directly insulted by TNBS, whereas neither necrosis nor increased myeloperoxidase activity occurred in the distal colon, indicating that TNBS-induced hypersensitivity is not caused by the local tissue damage or inflammation in the region of the gut where distention stimuli were applied. On the other hand, TNBS failed to elicit visceral hypersensitivity in Ws/Ws rats. This finding indicates that mast cells are essential for development of TNBS-induced visceral hypersensitivity in rats. Since the severity of TNBS-induced proximal colon injury and MPO activity was not affected by mast cell deficiency, it is unlikely that abolishment of visceral hypersensitivity in mast cell deficient rats was a result of altered development of the primary injury in the proximal colon. There was no difference between sham-operated Ws/Ws and W+/W+ rats in colonic pain threshold to distention stimuli, indicating that mast cells play no modulatory roles in normal colonic nociception. The present results support the view that mucosal mast cells play key roles in the pathogenesis of IBS.

  2. Hypothesis on how to measure electromagnetic hypersensitivity.

    Science.gov (United States)

    Tuengler, Andreas; von Klitzing, Lebrecht

    2013-09-01

    Electromagnetic hypersensitivity (EHS) is an ill-defined term to describe the fact that people who experience health symptoms in the vicinity of electromagnetic fields (EMFs) regard them as causal for their complaints. Up to now most scientists assume a psychological cause for the suffering of electromagnetic hypersensitive individuals. This paper addresses reasons why most provocation studies could not find any association between EMF exposure and EHS and presents a hypothesis on diagnosis and differentiation of this condition. Simultaneous recordings of heart rate variability, microcirculation and electric skin potentials are used for classification of EHS. Thus, it could be possible to distinguish "genuine" electromagnetic hypersensitive individuals from those who suffer from other conditions.

  3. 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.

  4. Colonic mast cell infiltration in rats with TNBS-induced visceral hypersensitivity.

    Science.gov (United States)

    Ohashi, Katsuyo; Sato, Yasushi; Iwata, Hiroshi; Kawai, Mitsuhisa; Kurebayashi, Yoichi

    2007-12-01

    Colonic mucosal mast cells are implicated in the pathogenesis of visceral hypersensitivity associated with irritable bowel syndromes. This study was designed to investigate the roles of mucosal mast cells in development of an experimental visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats. TNBS, when injected into the proximal colon through laparotomy, produced a significant decrease in pain threshold of the distal colon to mechanical distention, indicating a visceral hypersensitivity. In the proximal colon that was directly insulted by TNBS, mucosal necrosis and extensive inflammatory cell infiltration were observed with concomitant increase in tissue myeloperoxide (MPO) activity. In the distal colon where distention stimuli were applied, the number of mucosal mast cells significantly increased following TNBS treatment, although neither mucosal injury nor increase in tissue MPO activity was observed. In an organ culture, spontaneous release of a mucosal mast cell-specific protease (RMCP-2) from the distal colon tissue of TNBS-treated rats was significantly larger than that of sham animals. Furthermore, TNBS-induced visceral hypersensitivity was significantly suppressed by subcutaneous pretreatment with a mast cell stabilizer doxantrazole in a dose-dependent manner. These findings suggest that prominent colonic mast cell infiltration associated with an enhanced spontaneous mediator release is responsible, at least partly, for development of visceral hypersensitivity induced by TNBS in rats.

  5. 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.

    2014-01-01

    Study Objectives: 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. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: 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. Results: 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

  6. TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis

    National Research Council Canada - National Science Library

    Lapointe, Tamia K; Basso, Lilian; Iftinca, Mircea C; Flynn, Robyn; Chapman, Kevin; Dietrich, Gilles; Vergnolle, Nathalie; Altier, Christophe

    2015-01-01

    .... Although the transient receptor potential vanilloid 1 (TRPV1) ion channel has been postulated as an important mediator of visceral hypersensitivity, its functional role in postinflammatory pain remains elusive...

  7. Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

    Directory of Open Access Journals (Sweden)

    Tsao Douglas

    2012-04-01

    Full Text Available Abstract The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT, an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki = 44 μM. Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for β2- and β3-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions.

  8. A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity.

    Science.gov (United States)

    Kozachik, Sharon L; Page, Gayle G

    2016-05-01

    Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PAC-induced neuropathic pain. To determine the relative contributions of sex and hypothalamic-pituitary-adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the up-down method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy.

  9. Loss of central inhibition: implications for behavioral hypersensitivity after contusive spinal cord injury in rats.

    Science.gov (United States)

    Berrocal, Yerko A; Almeida, Vania W; Puentes, Rocio; Knott, Eric P; Hechtman, Jaclyn F; Garland, Mary; Pearse, Damien D

    2014-01-01

    Behavioral hypersensitivity is common following spinal cord injury (SCI), producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8) 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67) and the glycine receptor α3 (GLRA3), notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain.

  10. Loss of Central Inhibition: Implications for Behavioral Hypersensitivity after Contusive Spinal Cord Injury in Rats

    Directory of Open Access Journals (Sweden)

    Yerko A. Berrocal

    2014-01-01

    Full Text Available Behavioral hypersensitivity is common following spinal cord injury (SCI, producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67 and the glycine receptor α3 (GLRA3, notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain.

  11. Low-level laser therapy of dentin hypersensitivity: a short-term clinical trial.

    Science.gov (United States)

    Orhan, Kaan; Aksoy, Umut; Can-Karabulut, Deniz C; Kalender, Atakan

    2011-09-01

    The aim of this study was to evaluate low-level laser therapy in cervical dentin hypersensitivity. A randomized controlled clinical trial was conducted with a total of 64 teeth. Dentin desensitizer and diode laser were applied on the cervical dentin surfaces. Distilled water and placebo laser was used as the placebo groups. The irradiance used was 4 J/cm(2) per treatment site. The baseline measurement of hypersensitivity was made by using visual analog scale (VAS). Twenty-four hours and 7 days after the application of desensitizer, diode laser and placebo groups, a new VAS analysis was conducted for the patients' sensitivity level. The mean pain scores of placebo groups were significantly higher than the desensitizer's and diode laser's mean scores (ANOVA, p low-level laser therapy and no statistically significant difference was observed between these two treatments (p > 0.05). Although low-level laser and glutaraldehyde containing desensitizer present distinct modes of action, experimental agents caused a significant reduction of dentin hypersensitivity without showing secondary effects, not irritating the pulp or causing pain, not discoloring or staining the teeth, and not irritating the soft tissues at least for a period of 1 week with no drawbacks regarding handling and/or ease of application. Low-level laser therapy and desensitizer application had displayed similar effectiveness in reducing moderate dentin hypersensitivity.

  12. Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity.

    Science.gov (United States)

    Balemans, Dafne; Boeckxstaens, Guy E; Talavera, Karel; Wouters, Mira M

    2017-06-01

    Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders including functional dyspepsia, irritable bowel syndrome, and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM5, and TRPM8), and modulation of their function by increased activation or sensitization (decreased activation threshold) or altered expression in visceral afferents have been reported in visceral hypersensitivity. TRP channels directly detect or transduce osmotic, mechanical, thermal, and chemosensory stimuli. In addition, pro-inflammatory mediators released in tissue damage or inflammation can activate receptors of the G protein-coupled receptor superfamily leading to TRP channel sensitization and activation, which amplify pain and neurogenic inflammation. In this review, we highlight the present knowledge on the functional roles of neuronal TRP channels in visceral hypersensitivity and discuss the signaling pathways that underlie TRP channel modulation. We propose that a better understanding of TRP channels and their modulators may facilitate the development of more selective and effective therapies to treat visceral hypersensitivity. Copyright © 2017 the American Physiological Society.

  13. Reduction in Dental Hypersensitivity with Nano-Hydroxyapatite, Potassium Nitrate, Sodium Monoflurophosphate and Antioxidants#

    Science.gov (United States)

    B. Low, Samuel; Allen, Edward P.; Kontogiorgos, Elias D.

    2015-01-01

    Objective: This clinical study aimed to evaluate effectiveness of a commercially available toothpaste containing potassium nitrate, sodium monoflurophosphate, and nano-hydroxyapatite as well as antioxidants phloretin, ferulic acid and silymarin in reducing dental hypersensitivity in adults. Methods: The clinical trial enrolled patients with a history of dentin hypersensitivity. A test toothpaste was introduced into the daily routine, which included initial instruction on usage. Patients completed a five-question visual analog scale (VAS) at the inception/baseline, after two days and after two weeks of using the toothpaste to determine their level of tooth sensitivity at baseline with the use of the toothpaste over time. Results: Patients that had significant sensitivity at baseline had a range of 52% to 76 % improvement after 48 hours and a range of 70% to 84% improvement after two weeks. Conclusion: A toothpaste containing potassium nitrate, sodium monoflurophosphate, and nano-hydroxyapatite plus antioxidants phloretin, ferulic acid and silymarin applied daily significantly decreased tooth pain of dentin hypersensitivity within a two-day and two-week time period. Clinical Significance: Based on the clinical study results, a daily application of a toothpaste containing potassium nitrate, sodium monofluorophosphate, and nano-hydroxyapatite plus antioxidants phloretin, ferulic acid and silymarin can significantly and quickly reduce tooth pain of dentin hypersensitivity. PMID:25834655

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

    African Journals Online (AJOL)

    Contact allergic reactions due to hypersensitivity to dental materials in professionals and .... it, incisional biopsy was done under local anesthesia and the specimen was sent ... minimal technique sensitivity, amalgam for long has been used for ...

  15. Hypersensitivity reactions associated with endovascular devices.

    Science.gov (United States)

    Honari, Golara; Ellis, Stephen G; Wilkoff, Bruce L; Aronica, Mark A; Svensson, Lars G; Taylor, James S

    2008-07-01

    Allergic reactions to endoprostheses are uncommon and reported in association with orthopaedic, dental, endovascular and other implanted devices. Hypersensitivity reactions to the biomaterials used in endovascular prostheses are among the infrequent reactions that may lead to local or systemic complications following cardiovascular therapeutic interventions. This article reviews potential immunotoxic effects of commonly used biomaterials. Reports of putative hypersensitivity reactions to endovascular devices, including coronary stents, perforated foramen occluders, pacemakers and implantable cardioverter defibrillators are also reviewed.

  16. Food hypersensitivity to lamb in a cat.

    Science.gov (United States)

    Reedy, L M

    1994-04-01

    Severe facial pruritus in a cat was caused by food hypersensitivity to lamb. The cat had been fed an exclusive diet of lamb for 2 years after it had been diagnosed to have food hypersensitivity to fish. Signs, including erythema, alopecia, and excoriations of the head and neck, were poorly responsive to corticosteroid administration, but resolved within a few weeks after removal of the suspected allergen.

  17. The Pharmacology of Visceral Pain.

    Science.gov (United States)

    Johnson, Anthony C; Greenwood-Van Meerveld, Beverley

    2016-01-01

    Visceral pain describes pain emanating from the internal thoracic, pelvic, or abdominal organs. Unlike somatic pain, visceral pain is generally vague, poorly localized, and characterized by hypersensitivity to a stimulus such as organ distension. While current therapeutics provides some relief from somatic pain, drugs used for treatment of chronic visceral pain are typically less efficacious and limited by multiple adverse side effects. Thus, the treatment of visceral pain represents a major unmet medical need. Further, more basic research into the physiology and pathophysiology of visceral pain is needed to provide novel targets for future drug development. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. However, persistent stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders. We will focus on stress-induced exacerbation of chronic visceral pain and provide supporting evidence that centrally acting drugs targeting the pain and stress-responsive brain regions may represent a valid target for the development of novel and effective therapeutics. © 2016 Elsevier Inc. All rights reserved.

  18. Clinical evaluation of desensitizing treatments for cervical dentin hypersensitivity

    Directory of Open Access Journals (Sweden)

    Ana Cecilia Corrêa Aranha

    2009-09-01

    Full Text Available The aim of this study was to compare different treatments for dentin hypersensitivity in a 6-month follow-up. One hundred and one teeth exhibiting non carious cervical lesions were selected. The assessment method used to quantify sensitivity was the cold air syringe, recorded by the visual analogue scale (VAS, prior to treatment (baseline, immediately after topical treatment, after 1 week, 1, 3 and 6 months. Teeth were randomly assigned to five groups (n = 20: G1: Gluma Desensitizer (GD; G2: Seal&Protect (SP; G3: Oxa-gel (OG; G4: Fluoride (F; G5: Low intensity laser-LILT (660 nm/3.8 J/cm²/15 mW. Analysis was based on the non-parametric Kruskal-Wallis test that demonstrated statistical differences immediately after the treatment (p = 0.0165. To observe the individual effects of each treatment, data was submitted to Friedman test. It was observed that GD and SP showed immediate effect after application. Reduction in the pain level throughout the six-month follow-up was also observed. In contrast, LILT presented a gradual reduction of hypersensitivity. OG and F showed effects as of the first and third month respectively. It can be concluded that, after the 6-month clinical evaluation, all therapies showed lower VAS sensitivity values compared with baseline, independently of their different modes of action.

  19. Comparative Effectiveness Research of Dentin Hypersensitivity Intervention - A Mixed Systematic Review Analysis

    OpenAIRE

    Alaskar, Nouf

    2016-01-01

    Introduction and Objective: Dentin Hypersensitivity (DH) is one of the common oral conditions that affect adult population and defined as a short, sharp pain arising from exposed dentin in response to stimuli typically thermal, evaporative, tactile, osmotic or chemical and cannot ascribe to any other form of dental pathology or disease. DH development through two distinct but interrelated phases of tooth wear and gingival recession associated with different etiological factors.Morphological a...

  20. Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain

    Directory of Open Access Journals (Sweden)

    Lin Chih-Shin

    2009-07-01

    Full Text Available Abstract Background Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Despite the availability of pharmacologic treatments, chronic inflammatory pain remains inadequately treated. Understanding the nociceptive signaling pathways of such pain is therefore important in developing long-acting treatments with limited side effects. High local proton concentrations (tissue acidosis causing direct excitation or modulation of nociceptive sensory neurons by proton-sensing receptors are responsible for pain in some inflammatory pain conditions. We previously found that all four proton-sensing G-protein-coupled receptors (GPCRs are expressed in pain-relevant loci (dorsal root ganglia, DRG, which suggests their possible involvement in nociception, but their functions in pain remain unclear. Results In this study, we first demonstrated differential change in expression of proton-sensing GPCRs in peripheral inflammation induced by the inflammatory agents capsaicin, carrageenan, and complete Freund's adjuvant (CFA. In particular, the expression of TDAG8, one proton-sensing GPCR, was increased 24 hours after CFA injection because of increased number of DRG neurons expressing TDAG8. The number of DRG neurons expressing both TDAG8 and transient receptor potential vanilloid 1 (TRPV1 was increased as well. Further studies revealed that TDAG8 activation sensitized the TRPV1 response to capsaicin, suggesting that TDAG8 could be involved in CFA-induced chronic inflammatory pain through regulation of TRPV1 function. Conclusion Each subtype of the OGR1 family was expressed differently, which may reflect differences between models in duration and magnitude of hyperalgesia. Given that TDAG8 and TRPV1 expression increased after CFA-induced inflammation and that TDAG8 activation can lead to TRPV1 sensitization, it suggests that high concentrations of protons after

  1. 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

  2. Possible role for TRPV1 in neomycin-induced inhibition of visceral hypersensitivity in rat.

    Science.gov (United States)

    van den Wijngaard, R M; Welting, O; Bulmer, D C; Wouters, M M; Lee, K; de Jonge, W J; Boeckxstaens, G E

    2009-08-01

    Transient receptor ion channel 1 (TRPV1) is a nociceptor involved in visceral hypersensitivity. Aminoglycosides like neomycin are not only potent antibiotics but in vitro data suggest that neomycin also acts as a TRPV1-antagonist and alleviates somatic pain responses. To what extent neomycin reduces visceral hypersensitivity remains unknown. Therefore, we aimed to investigate whether neomycin can inhibit in vivo TRPV1-dependent hypersensitivity responses in two rat models of visceral pain. In the first model rats were pretreated with intraperitoneal (i.p.) capsazepine, the selective TRPV1 antagonist SB-705498, neomycin or vehicle alone and 30 min later instilled with intracolonic TRPV1-activating capsaicin. Likewise, rats were pretreated with 10 days oral neomycin and then subjected to intracolonic capsaicin. The visceromotor response (VMR) to distension was measured before and after capsaicin application. In addition, the VMR to distension was measured in adult maternal separated rats before and after acute stress. Before the 2nd distension protocol these rats were treated with i.p. neomycin, amoxycillin or vehicle alone. Our results showed that capsaicin administration induced an enhanced VMR to distension that was prevented by i.p. capsazepine, SB-705498 and neomycin. Oral neomycin treatment changed bacterial faecal content but could not inhibit capsaicin induced visceral hypersensitivity. In maternal separated rats acute stress induced an enhanced response to distension that was reversed by i.p. neomycin, but not amoxycillin. These data indicate that (i.p.) neomycin can inhibit visceral hypersensitivity to distension in a nonbactericidal manner and suggest that TRPV1-modulation may be involved.

  3. Contact hypersensitivity to oxazolone provokes vulvar mechanical hyperalgesia in mice.

    Directory of Open Access Journals (Sweden)

    Tijana Martinov

    Full Text Available The interplay among pain, allergy and dysregulated inflammation promises to yield significant conceptual advances in immunology and chronic pain. Hapten-mediated contact hypersensitivity reactions are used to model skin allergies in rodents but have not been utilized to study associated changes in pain perception in the affected skin. Here we characterized changes in mechanical hyperalgesia in oxazolone-sensitized female mice challenged with single and repeated labiar skin exposure to oxazolone. Female mice were sensitized with topical oxazolone on their flanks and challenged 1-3 times on the labia. We then measured mechanical sensitivity of the vulvar region with an electronic pressure meter and evaluated expression of inflammatory genes, leukocyte influx and levels of innervation in the labiar tissue. Oxazolone-sensitized mice developed vulvar mechanical hyperalgesia after a single labiar oxazolone challenge. Hyperalgesia lasted up to 24 hours along with local influx of neutrophils, upregulation of inflammatory cytokine gene expression, and increased density of cutaneous labiar nerve fibers. Three daily oxazolone challenges produced vulvar mechanical hyperalgesic responses and increases in nerve density that were detectable up to 5 days post-challenge even after overt inflammation resolved. This persistent vulvar hyperalgesia is resonant with vulvodynia, an understudied chronic pain condition that is remarkably prevalent in 18-60 year-old women. An elevated risk for vulvodynia has been associated with a history of environmental allergies. Our pre-clinical model can be readily adapted to regimens of chronic exposures and long-term assessment of vulvar pain with and without concurrent inflammation to improve our understanding of mechanisms underlying subsets of vulvodynia and to develop new therapeutics for this condition.

  4. 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.

  5. Heritability of nociception IV: neuropathic pain assays are genetically distinct across methods of peripheral nerve injury.

    Science.gov (United States)

    Young, Erin E; Costigan, Michael; Herbert, Teri A; Lariviere, William R

    2014-05-01

    Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified 5 genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional 9 assays of nociception and hypersensitivity, with the following goals: to replicate the previously identified 5 pain types; to test whether any of the newly added pain assays represent novel genetically distinct pain types; and to test the level of genetic relatedness among 9 commonly used neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the 2 previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. The 4 included mechanical hypersensitivity assays are genetically distinct and do not comprise a single pain type as previously reported. Among the 9 neuropathic pain assays including autotomy, chemotherapy, nerve ligation and spared nerve injury assays, at least 4 genetically distinct types of neuropathic sensory abnormalities were identified, corresponding to differences in nerve injury method. In addition, 2 itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types.

  6. Effects of electroacupuncture on c-Fos expression in the spinal cord and brain of rats with chronic visceral hypersensitivity

    Institute of Scientific and Technical Information of China (English)

    Xiaomei Wang; Huirong Liu; Guanghong Ding; Yunfei Chen; Huangan Wu; Na Li; Enhua Zhou; Xiudi Qin; Lingsong Yuan

    2009-01-01

    BACKGROUND: Visceral hypersensitivity is the main cause of irritable bowel syndrome, c-Fos is a marker of visceral hypersensitivity in the central nervous system. Electroacupuncture can relieve chronic visceral hypersensitivity in rats, but the mechanism is still unknown.OBJECTIVE: To identify c-Fos expression in the spinal cord and cerebral cortex of rats with chronic visceral hypersensitivity, and to test the effects of electroacupuncture on pain sensitivity in rats with chronic visceral hypersensitivity.DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at the Animal Experimental Center, Shanghai University of Traditional Chinese Medicine, from January to April, 2007.MATERIALS: A total of 24 neonatal, male, Sprague Dawley rats, aged five days old, were equally and randomly assigned into a normal group, a model group, and an electroacupuncture group. Rabbit anti-rat c-Fos antibody and Evision secondary antibody kits (Sigma, USA), diaminobenzidine kit (Dako, Denmark), and an LD202H electroacupuncture apparatus (Huawei, Beijing, China) were used in this study.METHODS: Neonatal rats from the model and electroacupuncture groups were used to establish rat models of chronic visceral hypersensitivity by the saccule stimulation method. After model establishment, 0.25 mm diameter electric needles were inserted into Tianshu (ST 25) and Shangjuxu (ST37) at a depth of approximately 0.5 cm, with an square wave (alternating current frequency at 100/20 Hz, amplitude ranged 0.2-0.6 ms, intensify at 1 mA) once for 20 minutes, once a day, for seven days. Rats in the normal and model groups were not treated.MAIN OUTCOME MEASURES: Following 7 days of treatment, c-Fos expression in the spinal cord and cerebral cortex was detected by immunohistochemistry. After the first electroacupuncture treatment, abdominal withdrawal reflex scores were investigated to evaluate the pain threshold for chronic visceral hypersensitivity in rats.RESULTS: Visceral

  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. Histamine in the locus coeruleus promotes descending noradrenergic inhibition of neuropathic hypersensitivity.

    Science.gov (United States)

    Wei, Hong; Jin, Cong-Yu; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2014-12-01

    Among brain structures receiving efferent projections from the histaminergic tuberomammillary nucleus is the pontine locus coeruleus (LC) involved in descending noradrenergic control of pain. Here we studied whether histamine in the LC is involved in descending regulation of neuropathic hypersensitivity. Peripheral neuropathy was induced by unilateral spinal nerve ligation in the rat with a chronic intracerebral and intrathecal catheter for drug administrations. Mechanical hypersensitivity in the injured limb was assessed by monofilaments. Heat nociception was assessed by determining radiant heat-induced paw flick. Histamine in the LC produced a dose-related (1-10μg) mechanical antihypersensitivity effect (maximum effect at 15min and duration of effect 30min), without influence on heat nociception. Pretreatment of LC with zolantidine (histamine H2 receptor antagonist), but not with pyrilamine (histamine H1 receptor antagonist), and spinal administration of atipamezole (an α2-adrenoceptor antagonist), prazosine (an α1-adrenoceptor antagonist) or bicuculline (a GABAA receptor antagonist) attenuated the antihypersensitivity effect of histamine. The histamine-induced antihypersensitivity effect was also reduced by pretreatment of LC with fadolmidine, an α2-adrenoceptor agonist inducing autoinhibition of noradrenergic cell bodies. Zolantidine or pyrilamine alone in the LC failed to influence pain behavior, while A-960656 (histamine H3 receptor antagonist) suppressed hypersensitivity. A plausible explanation for these findings is that histamine, due to excitatory action mediated by the histamine H2 receptor on noradrenergic cell bodies, promotes descending spinal α1/2-adrenoceptor-mediated inhibition of neuropathic hypersensitivity. Blocking the autoinhibitory histamine H3 receptor on histaminergic nerve terminals in the LC facilitates release of histamine and thereby, increases descending noradrenergic pain inhibition.

  9. Localized experimental bone metastasis drives osteolysis and sensory hypersensitivity at distant non-tumor-bearing sites.

    Science.gov (United States)

    Abdelaziz, Dareen M; Stone, Laura S; Komarova, Svetlana V

    2015-08-01

    Patients with breast cancer metastasis to bone suffer from inadequate pain relief. Animal models provide increased understanding of cancer-induced bone and sensory alterations. The objective of this study was to investigate the measures of pain at distant non-tumor-bearing sites in animals with localized bone metastasis. Immunocompetent BALB/c mice are injected intra-tibially with murine mammary carcinoma cells (4T1) or saline, and the sensitivity to mechanical and thermal stimuli in the contralateral paw was examined. In addition to previously demonstrated development of osteolysis and hypersensitivity to mechanical and thermal stimuli in the cancer-injected tibia, these animals exhibited an increase in sensory hypersensitivity in the contralateral limb. No bone lesions were evident on radiographs of the contralateral limbs. Histomorphometry detected decreased bone volume per tissue volume and increased osteoclast number in the contralateral tibia and vertebral bones of cancer-bearing animals. Neuroplasticity was examined by immunofluorescence for calcitonin gene-related peptide (CGRP) in sensory neurons and glial fibrillary acidic protein (GFAP) in lumbar spinal cords. CGRP-immunoreactivity and GFAP-immunoreactivity were significantly elevated both ipsilateral and contralateral in tumor-bearing animals. The anti-inflammatory and osteolysis-targeting drug rapamycin reduced hypersensitivity to mechanical and cold stimuli, attenuated GFAP over-expression, and lowered osteoclast number. The osteoclast-targeting drug pamidronate reduced sensitivity to cold and protected against bone loss. Localized bone cancer drives hypersensitivity, bone remodeling, and sensory neuron plasticity at sites distant from the primary tumor area. Drugs targeting these mechanisms may be useful in the treatment of pain distant from the primary tumor site.

  10. 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.

  11. Clinical Efficacy of Fluoride Varnish and Low-Level Laser Radiation in Treating Dentin Hypersensitivity.

    Science.gov (United States)

    Dantas, Euler Maciel; Amorim, Fernanda Kyarelly de Oliveira; Nóbrega, Fernando José de Oliveira; Dantas, Poliana Medeiros Cunha; Vasconcelos, Rodrigo Gadelha; Queiroz, Lélia Maria Guedes

    2016-01-01

    The objective of this study was to compare the efficacy of fluoride varnish (Fluorniz(r)) and irradiation with a gallium-arsenide-aluminum diode laser in the treatment of cervical dentin hypersensitivity. Cervical dentin hypersensitivity (CDH) is a painful condition that is highly prevalent in the world's adult population, with one in six patients presenting this symptom. Eighty-six teeth were divided into two groups: Group 1, teeth treated with Fluorniz; Group 2, teeth irradiated with a GaAlAs laser at a 4 J/cm2 dose. The two treatments were applied to the buccal cervical region in four sessions, at intervals of 72 to 96 h. The response of the patient to tactile and thermal-evaporative stimuli was rated on a visual analog scale. The results showed a reduction of hypersensitivity in response to tactile and thermal-evaporative stimulation at the end of treatment in both groups. In conclusion, short-term treatment with Fluorniz was found to be more effective than low-level laser radiation in reducing cervical dentin hypersensitivity.

  12. Perception of Dentine Hypersensitivity and Its Management by a ...

    African Journals Online (AJOL)

    Perception of Dentine Hypersensitivity and Its Management by a Group of Nigerian ... the hydrodynamic theory as the commonest theory of tooth hypersensitivity. ... The knowledge of Nigerian Dentists was found to be associated with the ...

  13. 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...

  14. The effects of menthol on cold allodynia and wind-up-like pain in upper limb amputees with different levels of phantom limb pain.

    Science.gov (United States)

    Vase, Lene; Svensson, Peter; Nikolajsen, Lone; Arendt-Nielsen, Lars; Jensen, Troels Staehelin

    2013-02-08

    The mechanisms underlying phantom limb pain are not fully known, but hypersensitivity appears to be a central element. Menthol has previously been suggested as a model for hypersensitivity, but it has not yet been investigated if different levels of neuropathic pain may influence the effects of menthol or if topical application of menthol may act as a model for hypersensitivity in patients with phantom limb pain. In the present study, menthol (l-menthol 40%) was applied to the affected and non-affected sides in 24 upper-limb amputees with different levels of phantom limb pain to test if menthol could induce cold allodynia and exacerbate wind-up-like pain. The average level of phantom limb pain was significantly related to cold allodynia (P=0.044). Prior to application of menthol, the level of phantom limb pain was significantly related to the level of wind-up-like pain following both brush (P=0.040) and pinprick (P=0.033) stimulation. After application of menthol, the level of phantom limb pain was only related to wind-up-like pain following brush (P=0.011) but not pinprick stimulation (P=0.233). This study indicates that menthol does influence hypersensitivity in phantom limb pain patients, and it is the first study to show that menthol may exacerbate wind-up-like pain in this group of neuropathic pain patients. The findings suggest that menthol may act as a model for studying sensitization in phantom limb patients.

  15. Role of Sigma-1 Receptor/p38 MAPK Inhibition in Acupoint Catgut Embedding-Mediated Analgesic Effects in Complete Freund's Adjuvant-Induced Inflammatory Pain.

    Science.gov (United States)

    Du, Kairong; Wang, Xue; Chi, Laiting; Li, Wenzhi

    2017-08-01

    The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia. Rats were prepared with intrathecal catheter implantation. ACE was applied to bilateral "Kunlun" (BL60), "Zusanli" (ST36), and "Sanyinjiao" (SP6) acupoints in the rat model of inflammatory pain (complete Freund's adjuvant [CFA] intraplantar injection). Then, Sig-1R agonist PRE084 or saline was intrathecally given daily. The paw withdrawal thresholds and paw edema were measured before CFA injection and at 1, 3, and 5 day after CFA injection. Western bolt was used to evaluate the protein expression of spinal Sig-1R, p38MAPK, and extracellular signal-regulated kinase (ERK), and immunohistochemistry of Sig-1R was detected at 1, 3, and 5 days after CFA injection. ACE exhibited specific analgesic effects. ACE increased paw withdrawal thresholds and markedly decreased CFA-induced paw edema at 1, 3, and 5 days. ACE downregulated the protein expression of Sig-1R, which was increased significantly at 1, 3, and 5 days after CFA injection. ACE decreased the expression of p38 MAPK and ERK at 1 and 3 days but not at 5 days. However, an injection of Sig-1R agonist PRE084 markedly reversed these alterations, except ERK expression. The present study demonstrated that ACE exhibited antihyperalgesic effects via the inhibition of the Sig-1R that modulated p38 MAPK, but not ERK, expression in the CFA-induced inflammatory pain model in rats.

