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Sample records for enhances inflammatory pain

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

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    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.

  2. Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages

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    Norikazu Kiguchi

    2017-11-01

    Full Text Available Neuropathic pain can have a major effect on quality of life but current therapies are often inadequate. Growing evidence suggests that neuropathic pain induced by nerve damage is caused by chronic inflammation. Upon nerve injury, damaged cells secrete pro-inflammatory molecules that activate cells in the surrounding tissue and recruit circulating leukocytes to the site of injury. Among these, the most abundant cell type is macrophages, which produce several key molecules involved in pain enhancement, including cytokines and chemokines. Given their central role in the regulation of peripheral sensitization, macrophage-derived cytokines and chemokines could be useful targets for the development of novel therapeutics. Inhibition of key pro-inflammatory cytokines and chemokines prevents neuroinflammation and neuropathic pain; moreover, recent studies have demonstrated the effectiveness of pharmacological inhibition of inflammatory (M1 macrophages. Nicotinic acetylcholine receptor ligands and T helper type 2 cytokines that reduce M1 macrophages are able to relieve neuropathic pain. Future translational studies in non-human primates will be crucial for determining the regulatory mechanisms underlying neuroinflammation-associated neuropathic pain. In turn, this knowledge will assist in the development of novel pharmacotherapies targeting macrophage-driven neuroinflammation for the treatment of intractable neuropathic pain.

  3. Sigma-1 receptor and inflammatory pain.

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    Gris, Georgia; Cobos, Enrique José; Zamanillo, Daniel; Portillo-Salido, Enrique

    2015-06-01

    The sigma-1 receptor (Sig-1R) is a unique ligand-regulated molecular chaperone that interacts with several protein targets such as G protein-coupled receptors and ion channels to modulate their activity. Sig-1R is located in areas of the central and peripheral nervous system that are key to pain control. Previous preclinical studies have suggested a potential therapeutic use of Sig-1R antagonists for the management of neuropathic pain. Recent studies using pharmacological and genetic tools have explored the role of Sig-1R in inflammatory pain conditions. Mice lacking the Sig-1R have shown different patterns of phenotypic responses to inflammatory injury. Systemic or peripheral administration of several Sig-1R antagonists, including the selective Sig-1R antagonist S1RA, inhibited both mechanical and thermal hypersensitivity in several preclinical models of inflammatory pain. These recent studies are summarized in the present commentary. Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain.

  4. Benfotiamine relieves inflammatory and neuropathic pain in rats.

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    Sánchez-Ramírez, Gabriela M; Caram-Salas, Nadia L; Rocha-González, Héctor I; Vidal-Cantú, Guadalupe C; Medina-Santillán, Roberto; Reyes-García, Gerardo; Granados-Soto, Vinicio

    2006-01-13

    Benfotiamine has shown therapeutic efficacy in the treatment of painful diabetic neuropathy in human beings. However, so far there is no evidence about the efficacy of this drug in preclinical models of pain. The purpose of this study was to assess the possible antinociceptive and antiallodynic effect of benfotiamine in inflammatory and neuropathic pain models in the rat. Inflammatory pain was induced by injection of formalin in non-diabetic and diabetic (2 weeks) rats. Reduction of flinching behavior was considered as antinociception. Neuropathic pain was induced by either ligation of left L5/L6 spinal nerves or administration of streptozotocin (50 mg/kg, i.p.) in Wistar rats. Benfotiamine significantly reduced inflammatory (10-300 mg/kg) and neuropathic (75-300 mg/kg) nociception in non-diabetic and diabetic rats. Results indicate that oral administration of benfotiamine is able to reduce tactile allodynia from different origin in the rat and they suggest the use of this drug to reduce inflammatory and neuropathic pain in humans.