  16. Flagellate erythema as manifestation of food hypersensitivity

    Directory of Open Access Journals (Sweden)

    Jaheersha Pakran

    2017-07-01

    Full Text Available Food hypersensitivity can present in myriad forms leaving the physician baffled. Here we present a case of flagellate dermatitis in an elderly female with bronchial asthma on omalizumab injections, after ingestion of canned shiitake mushrooms. Knowledge about shiitake mushroom dermatitis is important due to increasing prevalence worldwide because of changing culinary preferences.

  17. 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 ...

  18. Anticonvulsant hypersensitivity syndrome secondary to carbamazepine

    Science.gov (United States)

    Brown, Shannon C.

    2017-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a potentially fatal multiorgan drug reaction that presents with various cutaneous eruptions. There is a genetic predisposition to such reactions. We present a young woman with AHS due to carbamazepine that presented as an atypical erythema multiforme with elevated liver enzymes. PMID:28127149

  19. Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain

    Directory of Open Access Journals (Sweden)

    Cui Guang-bin

    2012-02-01

    Full Text Available Abstract Background Interleukin-8 (IL-8 is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC, is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain. Findings In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC, and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice. Conclusions Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain.

  20. Treatments for hypersensitive noncarious cervical lesions

    Science.gov (United States)

    Veitz-Keenan, Analia; Barna, Julie Ann; Strober, Brad; Matthews, Abigail G.; Collie, Damon; Vena, Donald; Curro, Frederick A.; Thompson, Van P.

    2014-01-01

    Background The Practitioners Engaged in Applied Research and Learning (PEARL) Network conducted a three-armed randomized clinical study to determine the comparative effectiveness of three treatments for hypersensitive noncarious cervical lesions (NCCLs): use of a potassium nitrate dentifrice for treatment of hypersensitivity, placement of a resin-based composite restoration and placement of a sealant. Methods Seventeen trained practitioner-investigators (P-Is) in the PEARL Network enrolled participants (N = 304) with hypersensitive posterior NCCLs who met enrollment criteria. Participants were assigned to treatments randomly. Evaluations were conducted at baseline and at one, three and six months thereafter. Primary outcomes were the reduction or elimination of hypersensitivity as measured clinically and by means of patient-reported outcomes. Results Lesion depth and pretreatment sensitivity (mean, 5.3 on a 0- to 10-point scale) were balanced across treatments, as was sleep bruxism (present in 42.2 percent of participants). The six-month participant recall rate was 99 percent. Treatments significantly reduced mean sensitivity (P dentifrice group. The dentifrice group’s mean (standard deviation) sensitivity at six months was 2.1 (2.1); those of the sealant and restoration groups were 1.0 (1.6) and 0.8 (1.4), respectively. Patient-reported sensitivity (to cold being most pronounced) paralleled clinical measurements at each evaluation. Conclusions Sealing and restoration treatments were effective overall in reducing NCCL hypersensitivity. The potassium nitrate dentifrice reduced sensitivity with increasing effectiveness through six months but not to the degree offered by the other treatments. Practical Implications Sealant or restoration placement is an effective method of immediately reducing NCCL sensitivity. Although a potassium nitrate dentifrice did reduce sensitivity slowly across six months, at no time was the reduction commensurate with that of sealants or

  1. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Erichsen, Helle K; Brown, David T

    2012-01-01

    this concept being tested in humans. Prior to assessing the efficacy of GABA-A receptor PAMs in a human volunteer pain model we have compared compounds capable of variously modulating GABA-A receptor function in comparable rat models of capsaicin-induced acute nocifensive flinching behaviour and secondary...... mechanical hypersensitivity. The subtype-selective PAM NS11394 (0.3-10 mg/kg), and the non-selective PAM diazepam (1-5 mg/kg) variously reduced capsaicin-induced secondary mechanical hypersensitivity (180 min post-injection). However, the low efficacy subtype-selective PAM TPA023 (3-30 mg/kg) was completely......, albeit at doses previously shown to impair locomotor function. Our data indicate that GABA-A receptor PAMs with optimal selectivity and efficacy profiles reduce centrally-mediated mechanical hypersensitivity in capsaicin-injected rats, an observation that we expect can translate directly to human...

  2. Intrathecal clonidine and adenosine: effects on pain and sensory processing in patients with chronic regional pain syndrome.

    Science.gov (United States)

    Rauck, Richard L; North, James; Eisenach, James C

    2015-01-01

    Chronic pain may be accompanied by hyperalgesia and allodynia, and analgesic interventions may reduce these hypersensitivity phenomena. Preclinical data suggest that intrathecal clonidine and adenosine reduce hypersensitivity, but only clonidine reduces pain; therefore, we tested the effects of these interventions in patients with chronic pain. Twenty-two subjects with pain and hyperalgesia in a lower extremity from complex regional pain syndrome were recruited in a double-blind crossover study to receive intrathecal clonidine, 100 μg, or adenosine, 2 mg. Primary outcome measure was proportion with ≥30% reduction in pain 2 hours after injection, and secondary measures were pain report, areas of hypersensitivity, and temporal summation to heat stimuli. Treatments did not differ in the primary outcome measure (10 met success criterion after clonidine administration and 5 after adenosine administration), although they did differ in pain scores over time, with clonidine having a 3-fold greater effect (P = 0.014). Both drugs similarly reduced areas of hyperalgesia and allodynia by approximately 30% and also inhibited temporal summation. The percentage change in pain report did not correlate with the percentage change in areas of hyperalgesia (P = 0.09, r = 0.08) or allodynia (P = 0.24, r = 0.24) after drug treatment. Both intrathecal clonidine and adenosine acutely inhibit experimentally induced and clinical hypersensitivity in patients with chronic regional pain syndrome. Although these drugs do not differ in analgesia by the primary outcome measure, their difference in effect on pain scores over time and lack of correlation between effect on pain and hypersensitivity suggest that analgesia does not parallel antihyperalgesia with these treatments.

  3. Nociceptor-expressed ephrin-B2 regulates inflammatory and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Kullander Klas

    2010-11-01

    Full Text Available Abstract Background EphB receptors and their ephrin-B ligands play an important role in nervous system development, as well as synapse formation and plasticity in the adult brain. Recent studies show that intrathecal treatment with EphB-receptor activator ephrinB2-Fc induced thermal hyperalgesia and mechanical allodynia in rat, indicating that ephrin-B2 in small dorsal root ganglia (DRG neurons and EphB receptors in the spinal cord modulate pain processing. To examine the role of ephrin-B2 in peripheral pain pathways, we deleted ephrin-B2 in Nav1.8+ nociceptive sensory neurons with the Cre-loxP system. Sensory neuron numbers and terminals were examined using neuronal makers. Pain behavior in acute, inflammatory and neuropathic pain models was assessed in the ephrin-B2 conditional knockout (CKO mice. We also investigated the c-Fos expression and NMDA receptor NR2B phosphorylation in ephrin-B2 CKO mice and littermate controls. Results The ephrin-B2 CKO mice were healthy with no sensory neuron loss. However, pain-related behavior was substantially altered. Although acute pain behavior and motor co-ordination were normal, inflammatory pain was attenuated in ephrin-B2 mutant mice. Complete Freund's adjuvant (CFA-induced mechanical hyperalgesia was halved. Formalin-induced pain behavior was attenuated in the second phase, and this correlated with diminished tyrosine phosphorylation of N-methyl-D-aspartic acid (NMDA receptor subunit NR2B in the dorsal horn. Thermal hyperalgesia and mechanical allodynia were significantly reduced in the Seltzer model of neuropathic pain. Conclusions Presynaptic ephrin-B2 expression thus plays an important role in regulating inflammatory pain through the regulation of synaptic plasticity in the dorsal horn and is also involved in the pathogenesis of some types of neuropathic pain.

  4. 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.

  5. Trigeminal nerve injury ErbB3/ErbB2 promotes mechanical hypersensitivity.

    Science.gov (United States)

    Ma, Fei; Zhang, Liping; Westlund, Karin N

    2012-08-01

    Chronic constriction injury of the trigeminal infraorbital nerve results in transient analgesia followed by whisker pad mechanical allodynia in rats. Neuregulin 1 expressed on axonal membranes binds receptor tyrosine kinase ErbB, promoting Schwann cell development and remyelination. This study investigated whether orofacial mechanical allodynia is signaled by ErbB3-ErbB2 heterodimers in injured nerves. Whisker pad mechanical allodynia (von Frey stimuli) was quantified in wild type rats and in transgenic rats with Sleeping Beauty transposon mutation for neuregulin 1 transgene. Pain-related behavior was retested after intraperitoneal injection of the ErbB2 inhibitor Lapatinib, an agent shown by others to reduce breast cancer pain. Infraorbital nerve injury was evaluated histologically with myelin and neuronal biomarkers. ErbB3 changes over time were measured with western blots. Whisker pad mechanical hypersensitivity began in week 2 in wild type rats (3.11 ± 5.93 g vs. 18.72 ± 0.00 g after sham surgery, n = 9, P wild type rats was alleviated by Lapatinib (15 ± 3.89 g vs. 2.45 ± 1.13 g, n = 6, P wild type and transgenic rats (week 10) coincided with time points when mechanical hypersensitivity was present. The Neuregulin 1-ErbB3-ErbB2 complex is a causal mechanism in nerve injury-induced trigeminal neuropathic pain. Understanding peripheral glial mechanisms after nerve injury will improve neuropathic pain treatment.

  6. Spinal processing of bee venom-induced pain and hyperalgesia

    Institute of Scientific and Technical Information of China (English)

    Jun CHEN

    2008-01-01

    Subcutaneous injection of bee venom causes long-term neural activation and hypersensitization in the dorsal horn of the spinal cord, which contributes to the development and maintenance of various pain-related behaviors. The unique behavioral 'pheno-types' of nociception and hypersensitivity identified in the rodent bee venom test are believed to reflect a complex pathological state of inflammatory pain and might be appropriate to the study of phenotype-based mechanisms of pain and hyperalgesia. In this review, the spinal processing of the bee venom-induced different 'phenotypes' of pain and hyperalgesia will be described. The accumulative electrophysiological, pharmacological, and behavioral data strongly suggest that different 'phenotypes' of pain and hyperalgesia are mediated by different spinal signaling pathways. Unraveling the phenotype-based mechanisms of pain might be useful in development of novel therapeutic drugs against complex clinic pathological pain.

  7. Clinical evaluation of the efficacy of fluoride adhesive tape (F-PVA) in reducing dentin hypersensitivity.

    Science.gov (United States)

    Lee, Sang-Ho; Lee, Nan-Young; Lee, In-Hwa

    2013-06-01

    To evaluate the in vivo effectiveness of an experimental 2.26% fluoride polyvinyl alcohol (F-PVA) tape in reducing dentin hypersensitivity. 30 healthy men and women (total of 79 teeth) in their third decade of life with dentin hypersensitivity were enrolled in this study. The subjects were divided into four groups: three experimental groups were treated with fluoride agents (F-PVA tape, Vanish varnish, and ClinPro XT varnish), and a control group was treated with gelatin as a placebo. Each fluoride agent was applied according to the manufacturer's instructions. Stimulation was applied to the subjects' teeth using compressed air and ice sticks before applying the agent, as well as at 3 days and 4, 8, and 12 weeks after applying the agent. The degree of pain was measured using a visual analogue scale (VAS). The VAS scores were significantly (P Vanish varnish and ClinPro XT varnish at 4 and 8 weeks of the examination period.

  8. 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...

  9. 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 pain

  10. Role of sympathetic nervous system in rat model of chronic visceral pain.

    Science.gov (United States)

    Gil, D W; Wang, J; Gu, C; Donello, J E; Cabrera, S; Al-Chaer, E D

    2016-03-01

    Changes in central pain modulation have been implicated in generalized pain syndromes such as irritable bowel syndrome (IBS). We have previously demonstrated that reduced descending inhibition unveils a role of sympathoneuronal outflow in decreasing peripheral sensory thresholds, resulting in stress-induced hyperalgesia. We investigated whether sympathetic nervous system (SNS) exacerbation of pain sensation when central pain inhibition is reduced is relevant to chronic pain disorders using a rat colon irritation (CI) model of chronic visceral hypersensitivity with hallmarks of IBS. Rats were treated to a series of colorectal balloon distensions (CRD) as neonates resulting in visceral and somatic hypersensitivity and altered stool function that persists into adulthood. The visceral sensitivity was assessed by recording electromyographic (EMG) responses to CRD. Somatic sensitivity was assessed by paw withdrawal thresholds to radiant heat. The effects on the hypersensitivity of (i) inhibiting sympathoneuronal outflow with pharmacological and surgical interventions and (ii) enhancing the outflow with water avoidance stress (WAS) were tested. The alpha2-adrenergic agonist, clonidine, and the alpha1-adrenergic antagonist, prazosin, reduced the visceral hypersensitivity and WAS enhanced the pain. Chemical sympathectomy with guanethidine and surgical sympathectomy resulted in a loss of the chronic visceral hypersensitivity. The results support a role of the SNS in driving the chronic visceral and somatic hypersensitivity seen in CI rats. The findings further suggest that treatments that decrease sympathetic outflow or block activation of adrenergic receptors on sensory nerves could be beneficial in the treatment of generalized pain syndromes. © 2015 John Wiley & Sons Ltd.

  11. Computerized cuff pressure algometry: A new method to assess deep-tissue hypersensitivity in fibromyalgia.

    Science.gov (United States)

    Jespersen, Anders; Dreyer, Lene; Kendall, Sally; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars; Bliddal, Henning; Danneskiold-Samsoe, Bente

    2007-09-01

    The aim of this study was to evaluate the use of computerized cuff pressure algometry (CPA) in fibromyalgia (FM) and to correlate deep-tissue sensitivity assessed by CPA with other disease markers of FM. Forty-eight women with FM and 16 healthy age-matched women were included. A computer-controlled, pneumatic tourniquet cuff was placed over the gastrocnemius muscle. The cuff was inflated, and the subject rated the pain intensity continuously on an electronic Visual Analogue Scale (VAS). The subject stopped the inflation at the pressure-pain tolerance and the corresponding VAS-score was determined (pressure-pain limit). The pressure at which VAS firstly exceeded 0 was defined as the pressure-pain threshold. Other disease markers (FM only): Isokinetic knee muscle strength, tenderpoint-count, myalgic score, Beck Depression Inventory, and Fibromyalgia Impact Questionnaire. Student's T-test was used to compare pressure-pain threshold and pressure-pain tolerance and the Mann-Whitney test to compare pressure-pain limit. Pearson's correlation was used to detect linear relationships. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in FM compared to healthy controls. There was no difference in pressure-pain limit. CPA-parameters were significantly correlated to isokinetic muscle strength where more hypersensitivity resulted in lower strength. Pressure-pain threshold and pressure-pain tolerance assessed by CPA were significantly lower in patients with FM indicating muscle hyperalgesia. CPA was associated with knee muscle strength but not with measures thought to be influenced by psychological distress and mood.

  12. 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...... of PEG's allergenic potential remains low, due to a general lack of suspicion towards excipients and insufficient product labelling. Information on immediate-type reactions to PEG is limited to anecdotal reports, and the potential for PEG sensitization and cross-sensitization to PEGylated drugs...... to a range of unrelated products in hospital and at home. Increased awareness of PEG prevalence, PEG hypersensitivity, and improved access to PEG allergy testing, should facilitate earlier diagnosis and reduce the risk of inadvertent re-exposure. This first comprehensive review provides practical information...

  13. Mechanisms of Myofascial Pain

    Science.gov (United States)

    Jafri, M. Saleet

    2014-01-01

    Myofascial pain syndrome is an important health problem. It affects a majority of the general population, impairs mobility, causes pain, and reduces the overall sense of well-being. Underlying this syndrome is the existence of painful taut bands of muscle that contain discrete, hypersensitive foci called myofascial trigger points. In spite of the significant impact on public health, a clear mechanistic understanding of the disorder does not exist. This is likely due to the complex nature of the disorder which involves the integration of cellular signaling, excitation-contraction coupling, neuromuscular inputs, local circulation, and energy metabolism. The difficulties are further exacerbated by the lack of an animal model for myofascial pain to test mechanistic hypothesis. In this review, current theories for myofascial pain are presented and their relative strengths and weaknesses are discussed. Based on new findings linking mechanoactivation of reactive oxygen species signaling to destabilized calcium signaling, we put forth a novel mechanistic hypothesis for the initiation and maintenance of myofascial trigger points. It is hoped that this lays a new foundation for understanding myofascial pain syndrome and how current therapies work, and gives key insights that will lead to the improvement of therapies for its treatment. PMID:25574501

  14. Drug hypersensitivity in clonal mast cell disorders

    DEFF Research Database (Denmark)

    Bonadonna, P; Pagani, M; Aberer, W

    2015-01-01

    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...... disorders using MEDLINE, EMBASE, and Cochrane Library, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation....

  15. [Rare, severe hypersensitivity reaction to potassium iodide].

    Science.gov (United States)

    Korsholm, Anne Sofie; Ebbehøj, Eva; Richelsen, Bjørn

    2014-07-07

    The literature reports a large variety of adverse reactions to potassium iodide. A severe hypersensitivity reaction to potassium iodide in a 51-year-old woman with Graves' thyrotoxicosis is described. Following administration the patient developed sialadenitis, conjunctivitis, stomatitis and acneiform iododerma that responded dramatically to withdrawal of the potassium iodide and administration with corticosteroids. Awareness of these adverse reactions may prevent prolonged hospitalization and unnecessary tests and treatments.

  16. Hypersensitivity manifestations to the fruit mango

    OpenAIRE

    Sareen, Richa; SHAH, ASHOK

    2011-01-01

    The objectives of this study are 1) To review the published data and document the current knowledge on allergic manifestations to the fruit mango 2) To highlight the two distinct clinical presentations of hypersensitivity reactions caused by mango 3) To discuss the role of cross-reactivity 4) To increase awareness of potentially life threatening complications that can be caused by allergy to mango. An extensive search of the literature was performed in Medline/PubMed with the key terms "mango...

  17. 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; Mckinnin, Elizabeth; Ostrov, David; Peters, Bjoern

    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 ...

  18. [A misleading form of hypersensitivity pneumonitis].

    Science.gov (United States)

    Gainet, M; Chaudemanche, H; Westeel, V; Lounici, A; Dubiez, A; Depierre, A; Dalphin, J C

    2000-11-01

    A 47-year-old woman, without significant past medical history, presented an acute dyspnea with hypoxia, marked pulmonary arterial hypertension (PAH) and signs of right heart failure. Chest x-ray showed a moderate dilatation of the right heart cavities. Pulmonary embolism was suggested. After detailed questioning and complete explorations, a bird hypersensitivity pneumonitis (HP) was demonstrated. This case illustrates a misleading presentation of an acute form of HP consisting of apparently isolated PAH.

  19. Hypersensitivity reactions to fluoroquinolones: analysis of the factors involved.

    Science.gov (United States)

    Blanca-López, N; Ariza, A; Doña, I; Mayorga, C; Montañez, M I; Garcia-Campos, J; Gomez, F; Rondón, C; Blanca, M; Torres, M J

    2013-05-01

    Hypersensitivity reactions to fluoroquinolones seem to be on the increase, especially immediate type reactions. The aim of this study was to determine whether several conditions, including gender, age, type of reaction, time interval between the reaction and the study, type of symptoms, the specific fluoroquinolone involved in the reaction and previous confirmed hypersensitivity to betalactams or to other drugs were factors contributing to the development of hypersensitivity to fluoroquinolones. We analysed retrospectively all patients attending our allergy department between January 2005 and December 2010 because of a reaction associated with fluoroquinolone administration. The diagnosis was confirmed by basophil activation test or drug provocation tests. In accordance with the results, patients were then classified as having hypersensitivity or non-hypersensitivity to fluoroquinolones. A group of 218 patients was evaluated; 69 were confirmed as having hypersensitivity, 146 as non-hypersensitivity and 3 were excluded. Comparisons between groups showed that the allergic patients more often had a previous confirmed hypersensitivity to betalactams (P = 0.029), immediate reactions (P = 0.001) and anaphylaxis (P = 0.000), and moxifloxacin was the fluoroquinolone most frequently involved (P = 0.027). The logistic regression analysis showed three factors associated with the diagnosis of hypersensitivity reactions to fluoroquinolones: previous hypersensitivity to betalactams (OR: 4.571; 95% CI: 0.987-21.171; adjusted OR: 23.654; 95% CI: 1.529-365.853), immediate reactions (OR: 17.333; 95% CI: 4.374-68.691; adjusted OR: 52.493; 95% CI: 6.621-416.200) and reactions induced by moxifloxacin (OR: 3.091; 95% CI: 1.160-8.239; adjusted OR: 13.610; 95% CI: 2.419-76.565). In patients who develop reactions to fluoroquinolones, hypersensitivity is more often confirmed in those with immediate reactions and when moxifloxacin is involved. Moreover, patients with hypersensitivity to

  20. Visceral pain: the ins and outs, the ups and downs.

    Science.gov (United States)

    Sikandar, Shafaq; Dickenson, Anthony H

    2012-03-01

    Visceral pain represents a major clinical problem, yet far less is known about its mechanisms compared with somatic pains, for example, from cutaneous and muscular structures. In this review, we describe the neuroanatomical bases of visceral pain signalling in the peripheral and central nervous system, comparing to somatic pains and also the channels and receptors involved in these events. We include an overview of potential new targets in the context of mechanisms of visceral pain and hypersensitivity. This review should inform on the recognition of what occurs in patients with visceral pain, why comorbidities are common and how analgesic treatments work.

  1. Visceral Pain and Psychiatric Disorders.

    Science.gov (United States)

    Felice, Valeria D; Moloney, Rachel D; Cryan, John F; Dinan, Timothy G; O'Mahony, Siobhain M

    2015-01-01

    The high comorbidity existing between visceral pain and psychiatric disorders such as depression and anxiety is well documented and it is gaining increasing interest among scientists. When visceral pain and psychiatric disorders are comorbid, they present a more debilitating condition than each disorder alone, impacting significantly on the quality of life of these patients. Despite several groups having shown that an overlapping pathophysiology exists between visceral pain and stress-related disorders the link between them is not clear yet. Moreover, it still remains to be elucidated if psychiatric conditions predispose the individual to develop visceral hypersensitivity or vice versa. The brain-gut-microbiome axis is the bidirectional communication between the CNS and the gastrointestinal tract. Alterations at different levels of this axis have been implicated in both visceral hypersensitivity and psychiatric disorders. Here we give an overview of what it is known about comorbid visceral pain and psychiatric disorders and provide evidence of potential overlapping pathophysiological mechanisms involved. Preclinical models of comorbid visceral pain and stress-related disorders are also discussed. © 2015 S. Karger AG, Basel.

  2. Self-reported somatosensory symptoms of neuropathic pain in fibromyalgia and chronic widespread pain correlate with tender point count and pressure-pain thresholds

    DEFF Research Database (Denmark)

    Amris, Kirstine; Jespersen, Anders; Bliddal, Henning

    2010-01-01

    Widespread pain and pain hypersensitivity are the hallmark of fibromyalgia, a complex pain condition linked to central sensitization. In this study the painDETECT questionnaire (PDQ), validated to identify neuropathic pain and based on pain quality items, was applied in a cross-sectional sample...... of patients with chronic widespread pain (CWP). The aims of the study were to assess the patient-reported sensory neuropathic symptoms by PDQ and to correlate these with tender point (TP) count and pressure-pain thresholds. Eighty-one patients (75 F, 6 M) with CWP (ACR-criteria) filled in the PDQ. Manual TP...... examination was conducted according to ACR guidelines. Computerized cuff pressure algometry was used for the assessment of pressure-pain detection thresholds (PDT, unit: kPa) and pressure-pain tolerance thresholds (PTT, unit: kPa). Mean TP count was 14.32 (range: 2-18), mean PDQ score 22.75 (range: 5...

  3. Spinal histamine in attenuation of mechanical hypersensitivity in the spinal nerve ligation-induced model of experimental neuropathy.

    Science.gov (United States)

    Wei, Hong; Viisanen, Hanna; You, Hao-Jun; Pertovaara, Antti

    2016-02-05

    Here we studied whether and through which mechanisms spinal administration of histamine dihydrochloride (histamine) attenuates pain behavior in neuropathic animals. Experiments were performed in rats with spinal nerve ligation-induced neuropathy and a chronic intrathecal catheter for spinal drug delivery. Mechanical hypersensitivity was assessed with monofilaments while radiant heat was used for assessing nociception. Ongoing neuropathic pain and its attenuation by histamine was assessed using conditioned place-preference test. Following spinal administration, histamine at doses 0.1-10µg produced a dose-related mechanical antihypersensitivity effect. With prolonged treatment (twice daily 10µg for five days), the antihypersensitivity effect of spinal histamine was reduced. In place-preference test, neuropathic animals preferred the chamber paired with histamine (10µg). Histamine (10µg) failed to influence heat nociception in neuropathic animals or mechanically induced pain behavior in a group of healthy control rats. Histamine-induced mechanical antihypersensitivity effect was prevented by spinal pretreatment with zolantidine (histamine H2 receptor antagonist), prazosine (α1-adrenoceptor antagonist) and bicuculline (γ-aminobutyric acid subtype A, GABA(A), receptor antagonist), but not by pyrilamine (histamine H1 receptor antagonist), atipamezole (α2-adrenoceptor antagonist), or raclopride (dopamine D2 receptor antagonist). A-960656, a histamine H3 receptor antagonist alone that presumably increased endogenous histamine levels reduced hypersensitivity. Additionally, histamine prevented central (presumably postsynaptically-induced) facilitation of hypersensitivity induced by N-methyl-d-aspartate. The results indicate that spinal histamine at the dose range of 0.1-10µg selectively attenuates mechanical hypersensitivity and ongoing pain in neuropathy. The spinal histamine-induced antihypersensitivity effect involves histamine H2 and GABA(A) receptors and

  4. What is known about the influence of dentine hypersensitivity on oral health-related quality of life?

    OpenAIRE

    Bekes,Katrin; Hirsch, Christian

    2012-01-01

    Objectives Oral health-related quality of life is a relatively new but rapidly growing concept in dentistry. It is an aspect of dental health addressing the patient’s perception of whether his/her current oral health status has an impact upon his/her actual quality of life. Dentine hypersensitivity (DHS), which is a common condition of transient tooth pain associated with a variety of exogenous stimuli, may disturb the patient during eating, drinking, toothbrushing and sometimes even breathin...

  5. Groin pain

    Science.gov (United States)

    Pain - groin; Lower abdominal pain; Genital pain; Perineal pain ... Common causes of groin pain include: Pulled muscle, tendon, or ligaments in the leg: This problem often occurs in people who play sports such as ...

  6. Desensitizing treatments for dentin hypersensitivity: a randomized, split-mouth clinical trial

    OpenAIRE

    Veridiana Camilotti; Juliana Zilly; Priscilla do Monte Ribeiro Busato; Carlos Augusto Nassar; Patrícia Oehlmeyer Nassar

    2012-01-01

    The aim of this randomized, controlled, split-mouth, clinical study was to differentiate and clinically qualify the effectiveness of different desensitizing agents in the treatment of painful symptoms caused by cervical dentin hypersensitivity (CDH). Two hundred-and-fifty-two teeth of 42 patients were distributed into seven groups (n = 36): G1 - placebo; G2, G3, G4 and G6 - fluoride varnishes; G5 - sodium fluoride; G7 - potassium oxalate. Three applications were made one week apart. A three-s...

  7. Mesalamine hypersensitivity and Kounis syndrome in a pediatric ulcerative colitis patient

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    5-aminosalicylic acid (mesalamine) rarely induces hyper-sensitivity reactions. If chest pain associated with atypical electrocardiographic changes are seen during its adminis-tration, one should always bear in mind type I variant of Kounis syndrome. This variant includes patients, of any age, with normal coronary arteries, without predisposing factors for coronary artery disease, in whom the acute release of inflammatory mediators from mast cells can induce either sudden coronary artery narrowing, without increase of cardiac enzymes and troponins, or coronary artery spasm that progresses to acute myocardial infarc-tion, with elevated cardiac enzymes and troponins.

  8. Effectiveness of Three Desensitizing Dentifrices on Cervical Dentin Hypersensitivity: A Pilot Clinical Trial.

    Science.gov (United States)

    Douglas de Oliveira, Dhelfeson Willya; Oliveira, Evandro Silveira de; Mota, André Felipe Miranda; Pereira, Victor Hugo Urzedo; Bastos, Vinícius Oliveira; Glória, José Cristiano Ramos; Gonçalves, Patricia Furtado; Flecha, Olga Dumont

    2016-04-08

    Cervical dentin hypersensitivity (CDH) is defined as an acute pain of short duration that occurs in dentin exposed to the oral environment. The aim of this study was to evaluate the effi cacy of three desensitizing toothpastes (Sensodyne® Rapid-Relief, Colgate® Sensitive Pro-Relief, Nano P®) for immediate and intermediate-term relief of CDH, when compared with a control toothpaste (Cocoricó®). Eight patients were enrolled in this clinical study. One hundred thirty-eight hypersensitive teeth were randomized into four groups according to the com- position of the desensitizing toothpaste tested: Group I) strontium acetate and calcium carbonate; II) calcium carbonate and arginine 8%; III) calcium phosphate nanoparticles; and IV) a control toothpaste. A split mouth design was used for one application each of the desensitizing dentifrices. Assessment of CDH was done by evaporative and cold stimuli at baseline, immediately, 24 hours and 30 days after the treatment. The toothpastes presented similar effectiveness and statistically significant improvement in 30 days compared to baseline. Group III showed statistically significant relief for cervical dentin hypersensitivity immediately after the treatment. The only toothpaste that presented immediate relief effect was the paste containing calcium phosphate nanoparticles in the form of hydroxyapatite. Copyright© by the International Academy of Periodontology.

  9. Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

    OpenAIRE

    2009-01-01

    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 neuropa...

  10. Lymphocyte transformation studies in drug hypersensitivity.

    Science.gov (United States)

    Warrington, R J; Tse, K S

    1979-05-05

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents.Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects.For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test.It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs.

  11. 7th Drug hypersensitivity meeting: part two

    OpenAIRE

    Elera, Javier Dionicio; Boteanu, Cosmin; Blanco, Maria Aranzazu Jimenez; Gonzalez-Mendiola, Rosario; García, Irene Carrasco; Alvarez, Antonio; Martinez, Jose Julio Laguna; Garrido, Jaume Martí; Barona, Carla Torán; Chorda, Carolina Perales; Salgueiro, Ramón López; Palacios, Miguel Díaz; de Rojas, Dolores Hernández Fernández; Acar, Emre Ali; Aktas, Ayse

    2016-01-01

    Table of contents Poster walk 11: miscellaneous drug hypersensitivity 2 (P92–P94, P96–P101) P92 16 years of experience with proton pump inhibitors (PPIs) Javier Dionicio Elera, Cosmin Boteanu, Maria Aranzazu Jimenez Blanco, Rosario Gonzalez-Mendiola, Irene Carrasco García, Antonio Alvarez, Jose Julio Laguna Martinez P93 Allergy evaluation of quinolone induced adverse reactions Jaume Martí Garrido, Carla Torán Barona, Carolina Perales Chorda, Ramón López Salgueiro, Miguel Díaz Palacios, Dolore...

  12. Comparative efficacy of two treatment modalities for dentinal hypersensitivity: A clinical trial

    Directory of Open Access Journals (Sweden)

    Aparna S

    2010-01-01

    Full Text Available Background: Dentin hypersensitivity is a recurrent condition causing discomfort and sometimes pain to the patient, which also deters him from maintaining adequate oral hygiene. Home care and office measures are used for treatment of this malady. Aim: To evaluate and compare the efficacy of 2 treatment modalities for dentinal hypersensitivity, iontophoresis with acidulated phosphate gel (APF gel, and dentin-bonding agent application. Materials and Methods: This split mouth randomized clinical study recruited subjects with a history of hypersensitivity with at least 2 teeth, verified by a light stroke with a dental explorer along the cervical third of the teeth. The patients were subjected to a 1-s air blast and cold water stimuli and their responses were recorded on a verbal rating scale. A total of 30 sites from 15 patients were divided into Group A-1.23% APF gel iontophoresis; and Group B-aqueous solution of hydroxyl-ethyl-methacrylate and glutaraldehyde. The teeth were evaluated immediately after the treatment and at the end of 2 weeks. In case of failure, the tooth was retreated with the same agent as before. Results: The results were statistically analyzed using Kruskal-Wallis analysis of variance and Mann-Whitney U tests. There was no statistically significant difference between the groups at the end of 2 weeks. However, Group A was more effective clinically, with fewer number of failures compared with Group B. Conclusion: Both the agents showed a statistically significant reduction in sensitivity compared with baseline; however, APF gel iontophoresis was more effective in reducing hypersensitivity over a longer time period.

  13. Cytokines in Neuropathic Pain and Associated Depression.

    Science.gov (United States)

    Lees, Justin G; Fivelman, Brett; Duffy, Samuel S; Makker, Preet G S; Perera, Chamini J; Moalem-Taylor, Gila

    2015-01-01

    Neuropathic pain occurs as a result of lesion or disease affecting the somatosensory nervous system and is present in a diverse set of peripheral and central pathologies such as nerve trauma, diabetic neuropathy, post-herpetic neuralgia, chemotherapy-induced peripheral neuropathy, spinal cord injury and multiple sclerosis. Debilitating symptoms including allodynia, hyperalgesia and spontaneous pain have a substantial negative impact on patients' quality of life. The currently available therapeutic treatments are generally ineffective and characterised by poor response rates. Accumulating evidence suggests that neuroinflammation and cytokine signalling play a critical role in neuropathic pain. Numerous experimental studies have demonstrated that certain pro-inflammatory cytokines are elevated in neuropathic pain conditions, and administration of these cytokines can elicit pain hypersensitivity in the absence of injury or disease. This phenomenon is also apparent in the 'sickness response', which encompasses a broad inflammatory response to disease and injury and involves a series of physiological and behavioural changes including pain hypersensitivity. Interestingly, the 'sickness response' is also similar in nature to some of the defining characteristics of the depressed state of affective disorder. In this review, we explore links that may relate the co-existence of depression in neuropathic pain patients with the activity of cytokines and discuss the role of several key pro-inflammatory and anti-inflammatory cytokines in neuropathic pain.

  14. [Prolonged pain in neonates: retrospective analysis].

    Science.gov (United States)

    Lilla, Michèle; Stadelman-Diaw, Corinne; Ramelet, Anne-Sylvie

    2013-12-01

    Infants hospitalised in neonatology are inevitably exposed to pain repeatedly. Premature infants are particularly vulnerable, because they are hypersensitive to pain and demonstrate diminished behavioural responses to pain. They are therefore at risk of developing short and long-term complications if pain remains untreated. Compared to acute pain, there is limited evidence in the literature on prolonged pain in infants. However, the prevalence is reported between 20 and 40 %. This single case study aimed to identify the bio-contextual characteristics of neonates who experienced prolonged pain. This study was carried out in the neonatal unit of a tertiary referral centre in Western Switzerland. A retrospective data analysis of seven infants' profile, who experienced prolonged pain ,was performed using five different data sources. The mean gestational age of the seven infants was 32weeks. The main diagnosis included prematurity and respiratory distress syndrome. The total observations (N=55) showed that the participants had in average 21.8 (SD 6.9) painful procedures that were estimated to be of moderate to severe intensity each day. Out of the 164 recorded pain scores (2.9 pain assessment/day/infant), 14.6 % confirmed acute pain. Out of those experiencing acute pain, analgesia was given in 16.6 % of them and 79.1 % received no analgesia. This study highlighted the difficulty in managing pain in neonates who are exposed to numerous painful procedures. Pain in this population remains underevaluated and as a result undertreated.Results of this study showed that nursing documentation related to pain assessment is not systematic.Regular assessment and documentation of acute and prolonged pain are recommended. This could be achieved with clear guidelines on the Assessment Intervention Reassessment (AIR) cyclewith validated measures adapted to neonates. The adequacy of pain assessment is a pre-requisite for appropriate pain relief in neonates.

  15. Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury

    Directory of Open Access Journals (Sweden)

    Hugues Petitjean

    2015-11-01

    Full Text Available Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV interneuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury.

  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. Frequency, treatment, and functional outcome in children with hypersensitivity pneumonitis

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Petersen, Bodil Laub; Damgaard, Karen;

    2011-01-01

    Hypersensitivity pneumonitis is a rare interstitial lung disease and very few data regarding frequency, treatment and outcome exist for children. Children identified with hypersensitivity pneumonia from a Danish national cohort with diffuse interstitial lung disease form the basis of this study...... focused on disease frequency, treatment, and functional outcome....

  18. 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.

  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. Colonic N-methyl-d-aspartate receptor contributes to visceral hypersensitivity in irritable bowel syndrome.

    Science.gov (United States)

    Qi, Qingqing; Chen, Feixue; Zhang, Wenxue; Wang, Peng; Li, Yanqing; Zuo, Xiuli

    2017-04-01

    N-methyl-d-aspartate receptor (NMDAR) in brain, spinal cord, and enteric nervous system is involved in visceral hypersensitivity. This study aimed to reveal the functional expression of NMDAR on mucosal cells in colon and to investigate the downstream signal pathway from colonic NMDAR activation to visceral hypersensitivity in irritable bowel syndrome (IBS). The expression of mucosal NMDAR in IBS patients and healthy controls was assessed by immunohistochemistry and Western blot and correlated with abdominal pain/discomfort scores quantified by a validated questionnaire. Electromyography recording in response to colorectal distension was recorded to measure the colonic sensitivity of mice receiving NMDA administration intracolonically. Brain-derived neurotrophic factor (BDNF) expression and extracellular signal-regulated kinase (ERK) pathway activation were examined in human colonic epithelial HT29 cells after NMDA stimulation, with or without MK801 or U0126 pretreatment. A significant upregulation of mucosal NMDAR was observed in IBS patients compared with controls, which was significantly correlated with abdominal pain/discomfort scores. Intracolonic administration of NMDA in normal mice produced increased colonic sensitivity to colorectal distension and elevated expression of BDNF and activation of ERK. Activation of NMDAR in colonic epithelial HT29 cells in vitro induced increased BDNF secretion in cell supernatants and higher BDNF expression in cells, as well as elevated phosphorylated ERK. This study demonstrated that the activation of mucosal NMDAR in colon may contribute to the visceral hypersensitivity in IBS, by increasing production of BDNF in an ERK-dependent pathway. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  1. Radiocontrast media hypersensitivity in the Asia Pacific region.

    Science.gov (United States)

    Lee, Suh-Young; Lim, Kyoung-Whan; Chang, Yoon-Seok

    2014-04-01

    Radiocontrast media (RCM) is a major cause of drug hypersensitivity reactions as the medical application of RCM is increasing recently. RCM induced hypersensitivity reactions are considered as unpredictable type B reactions. Underlying mechanism of RCM induced hypersensitivity was previously regarded as nonimmunological mechanisms but recent studies suggest that immunological mechanisms could also be involved. As a result, the roles of skin tests and premedication are revisiting. As there has been no report that comprehensively summarized and analyzed the results of the studies on RCM hypersensitivity in the Asia Pacific region, we aimed to review the literatures on hypersensitivity reactions to RCM in terms of prevalence clinical manifestations, diagnostic approach, and preventive measures in the Asia Pacific region.

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

    Science.gov (United States)

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

    2010-11-01

    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.

  3. Abdominal pain

    Science.gov (United States)

    Stomach pain; Pain - abdomen; Belly ache; Abdominal cramps; Bellyache; Stomachache ... Almost everyone has pain in the abdomen at some point. Most of the time, it is not serious. How bad your pain is does not always reflect the seriousness ...

  4. 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. ...

  5. Pain Management

    Science.gov (United States)

    ... of pain. In the 19th century, physician-scientists discovered that opiates such as morphine could relieve pain ... tissue damage.” TODAY Pain affects more Americans than diabetes, heart disease and cancer combined. Pain is cited ...

  6. Heel pain

    Science.gov (United States)

    Pain - heel ... Heel pain is most often the result of overuse. However, it may be caused by an injury. Your heel ... on the heel Conditions that may cause heel pain include: Swelling and pain in the Achilles tendon ...

  7. Flank pain

    Science.gov (United States)

    Pain - side; Side pain ... Flank pain can be a sign of a kidney problem. But, since many organs are in this area, other causes are possible. If you have flank pain and fever , chills, blood in the urine, or ...

  8. Rapid desensitization for hypersensitivity reactions to medications.

    Science.gov (United States)

    Castells, Mariana

    2009-08-01

    Drug desensitization is the induction of temporary clinical unresponsiveness to drug antigens to which patients have presented severe hypersensitivity reactions. It is typically achieved by gradual reintroduction of small doses of drug antigens at fixed time intervals, and it is aimed at providing increased safety and protection from side effects, including anaphylaxis. Delivery of full therapeutic doses is achieved during desensitization, allowing patients to receive firstline chemotherapy, antibiotics, or monoclonal antibodies, as well as other drugs such as insulin, aspirin, and iron. Desensitizations are high-risk interventions. Inhibition of cellular activation mechanisms occurs during drug desensitization, allowing for the protective clinical outcomes and lack of side effects in the majority of cases, but the cellular and molecular inhibitory mechanisms are incompletely understood. The indication for desensitization protocols can only be done by trained allergists and immunologists and should be implemented as standard of care because of their high success rates and outcomes-demonstrated safety profile.

  9. Selective immediate hypersensitivity reactions to NSAIDs.

    Science.gov (United States)

    Canto, Maria Gabriela; Andreu, Isabel; Fernandez, Javier; Blanca, Miguel

    2009-08-01

    Selective immediate reactions to NSAIDs imply that patients develop a urticarial/anaphylactic response to a single drug with good tolerance to other compounds. No systematic review of these reactions has yet been made. With the increase in consumption of NSAIDs, these have become one of the most common drugs inducing hypersensitivity reactions. Although cross-intolerance reactions are the most common, a significant proportion is selective responses. As specific IgE antibodies are not always found, there is only indirect evidence supporting an IgE-mediated mechanism in selective NSAID reactors. Selective immediate reactions to NSAIDs must be considered when a patient develops urticaria or anaphylaxis after intake of one drug with good tolerance to drugs from other groups or even a drug from the same group with a slightly different chemical structure. Further research is required to identify the antigenic determinant structures recognized.

  10. Non-surgical management of tooth hypersensitivity.

    Science.gov (United States)

    Clark, Danielle; Levin, Liran

    2016-10-01

    Tooth sensitivity is a common complaint of patients in dental practices. Studies have demonstrated dentinal hypersensitivity to affect 10-30% of the population. There are various potential causes of tooth sensitivity and a variety of available treatment options. This narrative review will discuss the possible aetiology of this condition, as well as the treatment modalities available. A tailor-made treatment plan that starts with the most non-invasive treatment options and escalates only when those options have proven insufficient in alleviating symptoms should be provided for each patient. Only after all non- and less-invasive methods have failed to reduce the symptoms should more invasive treatment options, such as root-coverage, be considered.

  11. Pain in fibromyalgia and related conditions.

    Science.gov (United States)

    Cassisi, G; Sarzi-Puttini, P; Casale, R; Cazzola, M; Boccassini, L; Atzeni, F; Stisi, S

    2014-06-06

    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.

  12. 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.

  13. A novel bioactive glass-ceramic for treating dentin hypersensitivity

    Directory of Open Access Journals (Sweden)

    Camila Tirapelli

    2010-12-01

    Full Text Available Dentin hypersensitivity (DH is a painful response to stimulus applied to the open dentinal tubules of a vital tooth. It's a common oral condition, however, without an ideal treatment available yet. This work evaluated in vitro the effect of micron-sized particles from a novel bioactive glass-ceramic (Biosilicate in occluding open dentinal tubules. A dentin disc model was employed to observe comparatively, using scanning electron microscopy (SEM, dentinal tubule occlusion by different products and deposition of hydroxyl carbonate apatite (HCA on dentin surface by Biosilicate, after a single application: G1 - Dentifrice with potassium nitrate and fluoride; G2 - Two-step calcium phosphate precipitation treatment; G3 - Water-free gel containing Biosilicate particles (1%; G4 - Biosilicate particles mixed with distilled water in a 1:10 ratio; all of them after 1, 12 and 24 hours of immersion in artificial saliva. Fourier transform infrared spectroscopy (FTIR was performed to detect HCA formation on dentin discs filled with Biosilicate after 2 minutes, 30 minutes and 12 hours of immersion in artificial saliva. SEM showed a layer of HCA formed on dentin surface after 24 hours by G4. G1, G2 and G3 promoted not total occlusion of open dentinal tubules after 24 hours. FTIR showed HCA precipitation on the dentin surface induced by Biosilicate after 30 minutes. The micron-sized particles from the bioactive glass-ceramic thus were able to induce HCA deposition in open dentinal tubules in vitro. This finding suggests that Biosilicate may provide a new option for treating DH.

  14. Sex differences in pain: a tale of two immune cells.

    Science.gov (United States)

    Mapplebeck, Josiane C S; Beggs, Simon; Salter, Michael W

    2016-02-01

    Substantial evidence has implicated microglia in neuropathic pain. After peripheral nerve injury, microglia in the spinal cord proliferate and increase cell-surface expression of the purinergic receptor P2X4. Activation of P2X4 receptors results in release of brain-derived neurotrophic factor, which acts on neurons to produce disinhibition of dorsal horn neurons which transmit nociceptive information to the brain. Disinhibition of these neurons produces pain hypersensitivity, a hallmark symptom of neuropathic pain. However, elucidating this microglia-neuronal signalling pathway was based on studies using only male rodents. Recent evidence has shown that the role of microglia in pain is sexually dimorphic. Despite similar microglia proliferation in the dorsal horn in both sexes, females do not upregulate P2X4Rs and use a microglia-independent pathway to mediate pain hypersensitivity. Instead, adaptive immune cells, possibly T cells, may mediate pain hypersensitivity in female mice. This profound sex difference highlights the importance of including subjects of both sexes in preclinical pain research.

  15. 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.

  16. 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.

  17. 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...

  18. 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

  19. Endogenous Opioid-Masked Latent Pain Sensitization

    DEFF Research Database (Denmark)

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

    2015-01-01

    naloxone dose (0.021 mg/kg). However, while LS was consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This difference is likely due to selection bias since the C57BL/6 mouse strain exhibits markedly enhanced pain sensitivity in assays of acute thermal nociception. Future......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 chronic pain, but LS has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous mild heat injury (MHI) we demonstrated a dose-dependent reinstatement of pain sensitization, assessed as primary (P

  20. SPONTANEOUS CHRONIC PAIN AFTER EXPERIMENTAL THORACTOMY REVEALED BY CONDITIONED PLACE PREFERENCE: morphine differentiates tactile evoked pain from spontaneous pain

    Science.gov (United States)

    Hung, Ching-Hsia; Wang, Jeffrey Chi-Fei; Strichartz, Gary

    2015-01-01

    Chronic pain following surgery limits social activity, interferes with work and causes emotional suffering. A major component of such pain is is reported as “resting” or spontaneous pain with no apparent external stimulus. Although experimental animal models can simulate the stimulus-evoked chronic pain that occurs after surgery, there have been no studies of spontaneous chronic pain in such models. Here the Conditioned Place Preference (CPP) paradigm was used to reveal resting pain after experimental thoracotomy. Male Sprague-Dawley rats received a thoracotomy with 1 hour rib retraction, resulting in evoked tactile hypersensitivity, previously shown to last for at least 9 weeks. Intraperitoneal injections of morphine (2.5 mg/kg) or gabapentin (40mg/kg) gave equivalent 2-3h long relief of tactile hypersensitivity, when tested 12-14 days post-operative. In separate experiments, single trial CPP was conducted 1 week before thoracotomy and then 12 days (gabapentin) or 14 days (morphine) after surgery, followed the next day by one conditioning sesssion with morphine or gabapentin, both vs saline. The gabapentin-conditioned, but not the morphine-conditioned rats showed a significant preference for the analgesia-paired chamber, despite the two agents’ equivalent effect in relieving tactile allodynia. These results show that experimental thoracotomy in rats causes spontaneous pain, and that some analgesics, such as morphine, that reduce evoked pain do not also relieve resting pain, suggesting that pathophysiological mechanisms differ between these two aspects of long-term post-operative pain. PMID:26116369

  1. Psychologic factors are related to some sensory pain thresholds but not nociceptive flexion reflex threshold in chronic whiplash.

    Science.gov (United States)

    Sterling, Michele; Hodkinson, Emily; Pettiford, Catherine; Souvlis, Tina; Curatolo, Michele

    2008-02-01

    Sensory hypersensitivity, central hyperexcitability [lowered nociceptive flexion reflex (NFR) thresholds], and psychologic distress are features of chronic whiplash. However, relationships between these substrates are not clear. This study tested the hypothesis that psychologic distress and catastrophization are correlated with sensory hypersensitivity and NFR responses in chronic whiplash. Pressure and thermal pain thresholds (mean values across 3 body sites), NFR threshold, and pain at threshold Visual Analog Scale were measured in 30 participants with chronic whiplash and 30 asymptomatic controls. Pain and disability levels Neck Disability Index, psychologic distress (GHQ-28), and catastrophization (PCS) were also measured in the whiplash group. Whiplash injured participants demonstrated lowered pain thresholds to pressure and cold (Pthresholds (P=0.003), and demonstrated above threshold levels of psychologic distress (GHQ-28) and levels of catastrophization comparable with other musculoskeletal conditions. There were no group differences for heat pain thresholds or pain at NFR threshold. In the whiplash group, PCS scores correlated moderately with cold pain threshold (r=0.51, P=0.01). In contrast, there were no significant correlations between GHQ-28 scores and pain threshold measures or between psychologic factors and NFR responses in whiplash participants. There were no significant correlations between psychologic factors and pain thresholds or NFR responses in controls. We have demonstrated that psychologic factors have some association with sensory hypersensitivity (cold pain threshold measures) in chronic whiplash but do not seem to influence spinal cord excitability. This suggests that psychologic disorders are important, but not the only, determinants of central hypersensitivity in whiplash patients.

  2. Hypersensitivity to biological agents-updated diagnosis, management, and treatment.

    Science.gov (United States)

    Galvão, Violeta Régnier; Castells, Mariana C

    2015-01-01

    Biological agents are used in the treatment of neoplastic, autoimmune, and inflammatory diseases and their clinical applications are becoming broader. Following their increased utilization, hypersensitivity reactions linked to these drugs have become more frequent, sometimes preventing the use of first-line therapies. The clinical presentation of hypersensitivity reactions to biological agents ranges from mild cutaneous manifestations to life-threatening reactions. In this scenario, rapid desensitization is a groundbreaking procedure that enables selected patients to receive the full treatment dose in a safe way, in spite of their immediate hypersensitivity reaction to the drug, and protects them against anaphylaxis. The aim of this review is to update and discuss some of the main biological agents used in clinical practice (rituximab, trastuzumab, cetuximab, ofatumumab, tocilizumab, brentuximab, omalizumab, and tumor necrosis factor alpha inhibitor agents) and their associated hypersensitivity reactions, including clinical presentations, diagnosis, and treatment in the acute setting. In addition, novel management options with rapid desensitization are presented.

  3. Type I immediate hypersensitivity reaction to cyanocobalamin but not hydroxycobalamin.

    Science.gov (United States)

    Moloney, F J; Hughes, R; O'Shea, D; Kirby, B

    2008-07-01

    We report a case of a 42-year-old woman with a background of autoimmune polyglandular syndrome, who developed a type I immediate hypersensitivity reaction to intramuscular cyanocobalamin. Intradermal testing showed a positive reaction to cyanocobalamin. The patient was subsequently treated with intramuscular hydroxycobalamin after negative intradermal testing to this alternative B(12) compound. A review of previously described cases of hypersensitivity to either compound provides a rationale for the management of this rare but serious side-effect.

  4. 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.

  5. 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......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...

  6. Auditory hypersensitivity in children and teenagers with autistic spectrum disorder

    OpenAIRE

    2004-01-01

    OBJECTIVE: To verify if the clinical behavior of auditory hypersensitivity, reported in interviews with parents/caregivers and therapists/teachers of 46 children and teenagers suffering from autistic spectrum disorder, correspond to audiological findings. METHOD: The clinical diagnosis for auditory hypersensitivity was investigated by means of an interview. Subsequently, a test of the acoustic stapedial reflex was conducted, and responses to intense acoustic stimulus in open field were observ...

  7. A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene

    OpenAIRE

    Kim, Young Jae; Hwang, Eu Dong; Leem, Ah Young; Kang, Beo Deul; Chang, Soo Yun; Kim, Ho Keun; Park, In Kyu; Kim, Song Yee; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon

    2014-01-01

    Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man w...

  8. Psychophysiological responses to visceral and somatic pain in functional chest pain identify clinically relevant pain clusters.

    Science.gov (United States)

    Farmer, A D; Coen, S J; Kano, M; Naqvi, H; Paine, P A; Scott, S M; Furlong, P L; Lightman, S L; Knowles, C H; Aziz, Q

    2014-01-01

    Despite chronic pain being a feature of functional chest pain (FCP) its experience is variable. The factors responsible for this variability remain unresolved. We aimed to address these knowledge gaps, hypothesizing that the psychophysiological profiles of FCP patients will be distinct from healthy subjects. 20 Rome III defined FCP patients (nine males, mean age 38.7 years, range 28-59 years) and 20 healthy age-, sex-, and ethnicity-matched controls (nine males, mean 38.2 years, range 24-49) had anxiety, depression, and personality traits measured. Subjects had sympathetic and parasympathetic nervous system parameters measured at baseline and continuously thereafter. Subjects received standardized somatic (nail bed pressure) and visceral (esophageal balloon distension) stimuli to pain tolerance. Venous blood was sampled for cortisol at baseline, post somatic pain and post visceral pain. Patients had higher neuroticism, state and trait anxiety, and depression scores but lower extroversion scores vs controls (all p visceral stimulus (p = 0.009) and had a higher cortisol at baseline, and following pain (all p pain they increased their parasympathetic tone (p ≤ 0.008). The amalgamating the data, we identified two psychophysiologically distinct 'pain clusters'. Patients were overrepresented in the cluster characterized by high neuroticism, trait anxiety, baseline cortisol, pain hypersensitivity, and parasympathetic response to pain (all p < 0.03). In future, such delineations in FCP populations may facilitate individualization of treatment based on psychophysiological profiling. © 2013 John Wiley & Sons Ltd.

  9. Visceral and Somatic Hypersensitivity in TNBS induced Colitis in Rats

    Science.gov (United States)

    Zhou, QiQi; Price, Donald D.; Caudle, Robert M.; Verne, G. Nicholas

    2010-01-01

    Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200g–250g) were treated with 20 mg of TNBS in 50% ethanol (n=40) or an equivalent volume of ethanol (n=40) or saline (n=25) via the colon. Colonic distension, Von-Frey, Hargreaves, and tail reflex test were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2–28 days following TNBS (p<0.0001). The ethanol treated rats also demonstrated visceral hypersensitivity that resolved after day 14. TNBS treated rats demonstrated somatic hypersensitivity at days 14–28 (p<0.0001) in response to somatic stimuli of the hind-paw. TNBS colitis is associated with visceral and somatic hypersensitivity in areas of somatotopic overlap. This model of colitis should allow further investigation into the mechanisms of visceral and somatic hypersensitivity. PMID:17703363

  10. Old, New and Hidden Causes of Perioperative Hypersensitivity.

    Science.gov (United States)

    Garvey, Lene Heise

    2016-01-01

    Perioperative hypersensitivity reactions are rare, often life-threatening events, and subsequent investigations to identify the culprit are important to avoid re-exposure. All exposures in the perioperative setting may potentially be the cause of a hypersensitivity reaction, but drugs administered 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 not necessarily be the case in all countries. New and hidden allergens have emerged as causes of perioperative hypersensitivity such as blue dyes, chlorhexidine and excipients. Detailed knowledge of the events at the time of reaction is necessary to identify potential culprits including rare and hidden allergens. Cooperation between allergists and anaesthetists, or other staff present perioperatively, is often needed to identify hidden or even undocumented exposures. The objectives of this review are to provide an overview of the history of investigation of perioperative hypersensitivity, to describe the differences 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.

  11. Fibromyalgia and Chronic Pain Syndromes

    Science.gov (United States)

    Choy, Ernest; Clauw, Daniel J.; Goldenberg, Don L.; Harris, Richard E.; Helfenstein, Milton; Jensen, Troels Staehelin; Noguchi, Koichi; Silverman, Stuart L.; Ushida, Takahiro; Wang, Guochun

    2016-01-01

    This manuscript, developed by a group of chronic pain researchers and clinicians from around the world, aims to address the state of knowledge about fibromyalgia (FM) and identify ongoing challenges in the field of FM and other chronic pain syndromes that may be characterized by pain centralization/amplification/hypersensitivity. There have been many exciting developments in research studies of the pathophysiology and treatment of FM and related syndromes that have the potential to improve the recognition and management of patients with FM and other conditions with FM-like pain. However, much of the new information has not reached all clinicians, especially primary care clinicians, who have the greatest potential to use this new knowledge to positively impact their patients’ lives. Furthermore, there are persistent misconceptions about FM and a lack of consensus regarding the diagnosis and treatment of FM. This paper presents a framework for future global efforts to improve the understanding and treatment of FM and other associated chronic pain syndromes, disseminate research findings, identify ways to enhance advocacy for these patients, and improve global efforts to collaborate and reach consensus about key issues related to FM and chronic pain in general. PMID:27022674

  12. Clinical evaluation of low-power laser and a desensitizing agent on dentin hypersensitivity.

    Science.gov (United States)

    Lopes, Anely Oliveira; Eduardo, Carlos de Paula; Aranha, Ana Cecília Correa

    2015-02-01

    The aim of this randomized, longitudinal clinical study was to evaluate different protocols for dentin hypersensitivity treatment with low-power laser at different dosages, desensitizing agent, and associations, for a period of 6 months. After analysis of the inclusion and exclusion criteria of volunteer participants, those who present pain resulting from non-carious cervical lesions were selected. Twenty-seven patients participated in the study, and 55 lesions were recorded. The lesions were divided into five groups (n = 11), treated, and evaluated: G1: Gluma Desensitizer (Heraeus); G2: low-power laser (Photon Lase, DMC) at low dose (three vestibular points and one apical point of irradiation: 30 mW, 10 J/cm(2), 9 s per point with wavelength of 810 nm), three sessions were performed with an interval of 72 h between them; G3: low-power laser at high dose (application at one cervical and one apical point: 100 mW, 90 J/cm(2), 11 s per point with wavelength of 810 nm), three sessions were performed with an interval of 72 h between irradiations; G4: low-power laser at low dose + Gluma Desensitizer; and G5: low-power laser at high dose + Gluma Desensitizer, the level of sensitivity of each volunteer was evaluated with a visual analog scale of pain (VAS) with the use of air from a triple syringe and exploration with a probe after time intervals of 5 min, 1 week, and 1, 3, and 6 months after treatment. Data were collected and subjected to statistical analysis. Kolmogorov-Smirnov test was used to verify the distribution of the data, and nonparametric Kruskal-Wallis and Friedman tests were performed for comparison among the experimental groups and time intervals studied, respectively. Statistically significant differences between the studied time intervals (p low-level lasers, it was observed that there were distinct effects for the different doses; however, both were efficient in reducing pain up to the 6 months of clinical follow-up. Therefore, it

  13. Chronic Pain

    Science.gov (United States)

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis ...