  5. Can We Distinguish between Inflammatory and Neuropathic Pain?

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    Gary J Bennett

    2006-01-01

    Full Text Available Inflammatory and neuropathic pain were once considered to be distinct entities. However, research over the past decade or so has brought to light many shared mechanisms, and the distinction between the two is no longer clear. Consideration of mechanisms, symptoms and the effects of analgesic drugs does not reveal any definitive or universally applicable differentiating factors. Given the present level of understanding, it may not be possible to distinguish between inflammatory and neuropathic pain in a large number of patients, and a satisfying definition of neuropathic pain may not be possible.

  6. Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy

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    Oliveira, K.G.; Zeidler, S.V. von; Lamas, A.Z.; Podestá, J.R.V. de; Sena, A.; Souza, E.D.; Lenzi, J.; Lemos, E.M.; Gouvea, S.A.; Bissoli, N.S.

    2014-01-01

    Pain is a common symptom in patients with cancer, including those with head and neck cancer (HNC). While studies suggest an association between chronic inflammation and pain, levels of inflammatory cytokines, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), have not been correlated with pain in HNC patients who are not currently undergoing anticancer treatment. The purpose of this study was to examine the relationship between these inflammatory markers and perceived pain in HNC patients prior to anticancer therapy. The study group consisted of 127 HNC patients and 9 healthy controls. Pain was assessed using the Brief Pain Inventory (BPI), and serum levels of CRP and TNF-α were determined using the particle-enhanced turbidimetric immunoassay (PETIA) and ELISA techniques, respectively. Patients experiencing pain had significantly higher levels of CRP (P<0.01) and TNF-α (P<0.05) compared with controls and with patients reporting no pain. There were significantly positive associations between pain, CRP level, and tumor stage. This is the first study to report a positive association between perceived pain and CRP in HNC patients at the time of diagnosis. The current findings suggest important associations between pain and inflammatory processes in HNC patients, with potential implications for future treatment strategies

  7. Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy

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    Oliveira, K.G. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Zeidler, S.V. von [Departamento de Patologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Lamas, A.Z. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Podestá, J.R.V. de; Sena, A.; Souza, E.D.; Lenzi, J. [Divisão de Cabeça e Pescoço, Hospital Santa Rita de Cássia, Vitória, ES (Brazil); Lemos, E.M. [Centro de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Gouvea, S.A.; Bissoli, N.S. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2014-05-30

    Pain is a common symptom in patients with cancer, including those with head and neck cancer (HNC). While studies suggest an association between chronic inflammation and pain, levels of inflammatory cytokines, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), have not been correlated with pain in HNC patients who are not currently undergoing anticancer treatment. The purpose of this study was to examine the relationship between these inflammatory markers and perceived pain in HNC patients prior to anticancer therapy. The study group consisted of 127 HNC patients and 9 healthy controls. Pain was assessed using the Brief Pain Inventory (BPI), and serum levels of CRP and TNF-α were determined using the particle-enhanced turbidimetric immunoassay (PETIA) and ELISA techniques, respectively. Patients experiencing pain had significantly higher levels of CRP (P<0.01) and TNF-α (P<0.05) compared with controls and with patients reporting no pain. There were significantly positive associations between pain, CRP level, and tumor stage. This is the first study to report a positive association between perceived pain and CRP in HNC patients at the time of diagnosis. The current findings suggest important associations between pain and inflammatory processes in HNC patients, with potential implications for future treatment strategies.

  8. Effect of Probiotic Administration on Acute Inflammatory Pain

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

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

    2016-08-17

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

  10. Treatment for non-inflammatory pain in a rheumatologist's practice

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    Natalia Vladimirovna Chichasova

    2013-01-01

    Full Text Available The paper presents data on different approaches to analgesia in relation to the mechanism of pain. Pregabalin (lyrica has demonstrated a rapid development of an analgesic effect in different types of non-inflammatory pain: neuropathic pain, pain in fibromyalgia syndrome. The dose-dependent effect of pregabalin and its satisfactory tolerance are noted.