  14. 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...

  15. Visceral Pain – the Ins and Outs, the Ups and Downs

    Science.gov (United States)

    Sikandar, Shafaq; Dickenson, Anthony H

    2012-01-01

    Purpose of review Visceral pain represents a major clinical problem, yet far less is known about its mechanisms compared to somatic pains, e.g. from cutaneous and muscular structures. Recent findings In this review we describe the neuroanatomical bases of visceral pain signalling in the peripheral and central nervous system, comparing to somatic pains and also the channels and receptors involved in these events. We include an overview of potential new targets in the context of mechanisms of visceral pain and hypersensitivity. Summary This review should inform on the recognition of what occurs in patients with visceral pain, why co-morbidities are common and how analgesic treatments work. PMID:22246042

  16. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain

    Science.gov (United States)

    Hama, Aldric T.; Plum, Ann Woodhouse; Sagen, Jacqueline

    2010-01-01

    Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na+ channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na+ channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggests that peripherally expressed Na+ channels could lend themselves as targets for the development of pharmacotherapies for SCI pain. PMID:20732348

  17. Gastroesophageal Reflux Symptoms not Responding to Proton Pump Inhibitor: GERD, NERD, NARD, Esophageal Hypersensitivity or Dyspepsia?

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    Mohammad Bashashati

    2014-01-01

    Full Text Available 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.

  18. Perception of dentine hypersensitivity and its management by a group of Nigerian dentists.

    Science.gov (United States)

    Afolabi, A O; Ogundipe, O K; Adegbulugbe, I C; Shaba, O P

    2012-01-01

    Dentists need to be aware of the management of dentine sensitivity in view of its high prevalence. The study is to determine by questionnaire the perception of dentine hypersensitivity (DH) and its management by Nigerian Dentists. A structured questionnaire was used to collect data from 176 Nigerian Dentists who attended professional dental workshops in Lagos, Ife and Jos, Nigeria. The majority (73.3%) of the responding dentists claimed to see patients with DH. Nearly half (45.1%) of the dentists mentioned cold as the commonest stimulus evoking pain in DH while 56.8% could correctly identified the hydrodynamic theory as the commonest theory of tooth hypersensitivity. Multifactorial aetiology identified as causing DH included tooth wear lesions, periodontal causes and bruxism. Treatment options suggested varies but non-invasive was mentioned more than the invasive techniques. Sensodyne toothpaste was the commonest desensitising paste mentioned. The knowledge of Nigerian Dentists was found to be associated with the specialty of the practitioners (p = 0.0004). Dental Practitioners, especially the General Dental Practitioners should be enthusiastic in updating their knowledge of DH and the management. Prevention of DH by the Patients and the Dentists should be emphasised.

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

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    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.

  20. Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury through vasopressin-1A receptors of the rat trigeminal ganglia.

    Science.gov (United States)

    Kubo, Asako; Shinoda, Masamichi; Katagiri, Ayano; Takeda, Mamoru; Suzuki, Tatsuro; Asaka, Junichi; Yeomans, David C; Iwata, Koichi

    2016-12-17

    Oxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In this study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin after PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG). The proportion of vasopressin-1A receptor (V1A-R)-immunoreactive, but not OXT-receptor-immunoreactive, neurons significantly increased among TG neurons innervating the whisker pad skin after PNL. In a patch-clamp recording from TG neurons isolated from PNL rats, the resting membrane potential of OXT-treated neurons was significantly decreased, and the current thresholds of OXT-treated neurons for spike generation (rheobases) were significantly greater than those of vehicle-treated neurons. In addition, OXT increased voltage-gated K channel currents in PNL animals. Furthermore, intra-TG administration of a selective V1A-R antagonist reversed the OXT-induced alleviation of mechanical hypersensitivity, and coapplication of the antagonist opposed OXT's effects on the resting membrane potential, rheobase, and K current. These findings suggest that OXT is effective at suppressing TG neuronal hyperexcitability after nerve injury, likely by modulation of voltage-gated K channels through V1A-R. This signaling mechanism represents a potential therapeutic target for the treatment of orofacial neuropathic pain.

  1. 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

  2. Isolation and Characterization of mAMSA-hypersensitive Mutants

    Science.gov (United States)

    Rogojina, Anna T.; Nitiss, John L.

    2008-01-01

    Topoisomerase II (Top2) is the primary target for active anti-cancer agents. We developed an efficient approach for identifying hypersensitive Top2 mutants and isolated a panel of mutants in yeast Top2 conferring hypersensitivity to the intercalator N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulphonanilide (mAMSA). Some mutants conferred hypersensitivity to etoposide as well as mAMSA, whereas other mutants exhibited hypersensitivity only to mAMSA. Two mutants in Top2, changing Pro473 to Leu and Gly737 to Val, conferred extraordinary hypersensitivity to mAMSA and were chosen for further characterization. The mutant proteins were purified, and their biochemical activities were assessed. Both mutants encode enzymes that are hypersensitive to inhibition by mAMSA and other intercalating agents and exhibited elevated levels of mAMSA-induced Top2:DNA covalent complexes. While Gly737 → Val Top2p generated elevated levels of Top2-mediated double strand breaks in vitro, the Pro473 → Leu mutant protein showed only a modest increase in Top2-mediated double strand breaks but much higher levels of Top2-mediated single strand breaks. In addition, the Pro473 → Leu mutant protein also generated high levels of mAMSA-stabilized covalent complexes in the absence of ATP. We tested the role of single strand cleavage in cell killing with alleles of Top2 that could generate single strand breaks, but not double strand breaks. Expression in yeast of a Pro473 → Leu mutant that could only generate single strand breaks conferred hypersensitivity to mAMSA. These results indicate that generation of single strand breaks by Top2-targeting agents can be an important component of cell killing by Top2-targeting drugs. PMID:18723844

  3. Distractibility and hypersensitivity. Two behavior factors in elementary school children.

    Science.gov (United States)

    Victor, J B; Halverson, C F

    1975-01-01

    The present paper reports on the development of a modified problem checklist for use in normal samples of elementary school children. The two factors, Hypersensitivity and Distractibility, replicated over male and female samples. Hypersensitivity showed a significant grade effect, with a decrease between the first and second grade for both boys and girls. In contrast, boys scored higher than girls on Distractibility and there were no grade differences. Convergent validitiy data from peer judgments, in-class activity level, physical fitness measures, standardized achievement scores, and a comparison with another teacher judgment are presented. In addition, three Behavioral Problem Checklist (Quay & Peterson, 1967) dimensions, Conduct Problem, Personality Problem, and Inadequacy--Immaturity, were developed and their relationships to the independent measures, as well as to the new dimensions, are presented. The pattern of correlations of Distractibility was quite similar for boys and girls, with both being rated as Mean-Noisy by their peers. The findings for Hypersensitivity were somewhat weaker. Distractibility and Conduct Problem scores reflected a similar pattern of correlations with other variables; in a like manner, Hypersensitivity and Personality Problem scores reflected a similar pattern of correlations with other variables. Distractibility was related to an increased activity level and Hypersensitivity was related to a decreased activity level in young boys. The total number of behavior problems was related to a decrease in activity level for young girls. Older Distractible and Hypersensitive girls showed different patterns of activity level. It is proposed that problem behavior is more complex for older children and that Distractibility may be less influenced by the usual socialization process of school than is Hypersensitivity and may have some congenital antecedents.

  4. Hypersensitivity responses in the central nervous system

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    Reza eKhorooshi

    2015-10-01

    Full Text Available Immune-mediated tissue damage or hypersensitivity can be mediated by autospecific IgG antibodies. Pathology results from activation of complement, and antibody-dependent cellular cytotoxicity (ADCC, mediated by inflammatory effector leukocytes include macrophages, natural killer cells (NK cells and granulocytes. Antibodies and complement have been associated to demyelinating pathology in multiple sclerosis (MS lesions, where macrophages predominate amongst infiltrating myeloid cells. Serum-derived autoantibodies with predominant specificity for the astrocyte water channel aquaporin-4 (AQP4 are implicated as inducers of pathology in neuromyelitis optica (NMO, a CNS demyelinating disease where activated neutrophils infiltrate, unlike in MS.The most widely-used model for MS, experimental autoimmune encephalomyelitis (EAE, is an autoantigen-immunized disease that can be transferred to naive animals with CD4+ T cells, but not with antibodies. By contrast NMO-like astrocyte and myelin pathology can be transferred to mice with AQP4-IgG from NMO patients. This is dependent on complement, and does not require T cells. Consistent with clinical observations that interferon-beta is ineffective as a therapy for NMO, NMO-like pathology is significantly reduced in mice lacking the Type I IFN receptor.In MS there is evidence for intrathecal synthesis of antibodies as well as blood-brain barrier (BBB breakdown, whereas in NMO, IgG accesses the CNS from blood. Transfer models involve either direct injection of antibody and complement to the CNS, or experimental manipulations to induce BBB breakdown. We here review studies in MS and NMO that elucidate roles for IgG and complement in the induction of BBB breakdown, astrocytopathy and demyelinating pathology. These studies point to significance of T-independent effector mechanisms in neuroinflammation.

  5. Animal models of gastrointestinal and liver diseases. Animal models of visceral pain: pathophysiology, translational relevance, and challenges.

    Science.gov (United States)

    Greenwood-Van Meerveld, Beverley; Prusator, Dawn K; Johnson, Anthony C

    2015-06-01

    Visceral pain describes pain emanating from the thoracic, pelvic, or abdominal organs. In contrast to somatic pain, visceral pain is generally vague, poorly localized, and characterized by hypersensitivity to a stimulus such as organ distension. Animal models have played a pivotal role in our understanding of the mechanisms underlying the pathophysiology of visceral pain. This review focuses on animal models of visceral pain and their translational relevance. In addition, the challenges of using animal models to develop novel therapeutic approaches to treat visceral pain will be discussed. Copyright © 2015 the American Physiological Society.

  6. ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable bowel syndrome-like rats.

    Science.gov (United States)

    Chen, Yu; Lin, Chun; Tang, Ying; Chen, Ai-Qin; Liu, Cui-Ying; Lu, Da-Li

    2014-02-28

    To investigate the effects of ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on rats with chronic visceral pain. Rats with visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously. Visceral hypersensitivity was evaluated using electromyographic (EMG) responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions (CRD). Abdominal withdrawal reflex (AWR) scores and pain thresholds were also detected in adult rats. Different doses of ZD 7288 (25, 50, and 100 nmol/L) were intrathecally administered in rats to study the role of spinal HCN channel in chronic visceral hypersensitivity. EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral hypersensitivity compared to control rats (P pain threshold in rats with visceral hypersensitivity significantly decreased compared to control rats (P pain thresholds (32%-77%, P visceral hypersensitivity.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. CXCL10 controls inflammatory pain via opioid peptide-containing macrophages in electroacupuncture.

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    Ying Wang

    Full Text Available Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao--gall bladder meridian (day 0 and 1 and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A. The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10--as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture.

  9. Pelvic Pain

    Science.gov (United States)

    Pelvic pain occurs mostly in the lower abdomen area. The pain might be steady, or it might come and go. If the pain is severe, it might get in the way ... re a woman, you might feel a dull pain during your period. It could also happen during ...

  10. Persistent Pain and Sensory Abnormalities after Abdominoplasty

    DEFF Research Database (Denmark)

    Presman, Benjamin; Finnerup, Kenneth; Andresen, Sven Robert

    2015-01-01

    and characteristics of persistent pain after abdominoplasty, which is one of the most frequent cosmetic surgical procedures. METHODS: In September 2014, a link to a web-based questionnaire was mailed to 217 patients who had undergone abdominoplasty between 2006 and 2014 at the Department of Plastic Surgery, Aalborg....... Fourteen patients (8.2%) reported pain within the past 7 days related to the abdominoplasty. Abnormal abdominal skin sensation was common and reported by 138 patients (81%). Sensory hypersensitivity was associated with the presence of persistent pain. Satisfaction with the procedure was reported by 149 (88...... sensation was common. However, there is a risk of developing persistent neuropathic pain after abdominoplasty, and patients should be informed about this before surgery....

  11. Persistent Pain and Sensory Abnormalities after Abdominoplasty

    DEFF Research Database (Denmark)

    Presman, Benjamin; Finnerup, Kenneth; Andresen, Sven Robert

    2015-01-01

    University Hospital, Denmark. The questionnaire included questions about pain and sensory abnormalities located to the abdominal skin, and physical and psychological function; patient satisfaction with surgery was rated on a 4-point scale. RESULTS: One hundred seventy patients answered the questionnaire......%) patients. The majority of patients reported improvement on all physical and psychological factors. Patients with pain were more often disappointed with the surgery and unwilling to recommend the surgery. CONCLUSIONS: Overall, patients were satisfied with the procedure, although abnormal abdominal skin....... Fourteen patients (8.2%) reported pain within the past 7 days related to the abdominoplasty. Abnormal abdominal skin sensation was common and reported by 138 patients (81%). Sensory hypersensitivity was associated with the presence of persistent pain. Satisfaction with the procedure was reported by 149 (88...

  12. Pain in fibromyalgia and related conditions

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    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.

  13. Alpha-1 Adrenoceptor Hyperresponsiveness in Three Neuropathic Pain States: Complex Regional Pain Syndrome 1, Diabetic Peripheral Neuropathic Pain and Central Pain States Following Spinal Cord Injury

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    Robert W Teasell

    2004-01-01

    Full Text Available The pathophysiology of the pain associated with complex regional pain syndrome, spinal cord injury and diabetic peripheral neuropathy is not known. The pain of complex regional pain syndrome has often been attributed to abnormal sympathetic nervous system activity based on the presence of vasomotor instability and a frequently reported positive response, albeit a temporary response, to sympathetic blockade. In contrast, the pain below the level of spinal cord injury and diabetic peripheral neuropathy are generally seen as deafferentation phenomena. Each of these pain states has been associated with abnormal sympathetic nervous system function and increased peripheral alpha-1 adrenoceptor activity. This increased responsiveness may be a consequence of alpha-1 adrenoceptor postsynaptic hypersensitivity, or alpha-2 adrenoceptor presynaptic dysfunction with diminished noradrenaline reuptake, increased concentrations of noradrenaline in the synaptic cleft and increased stimulation of otherwise normal alpha-1 adrenoceptors. Plausible mechanisms based on animal research by which alpha-1 adrenoceptor hyperresponsiveness can lead to chronic neuropathic-like pain have been reported. This raises the intriguing possibility that sympathetic nervous system dysfunction may be an important factor in the generation of pain in many neuropathic pain states. Although results to date have been mixed, there may be a greater role for new drugs which target peripheral alpha-2 adrenoceptors (agonists or alpha-1 adrenoceptors (antagonists.

  14. Dentists' perceptions of dentine hypersensitivity and knowledge of its treatment.

    Science.gov (United States)

    Gillam, D G; Bulman, J S; Eijkman, M A J; Newman, H N

    2002-03-01

    The aim of the present investigation was to determine by questionnaire, UK dentists' perception of Dentine Hypersensitivity (DH) and knowledge of its treatment. A total of 403 questionnaires were sent to a selected group of UK dentists who had either inquired about further postgraduate education or had attended a course at the Eastman Dental Institute/Hospital. A total of 181 of 403 dentists (44.9%) (118M; 36F, 17 no response, mean age 38.2 years [s.d. 8.97]) returned the questionnaire. About 92.8% (n=168) of responding dentists claimed to see patients with DH in their practice. According to the dentists' replies at least one of four of their patients suffered from the complaint. About 71.8% (n=130) of dentists reported that DH was a severe problem in at least 10% of their patients and that pain from DH lasted no more than 4 weeks. Most of responding dentists claimed to be asked about DH by their patients and stated that they offered advice or treatment to their patients. Nearly 87.3% (n=158) of responding dentists provided a wide range of treatment options/advice which included both in-office and over-the-counter (OTC) products. Popular responses included desensitizing pastes/gels, Topical F(-) varnishes and toothpastes/rinses/gels, advice on atraumatic tooth brushing, dentine bonding agents (DBA), glass-ionomer cements (GIC) and other unspecified restorations. Of the various in-office treatments Duraphat was the most cited choice of varnish/primer options. Sensodyne toothpaste was the most popular of the specified OTC products. Most dentists appeared to understand the aetiological features associated with DH and provided a wide range of factors including the effects of incorrect tooth brushing, dietary acids as well as the possible influence on non-dental topics such as stress. Most responding dentists believed that their advice on DH was generally effective although they did highlight that certain aspects on the condition were lacking such as appropriate

  15. [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.

  16. Hypersensitivity to proton pump inhibitors: lansoprazole-induced Kounis syndrome.

    Science.gov (United States)

    Vlahos, Nicholas P; Vavilis, George K; Giannelou, Ageliki G; Georgopoulou, Christina N; Kommata, Varvara J; Kougias, Constantinos T; Tsartsalis, Dimitrios N; Kounis, George N; Mazarakis, Andreas; Batsolaki, Maria; Gouvelou-Deligianni, Geogia V; Hahalis, George; Kounis, Nicholas G

    2009-05-29

    Proton pump inhibitors are commonly used in clinical practice for the treatment of peptic ulcer and gastroesophageal reflux and are well tolerated by the patients. Their use is rarely associated with hypersensitivity and anaphylactic reactions. According to the reports in the Uppsala Monitoring Center database the frequency of hypersensitivity reactions out of all reported adverse reactions for proton pump inhibitors and H2-histamine receptor antagonists was between 0.2% and 0.7%. A few cases of hypersensitivity to lansoprazole have been reported. We report a patient who developed Kounis syndrome after taking 30 mg of lansoprazole. This is the first report of Kounis syndrome associated with lansoprazole administration in the world literature.

  17. Contact hypersensitivity response to isophorone diisocyanate in mice

    Energy Technology Data Exchange (ETDEWEB)

    Stern, M.L.; Brown, T.A.; Brown, R.D.; Munson, A.E. (Virginial Commonwealth Univ., Richmond (USA))

    1989-09-01

    Isophorone diisocyanate was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 0.1, 0.3, and 1.0% isophorone diisocyanate and challenged with 3.0% isophorone diisocyanate. Doses of isophorone diisocyanate were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of complete Freund's adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity responses to isophorone diisocyanate with or without adjuvant pretreatment.

  18. 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.

  19. Hypersensitivity reactions and contrast medium injection: Are they always related?

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, Ingrid, E-mail: i.boehm@uni-bonn.de [Department of Radiology, Philipps University of Marburg, Baldingerstrasse, 35039 Marburg (Germany); Alfke, Heiko [Department of Radiology, Klinikum Luedenscheid, Luedenscheid (Germany); Klose, Klaus Jochen [Department of Radiology, Philipps University of Marburg, Baldingerstrasse, 35039 Marburg (Germany)

    2011-11-15

    Background: Hypersensitivity (allergic or non-allergic) reactions that occur after contrast medium (CM) injection are usually related to the CM. Recent studies, and case reports lack the analysis of alternate causes that could be also responsible in individual cases. Patients and methods: We investigated the individual relevant factor/causative agent of adult patients with hypersensitivity reactions that occurred in radiological units during CM-enhanced procedures (CT, angiography, urography, or MR-examinations). Both immediate and non-immediate (delayed) reactions were included. To find out the relevant agent a detailed patients' history was carefully analyzed. In addition, the records were retrospectively reviewed, and if indicated and possible laboratory (e.g. basophil activation test) and skin tests (e.g. prick) and/or provocations with CM-injections under routine conditions were performed. Results: 38 patients (men n = 21) suspected for CM-hypersensitivity reactions were identified. These reactions were in most cases mild (n = 21), moderate reactions occurred in 13 cases, and four patients had severe reactions. In 28 patients the reactions were induced by the CM (iodinated CM in 25 cases). Four patients had reactions that were not CM-related (latex allergy, adenosine reaction, vasovagal reaction, unknown cause) and in six cases the reaction was partly CM-related (immunological activation was present due to the patients' diseases). Conclusion: Our data support the hypothesis that in CM-enhanced procedures not only contrast materials but also a broad range of other factors may also induce hypersensitivity reactions. Therefore, the number of CM-induced hypersensitivity is smaller than initially suspected. The knowledge of the cause of a reaction is essential to effectively prevent its recurrence and to improve safety aspects in patients undergoing CM-injection. Larger trials should be performed to more specifically assess alternate causes in patients

  20. 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.

  1. 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

  2. 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.

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

    Science.gov (United States)

    Keohane, John; Quigley, Eamonn M M

    2006-05-01

    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.

  4. Hypersensitivity to Perturbations in the Quantum baker's Map

    CERN Document Server

    Schack, R

    1999-01-01

    We analyze a randomly perturbed quantum version of the baker's transformation, a prototype of an area-conserving chaotic map. By numerically simulating the perturbed evolution, we estimate the information needed to follow a perturbed Hilbert-space vector in time. We find that the Landauer erasure cost associated with this information grows very rapidly and becomes much larger than the maximum statistical entropy given by the logarithm of the dimension of Hilbert space. The quantum baker's map thus displays a hypersensitivity to perturbations that is analogous to behavior found earlier in the classical case. This hypersensitivity characterizes ``quantum chaos'' in a way that is directly relevant to statistical physics.

  5. 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.

  6. The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca(2+)-NOS pathway.

    Science.gov (United States)

    Gong, Liping; Li, Jing; Tang, Yan; Han, Ting; Wei, Chuanfei; Yu, Xiao; Li, Jingxin; Wang, Rong; Ma, Xuelian; Liu, Kejing; Geng, Lingyun; Liu, Shaozhuang; Yan, Bing; Liu, Chuanyong

    2016-08-19

    This study was conducted to investigate the effects of oxytocin (OT) on visceral hypersensitivity/pain and mast cell degranulation and the underlying mechanisms. We found that oxytocin receptor (OTR) was expressed in colonic mast cells in humans and rats, as well as in human mast cell line-1 (HMC-1), rat basophilic leukemia cell line (RBL-2H3) and mouse mastocytoma cell line (P815). OT decreased 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, colonic mast cell degranulation and histamine release after mast cell degranulation in rats. Also, OT attenuated the compound 48/80 (C48/80)-evoked histamine release in P815 cells and inward currents, responsible for the mast cell degranulation, in HMC-1, RBL-2H3 and P815 cells. Moreover, these protective effects of OT against visceral hypersensitivity and mast cell degranulation were eliminated by coadministration of OTR antagonist atosiban or a nonselective inhibitor of nitric oxide synthase (NOS), NG-Methyl-L-arginine acetate salt (L-NMMA). Notably, OT evoked a concentration-dependent increase of intracellular Ca(2+) in HMC-1, RBL-2H3 and P815 cells, which was responsible for the activation of neuronal NOS (NOS1) and endothelial NOS (NOS3). Our findings strongly suggest that OT might exert the antinociception on colonic hypersensitivity through inhibition of mast cell degranulation via Ca(2+)-NOS pathway.

  7. TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER DERMAL AND INTRATRACHAEL (IT) EXPOSURES

    Science.gov (United States)

    ABSTRACT for 2001 DMS213TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY INMICE AFTER DERMAL AND INTRATRACHEAL (IT) EXPOSURES. E Boykin, M Ward, MJ Selgrade, and D Sailstad. NHEERL, ORD, US EPA, RTP, NC, USA.TMA causes respiratory hypersensitivity (RH) responses. W...

  8. Effect of Probiotic Administration on Acute Inflammatory Pain

    Directory of Open Access Journals (Sweden)

    Shadnoush

    2016-11-01

    Full Text Available Background Acute inflammatory pain causes by direct stimulation of nociceptors and release of inflammatory mediators and cytokines. Probiotics are capable to modulate the immune system, down regulate the inflammatory mediators, and increase regulatory and anti-inflammatory cytokines. Objectives The aim of this study was to examine the effect of oral administration of probiotics on behavioral, cellular and molecular aspects of acute inflammatory pain in male rats. Methods Adult male Wistar rats (200 - 220 g were selected and randomly divided into 7 experimental groups (CFA, CFA control, CFA + vehicle (distilled water, CFA + 3 doses of probiotics, CFA + indomethacin and each group was divided into 3 subgroups based on different time points (days 0, 3, and 7 (n = 6 rats, each group. Complete Freund’s adjuvant (CFA-induced arthritis (AA was caused by a single subcutaneous injection of CFA into the rats’ left hind paw on day 0. Different doses of probiotics (1/250, 1/500 and 1/1000 (109 CFU/g was administered daily (gavage after the CFA injection. Blood samples were taken from the vessel retro-orbital corners of rat’s eyes. After behavioral and inflammatory tests, the lumbar segments of rat’s spinal cord (L1 - L5 were removed. Hyperalgesia, edema, serum TNF-α and IL-1β levels and NF-κB expression were assessed on days 0, 3, and 7 of the study. Results The results of this study showed the role of effective dose of probiotics (1/500 in reducing edema (P = 0.0009, hyperalgesia (P = 0.0002, serum levels of TNF-α (P = 0.0004 and IL-1β (P = 0.0004 and NF-κB expression (P = 0.0007 during the acute phase of inflammatory pain caused by CFA. Conclusions It seems that an effective dose of probiotics due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain in the acute phase.

  9. Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex specific visceral hypersensitivity in offspring

    Science.gov (United States)

    Winston, John H.; Li, Qingjie; Sarna, Sushil K.

    2014-01-01

    Background Irritable bowel syndrome (IBS) is a heterogeneous disorder with abdomen pain as one of the primary symptoms. The etiology of IBS remains unknown. Epidemiological studies found that a subset of these patients have a history of adverse early-life events. We tested the hypothesis that chronic prenatal stress (CPS) epigenetically enhances brain-derived neurotrophic factor (BDNF) in spinal cord to aggravate colon sensitivity to colorectal distension (CRD) differentially in male and female offspring. Methods We used heterotypic intermittent chronic stress (HeICS) protocols in pregnant dams from E11 until delivery. Results CPS induced significant visceral hypersensitivity (VHS) to CRD in male and female offspring. A second exposure to HeICS in adult offspring exacerbated VHS greater in female offspring that persisted longer than in male offspring. CPS upregulated BDNF expression in the lumbar-sacral dorsal horn that correlated with the exacerbation of VHS in female, but not in male offspring. The upregulation of BDNF was due to a significant increase in RNA Pol II binding, histone H3 acetylation and significant decrease in histone deacetylase 1 association with the core promoter of BDNF in female offspring. Other chronic prenatal and neonatal stress protocols were less effective than HeICS. Conclusion & Inferences The development of visceral hypersensitivity, which contributes to the symptom of intermittent abdominal pain, is a two-step process, chronic in utero stress followed by chronic stress in adult-life. This two-step process induces aggravated and persistent colon hypersensitivity in female than in male offspring. Our preclinical model explains several clinical features in IBS patients. PMID:24588943

  10. Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats.

    Science.gov (United States)

    Fang, Jian-Qiao; Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan

    2013-03-22

    Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat's paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.

  11. Antinociceptive Effect of Tephrosia sinapou Extract in the Acetic Acid, Phenyl-p-benzoquinone, Formalin, and Complete Freund’s Adjuvant Models of Overt Pain-Like Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Renata M. Martinez

    2016-01-01

    Full Text Available Tephrosia toxicaria, which is currently known as Tephrosia sinapou (Buc’hoz A. Chev. (Fabaceae, is a source of compounds such as flavonoids. T. sinapou has been used in Amazonian countries traditional medicine to alleviate pain and inflammation. The purpose of this study was to evaluate the analgesic effects of T. sinapou ethyl acetate extract in overt pain-like behavior models in mice by using writhing response and flinching/licking tests. We demonstrated in this study that T. sinapou extract inhibited, in a dose (1–100 mg/kg dependent manner, acetic acid- and phenyl-p-benzoquinone- (PBQ- induced writhing response. Furthermore, it was active via intraperitoneal, subcutaneous, and peroral routes of administration. T. sinapou extract also inhibited formalin- and complete Freund’s adjuvant- (CFA- induced flinching/licking at 100 mg/kg dose. In conclusion, these findings demonstrate that T. sinapou ethyl acetate extract reduces inflammatory pain in the acetic acid, PBQ, formalin, and CFA models of overt pain-like behavior. Therefore, the potential of analgesic activity of T. sinapou indicates that it deserves further investigation.

  12. Enhanced sensitivity to punctate painful stimuli in female patients with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Puta Christian

    2012-09-01

    Full Text Available Abstract Background Chronic low back pain (CLBP has been shown to be associated with various pathophysiological changes at several level of the sensorimotor system, pointing to a general hypersensitivity in CLBP patients. The aim of the present study was to investigate signs of generalized mechanical pain hypersensitivity in CLBP patients on the hand and on the painful site of the back. Methods Pinprick stimulation according to a validated standardized quantitative sensory testing protocol was used in 14 female CLBP patients and 14 healthy controls (HC matched for sex and age. Stimulus response functions to pinprick stimulation on the skin were examined at the affected back and reference sites (hand palmar and hand dorsum. Data from CLBP patients were compared with HC and with reference data from the German Research Network on Neuropathic Pain. Results We found significant differences in the stimulus response functions between CLBP patients and HC. Pain ratings to the pinpricks were increased for low and moderate pinprick stimuli in CLBP patients. Importantly, this kind of specific pinprick hyperalgesia was found not only for the affected body site (back, but also for the remote reference sites (hand dorsum and hand palmar. Conclusions We interpret our results as pointing to changes in the nociceptive processing in CLBP at higher levels of the neuraxis, possibly thalamus and/or attentional control, rather than changes of spinal processing. Alternatively, there might be a higher vulnerability to noxious stimulation in CLBP patients.

  13. The effect of a novel crystallised bioactive glass-ceramic powder on dentine hypersensitivity: a long-term clinical study.

    Science.gov (United States)

    Tirapelli, C; Panzeri, H; Lara, E H G; Soares, R G; Peitl, O; Zanotto, E D

    2011-04-01

    The aim of this comparative clinical study was to evaluate a novel bioactive glass-ceramic (Biosilicate® 1-20 μm particles) to treat dentine hypersensitivity (DH). Volunteers (n = 120 patients/ 230 teeth) received the following treatments: G1-Sensodyne® , G2-SensiKill®, G3-Biosilicate® incorporated in a 1% water-free-gel and G4-Biosilicate® mixed with distilled water at 1:10 ratio. G1 and G3 were applied at home, daily for 30 days; G2 and G4 were applied once a week by a dentist (four applications). A visual analogue scale (VAS) was employed to evaluate pain for each quadrant in one sensitive tooth at baseline, weekly during treatment and during a 6-month follow-up period. Dentine hypersensitivity values (G1/n= 52), (G2/n =62), (G3/n = 59) and (G4/n = 59) were analysed with Kruskal-Wallis/Dunn tests. All the products were efficient in reducing DH after 4 weeks. Among the four materials tested, G4 demonstrated the best clinical performance and provided the fastest treatment to reduce DH pain. Distilled water proved to be an adequate vehicle to disperse Biosilicate®. Low DH scores were maintained during the 6-month follow-up period. The hypothesis that the novel bioactive glass-ceramic may be an efficient treatment for DH was confirmed. © 2010 Blackwell Publishing Ltd.

  14. 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 ... lower back supports most of your body's weight. Low back pain is the number two reason that ...

  15. Back Pain

    Science.gov (United States)

    ... Oh, my aching back!", you are not alone. Back pain is one of the most common medical problems, ... 10 people at some point during their lives. Back pain can range from a dull, constant ache to ...

  16. Breast pain

    Science.gov (United States)

    Pain - breast; Mastalgia; Mastodynia; Breast tenderness ... There are many possible causes for breast pain. For example, hormone level changes from menstruation or pregnancy often cause breast tenderness. Some swelling and tenderness just before your period ...

  17. Muscle pain

    African Journals Online (AJOL)

    Causes of muscle pain include stress, physical activity, infections, hyper or .... Acupuncture. It is a traditional Chinese-based therapeutic method which ..... and Spinal Mechanisms of Pain and Dry Needling Mediated Analgesia: A Clinical.

  18. Face pain

    Science.gov (United States)

    ... begin in other places in the body. Abscessed tooth (ongoing throbbing pain on one side of the lower face that ... face, and aggravated by eating. Call a dentist. Pain is persistent, ... by other unexplained symptoms. Call your primary provider.

  19. Pain Assessment

    Science.gov (United States)

    ... acupuncture, chiropractic care, massage or other manual therapies, yoga, herbal and nutritional therapies, or others. This information helps the health care provider understand the nature of the pain or the potential benefits of treatment. The goals of the comprehensive pain ...

  20. Urination Pain

    Science.gov (United States)

    ... Health Growth & Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & ... decreased appetite or activity irritability nausea or vomiting lower back pain or abdominal (belly) pain wetting accidents (in potty- ...

  1. Period Pain

    Science.gov (United States)

    ... You may also have other symptoms, such as lower back pain, nausea, diarrhea, and headaches. Period pain is not ... Taking a hot bath Doing relaxation techniques, including yoga and meditation You might also try taking over- ...

  2. Neck Pain

    Science.gov (United States)

    ... antidepressants for pain relief. Therapy Physical therapy. A physical therapist can teach you correct posture, alignment and neck- ... therapy, under supervision of a medical professional and physical therapist, may provide relief of some neck pain, especially ...

  3. The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

    Science.gov (United States)

    Farzaei, Mohammad H; Bahramsoltani, Roodabeh; Abdollahi, Mohammad; Rahimi, Roja

    2016-01-01

    Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH. PMID:27431236

  4. Early changes in somatosensory function in spinal pain: a systematic review and meta-analysis.

    Science.gov (United States)

    Marcuzzi, Anna; Dean, Catherine M; Wrigley, Paul J; Hush, Julia M

    2015-02-01

    Alterations in sensory processing have been demonstrated in chronic low back and neck pain. However, it has not been yet systematically summarized how early these changes occur in spinal pain. This systematic review examines the available literature measuring somatosensory function in acute (<6 weeks) and subacute (6-12 weeks) spinal pain. The protocol for this review has been registered on the International Prospective Register of Systematic Reviews (PROSPERO). An electronic search of 4 databases was conducted to retrieve studies assessing somatosensory function by quantitative sensory testing in adults with spinal pain of up to 12 weeks duration. Two reviewers independently screened the studies and assessed the risk of bias. Studies were grouped according to spinal pain condition (whiplash injury, idiopathic neck pain, and nonspecific low back pain), and, where possible, meta-analyses were performed for comparable results. Fifteen studies were included. Sources of bias included lack of assessor blinding, unclear sampling methods, and lack of control for confounders. We found that: (1) there is consistent evidence for thermal and widespread mechanical pain hypersensitivity in the acute stage of whiplash, (2) there is no evidence for pain hypersensitivity in the acute and subacute stage of idiopathic neck pain, although the body of evidence is small, and (3) hyperalgesia and spinal cord hyperexcitability have been detected in early stages of nonspecific low back pain, although evidence about widespread effects are conflicting. Future longitudinal research using multiple sensory modalities and standardized testing may reveal the involvement of somatosensory changes in the development and maintenance of chronic pain.

  5. 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 ex...... contributes to HR PCD and can function in parallel with other prodeath pathways....

  6. Equine insect bite hypersensitivity : Pathogenesis, diagnosis and immunomodulation

    NARCIS (Netherlands)

    Meulenbroeks, C.

    2016-01-01

    Insect bite hypersensitivity (IBH) is a seasonal allergic dermatitis primarily caused by Culicoides midges like C. obsoletus. The welfare of IBH-affected horses is compromised due to severe itch with secondary dermatitis and skin infections. Similar to most allergies, IBH can only be controlled rath

  7. Delayed-type hypersensitivity reaction to anthrax vaccine.

    Science.gov (United States)

    Greidanus, Thomas G; Honl, Beth A

    2002-01-01

    The Anthrax Vaccine Immunization Program is a Department of Defense initiative to protect military personnel against the threat of anthrax. Surveillance for adverse events associated with anthrax vaccination has shown that mild local reactions are not uncommon while systemic reactions are extremely rare. We present a case of 26-year-old male with delayed-type hypersensitivity after two doses of anthrax vaccine.

  8. Old, new and hidden causes of perioperative hypersensitivity

    DEFF Research Database (Denmark)

    Garvey, Lene Heise

    2016-01-01

    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...

  9. Increasing awareness of corticosteroid hypersensitivity reactions is important

    DEFF Research Database (Denmark)

    Knarborg, Malene; Bendstrup, Elisabeth; Hilberg, Ole

    2013-01-01

    the tolerability to other corticosteroid preparations and thus identify a safe treatment alternative. We report a case of corticosteroid hypersensitivity in a 65-year-old woman with a history of difficult-to-treat asthma and systemic corticosteroid allergy admitted with increasing dyspnea and dry cough...

  10. 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.

  11. 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 h

  12. Phantom Pain

    NARCIS (Netherlands)

    Wolff, Andre; Vanduynhoven, Eric; van Kleef, Maarten; Huygen, Frank; Pope, Jason E.; Mekhail, Nagy

    2011-01-01

    Phantom pain is pain caused by elimination or interruption of sensory nerve impulses by destroying or injuring the sensory nerve fibers after amputation or deafferentation. The reported incidence of phantom limb pain after trauma, injury or peripheral vascular diseases is 60% to 80%. Over half the p

  13. 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

  14. Correlations between edema and the immediate and prolonged painful consequences of inflammation: therapeutic implications?

    Energy Technology Data Exchange (ETDEWEB)

    Chesler, Elissa J [ORNL; Lariviere, William R [University of Pittsburgh; Zhen, Li [Institute for Biomedical Sciences of Pain, Beijing, China; Shang, G [Institute for Biomedical Sciences of Pain, Beijing, China; Chen, Ya [Institute for Biomedical Sciences of Pain, Beijing, China; Yu, Yao [Institute for Biomedical Sciences of Pain, Beijing, China; Lu, Zhuo [Institute for Biomedical Sciences of Pain, Beijing, China; Chang, Ying [Institute for Biomedical Sciences of Pain, Beijing, China; Luo, Ceng [Institute for Biomedical Sciences of Pain, Beijing, China; Li, KaiCheng [Institute for Biomedical Sciences of Pain, Beijing, China; Chen, Jun [Institute for Biomedical Sciences of Pain, Beijing, China

    2005-06-01

    The precise relationship between the degree of pan and the degree of inflammation in the individual remains debated. A quantitative analysis simultaneously applied to the immediate and prolonged painful consequences of inflammation has not yet been done. Thus, the correlations between edema, nociception and hypersensitivity following an inflammatory insult were assessed in rodents. To better understand the therapeutic value of modifying specific aspects of inflammation, the effects of anti-inflammatory drug were compared to the results. Inbred strains of mice and outbred rats received an intraplantar injection of honeybee venom and the between group and within-group correlations were calculated for spontaneous nociceptive measures, thermal and mechanical hypersensitivity, and edema and temperature. The effect of indomethacin on the pain and the inflammation measures was examined. Edema correlated with spontaneous flinching, licking and lifting of the inject paw, and not with thermal or mechanical hypersensitivity. Indomethacin affected edema and spontaneous nociception dose-dependently, and affected hypersensitivity only at the highest dose test (P <0.005). These results suggest that edema may contribute only to immediate spontaneous nociceptive responses to an inflammatory insult, and not to the more clinically relevant prolonged hypersensitivity. This analysis represents a method for determine which inflammatory processes are the most promising therapeutic targets against the multiple painful consequences of inflammation.

  15. Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood.

    Science.gov (United States)

    Yi, Lisha; Zhang, Haiqin; Sun, Huihui; Zhou, Lu; Chen, Ying; Xuan, Liqian; Jiang, Yuanxi; Xu, Shuchang

    2017-04-30

    Early adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. One hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2-14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. Compared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxiety-like behaviors in adulthood. MS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome.

  16. 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.

  17. Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity.

    Science.gov (United States)

    Wetzel, Christiane; Pifferi, Simone; Picci, Cristina; Gök, Caglar; Hoffmann, Diana; Bali, Kiran K; Lampe, André; Lapatsina, Liudmila; Fleischer, Raluca; Smith, Ewan St John; Bégay, Valérie; Moroni, Mirko; Estebanez, Luc; Kühnemund, Johannes; Walcher, Jan; Specker, Edgar; Neuenschwander, Martin; von Kries, Jens Peter; Haucke, Volker; Kuner, Rohini; Poulet, James F A; Schmoranzer, Jan; Poole, Kate; Lewin, Gary R

    2017-02-01

    The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors in vivo. STOML3 inhibitors in the skin also reversibly attenuate fine touch perception in normal mice. Under pathophysiological conditions following nerve injury or diabetic neuropathy, the slightest touch can produce pain, and here STOML3 inhibitors can reverse mechanical hypersensitivity. Thus, small molecules applied locally to the skin can be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pain following neuropathy.

  18. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study

    DEFF Research Database (Denmark)

    Demant, Dyveke T; Lund, Karen; Vollert, Jan

    2014-01-01

    by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing. Ninety-seven patients with peripheral neuropathic pain due to polyneuropathy, surgical or traumatic nerve injury, or postherpetic neuralgia were randomised. The intention-to-treat population comprised 83...

  19. 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

  20. 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

  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 b

  2. 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 b

  3. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Kim, Seung-Hyun; Sanak, Marek; Park, Hae-Sim

    2013-05-01

    Various hypersensitivity reactions have been reported with aspirin and nonsteroidal anti-inflammatory drugs. Hypersensitivity can occur regardless of a chemical drug structure or its therapeutic potency. Allergic conditions include aspirin-exacerbated respiratory disease (AERD or aspirin-induced asthma), aspirin-induced urticaria/angioedema (AIU), and anaphylaxis. Several genetic studies on aspirin hypersensitivity have been performed to discover the genetic predisposition to aspirin hypersensitivity and to gain insight into the phenotypic diversity. This article updates data on the genetic mechanisms that govern AERD and AIU and summarizes recent findings on the molecular genetic mechanism of aspirin hypersensitivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. 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.

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

    Science.gov (United States)

    Li, Qian; Guo, Cheng-Hao; Chowdhury, Mohammed Ali; Dai, Tao-Li; Han, Wei

    2016-01-01

    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 (Pcolon 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 that upregulation of TRPA1 expression in the SDH is associated with persistent post-inflammatory visceral hypersensitivity in the rat and provides insight into potential therapeutic targets for the control of persistent visceral hypersensitivity. PMID:27980434

  6. Periploca forrestii Saponin Ameliorates Murine CFA-Induced Arthritis by Suppressing Cytokine Production.

    Science.gov (United States)

    Liu, Yingqin; Li, Minghui; He, Qiuhong; Yang, Xinping; Ruan, Fang; Sun, Guangchen

    2016-01-01

    Periploca forrestii Schltr. has been used as a Chinese folk medicine due to its versatile pharmacological effects such as promoting wounds and rheumatoid arthritis. However, the antiarthritic activity of Periploca forrestii saponin (PFS) and its active compound Periplocin has still not been demonstrated. Here, we evaluated the antiarthritic effects of PFS in adjuvant-induced arthritis (AIA) rats by intragastric administration at a dose of 50 mg/kg. The anti-inflammatory activities of Periplocin were also examined in LPS-induced AIA splenocytes and synoviocytes. PFS significantly ameliorated joint swelling; inhibited bone erosion in joints; lowered levels of IL-6 and TGF-β1 in AIA rat splenocyte; and reduced joint protein expression levels of phospho-STAT3 and IKKα. Using LPS-induced AIA splenocytes, we demonstrate that Periplocin suppressed the key proinflammatory cytokines levels of IL-6, IFN-γ, TGF-β1, and IL-13 and IL-22 and transcription factor levels of T-bet, GATA3, and C-Jun genes. Periplocin also suppressed LPS-induced cytokine secretion from synoviocytes. Our study highlights the antiarthritic activity of PFS and its derived Periplocin and the underlying mechanisms. These results provide a strong rationale for further testing and validation of the use of Periploca forrestii Schltr. as an alternative modality for the treatment of RA.

  7. 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.

  8. Spinal 5-HT(3) receptor activation induces behavioral hypersensitivity via a neuronal-glial-neuronal signaling cascade.

    Science.gov (United States)

    Gu, Ming; Miyoshi, Kan; Dubner, Ronald; Guo, Wei; Zou, Shiping; Ren, Ke; Noguchi, Koichi; Wei, Feng

    2011-09-07

    Recent studies indicate that the descending serotonin (5-HT) system from the rostral ventromedial medulla (RVM) in the brainstem and the 5-HT(3) receptor subtype in the spinal dorsal horn are involved in enhanced descending pain facilitation after tissue and nerve injury. However, the mechanisms underlying the activation of the 5-HT(3) receptor and its contribution to facilitation of pain remain unclear. In the present study, activation of spinal 5-HT(3) receptor by intrathecal injection of a selective 5-HT(3) receptor agonist, SR57227, induced spinal glial hyperactivity, neuronal hyperexcitability, and pain hypersensitivity in rats. We found that there was neuron-to-microglia signaling via chemokine fractalkine, microglia to astrocyte signaling via the cytokine IL-18, astrocyte to neuronal signaling by IL-1β, and enhanced activation of GluN (NMDA) receptors in the spinal dorsal horn. In addition, exogenous brain-derived neurotrophic factor-induced descending pain facilitation was accompanied by upregulation of CD11b and GFAP expression in the spinal dorsal horn after microinjection in the RVM, and these events were significantly prevented by functional blockade of spinal 5-HT(3) receptors. Enhanced expression of spinal CD11b and GFAP after hindpaw inflammation was also attenuated by molecular depletion of the descending 5-HT system by intra-RVM Tph-2 shRNA interference. Thus, these findings offer new insights into the cellular and molecular mechanisms at the spinal level responsible for descending 5-HT-mediated pain facilitation during the development of persistent pain after tissue and nerve injury. New pain therapies should focus on prime targets of descending facilitation-induced glial involvement, and in particular the blocking of intercellular signaling transduction between neuron and glia.

  9. TRPV1 sensitization mediates postinflammatory visceral pain following acute colitis.

    Science.gov (United States)

    Lapointe, Tamia K; Basso, Lilian; Iftinca, Mircea C; Flynn, Robyn; Chapman, Kevin; Dietrich, Gilles; Vergnolle, Nathalie; Altier, Christophe

    2015-07-15

    Quiescent phases of inflammatory bowel disease (IBD) are often accompanied by chronic abdominal pain. Although the transient receptor potential vanilloid 1 (TRPV1) ion channel has been postulated as an important mediator of visceral hypersensitivity, its functional role in postinflammatory pain remains elusive. This study aimed at establishing the role of TRPV1 in the peripheral sensitization underlying chronic visceral pain in the context of colitis. Wild-type and TRPV1-deficient mice were separated into three groups (control, acute colitis, and recovery), and experimental colitis was induced by oral administration of dextran sulfate sodium (DSS). Recovery mice showed increased chemically and mechanically evoked visceral hypersensitivity 5 wk post-DSS discontinuation, at which point inflammation had completely resolved. Significant changes in nonevoked pain-related behaviors could also be observed in these animals, indicative of persistent discomfort. These behavioral changes correlated with elevated colonic levels of substance P (SP) and TRPV1 in recovery mice, thus leading to the hypothesis that SP could sensitize TRPV1 function. In vitro experiments revealed that prolonged exposure to SP could indeed sensitize capsaicin-evoked currents in both cultured neurons and TRPV1-transfected human embryonic kidney (HEK) cells, a mechanism that involved TRPV1 ubiquitination and subsequent accumulation at the plasma membrane. Importantly, although TRPV1-deficient animals experienced similar disease severity and pain as wild-type mice in the acute phase of colitis, TRPV1 deletion prevented the development of postinflammatory visceral hypersensitivity and pain-associated behaviors. Collectively, our results suggest that chronic exposure of colon-innervating primary afferents to SP could sensitize TRPV1 and thus participate in the establishment of persistent abdominal pain following acute inflammation. Copyright © 2015 the American Physiological Society.

  10. Novel nervous system mechanisms in visceral pain.

    Science.gov (United States)

    De Winter, B Y; Deiteren, A; De Man, J G

    2016-03-01

    Visceral hypersensitivity is an important factor underlying abdominal pain in functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and can result from aberrant signaling from the gut to the brain or vice versa. Over the last two decades, research has identified several selective, intertwining pathways that underlie IBS-related visceral nociception, including specific receptors on afferent and efferent nerve fibers such as transient receptor potential channels (TRP) channels, opioid, and cannabinoid receptors. In this issue of Neurogastroenterology and Motility Gil et al. demonstrate that in an animal model with reduced descending inhibitory control, the sympathetic nervous system outflow is enhanced, contributing to visceral and somatic hypersensitivity. They also provide evidence that interfering with the activation of adrenergic receptors on sensory nerves can be an interesting new strategy to treat visceral pain in IBS. This mini-review places these findings in a broader perspective by providing an overview of promising novel mechanisms to alter the nervous control of visceral pain interfering with afferent or efferent neuronal signaling. © 2016 John Wiley & Sons Ltd.

  11. 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....

  12. Neuropathic pain

    DEFF Research Database (Denmark)

    Colloca, Luana; Ludman, Taylor; Bouhassira, Didier

    2017-01-01

    Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7-10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing...... to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central...... nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased...

  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. Low back pain - chronic

    Science.gov (United States)

    Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause ...

  15. Employees with Chronic Pain

    Science.gov (United States)

    ... one in five Americans suffer from chronic pain (Sternberg, 2005). What is chronic pain? While acute pain ... nih.gov/disorders/chronic_pain/chronic_pain.htm Sternberg, S. (2005). Chronic pain: The enemy within. Retrieved December ...

  16. 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.

  17. Mechanism of action of a desensitizing fluoride toothpaste delivering calcium and phosphate ingredients in the treatment of dental hypersensitivity. Part II: comparison with a professional treatment for tooth hypersensitivity.

    Science.gov (United States)

    Charig, Andrew J; Thong, Stephen; Flores, Florita; Gupta, Shivank; Major, Elizabeth; Winston, Anthony E

    2009-01-01

    Tooth hypersensitivity can occur when gum recession causes exposure of dentin. Tiny tubules, which permeate dentin, provide open passageways from the mouth to the intradental nerve in the pulpal cavity. Under such circumstances, stimuli in the mouth can cause pressure on the intradental nerve, leading to pain. Sealing the outside of the tubules with an impermeable substance can effectively treat hypersensitivity. One such clinically proven composition is a professionally applied tooth desensitizer, which has been shown to initially produce a layer of amorphous calcium phosphate (ACP) on the surface of dentin. Under the influence of fluoride, ACP reforms as hydroxyapatite (HAP), which has essentially the same composition as tooth mineral. Three fluoride toothpastes that deliver calcium and phosphate salts to the teeth also have been demonstrated in clinical trials to relieve hypersensitivity. This study compared the mechanism of action of these toothpastes to that of the professional desensitizer. A single application of the professional desensitizer or multiple applications of any of the three toothpastes was shown to reduce dentin permeability. A conventional fluoride toothpaste also was found to inhibit fluid flow through the dentin but to a lesser degree than the other toothpastes. The desensitizer and the three toothpastes were found to occlude the dentinal tubules with a layer of calcium phosphate that had a calcium-to-phosphate ratio consistent with the formation of ACP or HAP. The morphology of the coherent mineral layer formed by Arm & Hammer Enamel Care Sensitive was similar, especially to that produced by the desensitizer. In contrast, the conventional toothpaste left localized areas of surface residue composed of silica particles. The mechanism of action of the three toothpastes that deliver calcium and phosphate salts is the same as that of the professional desensitizer.

  18. Central pain.

    Science.gov (United States)

    Singh, Supreet

    2014-12-01

    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is central pain, a neuropathic pain syndrome caused by a lesion in the brain or spinal cord that sensitizes one's perception of pain. It is a debilitating condition caused by various diseases such as multiple sclerosis, strokes, spinal cord injuries, or brain tumors. Varied symptoms and the use of pharmacological medicines and nonpharmacological therapies will be addressed.

  19. A severe hypersensitivity reaction to abacavir following re-challenge.

    Science.gov (United States)

    Todd, Sej; Emerson, C R

    2017-03-01

    We report this case to highlight the possibility of a severe hypersensitivity reaction as an important potential consequence of couples, living with HIV, sharing anti-retroviral treatment. An HIV-1 positive and carrier of HLA-B*57:01 allele, treatment experienced man was commenced one pill Regimen Stribild (tenofovir, emtricitabine, elvitegravir and cobicistat) in July 2015. On running short of medication, he admitted to sharing his partner's treatment (Triumeq; abacavir, lamivudine and dolutegravir). On the second occasion, re-introduction resulted in whole body rash 4 h post dose and was associated with fever, respiratory symptoms, headache and vomiting. On examination, he was pyrexic, tachyponeic, tachycardiac and hypotensive. Hypersensitivity to abacavir can cause significant morbidity. Re-challenge can result in a more rapid, severe and potentially life-threatening reaction. This potentially could become an increasing problem with more couples, living with HIV, sharing medication.

  20. 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

    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...... to diabetic autonomic neuropathy. Regardless of the mechanism of adrenergic denervation hypersensitivity in such patients, these data provide further evidence that measurements of cellular adrenergic receptors (and adenylate cyclase) in vitro are a fallible index of sensitivity to catecholamines in vivo....

  1. 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

    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...... to diabetic autonomic neuropathy. Regardless of the mechanism of adrenergic denervation hypersensitivity in such patients, these data provide further evidence that measurements of cellular adrenergic receptors (and adenylate cyclase) in vitro are a fallible index of sensitivity to catecholamines in vivo....

  2. Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F;

    1989-01-01

    The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common...... delayed-type antigens in 83 consecutive patients undergoing major elective abdominal surgery. Sixty-six of these patients were randomly divided into ranitidine or no-ranitidine-treatment groups, and the remaining 17 patients were operated on without ranitidine. Thus, 50 patients were operated on without.......0001). It is concluded that perioperative transfusion with whole blood amplifies the postoperative impairment in delayed hypersensitivity and that transfusion-induced postoperative impairment in delayed hypersensitivity may be prevented by perioperative ranitidine treatment....

  3. Evaluation of delayed hypersensitivity: from PPD to poison ivy.

    Science.gov (United States)

    Rosenstreich, D L

    1993-01-01

    Intact cell mediated immunity (CMI) requires a complex interaction between lymphocytes, macrophages, and cytokines. The presence of functional CMI can be easily tested in vivo by delayed hypersensitivity (DTH) skin testing. Delayed hypersensitivity skin testing has been commonly used in three ways; anergy screening, testing for infection with intracellular pathogens, and testing for sensitivity to contact allergens. Accurate anergy screening requires intradermal testing with four or more common recall antigens such as Candida albicans, tetanus toxoid, mumps, and purified protein derivative. Problems of antigen potency and availability can be overcome by using a multiple time test-like device that contains seven different recall antigens (Multitest CMI). Although testing for infection was once common, it is now only recommended for tuberculosis screening because most other antigens are either not predictive of infection or not commercially available. Accurate testing for contact allergy requires careful attention to technique, and limitation of allergens to the 20 antigens that are approved by the American Academy of Dermatology.

  4. Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F;

    1989-01-01

    The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common...... ranitidine, 50 mg intravenously every 6 hours for 72 hours, received perioperative blood transfusion. Eleven of these patients could be matched to 11 transfused patients not receiving perioperative ranitidine. Ranitidine prevented postoperative reduction in skin test response (+6% vs -55%, p less than 0.......0001). It is concluded that perioperative transfusion with whole blood amplifies the postoperative impairment in delayed hypersensitivity and that transfusion-induced postoperative impairment in delayed hypersensitivity may be prevented by perioperative ranitidine treatment....

  5. Hypersensitivity and chaos signatures in the quantum baker's maps

    CERN Document Server

    Scott, A J; Caves, C M; Schack, R; Brun, Todd A.; Caves, Carlton M.; Schack, Ruediger

    2006-01-01

    Classical chaotic systems are distinguished by their sensitive dependence on initial conditions. The absence of this property in quantum systems has lead to a number of different criteria being proposed for quantum chaos, including linear growth of entropy, exponential decay of fidelity, and hypersensitivity to perturbation. All of these accurately predict chaos in the classical limit, but it is not clear that they behave the same far from the classical realm. We investigate the dynamics of a family of quantizations of the baker's map, which range from a highly entangling unitary transformation to an essentially trivial shift map. Linear entropy growth and fidelity decay are exhibited by this entire family of maps, but hypersensitivity distinguishes between the simple dynamics of the trivial shift map and the more complicated dynamics of the other quantizations. This is supported by an analytical argument for short times and numerical evidence at later times.

  6. 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

  7. Spotlight on the diagnosis of extrinsic allergic alveolitis (hypersensitivity pneumonitis).

    Science.gov (United States)

    Baur, Xaver; Fischer, Axel; Budnik, Lygia T

    2015-01-01

    Repeated inhalative exposures to antigenic material from a variety of sources, mainly from moulds, thermophilic Actinomycetes, and avians, respectively, can induce immune responses with the clinical picture of extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis. Delays of years or even decades till the diagnosis is made are not uncommon; frequent misdiagnoses include allergic asthma, COPD, recurrent flue and other infections. We provide here the state of the art references, a detailed case description and recommend a current diagnostics schema.

  8. Severe delayed-onset hypersensitivity reactions to amoxicillin in children.

    OpenAIRE

    Chopra, R; Roberts, J.; Warrington, R. J.

    1989-01-01

    Amoxicillin, a semisynthetic aminopenicillin, has achieved widespread use in recent years for the treatment of respiratory tract and otic infections. Serious reactions have been relatively infrequent. From July 1986 to June 1987, 11 children aged 6 months to 10 years presented with delayed-onset hypersensitivity reactions. In 10 the symptoms were consistent with a serum-sickness-like illness, including urticaria, angioedema, arthritis and arthralgia. Radioallergosorbent testing for IgE antibo...

  9. Piperacillin plus Tazobactam induced Drug Hypersensitivity Reaction: A Case Report

    OpenAIRE

    Modi RS; Sattigeri BM; Patel AH

    2015-01-01

    Penicillin alone or with combination should be used in hospitalized patients to treat bacterial infections with great precautions since penicillin is known to produce hypersensitivity reactions very commonly. A 53 year old hospitalized male patient having tibia fracture was initially given ceftriaxone plus salbactum and amikacin as an antibacterial therapeutics. Subsequently patient was treated with Pipzo (Inj. Piperacillin plus Tezobactum; 4.5 gm.) on the basis of anti- bacterial sensitivity...