  11. A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

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    Yang Qi

    2009-12-01

    Full Text Available Abstract The midbrain periaqueductal grey (PAG is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp, one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

  12. Non-steroidal anti-inflammatory drugs for chronic low back pain

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    W.T.M. Enthoven (Wendy); P.D.D.M. Roelofs (Pepijn); R.A. Deyo (Richard); M.W. van Tulder (Maurits); B.W. Koes (Bart)

    2016-01-01

    textabstractBackground: Chronic back pain is an important health problem. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back

  13. The Effect of Electroacupuncture on PKMzeta in the ACC in Regulating Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain

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    Junying Du

    2017-01-01

    Full Text Available Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC. We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560, PKMzeta, p-PKMzeta (T560, and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560 in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC.

  14. Monocytes/Macrophages Control Resolution of Transient Inflammatory Pain

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    Willemen, Hanneke L. D. M.; Eijkelkamp, Niels; Carbajal, Anibal Garza; Wang, Huijing; Mack, Matthias; Zijlstra, Jitske; Heijnen, Cobi J.; Kavelaars, Annemieke

    2014-01-01

    Insights into mechanisms governing resolution of inflammatory pain are of great importance for many chronic pain–associated diseases. Here we investigate the role of macrophages/monocytes and the anti-inflammatory cytokine interleukin-10 (IL-10) in the resolution of transient inflammatory pain. Depletion of mice from peripheral monocytes/macrophages delayed resolution of intraplantar IL-1β- and carrageenan-induced inflammatory hyperalgesia from 1 to 3 days to >1 week. Intrathecal administration of a neutralizing IL-10 antibody also markedly delayed resolution of IL-1β- and carrageenan-induced inflammatory hyperalgesia. Recently, we showed that IL-1β- and carrageenan-induced hyperalgesia is significantly prolonged in LysM-GRK2+/− mice, which have reduced levels of G-protein-coupled receptor kinase 2 (GRK2) in LysM+ myeloid cells. Here we show that adoptive transfer of wild-type, but not of GRK2+/−, bone marrow-derived monocytes normalizes the resolution of IL-1β-induced hyperalgesia in LysM-GRK2+/− mice. Adoptive transfer of IL-10−/− bone marrow-derived monocytes failed to normalize the duration of IL-1β-induced hyperalgesia in LysM-GRK2+/− mice. Mechanistically, we show that GRK2+/− macrophages produce less IL-10 in vitro. In addition, intrathecal IL-10 administration attenuated IL-1β-induced hyperalgesia in LysM-GRK2+/− mice, whereas it had no effect in wild-type mice. Our data uncover a key role for monocytes/macrophages in promoting resolution of inflammatory hyperalgesia via a mechanism dependent on IL-10 signaling in dorsal root ganglia. Perspective We show that IL-10-producing monocytes/macrophages promote resolution of transient inflammatory hyperalgesia. Additionally, we show that reduced monocyte/macrophage GRK2 impairs resolution of hyperalgesia and reduces IL-10 production. We propose that low GRK2 expression and/or impaired IL-10 production by monocytes/macrophages represent peripheral biomarkers for the risk of developing

  15. Peripheral analgesic effects of ketamine in acute inflammatory pain

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    Pedersen, J L; Galle, T S; Kehlet, H

    1998-01-01

    BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers...... on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo...... hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P ketamine treatment compared with placebo immediately after injection (P

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

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    Fang Xu

    2018-05-01

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

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

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    Gui-Lin Jin

    2018-01-01

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

  18. Protective Effects of Sinomenine on CFA-Induced Inflammatory Pain in Rats.

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    Yuan, Yan; Zhang, Yongjun; He, Xiaofeng; Fan, Shengdeng