  10. Sauna lung: hypersensitivity pneumonitis due to Exophiala jeanselmei.

    Science.gov (United States)

    Huang, Wei-Chen; Lu, Yin-Hsiu; Lin, Zih-Gong; Su, Wen-Lin

    2010-04-01

    A 55-year-old man developed progressive cough and dyspnoea after regular attendance at a public steam bath. Hypoxaemia, diffuse pulmonary infiltrates and a predominance of lymphocytes with an increased percentage of CD8+ T cells in his bronchoalveolar lavage fluid suggested hypersensitivity pneumonitis. Microbial cultures from the steam bath room and tank identified Exophiala jeanselmei. Immunoblotting assays from the patient's serum confirmed the major antigenic stimulus. The patient recovered fully after systemic corticosteroid treatment and cessation of further exposure.

  11. Working with argan cake: a new etiology for hypersensitivity pneumonitis

    OpenAIRE

    Paris, Christophe; Herin, Fabrice; Reboux, Gabriel; Penven, Emmanuelle; Barrera, Coralie; Guidat, Cécile; Thaon, Isabelle

    2015-01-01

    Background Argan is now used worldwide in numerous cosmetic products. Nine workers from a cosmetic factory were examined in our occupational medicine department, following the diagnosis of a case of hypersensitivity pneumonitis (HP) related to handling of argan cakes. Methods Operators were exposed to three forms of argan (crude granulates, powder or liquid) depending on the step of the process. All workers systematically completed standardized questionnaires on occupational and medical histo...

  12. Hypersensitivity to Etoposide in Case of Metastatic Gestational Choriocarcinoma

    Directory of Open Access Journals (Sweden)

    Biljana Lazović

    2013-09-01

    Full Text Available Etoposide is commonly used in the treatment of a variety of neoplasms. Hypersensitivity reactions to etoposide are infrequently reported and include hypotension, hypertension, flushing, diaphoresis, chest discomfort, dyspnea, bronchospasm and loss of consciousness. We report the case of a 39-year-old woman who experienced acute bronchospasm, tachycardia, hypoxia and hypotension. The symptoms resolved within an hour after administration of intravenous fluids, methylprednisolone, diphenhydramine and oxygen. Subsequently, the patient was given etoposide phosphate without incident.

  13. Hypersensitivity to antineoplastic agents: mechanisms and treatment with rapid desensitization.

    Science.gov (United States)

    Castells, Mariana; Sancho-Serra, Maria del Carmen; Simarro, Maria

    2012-09-01

    Hypersensitivity reactions (HSRs) to chemotherapy drugs, such as taxanes and platins, and to monoclonal antibodies limit their therapeutic use due to the severity of some reactions and the fear of inducing a potentially lethal reaction in highly sensitized patients. Patients who experience hypersensitivity reactions face the prospect of abandoning first-line treatment and switching to a second-line, less effective therapy. Some of these reactions are mast cell-mediated hypersensitivity reactions, a subset of which occur through an immunoglobulin (IgE)-dependent mechanism, and are thus true allergies. Others involve mast cells without a demonstrable IgE mechanism. Whether basophils can participate in these reactions has not been demonstrated. Rapid drug desensitization (RDD) is a procedure that induces temporary tolerance to a drug, allowing a medication allergic patient to receive the optimal agent for his or her disease. Through RDD, patients with IgE and non-IgE HSRs can safely be administered important medications while minimizing or completely inhibiting adverse reactions. Due to the clinical expansion and success of RDD, the molecular mechanisms inducing the temporary tolerization have been investigated and are partially understood, allowing for safer and more effective protocols. This article reviews the current literature on molecular mechanisms of RDD with an emphasis in our recent contributions to this field as well as the indications, methods and outcomes of RDD for taxanes, platins, and monoclonal antibodies.

  14. 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.

  15. 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.

  16. Immediate hypersensitivity reactions to penicillins and other betalactams.

    Science.gov (United States)

    Antúnez, C; Martín, E; Cornejo-García, J A; Blanca-Lopez, N; R-Pena, R; Mayorga, C; Torres, M J; Blanca, M

    2006-01-01

    Immediate hypersensitivity reactions to betalactams are IgE mediated and constitute the most frequent allergic reactions mediated by specific immunological mechanisms. IgE responses to benzyl penicillin (BP), the first antibiotic producing the benzyl penicilloyl structure (BPO), are characterized by a quick release of inflammatory mediators, resulting in anaphylactic shock, urticaria and angioedema. With the progressive appearance of other structures, comprising cephalosporins, carbapenems, monobactams and clavulanic acid, IgE selective responses and cross-reactivity reactions were observed. The diagnosis of betalactam hypersensitivity, classically based on skin testing with major and minor determinants of benzyl penicillin or in vitro IgE antibodies to BP, has been modified by the inclusion of different determinants generated from these compounds, for which amoxicillin (AX) is the most relevant, followed by cephalosporins. Some subjects develop positive responses to several betalactams, mostly within the same family, but others develop a selective response. These are relevant for the appropriate selection of antimicrobial drugs in patients who have immediate hypersensitivity to betalactams.

  17. Hypersensitivity and the Working Environment for Allergy Nurses in Sweden

    Directory of Open Access Journals (Sweden)

    Pia Kalm-Stephens

    2014-01-01

    Full Text Available Background. Allergy nurses are exposed to allergens and respiratory irritants, and there are no national guidelines addressing personnel safety when working with these agents. Objective. To investigate the prevalence of allergies, asthma, and hypersensitivity symptoms among allergy nurses and the use of protective equipment and measures when working with allergen concentrates and respiratory irritants. Methods. A questionnaire survey was performed among the members of the Swedish Association of Allergy Nurses. Results. Diagnosed asthma was reported by 17%, while 18% had allergy to pets, 28% had allergy to pollens, and 26% reported nasal symptoms. Fifty-one percent reported a history of asthma, allergic diseases, or hypersensitivity symptoms in their family. Exhaust ventilation was used by 24% during skin prick tests, 17% during allergen specific immunotherapy, and 33% when performing methacholine challenge tests. Tightly closed containers for disposable waste were used by 58% during skin prick tests, by 60% during immunotherapy, and by 40% during Pc provocation tests. Conclusion. Allergy nurses had a tendency to increased prevalence of lower respiratory symptoms, asthma, and allergic rhinitis and more than half of the nurses had a family history of asthma, allergic diseases, or hypersensitivity symptoms. Additional studies are needed to evaluate the validity of these results.

  18. Immediate hypersensitivity responses in the immunopathogenesis of human onchocerciasis.

    Science.gov (United States)

    Ottesen, E A

    1985-01-01

    It is not clear what role immediate hypersensitivity immune responses have in the pathogenesis of human onchocerciasis, but it is certain that these responses are prominent both in the course of natural infection and during the Mazzotti reactions that follow treatment with diethylcarbamazine. In humans, the levels of total serum IgE associated with onchocerciasis are as high or higher than those associated with almost any helminth infection, although specific IgE antibodies to Onchocerca volvulus appear to be a small and still poorly characterized fraction of the total serum IgE. Evidence about the relationship of these prominent IgE responses in patients with onchocerciasis to the onchocercal skin disease that manifests as pruritus and papular eruptions is conflicting, but in a guinea pig model of ocular pathology induced by onchocerca microfilariae evidence for the pathogenetic importance of IgE and immediate hypersensitivity is much less equivocal. The suggestive findings from this model make it imperative to carry out similar studies of Onchocerca-affected human eyes to determine whether immediate hypersensitivity responses play a similar critical role in the pathogenesis of the ocular lesions in humans.

  19. Behavioral and neurochemical analysis of ongoing bone cancer pain in rats.

    Science.gov (United States)

    Remeniuk, Bethany; Sukhtankar, Devki; Okun, Alec; Navratilova, Edita; Xie, Jennifer Y; King, Tamara; Porreca, Frank

    2015-10-01

    Cancer-induced bone pain is described as dull, aching ongoing pain. Ongoing bone cancer pain was characterized after intratibial injection of breast cancer cells in rats. Cancer produced time-dependent bone remodeling and tactile hypersensitivity but no spontaneous flinching. Conditioned place preference (CPP) and enhanced dopamine (DA) release in the nucleus accumbens (NAc) shell was observed after peripheral nerve block (PNB) selectively in tumor-bearing rats revealing nociceptive-driven ongoing pain. Oral diclofenac reversed tumor-induced tactile hypersensitivity but did not block PNB-induced CPP or NAc DA release. Tumor-induced tactile hypersensitivity, and PNB-induced CPP and NAc DA release, was blocked by prior subcutaneous implantation of a morphine pellet. In sham rats, morphine produced a modest but sustained increase in NAc DA release. In contrast, morphine produced a transient 5-fold higher NAc DA release in tumor bearing rats compared with sham morphine rats. The possibility that this increased NAc DA release reflected the reward of pain relief was tested by irreversible blockade of rostral anterior cingulate cortex (rACC) μ-opioid receptors (MORs). The rACC MOR blockade prevented the morphine-induced transient increased NAc DA release in tumor bearing rats but did not affect morphine-induced effects in sham-operated animals. Consistent with clinical experience, ongoing cancer pain was controlled by morphine but not by a dose of diclofenac that reversed evoked hypersensitivity. Additionally, the intrinsic reward of morphine can be dissociated from the reward of relief of cancer pain by blockade of rACC MOR. This approach allows mechanistic and therapeutic assessment of ongoing cancer pain with likely translation relevance.

  20. Pain frequency moderates the relationship between pain catastrophizing and pain

    OpenAIRE

    2014-01-01

    Background: Pain frequency has been shown to influence sensitization, psychological distress, and pain modulation. The present study examined if pain frequency moderates the relationship between pain catastrophizing and pain. Method: A non-clinical (247 students) and a clinical (223 pain patients) sample completed the Danish versions of the Pain Catastrophizing Scale (PCS), Beck Depression Inventory, and the State Trait Anxiety Inventory and rated pain intensity, unpleasantness and frequen...

  1. Pain frequency moderates the relationship between pain catastrophizing and pain

    OpenAIRE

    2014-01-01

    Background Pain frequency has been shown to influence sensitization, psychological distress and pain modulation. The present study examined if pain frequency moderates the relationship between pain catastrophizing and pain. Method A non-clinical (247 students) and a clinical (223 pain patients) sample completed the Danish versions of the Pain Catastrophizing Scale, Beck Depression Inventory and the State Trait Anxiety Inventory and rated pain intensity, unpleasantness and frequency Results In...

  2. Visceral versus somatic pain: similarities and differences.

    Science.gov (United States)

    Cervero, Fernando

    2009-01-01

    Inflammatory bowel disease and the irritable bowel syndrome are conditions characterized by chronic pain that generates persistent, hyperalgesic states in many regions of the body. It is difficult to explain the pain of conditions such as inflammatory bowel disease and irritable bowel syndrome by extrapolating directly from what is known about the mechanisms of somatic pain. Visceral and somatic pain show many differences not only in the psychophysics of the sensation, but also in the neurobiological mechanisms that mediate the sensory process. The activation and sensitization of visceral nociceptors are heavily influenced by the secretory and motor properties of the microenvironment where the sensory receptors are located. In some cases, epithelial cells can play a direct role in the activation of primary sensory neurons. Subclinical alterations of the epithelium can contribute to enhanced visceral sensitivity. Central hypersensitivity induced by visceral activation also shows differences with its somatic counterpart. Mobilization of AMPA receptors from the cytosol to the membrane of nociceptive neurons has been identified as a mechanism of sensitization of visceral pain pathways. Finally, functional pain syndromes, such as irritable bowel syndrome could be triggered or maintained by hormonal alterations, particularly those involving sex hormones such as estrogen.

  3. [Chest pain].

    Science.gov (United States)

    Horn, Benedikt

    2015-01-01

    Chest pain in ambulatory setting is predominantly not heart-associated. Most patients suffer from muskuloskeletal or functional (psychogenic) chest pain. Differential diagnosis covers aortic dissection, rib-fracture, shingles, GERD, Tietze-Syndrome, pulmonary embolism, pleuritis, pneumothorax, pleurodynia and metastatic disease. In most cases history, symptoms and signs allow a clinical diagnosis of high pretest-probability.

  4. 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.

  5. 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.

  6. Pain channelopathies

    Science.gov (United States)

    Cregg, Roman; Momin, Aliakmal; Rugiero, Francois; Wood, John N; Zhao, Jing

    2010-01-01

    Pain remains a major clinical challenge, severely afflicting around 6% of the population at any one time. Channelopathies that underlie monogenic human pain syndromes are of great clinical relevance, as cell surface ion channels are tractable drug targets. The recent discovery that loss-of-function mutations in the sodium channel Nav1.7 underlie a recessive pain-free state in otherwise normal people is particularly significant. Deletion of channel-encoding genes in mice has also provided insights into mammalian pain mechanisms. Ion channels expressed by immune system cells (e.g. P2X7) have been shown to play a pivotal role in changing pain thresholds, whilst channels involved in sensory transduction (e.g. TRPV1), the regulation of neuronal excitability (potassium channels), action potential propagation (sodium channels) and neurotransmitter release (calcium channels) have all been shown to be potentially selective analgesic drug targets in some animal pain models. Migraine and visceral pain have also been associated with voltage-gated ion channel mutations. Insights into such channelopathies thus provide us with a number of potential targets to control pain. PMID:20142270

  7. Whiplash-like facet joint loading initiates glutamatergic responses in the DRG and spinal cord associated with behavioral hypersensitivity

    Science.gov (United States)

    Dong, Ling; Quindlen, Julia C.; Lipschutz, Daniel E.; Winkelstein, Beth A.

    2012-01-01

    The cervical facet joint and its capsule are a common source of neck pain from whiplash. Mechanical hyperalgesia elicited by painful facet joint distraction is associated with spinal neuronal hyperexcitability that can be induced by transmitter/receptor systems that potentiate the synaptic activation of neurons. This study investigated the temporal response of a glutamate receptor and transporters in the dorsal root ganglia (DRG) and spinal cord. Bilateral C6/C7 facet joint distractions were imposed in the rat either to produce behavioral sensitivity or without inducing any sensitivity. Neuronal metabotropic glutamate receptor-5 (mGluR5) and protein kinase C-epsilon (PKCε) expression in the DRG and spinal cord were evaluated on days 1 and 7. Spinal expression of a glutamate transporter, excitatory amino acid carrier 1 (EAAC1), was also quantified at both time points. Painful distraction produced immediate behavioral hypersensitivity that was sustained for 7 days. Increased expression of mGluR5 and PKCε in the DRG was not evident until day 7 and only following painful distraction; this increase was observed in small-diameter neurons. Only painful facet joint distraction produced a significant increase (p<0.001) in neuronal mGluR5 over time, and this increase also was significantly elevated (p ≤ 0.05) over responses in the other groups at day 7. However, there were no differences in spinal PKCε expression on either day or between groups. Spinal EAAC1 expression was significantly increased (p<0.03) only in the nonpainful groups on day 7. Results from this study suggest spinal glutamatergic plasticity is selectively modulated in association with facet-mediated pain. PMID:22578356

  8. PKMζ is essential for spinal plasticity underlying the maintenance of persistent pain

    Directory of Open Access Journals (Sweden)

    Laferrière Andre

    2011-12-01

    Full Text Available Abstract Background Chronic pain occurs when normally protective acute pain becomes pathologically persistent. We examined here whether an isoform of protein kinase C (PKC, PKMζ, that underlies long-term memory storage in various brain regions, also sustains nociceptive plasticity in spinal cord dorsal horn (SCDH mediating persistent pain. Results Cutaneous injury or spinal stimulation produced persistent increases of PKMζ, but not other atypical PKCs in SCDH. Inhibiting spinal PKMζ, but not full-length PKCs, reversed plasticity-dependent persistent painful responses to hind paw formalin and secondary mechanical hypersensitivity and SCDH neuron sensitization after hind paw capsaicin, without affecting peripheral sensitization-dependent primary heat hypersensitivity after hind paw capsaicin. Inhibiting spinal PKMζ, but not full-length PKCs, also reversed mechanical hypersensitivity in the rat hind paw induced by spinal stimulation with intrathecal dihydroxyphenylglycine. Spinal PKMζ inhibition also alleviated allodynia 3 weeks after ischemic injury in rats with chronic post-ischemia pain (CPIP, at a point when allodynia depends on spinal changes. In contrast, spinal PKMζ inhibition did not affect allodynia in rats with chronic contriction injury (CCI of the sciatic nerve, or CPIP rats early after ischemic injury, when allodynia depends on ongoing peripheral inputs. Conclusions These results suggest spinal PKMζ is essential for the maintenance of persistent pain by sustaining spinal nociceptive plasticity.

  9. mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK.

    Science.gov (United States)

    Melemedjian, Ohannes K; Khoutorsky, Arkady; Sorge, Robert E; Yan, Jin; Asiedu, Marina N; Valdez, Arely; Ghosh, Sourav; Dussor, Gregory; Mogil, Jeffrey S; Sonenberg, Nahum; Price, Theodore J

    2013-07-01

    Mammalian target of rapamycin complex 1 (mTORC1) inhibitors are extensively used as immunosuppressants to prevent transplant rejection and in treatment of certain cancers. In patients, chronic treatment with rapamycin or its analogues (rapalogues) has been reported to lead to sensory hypersensitivity and pain conditions via an unknown mechanism. Here, we show that pharmacological or genetic inhibition of mTORC1 activates the extracellular signal-regulated kinase (ERK) pathway in sensory neurons via suppression of S6K1 to insulin receptor substrate 1 negative feedback loop. As a result, increased ERK activity induces sensory neuron sensitization, mechanical hypersensitivity, and spontaneous pain. The clinically available adenosine monophosphate-activated protein kinase activator, metformin, which is an antidiabetic drug, prevents rapamycin-induced ERK activation and the development of mechanical hypersensitivity and spontaneous pain. Taken together, our findings demonstrate that activation of the ERK pathway in sensory neurons as a consequence of mTORC1 inhibition leads to the development of pain. Importantly, this effect is abolished by co-treatment with metformin, thus providing a potential treatment option for rapalogue-evoked pain. Our findings highlight the physiological relevance of feedback signaling through mTORC1 inhibition and have important implications for development of pain therapeutics that target the mTOR pathway.

  10. Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders: consistent findings from five different patient cohorts.

    Science.gov (United States)

    Simrén, Magnus; Törnblom, Hans; Palsson, Olafur S; van Tilburg, Miranda A L; Van Oudenhove, Lukas; Tack, Jan; Whitehead, William E

    2017-01-19

    Our aim was to evaluate the association between visceral hypersensitivity and GI symptom severity in large cohorts of patients with functional GI disorder (FGID) and to adjust for psychological factors and general tendency to report symptoms. We included five cohorts of patients with FGIDs (IBS or functional dyspepsia; n=1144), who had undergone visceral sensitivity testing using balloon distensions (gastric fundus, descending colon or rectum) and completed questionnaires to assess GI symptom severity, non-GI somatic symptoms, anxiety and depression. Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds. GI symptom severity was compared between sensitivity tertiles in each cohort and corrected for somatisation, and anxiety and depression. In all five cohorts, GI symptom severity increased gradually with increasing visceral sensitivity, with significant differences in GI symptom severity between the sensitivity tertiles (pGI somatic symptom reporting in all of the cohorts (pGI symptom severity with increasing GI sensitivity was demonstrated in IBS and functional dyspepsia, which was consistent across several large patient groups from different countries, different methods to assess sensitivity and assessments in different parts of the GI tract. This association was independent of tendency to report symptoms or anxiety/depression comorbidity. These findings confirm that visceral hypersensitivity is a contributor to GI symptom generation in FGIDs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Chemokine contribution to neuropathic pain: respective induction of CXCL1 and CXCR2 in spinal cord astrocytes and neurons.

    Science.gov (United States)

    Zhang, Zhi-Jun; Cao, De-Li; Zhang, Xin; Ji, Ru-Rong; Gao, Yong-Jing

    2013-10-01

    Recent studies have indicated an important role of chemokines such as CCL2 in the development of chronic pain. However, the distinct roles of different chemokines in the development and maintenance of neuropathic pain and in their interactions with neurons have not been clearly elucidated. We found that spinal nerve ligation (SNL) not only induced persistent neuropathic pain symptoms, including mechanical allodynia and heat hyperalgesia, but also produced sustained CXCL1 upregulation in the spinal cord. Double staining of immunofluorescence and in situ hybridization revealed that CXCL1 was primarily induced in spinal astrocytes. In cultured astrocytes, tumor necrosis factor-α induced robust CXCL1 expression via the activation of the c-jun N-terminal kinase. Intrathecal administration of CXCL1 neutralizing antibody transiently reduced SNL-induced pain hypersensitivity, suggesting an essential role of CXCL1 in neuropathic pain sensitization. In particular, intraspinal delivery of CXCL1 shRNA lentiviral vectors, either before or after SNL, persistently attenuated SNL-induced pain hypersensitivity. Spinal application of CXCL1 not only elicited pain hypersensitivity but also induced rapid neuronal activation, as indicated by the expression of phosphorylated extracellular signal-regulated kinase and cAMP response element binding protein, and c-Fos in spinal cord neurons. Interestingly, CXCR2, the primary receptor of CXCL1, was upregulated in dorsal horn neurons after SNL, and the CXCR2 antagonist SB225002 completely blocked the CXCL1-induced heat hyperalgesia. SB225002 also attenuated SNL-induced pain hypersensitivity. Collectively, our results have demonstrated a novel form of chemokine-mediated glial-neuronal interaction in the spinal cord that can drive neuropathic pain. Inhibition of the CXCL1-CXCR2 signaling may offer a new therapy for neuropathic pain management.

  12. Visceral and somatic hypersensitivity in TNBS-induced colitis in rats.

    Science.gov (United States)

    Zhou, QiQi; Price, Donald D; Caudle, Robert M; Verne, G Nicholas

    2008-02-01

    Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200-250 g) were treated with 20 mg of TNBS in 50% ethanol (n = 40) or an equivalent volume of ethanol (n = 40) or saline (n = 25) via the colon. Colonic distension, Von Frey, Hargreaves, and tail reflex tests were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2-28 days following TNBS administration (P rats also demonstrated visceral hypersensitivity that resolved after day 14. TNBS-treated rats demonstrated somatic hypersensitivity at days 14-28 (P TNBS colitis is associated with visceral and somatic hypersensitivity in areas of somatotopic overlap. This model of colitis should allow further investigation into the mechanisms of visceral and somatic hypersensitivity.

  13. Pain Control After Surgery: Pain Medicines

    Science.gov (United States)

    ... receive pain medicine. If you feel pain, you push a button to inject medicine into your vein. ... without abusing pain medicine. There are pain management strategies you can try that do not include medicines. ...

  14. Fetal pain?

    Science.gov (United States)

    Vanhatalo, S; van Nieuwenhuizen, O

    2000-05-01

    During the last few years a vivid debate, both scientifically and emotionally, has risen in the medical literature as to whether a fetus is able to feel pain during abortion or intrauterine surgery. This debate has mainly been inspired by the demonstration of various hormonal or motor reactions to noxious stimuli at very early stages of fetal development. The aims of this paper are to review the literature on development of the pain system in the fetus, and to speculate about the relationship between "sensing" as opposed to "feeling" pain and the number of reactions associated with painful stimuli. While a cortical processing of pain theoretically becomes possible after development of the thalamo-cortical connections in the 26th week of gestation, noxious stimuli may trigger complex reflex reactions much earlier. However, more important than possible painfulness is the fact that the noxious stimuli, by triggering stress responses, most likely affect the development of an individual at very early stages. Hence, it is not reasonable to speculate on the possible emotional experiences of pain in fetuses or premature babies. A clinically relevant aim is rather to avoid and/or treat any possibly noxious stimuli, and thereby prevent their potential adverse effects on the subsequent development.

  15. [Musculoskeletal pain].

    Science.gov (United States)

    Casser, H-R; Schaible, H-G

    2015-10-01

    Among the clinically relevant pain conditions, pain in the musculoskeletal system is most frequent. This article reports extensive epidemiological data on musculoskeletal system pain in Germany and worldwide. Since back pain is most frequent, the diagnostics and therapeutic algorithms of acute, recurring, and chronic lower back pain in Germany will be particularly addressed. The importance of the physiologic-organic, the cognitive-emotional, the behavioral, and the social level to diagnostics and treatment will be discussed. We will also focus on osteoarthritic pain and address its epidemiology, clinical importance, and significance for the health care system. This article will list some reasons why the musculoskeletal system in particular is frequently the site of chronic pain. The authors believe that these reasons are to be sought in the complex structures of the musculoskeletal system; in the particular sensitivity of the deep somatic nociceptive system for long-term sensitization processes, as well as the ensuing nervous system reactions; and in the interactions between the nervous and immune systems. The article will give some insights into the research carried out on this topic in Germany.

  16. Pain Disorder

    Directory of Open Access Journals (Sweden)

    Carlos Capela

    2014-06-01

    Full Text Available Pain disorder is a psychiatric disorder diagnosed when the pain becomes the predominant focus of the clinical presentation and causes significant distress or impairment. Besides the high economic impact, there is a reciprocal relationship with the affective state. Pain is a subjective sensation and its severity and quality of experience in an individual is dependent on a complex mix of factors. In the treatment of acute pain, the primary purpose is pain relief, while chronic pain typically requires a combination of psychotropic drugs. In this context, it is also important to recognize and treat depression. Psychological treatments aimed at providing mechanisms to allow patients to "control and live with the pain" rather than aspire to eliminate it completely. A growing group of researchers proposes the elimination of the chapter of Somatoform Disorders and the modification of the category "psychological factors affecting a medical condition" to "psychological factors affecting an identified or feared medical condition" with clinical entities as ubchapters, largely based upon Diagnostics for Psychosomatic Research criteria.

  17. 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.

  18. Development of New Treatment Method for Dentin Hypersensitivity Using Ammonium Hexafluorosilicate

    OpenAIRE

    菅, 俊行

    2010-01-01

    Dentin hypersensitivity is a common disease, the incidence is approximately 30% in the general population. However, knowledge is limited regarding the etiology of dentin hypersensitivity, and there is no consistent treatment method. Therefore, relationship between the etiology of dentin hypersensitivity and condition of plaque control was evaluated in vivo using the vital teeth of dogs. In the plaque control group, the average diameter of dentin tubules decreased over time. In contrast, the d...

  19. Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Maw Pin Tan

    Full Text Available Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity.Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG scanning. Heart to mediastinal uptake ratio (H:M were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG.Forty-two subjects: carotid sinus syndrome (n = 21, asymptomatic carotid sinus hypersensitivity (n = 12 and no carotid sinus hypersensitivity (n = 9 were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005 and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032. There was, however, no significant difference in early H:M (p = 0.326 or late H:M (p = 0.351 between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls.Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to

  20. Type I hypersensitivity to Parthenium hysterophorus in patients with parthenium dermatitis

    OpenAIRE

    Lakshmi Chembolli; Srinivas C

    2007-01-01

    Background: Parthenium dermatitis is a major problem in urban and rural India. Patients with severe allergic rhinitis due to exposure to pollens of parthenium are reported to have parthenium specific IgE and IgG antibodies. Parthenium induces contact dermatitis by Type IV hypersensitivity and allergic rhinitis by Type-I hypersensitivity. Aims: The study was undertaken to detect Type-I and Type-IV hypersensitivity amongst patients with parthenium dermatitis. Methods: Fourteen patients wit...

  1. Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli.

    Science.gov (United States)

    Kato, Fumi; Iwanaga, Ryoichiro; Chono, Mami; Fujihara, Saori; Tokunaga, Akiko; Murata, Jun; Tanaka, Koji; Nakane, Hideyuki; Tanaka, Goro

    2014-07-01

    [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli.

  2. 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

  3. What a Pain! Kids and Growing Pains

    Science.gov (United States)

    ... What Happens in the Operating Room? What a Pain! Kids and Growing Pains KidsHealth > For Kids > What a Pain! Kids and ... something doctors call growing pains . What Are Growing Pains? Growing pains aren't a disease. You probably ...

  4. An increased response to experimental muscle pain is related to psychological status in women with chronic non-traumatic neck-shoulder pain

    Directory of Open Access Journals (Sweden)

    Persson Ann L

    2011-10-01

    Full Text Available Abstract Background Neck-shoulder pain conditions, e.g., chronic trapezius myalgia, have been associated with sensory disturbances such as increased sensitivity to experimentally induced pain. This study investigated pain sensitivity in terms of bilateral pressure pain thresholds over the trapezius and tibialis anterior muscles and pain responses after a unilateral hypertonic saline infusion into the right legs tibialis anterior muscle and related those parameters to intensity and area size of the clinical pain and to psychological factors (sleeping problems, depression, anxiety, catastrophizing and fear-avoidance. Methods Nineteen women with chronic non-traumatic neck-shoulder pain but without simultaneous anatomically widespread clinical pain (NSP and 30 age-matched pain-free female control subjects (CON participated in the study. Results NSP had lower pressure pain thresholds over the trapezius and over the tibialis anterior muscles and experienced hypertonic saline-evoked pain in the tibialis anterior muscle to be significantly more intense and locally more widespread than CON. More intense symptoms of anxiety and depression together with a higher disability level were associated with increased pain responses to experimental pain induction and a larger area size of the clinical neck-shoulder pain at its worst. Conclusion These results indicate that central mechanisms e.g., central sensitization and altered descending control, are involved in chronic neck-shoulder pain since sensory hypersensitivity was found in areas distant to the site of clinical pain. Psychological status was found to interact with the perception, intensity, duration and distribution of induced pain (hypertonic saline together with the spreading of clinical pain. The duration and intensity of pain correlated negatively with pressure pain thresholds.

  5. The role of toothpaste in the aetiology and treatment of dentine hypersensitivity.

    Science.gov (United States)

    Addy, M; West, N X

    2013-01-01

    Dentine hypersensitivity (DH) is a common, painful dental condition with a multi-factorial aetiology. The hydrodynamic mechanism theory to explain dentine sensitivity also appears to fit DH: lesions exhibiting large numbers of open dentinal tubules at the surface and patent to the pulp. By definition, DH can only occur when dentine becomes exposed (lesion localisation) and tubules opened (lesion initiation), thus permitting increased fluid flow in tubules on stimulation. Erosion, particularly from dietary acids appears to play a dominant role in both processes. Toothbrushing with most toothpaste products alone cause clinically insignificant wear of enamel but are additive, even synergistic, to erosive enamel loss. Additionally, toothbrushing with toothpaste is implicated in 'healthy' gingival recession. Toothbrushing with most toothpastes removes the smear layer to expose tubules and again can exacerbate erosive loss of dentine. These findings thereby implicate toothbrushing with toothpaste in the aetiology of DH. Management of the condition should have secondary prevention at the core of treatment and therefore, must consider first and foremost the aetiology. Fluoride toothpaste at present appears to provide little primary or secondary preventive benefits to DH; additional ingredients can provide therapeutic benefits. Potassium-based products to block pulpal nerve response have caused much debate and are considered by many as unproven, which should not translate to ineffective. Several toothpaste technologies formulated to block tubules are from studies in vitro, in situ and controlled clinical trials considered proven for the treatment of DH.

  6. Ion channels, ion channel receptors, and visceral hypersensitivity in irritable bowel syndrome.

    Science.gov (United States)

    Fuentes, I M; Christianson, J A

    2016-11-01

    Ion channels are expressed throughout the gastrointestinal system and regulate nearly every aspect of digestion, including fluid secretion and absorption, motility, and visceral sensitivity. It is therefore not surprising that in the setting of functional bowel disorders, such as irritable bowel syndrome (IBS), ion channels are often altered in terms of expression level and function and are a target of pharmacological intervention. This is particularly true of their role in driving abdominal pain through visceral hypersensitivity (VH), which is the main reason IBS patients seek medical care. In the study by Scanzi et al., in the current issue of this journal, they provide evidence that the T-type voltage-gated calcium channel (Cav ) Cav 3.2 is upregulated in human IBS patients, and is necessary for the induction of an IBS-like disease state in mice. In this mini-review, we will discuss the contribution of specific ion channels to VH in IBS, both in human patients and rodent models. We will also discuss how Cav 3.2 may play a role as an integrator of multiple environmental stimuli contributing toward VH.

  7. Chronic Pelvic Pain

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pelvic Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  8. Chronic Pelvic Pain

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Chronic Pelvic Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  9. Efficacy of a commercial dentifrice containing 2% strontium chloride and 5% potassium nitrate for dentin hypersensitivity: a 3-day clinical study in adults in China.

    Science.gov (United States)

    Liu, Hongchun; Hu, Deyu

    2012-03-01

    Studies of dentifrices containing strontium chloride or potassium nitrate have documented the clinical efficacy of these formulations for dentin hypersensitivity (DH), but few studies have evaluated dentifrices containing both active ingredients. The objective of this study was to compare the effects on DH of a dentifrice containing 2% strontium chloride and 5% potassium nitrate in a silica base (experimental dentifrice) with those of a dentifrice containing the same silica base without any active ingredient (control dentifrice). Male and female patients aged 20 to 65 years with DH were eligible to participate in this randomized, double-blind, placebo-controlled study in China. Patients were assigned to receive the experimental or control dentifrice. At baseline, immediately after topical dentifrice use, and after 3 days, patients received an oral examination of their hard and soft tissues, followed by an evaluation of DH that used the Yeaple Probe to measure tactile hypersensitivity and the Schiff Cold Air Scale to measure the perception of pain from an air blast stimulus. Adverse events (in particular, discomfort while brushing or alteration in taste) in the oral hard or soft tissues were monitored throughout the study. A total of 81 patients were enrolled (40 in the experimental group; 41 in the control group), of whom 79 (55 women; 24 men) completed the study. After topical use, the experimental group had a significantly higher mean (SD) tactile hypersensitivity score (19.47 [14.69] vs 14.27 [5.76]; P = 0.047) and a significantly lower mean air blast hypersensitivity score (1.93 [0.51] vs 2.22 [0.60]; P = 0.026) than did the control group. After 3 days, the experimental group had a significantly higher mean tactile hypersensitivity score (19.87 [14.95] vs 14.51 [6.00]; P = 0.045) and a significantly lower air blast hypersensitivity score (1.80 [0.56] and 2.13 [0.60]; P = 0.014) than the control group. After topical use and after 3 days, the experimental group

  10. 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

  11. Fetal pain.

    Science.gov (United States)

    Rokyta, Richard

    2008-12-01

    The fetus reacts to nociceptive stimulations through different motor, autonomic, vegetative, hormonal, and metabolic changes relatively early in the gestation period. With respect to the fact that the modulatory system does not yet exist, the first reactions are purely reflexive and without connection to the type of stimulus. While the fetal nervous system is able to react through protective reflexes to potentially harmful stimuli, there is no accurate evidence concerning pain sensations in this early period. Cortical processes occur only after thalamocortical connections and pathways have been completed at the 26th gestational week. Harmful (painful) stimuli, especially in fetuses have an adverse effect on the development of humans regardless of the processes in brain. Moreover, pain activates a number of subcortical mechanisms and a wide spectrum of stress responses influence the maturation of thalamocortical pathways and other cortical activation which are very important in pain processing.

  12. Habituating pain

    DEFF Research Database (Denmark)

    Ajslev, Jeppe Zielinski Nguyen; Lund, Henrik Lambrecht; Møller, Jeppe Lykke

    2013-01-01

    In this article, we investigate the relations between discursive practices within the Danish construction industry and the perceived pain, physical deterioration, and strain affecting the construction workers. Of central importance is the widely accepted hegemonic discourse on physical strain...... and pain as unavoidable conditions in construction work. Based on 32 semi-structured interviews performed in eight case studies within four different construction professions, workers’ descriptions of physical strain and its relation to the organizational and social context are analyzed through concepts...... the industry reproduce physical strain and the habituation of pain as unquestioned conditions in construction work. The understanding of this mutual reinforcement of the necessity of physically straining, painful, high-paced construction work provides fruitful perspectives on the overrepresentation...

  13. Finger pain

    Science.gov (United States)

    ... be a sign of infection or inflammation. Causes Injuries are a common cause of finger pain. Your finger may become injured from: Playing contact sports such as football, baseball, or soccer Doing recreational activities such as ...

  14. 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 ...

  15. Shoulder pain

    Science.gov (United States)

    ... This condition is called rotator cuff tendinitis or bursitis. Shoulder pain may also be caused by: Arthritis ... shoulder joint Bone spurs in the shoulder area Bursitis , which is inflammation of a fluid-filled sac ( ...

  16. Heel Pain

    Science.gov (United States)

    ... in the big toe joint; an inflamed bursa (bursitis), a small, irritated sac of fluid; a neuroma ( ... sometimes painful deformity generally is the result of bursitis caused by pressure against the shoe and can ...

  17. Knee pain

    Science.gov (United States)

    ... of home treatment What to Expect at Your Office Visit Your health care provider will perform a ... pain and inflammation. You may need to learn stretching and strengthening exercises. You also may need to ...

  18. 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 < .0001). Urticaria and angioedema accounted for the most frequent clinical presentations (71%), whereas anaphylaxis was present in 27.3% of cases. There were no deaths reported. Nonsteroidal anti-inflammatory drugs (52.3%), β-lactam antibiotics (13.8%), and other antibiotics (10.1%) were the drugs used most frequently. Skin prick tests (16.7%) and provocation tests (34.2%) were the study procedures most commonly used. A large proportion of patients were treated in the emergency department (62%) with antihistamines (68%) and/or corticosteroids (53%). Only 22.8% of patients presenting with anaphylaxis received epinephrine. Nonsteroidal anti-inflammatory drugs and antibiotics were the drugs used in at least 75% of patients. More than half the reactions were treated in the emergency department, whereas epinephrine was administered in fewer than 25% of patients with anaphylaxis. Dissemination of guidelines for anaphylaxis among primary and emergency department physicians should be encouraged. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. Hypersensitivity reaction to components of parenteral nutrition in pediatrics.

    Science.gov (United States)

    Hernández, Carlos Ruiz; Ponce, Esperanza Castejón; Busquets, Ferran Bossacoma; Hernández, Diana Sánchez; Oliva, Silvia Meavilla; Santacruz, Enrique Llerena; Pérez, Naymar; De Los Santos Pelegrini, Mariela; Flaque, Miquel Villaronga

    2016-01-01

    Very rare cases of hypersensitivity reactions to various constituents of parenteral nutrition (PN) have been reported in children. Adverse effects associated with PN administration have centered on metabolic, infectious, and mechanical complications. Here we describe three cases of hypersensitivity to components of PN. Case 1 is a 1-mo-old breastfed baby with a diagnosis of acute gastroenteritis associated with an infection with cytomegalovirus. On the second day of PN, 60 min after the initiation of the infusion, the patient had an allergic reaction with an overall diffused rash. On day 4 of PN, the multivitamin solution and the trace element mix were excluded, showing a good tolerance. Case 2 is a 4-y-old girl with a background of stage III neuroblastoma. On day 3 of PN, 15 min after the initiation of the infusion, the patient showed sudden facial edema. On day 5, suspecting the amino acid solution to be the etiology of her reaction, PN was infused with another amino acid preparation, and the patient showed good tolerance. Case 3 is a 10-y-old boy with a diagnosis of an acute peritonitis. Two h after the initiation of the infusion, the patient showed a general wheal rash. He referred a background of fish allergy. Considering that the lipid emulsion used had components from fish oil (SMOF Lipid), a new PN was infused on day 2. The new PN contained a lipid emulsion containing vegetable oil (ClinOleic). The patient showed good tolerance. In conclusion, we consider that, although the hypersensitivity to PN components is infrequent, there is an increase in reports of pediatric cases describing this allergic pathology.

  20. Neck pain

    OpenAIRE

    2002-01-01

    Non-specific neck pain has a postural or mechanical basis, and affects about two thirds of people at some stage, especially in middle age. Acute neck pain resolves within days or weeks, but becomes chronic in about 10% of people.Whiplash injuries follow sudden acceleration–deceleration of the neck, such as in road traffic or sporting accidents. Up to 40% of people continue to report symptoms 15 years after the accident.

  1. Quantitative sensory testing response patterns to capsaicin- and ultraviolet-B-induced local skin hypersensitization in healthy subjects: a machine-learned analysis.

    Science.gov (United States)

    Lötsch, Jörn; Geisslinger, Gerd; Heinemann, Sarah; Lerch, Florian; Oertel, Bruno G; Ultsch, Alfred

    2017-08-16

    The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat stimulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain). This study provided a 246 × 10-sized data matrix (82 subjects assessed at baseline, following UV-B application, and following capsaicin application) with respect to 10 QST parameters, which we analyzed using machine-learning techniques. We observed statistically significant effects of the hypersensitization treatments in 9 different QST parameters. Supervised machine-learned analysis implemented as random forests followed by ABC analysis pointed to heat pain thresholds as the most relevantly affected QST parameter. However, decision tree analysis indicated that UV-B additionally modulated sensitivity to cold. Unsupervised machine-learning techniques, implemented as emergent self-organizing maps, hinted at subgroups responding to topical application of capsaicin. The distinction among subgroups was based on sensitivity to pressure pain, which could be attributed to sex differences, with women being more sensitive than men. Thus, while UV-B and capsaicin share a major component of heat pain sensitization, they differ in their effects on QST parameter patterns in healthy subjects, suggesting a lack of redundancy between these models.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible

  2. 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.

  3. O-antigen modulates infection-induced pain states.

    Directory of Open Access Journals (Sweden)

    Charles N Rudick

    Full Text Available The molecular initiators of infection-associated pain are not understood. We recently found that uropathogenic E. coli (UPEC elicited acute pelvic pain in murine urinary tract infection (UTI. UTI pain was due to E. coli lipopolysaccharide (LPS and its receptor, TLR4, but pain was not correlated with inflammation. LPS is known to drive inflammation by interactions between the acylated lipid A component and TLR4, but the function of the O-antigen polysaccharide in host responses is unknown. Here, we examined the role of O-antigen in pain using cutaneous hypersensitivity (allodynia to quantify pelvic pain behavior and using sacral spinal cord excitability to quantify central nervous system manifestations in murine UTI. A UPEC mutant defective for O-antigen biosynthesis induced chronic allodynia that persisted long after clearance of transient infections, but wild type UPEC evoked only acute pain. E. coli strains lacking O-antigen gene clusters had a chronic pain phenotype, and expressing cloned O-antigen gene clusters altered the pain phenotype in a predictable manner. Chronic allodynia was abrogated in TLR4-deficient mice, but inflammatory responses in wild type mice were similar among E. coli strains spanning a wide range of pain phenotypes, suggesting that O-antigen modulates pain independent of inflammation. Spinal cords of mice with chronic allodynia exhibited increased spontaneous firing and compromised short-term depression, consistent with centralized pain. Taken together, these findings suggest that O-antigen functions as a rheostat to modulate LPS-associated pain. These observations have implications for an infectious etiology of chronic pain and evolutionary modification of pathogens to alter host behaviors.

  4. Visceral and Somatic Hypersensitivity in TNBS induced Colitis in Rats

    OpenAIRE

    Zhou, Qiqi; Price, Donald D.; Caudle, Robert M; Verne, G Nicholas

    2007-01-01

    Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200g–250g) were treated with 20 mg of TNBS in 50% ethanol (n=40) or an equivalent volume of ethanol (n=40) or saline (n=25) via the colon. Colonic distension, Von-Frey, Hargreaves, and tail reflex test were used to evaluate for v...

  5. 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.

  6. Hypersensitivity pneumonitis due to residential mosquito-coil smoke exposure

    Institute of Scientific and Technical Information of China (English)

    Gopall Roshnee; CAO Guo-qiang; CHEN Hong

    2011-01-01

    We reported a previously healthy 25-year-old female patient who developed hypersensitivity pneumonitis following repeated exposures to the smoke of mosquito coils. The patient presented with vague symptoms of cough and fever for 3 days. Diagnostic criteria proposed for clinical use in this case included history, exposure to a recognized antigen, physical examination, consistent radiographic images, bronchoalveolar lavage and lung biopsy. Much symptomatic relief and better radiographic response were noted after short-term use of oral corticosteroid and removal of the offending antigen.

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

    Science.gov (United States)

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

    2017-09-01

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

  8. 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.

  9. 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.

  10. Pain relief can be painful

    Directory of Open Access Journals (Sweden)

    Ashish Bindra

    2015-01-01

    Full Text Available Mandibular nerve block is periodically used procedure used to treat neuralgic pain in the distribution of trigeminal nerve. It is a commonly performed block in outpatient settings at our institute. We present a case of an elderly edentulous patient with trigeminal neuralgia who suffered recurrent temporomandibular joint (TMJ dislocation following mandibular nerve block. The patient presented with complaints of severe pain, inability to close mouth, and eat food since 2 days. Anterior closed reduction of TMJ resulted in reduction of joint and immediate pain relief. However, the maneuver failed due to recurrent dislocation of the joint. A Barton dressing was applied to prevent another dislocation. This was followed by autologous blood injection into the joint. This case focuses on the preponderance of clinical evaluation and accentuates the need for additional forethought to be taken during pain procedures, particularly in the geriatric population.

  11. Elite swimmers with and without unilateral shoulder pain: mechanical hyperalgesia and active/latent muscle trigger points in neck-shoulder muscles.

    Science.gov (United States)

    Hidalgo-Lozano, A; Fernández-de-las-Peñas, C; Calderón-Soto, C; Domingo-Camara, A; Madeleine, P; Arroyo-Morales, M

    2013-02-01

    Our aim was to investigate the presence of mechanical hypersensitivity and active trigger points (TrPs) in the neck-shoulder muscles in elite swimmers with/without unilateral shoulder pain. Seventeen elite swimmers with shoulder pain; 18 swimmers without shoulder pain; and 15 elite athletes matched controls were recruited. Pressure pain thresholds (PPT) were assessed over the levator scapulae, sternocleidomastoid, upper trapezius, infraspinatus, scalene, subscapularis and tibialis anterior muscles. TrPs in the levator scapulae, upper trapezius, infraspinatus, scalene, sternocleidomastoid and subscapularis muscles were also explored. Swimmers with shoulder pain showed significant lower PPT in all muscles compared with controls (Ppain, underlining widespread mechanical hypersensitivity. The mean number of TrPs for elite swimmer with and without shoulder pain was, respectively, 4.7 ± 1 (2.1 ± 1.5 active; 2.6 ± 1.4 latent) and 4.7 ± 1.3 (1.3 ± 1.3 active; 3.4 ± 1.5 latent), whereas healthy athletes only showed latent TrPs (2.4 ± 1.2). Elite swimmers with shoulder pain showed higher number of active TrPs than swimmers without pain, whereas it was the opposite for the number of latent muscle TrP (Pmechanical hypersensitivity suggests that active TrPs play a role in the development of shoulder pain in elite swimmers.

  12. The antinociceptive effects of the tetracyclic triterpene euphol in inflammatory and neuropathic pain models: The potential role of PKCε.

    Science.gov (United States)

    Dutra, R C; Bicca, M A; Segat, G C; Silva, K A B S; Motta, E M; Pianowski, L F; Costa, R; Calixto, J B

    2015-09-10

    Evidences suggest protein kinase C epsilon (PKCε) activation is involved in both inflammatory and neuropathic pains. We have previously shown that tetracyclic triterpene euphol produces antinociception in different models of persistent pain, an action associated with its anti-inflammatory properties. Among these properties are the cannabinoid system activation and different PKC isozymes modulation. Herein, we sought to explore the potential role of PKCε modulation on euphol antinociceptive effect, in inflammatory and neuropathic pain models, in rodents. Also, we investigated further mechanisms associated with euphol effects. Oral treatment with euphol (30 mg/kg) prevented the putative effect of PGE2-induced acute and persistent mechanical hypersensitivity in mice and rats, respectively. In the PGE2-induced acute mechanical hypersensitivity euphol promoted an inhibitory effect similar to a PKCε inhibitor peptide. Likewise, in rats it prevented the mechanical hypersensitivity induced by a PKCε activator. Conversely, euphol effectiveness was not observed in a cAMP/PKA-induced mechanical hypersensitivity in mice. Single (1h prior) or repeated (twice daily during 3 or 13 days) treatments with euphol ameliorated painful peripheral neuropathy induced by paclitaxel and also the mechanical hypersensitivity induced by B16F10 melanoma cells injection, in mice. Additionally, in both inflammatory and neuropathic pain models, euphol consistently prevented PKCε up-regulation, as well as, inhibited the up-regulation of PKCε-activated intracellular pathways; namely nuclear factor-κB (NF-κB), cyclic AMP response element binding protein (CREB) and cyclo-oxygenase-2 (COX-2). The present results suggest the antinociceptive effect on persistent pain caused by euphol is likely dependent on the inhibition of pro-inflammatory mediators modulated by PKCε.

  13. [Myofascial pain syndrome--fascial muscle pain].

    Science.gov (United States)

    Partanen, Juhani; Ojala, Tuula; Arokoski, Jari P A

    2010-01-01

    Symptoms of myofascial pain syndrome, i.e. fascial muscle pain may occur in several areas of the body, particularly in the neck-shoulder region. The muscle pain symptom in the neck-shoulder region is commonly termed tension neck pain or nonspecific neck pain, but myofascial pain syndrome can also be distinguished into its own diagnosis. This review deals with the clinical picture of myofascial pain syndrome along with pathophysiological hypotheses and treatment options.

  14. Rice Hypersensitive Induced Reaction Protein 1 (OsHIR1 associates with plasma membrane and triggers hypersensitive cell death

    Directory of Open Access Journals (Sweden)

    Sun Sai-Ming

    2010-12-01

    Full Text Available Abstract Background 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. Result 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. Conclusion 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

  15. Beta-lactam hypersensitivity and cross-reactivity.

    Science.gov (United States)

    Terico, Adrienne T; Gallagher, Jason C

    2014-12-01

    Penicillin is the most frequently reported cause of drug allergy, and cross-reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered.

  16. Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis

    Energy Technology Data Exchange (ETDEWEB)

    Zipser, R.D.; Patterson, J.B.; Kao, H.W.; Hauser, C.J.; Locke, R.

    1985-10-01

    Inflammation of the colon is associated with increased production of prostaglandins (PG) and thromboxanes (Tx), and these eicosanoids may contribute to the inflammatory, secretory, and motility dysfunctions in colitis. To evaluate the potential role of peptide hormones in the enhanced eicosanoid release, colitis was established in rabbits by a delayed-type hypersensitivity reaction to dinitrochlorobenzene and by an immune-complex-mediated reaction. PG and Tx were identified in the venous effluent of isolated perfused colons by radiochromatography after ( UC)arachidonic acid prelabeling, as well as by bioassay, and then quantitated by immunoassay. The two colitis models were morphologically similar. Basal release of PGE2, PGI2, and TxA2 was two- to threefold greater from colitis tissue than from control tissue. Bradykinin (BK) and angiotensin II (ANG II) increased release of UC-labeled eicosanoids, whereas several gastrointestinal hormones had no effect. In control colons, BK and ANG II increased PGE2 and PGI2 release (by about 2-fold) but did not alter TxA2. In contrast, BK and ANG II markedly exaggerated the release of eicosanoids in colitis. Since BK and possibly ANG II are increased at sites of inflammation, the hypersensitive eicosanoid response to these peptides may augment the eicosanoid-mediated manifestations of colitis.

  17. [Behavior of delayed-type hypersensitivity in parapsoriasis].

    Science.gov (United States)

    Paschoal, L H; Trindade Filho, P E

    1987-01-01

    The authors present a study of behaviour of the late hypersensitivity in fourteen patients carrying parapsoriasis with age varying from 36 to 64 years being nine men and five women with time of the illness development from one to eleven years. There were thirteen white sick people and a yellow one. The parapsoriasis diagnosis was confirmed in all of them clinica and histopathologica. The patients were not getting any therapeutic with corticosteroids or immunosuppressive drugs at the time of study. They were studied immunological through methods in vivo. 1. Methods in vivo. a) Intradermoreactions with the infectious antigens: PPD, trichophytin, levedurin, E. coli. It was used as a control group of fourty normal fellows. b) Sensibility to DNCB. The results obtained allow the following thesis: 1. Low table of positivity to the intradermal reactions to the late reading only one of the antigens tested on the patients (E. coli) related to the others. According to these elements we cannot get at a conclusion for depression of the inespecific cellular immunity in our sick patients. 2. Significant statistics difference on the sensibility test to DNCB on the sick patients related to the controls, a fact which shows a certain degree of the depression of the inespecific cellular immunity. 3. The sick patients with parapsoriasis before taking some treatment should go through the study of a late hypersensitivity.

  18. Comparative effects of α2δ-1 ligands in mouse models of colonic hypersensitivity

    Science.gov (United States)

    Meleine, Mathieu; Boudieu, Ludivine; Gelot, Agathe; Muller, Emilie; Lashermes, Amandine; Matricon, Julien; Silberberg, Celine; Theodorou, Vassilia; Eschalier, Alain; Ardid, Denis; Carvalho, Frederic A

    2016-01-01

    AIM To investigate anti-hypersensitive effects of α2δ-1 ligands in non-inflammatory and inflammation-associated colonic hypersensitivity (CHS) mouse models. METHODS To induce an inflammation-associated CHS, 1% dextran sulfate sodium (DSS) was administered to C57Bl/6J male mice, in drinking water, for 14 d. Regarding the non-inflammatory neonatal maternal separation (NMS) -induced CHS model, wild-type C57BI/6J pups were isolated from their mother from day 2 to day 14 (P2 to P14), three hours per day (from 9:00 a.m. to 12:00 p.m.). Colorectal distension was performed by inflating distension probe from 20 μL to 100 μL by 20 μL increment step every 10 s. After a first colorectal distension (CRD), drugs were administered subcutaneously, in a cumulative manner, (Gabapentin at 30 mg/kg and 100 mg/kg; Pregabalin at 10 mg/kg and 30 mg/kg; Carbamazepine at 10 mg/kg and 30 mg/kg) and a second CRD was performed one hour after each injection. RESULTS The visceromotor response (VMR) to CRD was increased by our NMS paradigm protocol in comparison to non-handled (NH) mice, considering the highest distension volumes (80 μL: 0.783 ± 0.056 mV/s vs 0.531 ± 0.034 mV/s, P NMS and NH mice, respectively). In the inflammation-associated CHS, DSS-treated mice showed a dramatic and significant increase in VMR at 60 and 80 μL distension volumes when compared to control mice (60 μL: 0.920 ± 0.079 mV/s vs 0.426 ± 0.100 mV/s P NMS-induced CHS model for the acute subcutaneous administration of the highest cumulative dose (30 mg/kg) and significantly reduced CHS in low-dose DSS-treated mice in a dose-dependent manner. Finally, the percent decrease of AUC induced by acute GBP or Pregabalin treatment were higher in the inflammatory DSS-induced CHS model in comparison to the non-inflammatory NMS-induced CHS model. CONCLUSION This preclinical study demonstrates α2δ-1 ligands efficacy on inflammation-associated CHS, highlighting their potential clinical interest in patients with chronic

  19. Evaluation of different treatment protocols for dentin hypersensitivity: an 18-month randomized clinical trial.

    Science.gov (United States)

    Lopes, Anely Oliveira; de Paula Eduardo, Carlos; Aranha, Ana Cecília Correa

    2017-07-01

    This randomized and longitudinal in vivo study aimed to assess different protocols for the treatment of dentin hypersensitivity with low-power laser (with different doses), high-power laser, and a desensitizing agent, for a period of 12 and 18 months. The lesions from 32 patients (117 lesions), who were submitted to the inclusion and exclusion criteria, were divided into nine groups (n = 13): G1: Gluma Desensitizer (Heraeus Kulzer), G2: low-power laser with low dose (three points of irradiation in vestibular portion and an apical point 30 mW, 10 J/cm(2), 9 s per point with the wavelength of 810 nm, with three sessions with an interval of 72 h), G3: low-power laser with high dose (one point in the cervical area, and one apical point 100 mW, 40 J/cm(2), 11 s per point with the wavelength of 810 nm in three sessions with an interval of 72 h), G4: low-power laser with low dose + Gluma Desensitizer, G5: low-power laser with high dose + Gluma Desensitizer, G6: Nd:YAG laser (Power Laser™ ST6, Research® in contact 1.0 W, 10 Hz and 100 mJ, ≈85 J/cm(2), with the wavelength of 1064 nm), G7: Nd:YAG laser + Gluma Desensitizer, G8: low-power laser with low dose + Nd:YAG laser, and G9: low-power laser with high dose + Nd:YAG laser. The level of sensitivity of each volunteer was assessed by visual analog scale of pain (VAS) with the aid of air from the triple syringe and exploration probe, 12 and 18 months after treatment. All analyses were performed separately for air and probe stimulus. The level of significance was considered for values of p < 0.05. After statistical analysis, all treatments were shown to be effective in reducing dentinal hypersensitivity, and the results were considered not statistically different from those at 12 months. Therefore, until the 18-month evaluation, it could be said that no statistical differences were observed in the sensitivity levels for all treatments.

  20. [Forefoot pain].

    Science.gov (United States)

    Damiano, Joël

    2010-03-20

    Forefoot chronic pain is a frequent problem in daily clinical practice. Mechanical pathology of the forefoot, usually called static metatarsalgia, represents the most frequent reason for consultation in pathology of the foot. The cause is a functionnal disorder or anatomic derangement of the forefoot architecture. Metatarsalgia can originate from a wide range of affections. Etiologies of chronic pain are described from medial to lateral with first ray pathologies (hallux valgus, hallux rigidus and sesamoid pathology) and first ray insufficiency, pathologies of the second, third and fourth ray and intermetatarsal spaces (second ray syndrome, Freiberg's disease, Morton neuroma, stress or bone insufficiency metatarsal fractures, intermetatarsal bursitis) and fifth ray pathology (lateral bursitis, quintus varus). Sometimes forefoot pain could also be caused by chronic inflammatory rheumatic diseases (rheumatoid and psoriatic arthritis) with a risk of structural metatarsophalangeal joints alteration. The pathology of the toes can, more rarely, explain a forefoot pain. So, several pathologic conditions can produce forefoot pain and the diagnostic approach must always be based on the anamnesis and clinical examination. In a second time if the cause is difficult to establish based solely on clinical findings, radiography and ultrasonography are today the most usefull auxiliary investigations.

  1. [Visceral pain].

    Science.gov (United States)

    Elsenbruch, S; Häuser, W; Jänig, W

    2015-10-01

    Chronic visceral pain is an unresolved neurobiological, medical and socioeconomic challenge. Up to 20% of the adult population suffer from chronic visceral pain and abdominal complaints constitute a prevalent symptom also in children and adolescents. Existing treatment approaches are often unsuccessful and patients typically suffer from multiple somatic and psychological symptoms. This complex situation requires integrative treatment approaches. This review summarizes current basic and clinical research on acute and chronic visceral pain with a focus on research groups in Germany. Despite significant clinical and scientific advances, a number of questions remain open calling for more funding to support research to elucidate the complex pathophysiology of chronic visceral pain and to develop and test new treatment approaches. Research support should focus on interdisciplinary concepts and methodology using expertise from multiple disciplines. The field would also benefit from a broader integration of visceral pain into teaching curricula in medicine and psychology and should aim to motivate young clinicians and scientists to strive for a career within this important and highly fascinating area.

  2. Toll-like receptor 4 regulates chronic stress-induced visceral pain in mice.

    Science.gov (United States)

    Tramullas, Monica; Finger, Beate C; Moloney, Rachel D; Golubeva, Anna V; Moloney, Gerard; Dinan, Timothy G; Cryan, John F

    2014-08-15

    Functional gastrointestinal disorders, which have visceral hypersensitivity as a core symptom, are frequently comorbid with stress-related psychiatric disorders. Increasing evidence points to a key role for toll-like receptor 4 (TLR4) in chronic pain states of somatic origin. However, the central contribution of TLR4 in visceral pain sensation remains elusive. With pharmacological and genetic approaches, we investigated the involvement of TLR4 in the modulation of visceral pain. The TLR4-deficient and wild-type mice were exposed to chronic stress. Visceral pain was evaluated with colorectal distension. Protein expression levels for TLR4, Cd11b, and glial fibrillary acidic protein (glial cells markers) were quantified in the lumbar region of the spinal cord, prefrontal cortex (PFC), and hippocampus. To evaluate the effect of blocking TLR4 on visceral nociception, TAK-242, a selective TLR4 antagonist, was administered peripherally (intravenous) and centrally (intracerebroventricular and intra-PFC) (n = 10-12/experimental group). The TLR4 deficiency reduced visceral pain and prevented the development of chronic psychosocial stress-induced visceral hypersensitivity. Increased expression of TLR4 coupled with enhanced glia activation in the PFC and increased levels of proinflammatory cytokines were observed after chronic stress in wild-type mice. Administration of a TLR4 specific antagonist, TAK-242, attenuated visceral pain sensation in animals with functional TLR4 when administrated centrally and peripherally. Moreover, intra-PFC TAK-242 administration also counteracted chronic stress-induced visceral hypersensitivity. Our results reveal a novel role for TLR4 within the PFC in the modulation of visceral nociception and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  3. 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.

  4. Different Brain Responses to Pain and Its Expectation in the Dental Chair.

    Science.gov (United States)

    Racek, A J; Hu, X; Nascimento, T D; Bender, M C; Khatib, L; Chiego, D; Holland, G R; Bauer, P; McDonald, N; Ellwood, R P; DaSilva, A F

    2015-07-01

    A dental appointment commonly prompts fear of a painful experience, yet we have never fully understood how our brains react to the expectation of imminent tooth pain once in a dental chair. In our study, 21 patients with hypersensitive teeth were tested using nonpainful and painful stimuli in a clinical setting. Subjects were tested in a dental chair using functional near-infrared spectroscopy to measure cortical activity during a stepwise cold stimulation of a hypersensitive tooth, as well as nonpainful control stimulation on the same tooth. Patients' sensory-discriminative and emotional-cognitive cortical regions were studied through the transition of a neutral to a painful stimulation. In the putative somatosensory cortex contralateral to the stimulus, 2 well-defined hemodynamic peaks were detected in the homuncular orofacial region: the first peak during the nonpainful phase and a second peak after the pain threshold was reached. Moreover, in the upper-left and lower-right prefrontal cortices, there was a significant active hemodynamic response in only the first phase, before the pain. Subsequently, the same prefrontal cortical areas deactivated after a painful experience had been reached. Our study indicates for the first time that pain perception and expectation elicit different hemodynamic cortical responses in a dental clinical setting.

  5. Culicoides obsoletus allergens for diagnosis of insect bite hypersensitivity in horses

    NARCIS (Netherlands)

    Meide, van der N.M.A.

    2013-01-01

    AInsect Bite Hypersensitivity (IBH) is the most common skin allergy in horses and involves a Type I (IgE mediated) hypersensitivity reaction against bites of insects, mainly of the Culicoides species. Welfare of affected horses is seriously reduced and no fully curative treatment is yet available. F

  6. Evaluation of the Effect of Low Level Laser Therapy Toothbrush in Treatment of Dentin Hypersensitivity

    OpenAIRE

    Yaghini, Jaber; Mogharehabed, Ahmad; Safavi, Nassimeh; Mohamadi, Mehrnush; Ashtiju, Fahime

    2015-01-01

    Introduction: Dentin hypersensitivity is one of the most common complications that affect patients after periodontal therapy. Recently low level laser therapy has been introduced as a new treatment modality and has produced beneficial results. The purpose of this study is to evaluate the effect of low level laser therapy toothbrushes in reduction of dentin hypersensitivity.

  7. 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.

  8. 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

    Syncope in the elderly may be caused by an apparent hypersensitivity in the high pressure baroreflex control of heart rate and blood pressure - carotid sinus hypersensitivity. Previous studies have found ambiguous results regarding the baroreceptor sensitivity in patients with carotid sinus hyper...... sensitivity may not follow the same neuronal pathways as those responding to the crude external pressures applied during carotid sinus massage...

  9. Hypersensitivity to Parietaria officinalis pollen in newcomers to the area with the plant.

    Science.gov (United States)

    Cvitanović, S; Marusić, M; Juricić, M; Vrdoljak, E; Petrovecki, M; Rozga, A; Stavljenić-Rukavina, A

    1993-11-01

    Hypersensitivity to Parietaria officinalis (wall pellitory) pollen and other environmental allergens was studied in pollinosis patients allergic to P. officinalis pollen who were born in areas without P. officinalis and later moved to the city of Split, where P. officinalis is responsible for some 65% of pollinosis cases. Highly significant positive correlations were found for both the intensity of skin test reaction and concentration of specific serum IgE with the length of residence in the area. In contrast, the respective data on subjects hypersensitive to P. officinalis pollen allergen, but born and living in the area of Split, revealed a tendency to negative correlation between age and intensity of hypersensitivity to P. officinalis. A number of patients from both groups were tested for presence of serum IgE antibodies specific for 14 common environmental allergens. Hypersensitivity to P. officinalis pollen was associated with hypersensitivity to olive, mugwort, and birch pollen in newcomers; hypersensitivity to birch and, to some extent, olive pollen was significantly more frequent in newcomers than in autochthonous patients who were allergic to P. officinalis pollen. Regardless of whether the patients were autochthons or newcomers to the area with P. officinalis, hypersensitivity to P. officinalis mostly excluded hypersensitivity to Dermatophagoides farinae and D. pteronyssinus, and vice versa.

  10. 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

  11. TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER MULTIPLE INTRATRACHAEL (IT) EXPOSURE

    Science.gov (United States)

    SOT 2001 DMS214TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY INMICE AFTER MULTIPLE INTRATRACHEAL (IT) EXPOSURES. D Sailstad, E Boykin, M Ward, and MJ Selgrade. NHEERL, ORD, US EPA, RTP, NC, USA.TMA causes Th2 related respiratory hypersensitivity (RH) responses. W...

  12. P-selectin is required for neutrophils and macrophage infiltration into injured site and contributes to generation of behavioral hypersensitivity following peripheral nerve injury in mice.

    Science.gov (United States)

    Liou, Jiin-Tarng; Lee, Chiou-Mei; Lin, Yi-Chiao; Chen, Chun-Yu; Liao, Chia-Chih; Lee, Hung-Chen; Day, Yuan-Ji

    2013-10-01

    Growing evidence suggests that leukocyte extravasation is initiated by the interaction of selectins with their ligands; as well as an essential role for P-selectin in the initial recruitment of inflammatory cells to sites of inflammation. In this study, P-selectin-deficient (P-sel-/-) mice were used to test the hypothesis that lack of P-selectin would attenuate the recruitment of inflammatory cells to the site of inflammation, thereby modulating pain in a murine chronic neuropathic pain model. Nociceptive sensitization and the microenvironment of the peripheral injury site were studied in wild-type (P-sel+/+) and P-selectin-deficient (P-sel-/-) mice after partial sciatic nerve ligation (PSNL). Variables measured included myeloperoxidase (MPO) activity, several inflammatory cell infiltration profiles, cytokines, and endogenous opioid peptide expression in damaged nerves. Results indicate that behavioral hypersensitivity, MPO activity, and infiltration of neutrophils and macrophages were attenuated in P-sel-/- mice after PSNL. Proinflammatory cytokines, tumor necrosis factor α, and interleukin (IL)-6, were reduced in damaged nerves following PSNL; however, several antiinflammatory cytokines - IL-1Ra, IL-4, and IL-10 - were significantly increased in P-sel-/- mice. In addition, endogenous opioid peptides mRNA was significantly lower in P-sel-/- mice compared with P-sel +/+ mice. The current results demonstrated that the absence of P-selectin in mice leads to an altered microenvironment that attenuated behavioral hypersensitivity. The specific role of P-selectin could have been a result of decreased neutrophils, as well as the accumulation of macrophages at the site of injury, which may subsequently modulate the inflammatory cytokine expression and impact behavioral hypersensitivity within the injured nerve.

  13. Clinical importance of carbapenem hypersensitivity in patients with self-reported and documented penicillin allergy.

    Science.gov (United States)

    Prescott, William A; Kusmierski, Kristen A

    2007-01-01

    The risk of carbapenem hypersensitivity in patients with self-reported or documented penicillin allergy needs to be determined so that practitioners can make better-informed decisions regarding antibiotic therapy for this patient population. The risk of cross-reactivity between penicillin and carbapenem antibiotics initially was reported to approach 50%. Recent retrospective studies have suggested that the clinical risk of cross-hypersensitivity between these two drug classes is 9.2-11%, which is significantly lower than initially reported. Patients whose history of penicillin allergy is self-reported and is not type 1 may be at moderate risk for hypersensitivity when treated with a carbapenem antibiotic. The risk of hypersensitivity appears to be higher in patients whose penicillin allergy was documented by a health care provider, those with several antibiotic allergies, and those with a positive penicillin skin test result or a history of type 1 penicillin hypersensitivity.

  14. Abdominal Pain (Stomach Pain), Short-Term

    Science.gov (United States)

    ... in Children and TeensRead MoreBMI Calculator Abdominal Pain (Stomach Pain), Short-termJust about everyone has had a " ... time or another. But sudden severe abdominal pain (stomach pain), also called acute pain, shouldn't be ...

  15. Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy.

    Science.gov (United States)

    Rahman, Md Habibur; Jha, Mithilesh Kumar; Kim, Jong-Heon; Nam, Youngpyo; Lee, Maan Gee; Go, Younghoon; Harris, Robert A; Park, Dong Ho; Kook, Hyun; Lee, In-Kyu; Suk, Kyoungho

    2016-03-11

    The dorsal root ganglion (DRG) is a highly vulnerable site in diabetic neuropathy. Under diabetic conditions, the DRG is subjected to tissue ischemia or lower ambient oxygen tension that leads to aberrant metabolic functions. Metabolic dysfunctions have been documented to play a crucial role in the pathogenesis of diverse pain hypersensitivities. However, the contribution of diabetes-induced metabolic dysfunctions in the DRG to the pathogenesis of painful diabetic neuropathy remains ill-explored. In this study, we report that pyruvate dehydrogenase kinases (PDK2 and PDK4), key regulatory enzymes in glucose metabolism, mediate glycolytic metabolic shift in the DRG leading to painful diabetic neuropathy. Streptozotocin-induced diabetes substantially enhanced the expression and activity of the PDKs in the DRG, and the genetic ablation of Pdk2 and Pdk4 attenuated the hyperglycemia-induced pain hypersensitivity. Mechanistically, Pdk2/4 deficiency inhibited the diabetes-induced lactate surge, expression of pain-related ion channels, activation of satellite glial cells, and infiltration of macrophages in the DRG, in addition to reducing central sensitization and neuroinflammation hallmarks in the spinal cord, which probably accounts for the attenuated pain hypersensitivity. Pdk2/4-deficient mice were partly resistant to the diabetes-induced loss of peripheral nerve structure and function. Furthermore, in the experiments using DRG neuron cultures, lactic acid treatment enhanced the expression of the ion channels and compromised cell viability. Finally, the pharmacological inhibition of DRG PDKs or lactic acid production substantially attenuated diabetes-induced pain hypersensitivity. Taken together, PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic DRG, thereby contributing to the pathogenesis of painful diabetic neuropathy.

  16. Painful menstrual periods

    Science.gov (United States)

    Menstruation - painful; Dysmenorrhea; Periods - painful; Cramps - menstrual; Menstrual cramps ... related activities for a few days during each menstrual cycle. Painful menstruation is the leading cause of ...

  17. Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Nedergaard, S; Hansen, RR;

    2009-01-01

    Activation of spinal cord microglia and astrocytes is a common phenomenon in nerve injury pain models and is thought to exacerbate pain perception. Following a nerve injury, a transient increase in the presence of microglia takes place while the increased numbers of astrocytes stay elevated for a....... In contrast, sciatic nerve injury led to a transient activation of microglia and sustained astrogliosis. These results show that development of hypersensitivity and astrocyte activation in pain models can take place independent of microglial activation. Udgivelsesdato: 2009 Feb...

  18. Milk as Desensitizing Agent for Treatment of Dentine Hypersensitivity Following Periodontal Treatment Procedures

    Science.gov (United States)

    Sabir, Mohammad

    2015-01-01

    Background Dentinal hypersensitivity is a commonly observed problem after periodontal treatment procedures in periodontal patients. This further complicates preventive oral hygiene procedures by patients which jeopardize periodontal treatment, or even may aid in periodontal treatment failure. Aims and Objectives The aims and objectives of present study were to assess the problem of dentine hypersensitivity after non-surgical periodontal treatment and selection of cases for evaluation of commercially available milk at room temperature as mouth rinse for the treatment of dentinal hypersensitivity caused by periodontal treatment. Materials and Methods Patients were selected randomly for nonsurgical periodontal treatment and then were assessed for dentine hypersensitivity. Those having dentine hypersensitivity were assigned in two groups. Group one patients were advised to rinse with commercially available milk at room temperature, group two patients were advised to rinse with luke warm water as control. A four point Verbal Rating Score (VRS) was designed to record the numerical value of dentine hypersensitivity. Results The results show incidence of 42.5% and prevalence of 77.5% for dentine hypersensitivity after periodontal treatment procedures. After rinsing with milk following periodontal treatment procedures, there was found a significant reduction of dentine hypersensitivity with probability by unpaired t-test as 0.0007 and 0.0001 at tenth and fifteenth day post periodontal treatment procedures respectively. Conclusion This study demonstrated that the milk rinse is a suitable, cheaper, fast acting, home-use and easily available solution to the problem of dentine hypersensitivity after non-surgical periodontal treatment. Milk can be used as desensitizing agent and rinsing with milk for few days is effective in quick reduction of dentine hypersensitivity due to periodontal treatment procedures. PMID:26674005

  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. Orofacial neuropathic pain induced by oxaliplatin

    Science.gov (United States)

    Ling, Jennifer; Erol, Ferhat; Viatchenko-Karpinski, Viacheslav; Kanda, Hirosato

    2017-01-01

    Neuropathic pain induced by chemotherapy drugs such as oxaliplatin is a dose-limiting side effect in cancer treatment. The mechanisms underlying chemotherapy-induced neuropathic pain are not fully understood. KCNQ2 channels are low-threshold voltage-gated K+ channels that play a role in controlling neuronal excitability. Downregulation of KCNQ2 channels has been proposed to be an underlying mechanism of sensory hypersensitivity that leads to neuropathic pain. However, it is currently unknown whether KCNQ channels may be downregulated by chemotherapy drugs in trigeminal ganglion neurons to contribute to the pathogenesis of chemotherapy-induced orofacial neuropathic pain. In the present study, mechanical sensitivity in orofacial regions is measured using the operant behavioral test in rats treated with oxaliplatin. Operant behaviors in these animals show the gradual development of orofacial neuropathic pain that manifests with orofacial mechanical allodynia. Immunostaining shows strong KCNQ2 immunoreactivity in small-sized V2 trigeminal ganglion neurons in controls, and the numbers of KCNQ2 immunoreactivity positive V2 trigeminal ganglion neurons are significantly reduced in oxaliplatin-treated animals. Immunostaining is also performed in brainstem and shows strong KCNQ2 immunoreactivity at the trigeminal afferent central terminals innervating the caudal spinal trigeminal nucleus (Vc) in controls, but the KCNQ2 immunoreactivity intensity is significantly reduced in oxaliplatin-treated animals. We further show with the operant behavioral test that oxaliplatin-induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine. Taken together, these findings suggest that KCNQ2 downregulation may be a cause of oxaliplatin-induced orofacial neuropathic pain and KCNQ2 potentiators may be useful for alleviating the neuropathic pain. PMID:28741430

  1. Subjective Welfare, Well-Being, and Self-Reported Food Hypersensitivity in Four European Countries : Implications for European Policy

    NARCIS (Netherlands)

    Voordouw, Jantine; Antonides, Gerrit; Fox, Margaret; Cerecedo, Inmaculada; Zamora, Javier; de la Hoz Caballer, Belen; Rokicka, Ewa; Cornelisse-Vermaat, Judith; Jewczak, Maciej; Starosta, Pawel; Kowalska, Marek L.; Jedrzejczak-Czechowicz, Monika; Vazquez-Cortes, Sonia; Escudero, Cano; de Blok, Bertine Flokstra; Dubois, Anthony; Mugford, Miranda; Frewer, Lynn J.

    This study estimates the effects of food hypersensitivity on individuals' perceived welfare and well-being compared to non-food hypersensitive individuals. Study respondents were recruited in the Netherlands, Poland, Spain and UK. The difference in welfare between food hypersensitive respondents and

  2. Subjective Welfare, Well-Being, and Self-Reported Food Hypersensitivity in Four European Countries: Implications for European Policy

    Science.gov (United States)

    Voordouw, Jantine; Antonides, Gerrit; Fox, Margaret; Cerecedo, Inmaculada; Zamora, Javier; de la Hoz Caballer, Belen; Rokicka, Ewa; Cornelisse-Vermaat, Judith; Jewczak, Maciej; Starosta, Pawel; Kowalska, Marek L.; Jedrzejczak-Czechowicz, Monika; Vazquez-Cortes, Sonia; Escudero, Cano; de Blok, Bertine Flokstra; Dubois, Anthony; Mugford, Miranda; Frewer, Lynn J.

    2012-01-01

    This study estimates the effects of food hypersensitivity on individuals' perceived welfare and well-being compared to non-food hypersensitive individuals. Study respondents were recruited in the Netherlands, Poland, Spain and UK. The difference in welfare between food hypersensitive respondents and those asymptomatic to foods was estimated using…

  3. Subjective Welfare, Well-Being, and Self-Reported Food Hypersensitivity in Four European Countries : Implications for European Policy

    NARCIS (Netherlands)

    Voordouw, Jantine; Antonides, Gerrit; Fox, Margaret; Cerecedo, Inmaculada; Zamora, Javier; de la Hoz Caballer, Belen; Rokicka, Ewa; Cornelisse-Vermaat, Judith; Jewczak, Maciej; Starosta, Pawel; Kowalska, Marek L.; Jedrzejczak-Czechowicz, Monika; Vazquez-Cortes, Sonia; Escudero, Cano; de Blok, Bertine Flokstra; Dubois, Anthony; Mugford, Miranda; Frewer, Lynn J.

    2012-01-01

    This study estimates the effects of food hypersensitivity on individuals' perceived welfare and well-being compared to non-food hypersensitive individuals. Study respondents were recruited in the Netherlands, Poland, Spain and UK. The difference in welfare between food hypersensitive respondents and

  4. Subjective Welfare, Well-Being, and Self-Reported Food Hypersensitivity in Four European Countries: Implications for European Policy

    NARCIS (Netherlands)

    Voordouw, J.; Antonides, G.; Fox, M.; Cerecedo, I.; Zamora, J.; Hoz Caballer, de la B.; Rokicka, E.; Cornelisse-Vermaat, J.R.; Jewczak, M.; Starosta, P.; Kowalska, M.L.; Jedrzejczak-Czechowicz, M.; Vázquez-Cortés, S.; Escudero, C.; Flokstra-de Blok, B.M.; Dubois, A.E.J.; Mugford, M.; Frewer, L.J.

    2012-01-01

    This study estimates the effects of food hypersensitivity on individuals’ perceived welfare and well-being compared to non-food hypersensitive individuals. Study respondents were recruited in the Netherlands, Poland, Spain and UK. The difference in welfare between food hypersensitive respondents and

  5. Cold and L-menthol-induced sensitization in healthy volunteers--a cold hypersensitivity analogue to the heat/capsaicin model.

    Science.gov (United States)

    Andersen, Hjalte H; Poulsen, Jeppe N; Uchida, Yugo; Nikbakht, Anahita; Arendt-Nielsen, Lars; Gazerani, Parisa

    2015-05-01

    Topical high-concentration L-menthol is the only established human experimental pain model to study mechanisms underlying cold hyperalgesia. We aimed at investigating the combinatorial effect of cold stimuli and topical L-menthol on cold pain and secondary mechanical hyperalgesia. Analogue to the heat-capsaicin model on skin sensitization, we proposed that cold/menthol enhances or prolong L-menthol-evoked sensitization. Topical 40% L-menthol or vehicle was applied (20 minutes) on the volar forearms of 20 healthy females and males (age, 28.7 ± 0.6 years). Cold stimulation of 5°C for 5 minutes was then applied to the treated area 3 times with 40-minute intervals. Cold detection threshold and pain, mechanical hyperalgesia (pinprick), static and dynamic mechanical allodynia (von Frey and brush), skin blood flow (laser speckle), and temperature (thermocamera) were assessed. Cold detection threshold and cold pain threshold (CPT) increased after L-menthol and remained high after the cold rekindling cycles (P menthol evoked secondary hyperalgesia to pinprick (P menthol (P menthol facilitated and prolonged L-menthol-induced cold pain and hyperalgesia. This model may prove beneficial for testing analgesic compounds when a sufficient duration of time is needed to see drug effects on CPT or mechanical hypersensitivity.

  6. Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

    Science.gov (United States)

    Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

    2016-01-01

    Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

  7. 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.

  8. Chronic Pain

    Science.gov (United States)

    ... therapy – methods that help you relax and decrease stress. They could include meditation, tai chi, or yoga.Almost anything you do to relax or get your mind off your problems may help control pain. Even if you are ... have to use stress-reduction methods for several weeks before you notice ...

  9. Orofacial Pain

    Science.gov (United States)

    ... and neck. Maintaining or correcting your bite ensures optimal health, and proper care will help reduce or eliminate orofacial pain or discomfort. Reviewed: January 2012 ?xml:namespace> Related Articles: Frequent Headaches? Can't Sleep? Check Your Bite What Causes a Toothache? Your ...

  10. Neuropathic Pain

    African Journals Online (AJOL)

    gnac/0@med.u0vs.ac.za. Southern ... dition will respond differently to exactly the same treatment regime. 3. ... When trying to identify the location of the pain, it is important .... triggers central sprouting of myelinated afferents " Nature 7992;.

  11. [Elbow pain].

    Science.gov (United States)

    Viikari-Juntura, Eira; Miintyselkii, Pekka; Havulinna, Jouni

    2010-01-01

    Pain and disability in the elbow are not as common as in the neck, shoulder or wrist, for example. The elbow may, however, present disorders that may in a prolonged state be difficult and cause significant loss of working capacity. These include epicondylitis, osteoarthritis and entrapment of the ulnar nerve.

  12. Achilles Pain.

    Science.gov (United States)

    Connors, G. Patrick

    Five ailments which can cause pain in the achilles tendon area are: (1) muscular strain, involving the stretching or tearing of muscle or tendon fibers; (2) a contusion, inflammation or infection called tenosynovitis; (3) tendonitis, the inflammation of the tendon; (4) calcaneal bursitis, the inflammation of the bursa between the achilles tendon…

  13. Leg pain

    Science.gov (United States)

    ... when you walk or exercise and improves with rest. The leg is black and blue. The leg is cold ... chap 81. Marcussen B, Hogrefe C, Amendola A. Leg pain and exertional compartment syndromes. In: Miller MD, Thompson SR, eds. DeLee & Drez's ...

  14. Orofacial pain

    Directory of Open Access Journals (Sweden)

    Marjolijn Oomens

    2016-06-01

    Full Text Available In the primary care sector, diagnosis and initial management of orofacial pain are often performed by familydoctors and dentists. Knowledge of the different types of orofacial pain and headache disorders is therefor of great importance. The International Classification of Headache Disorders (ICHD-3 provides an overview of the different types of orofacial pain and will be discussed in this lecture. The main focus will be on trigeminal neuralgia and cluster headache and the current research in this field. Trigeminal Neuralgia (TN is defined as a disorder characterized by recurrent, unilateral, brief, electricshock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of thetrigeminal nerve and triggered by innocuous stimuli. Unfortunately, most TN is idiopathic, and the aetiology isnot clear. The guidelines on pharmaceutical TN management published by the American Academy of Neurology (AAN and the European Federation of Neurological Societies (EFNS recommend carbamazepine (CBZ; 200–1200 mg/day or oxcarbazepine (OXC; 600–1800 mg/day as first-line therapy. Both are antiepileptics with well known interactions with other drugs and safety problems. An overview of the currently available literature on the pharmaceutical management of TN patients is discussed. Cluster headache (CH is one of the most painful primary headache disorders. It is characterized by daily or almost daily attacks of unilateral excruciating periorbital pain associated with ipsilateral cranial autonomic symptoms, typically lasting between 15 and 180 minutes if untreated. Cluster headache is caused by the relaesement of neurotransmitters and vasodilators from the sphenopalatine ganglion (SPH. The SPG is a large extracranial parasympathetic ganglion located in the pterygopalatine fossa (PPF. The current treatments for CH attacks are injectable sumatriptan and oxygen inhalation. Both treatments have well known side effects and

  15. TRPA1 mediates formalin-induced pain.

    Science.gov (United States)

    McNamara, Colleen R; Mandel-Brehm, Josh; Bautista, Diana M; Siemens, Jan; Deranian, Kari L; Zhao, Michael; Hayward, Neil J; Chong, Jayhong A; Julius, David; Moran, Magdalene M; Fanger, Christopher M

    2007-08-14

    The formalin model is widely used for evaluating the effects of analgesic compounds in laboratory animals. Injection of formalin into the hind paw induces a biphasic pain response; the first phase is thought to result from direct activation of primary afferent sensory neurons, whereas the second phase has been proposed to reflect the combined effects of afferent input and central sensitization in the dorsal horn. Here we show that formalin excites sensory neurons by directly activating TRPA1, a cation channel that plays an important role in inflammatory pain. Formalin induced robust calcium influx in cells expressing cloned or native TRPA1 channels, and these responses were attenuated by a previously undescribed TRPA1-selective antagonist. Moreover, sensory neurons from TRPA1-deficient mice lacked formalin sensitivity. At the behavioral level, pharmacologic blockade or genetic ablation of TRPA1 produced marked attenuation of the characteristic flinching, licking, and lifting responses resulting from intraplantar injection of formalin. Our results show that TRPA1 is the principal site of formalin's pain-producing action in vivo, and that activation of this excitatory channel underlies the physiological and behavioral responses associated with this model of pain hypersensitivity.

  16. Microbiota regulates visceral pain in the mouse

    Science.gov (United States)

    Luczynski, Pauline; Tramullas, Monica; Viola, Maria; Shanahan, Fergus; Clarke, Gerard; O'Mahony, Siobhain; Dinan, Timothy G; Cryan, John F

    2017-01-01

    The perception of visceral pain is a complex process involving the spinal cord and higher order brain structures. Increasing evidence implicates the gut microbiota as a key regulator of brain and behavior, yet it remains to be determined if gut bacteria play a role in visceral sensitivity. We used germ-free mice (GF) to assess visceral sensitivity, spinal cord gene expression and pain-related brain structures. GF mice displayed visceral hypersensitivity accompanied by increases in Toll-like receptor and cytokine gene expression in the spinal cord, which were normalized by postnatal colonization with microbiota from conventionally colonized (CC). In GF mice, the volumes of the anterior cingulate cortex (ACC) and periaqueductal grey, areas involved in pain processing, were decreased and enlarged, respectively, and dendritic changes in the ACC were evident. These findings indicate that the gut microbiota is required for the normal visceral pain sensation. DOI: http://dx.doi.org/10.7554/eLife.25887.001 PMID:28629511

  17. 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.

  18. Lithium treatment induces a hypersensitive-like response in tobacco.

    Science.gov (United States)

    Naranjo, Miguel A; Romero, Carlos; Bellés, José M; Montesinos, Consuelo; Vicente, Oscar; Serrano, Ramón

    2003-07-01

    Treatment of tobacco ( Nicotiana tabacum L.) plants with lithium induces the formation of necrotic lesions and leaf curling as in the case of incompatible pathogen interactions. Further similarities at the molecular level include accumulation of ethylene and of salicylic and gentisic acids, and induced expression of pathogenesis-related PR-P, PR5 and PR1 genes. With the exception of PR1 induction, lithium produced the same effects in transgenic tobacco plants that do not accumulate salicylate because of overexpression of the bacterial hydroxylase gene nahG. On the other hand, inhibition of ethylene biosynthesis with aminoethoxyvinylglycine prevented lithium-induced cell death and PR5 expression. These results suggest that lithium triggers a hypersensitive-like response where ethylene signalling is essential.

  19. 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...... of therapy within which abacavir was received, geographical regions, calendar time and drug formulation (abacavir/lamivudine combination tablet versus abacavir as a single drug or abacavir/zidovudine/lamivudine combination). RESULTS: Of 3,278 patients that started abacavir, 2,101 (64.1%) discontinued....... Of these, 167 (5.1%) discontinued abacavir within 3 months due to HSR with an incidence of 22.1 (95% confidence interval [CI] 18.7-25.4) per 100 person-years of follow-up. After adjustment for gender, prior AIDS, hepatitis C serostatus, baseline CD4+ T-cell count, region and calendar time, HSR incidence...

  20. Combined pulmonary fibrosis and emphysema in hypersensitivity pneumonitis.

    Science.gov (United States)

    Soumagne, Thibaud; Pana-Katatali, Héloïse; Degano, Bruno; Dalphin, Jean-Charles

    2015-12-21

    Combined pulmonary fibrosis and emphysema is a distinct syndrome reported in patients who smoke. A 72-year-old, never-smoking female dairy farmer was referred for progressive dyspnoea on exertion, basal crackles on auscultation, normal spirometry and normal lung volumes but decreased diffusing capacity of the lung for carbon monoxide, centrilobular emphysema in the upper zones of the lungs and diffuse infiltrative lung disease in the lower zones on high-resolution CT scan. Bronchoalveolar lavage differential cell count showed 35% lymphocytosis,