    2018-04-05

    BACKGROUND The purpose of this study was to investigate the effects of sinomenine (SIN) on CFA-induced inflammatory pain in rats, and to explore the underlying molecular mechanisms. MATERIAL AND METHODS To determine the potential influences of SIN in the pathogenesis of inflammatory pain, an inflammatory pain (IP) mouse model was established and rats were treated with SIN (30 mg/kg). Behavioral tests were used to assess the MWT and TWL of the rats. ELISA assay was used to detect the level of inflammation cytokines. Western blotting and qRT-PCR were carried out to measure the related protein and mRNA expression level, respectively. RESULTS We found that the MWT and TWL of the CFA-treated rats were markedly lower than that of the control rats, and they were significantly increased by SIN administration. The results suggest that IP rats had higher levels of TNF-α, IL-1β and IL-6 compared with the control rats. SIN administration decreased the levels of TNF-α, IL-1β, and IL-6. In addition, we found that p-p65 and p-p38 expression notably decreased after SIN treatment in IP rats. Moreover, the results showed that SIN inhibited Cox-2 and PGE2 expression in IP rats. CONCLUSIONS The data indicate that SIN had a protective role in inflammatory pain through repressing inflammatory mediators via preventing the p38MAPK-NF-κB pathway.

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

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    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.

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

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    Wei-Hsin Chen

    2012-01-01

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

  1. Enhanced Gamma Oscillatory Activity in Rats with Chronic Inflammatory Pain

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    Wang, Jing; Wang, Jing; Xing, Guo-Gang; Li, Xiaoli; Wan, You

    2016-01-01

    It has been reported that oscillatory gamma activity participates in brief acute pain and tonic ongoing pain. It is of great interest to determine whether the gamma activity is involved in chronic pain since chronic pain is a more severe pathological condition characterized by pain persistency. To investigate the oscillatory gamma activity in chronic pain, in the present study, we recorded spontaneous electrocorticogram (ECoG) signals during chronic pain development in rats with chronic infla...

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

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    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

  3. Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

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    O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

    2015-09-01

    rat dorsal horn neurones and enhanced perceptual responses of human subjects to both mechanical and thermal stimulation. Additional heat rekindling produces markers of central sensitisation in both species, including enhanced receptive field sizes. Importantly, we also showed a correlation in the evoked activity of rat spinal neurones to human thermal pain thresholds. The parallel results in rats and humans validate the translational use of both models and the potential for such models for preclinical assessment of prospective analgesics in inflammatory pain states. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  4. Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

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    Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

    2017-03-01

    Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

  5. Analgesic effect of the neuropeptide cortistatin in murine models of arthritic inflammatory pain.

    Science.gov (United States)

    Morell, Maria; Souza-Moreira, Luciana; Caro, Marta; O'Valle, Francisco; Forte-Lago, Irene; de Lecea, Luis; Gonzalez-Rey, Elena; Delgado, Mario

    2013-05-01

    To investigate the role of the antiinflammatory neuropeptide cortistatin in chronic pain evoked by joint inflammation. Thermal and mechanical hyperalgesia was evoked in mouse knee joints by intraplantar injection of tumor necrosis factor α and intraarticular infusion of Freund's complete adjuvant, and the analgesic effects of cortistatin, administered centrally, peripherally, and systemically, were assessed. In addition, the effects of cortistatin on the production of nociceptive peptides and the activation of pain signaling were assayed in dorsal root ganglion cultures and in inflammatory pain models. The role of endogenous cortistatin in pain sensitization and perpetuation of chronic inflammatory states was evaluated in cortistatin-deficient mice. Finally, the effect of noxious/inflammatory stimuli in the production of cortistatin by the peripheral nociceptive system was assayed in vitro and in vivo. Expression of cortistatin was observed in peptidergic nociceptors of the peripheral nociceptive system, and endogenous cortistatin was found to participate in the tuning of pain sensitization, especially in pathologic inflammatory conditions. Results showed that cortistatin acted both peripherally and centrally to reduce the tactile allodynia and heat hyperalgesia evoked by arthritis and peripheral tissue inflammation in mice, via mechanisms that were independent of its antiinflammatory action. These mechanisms involved direct action on nociceptive neurons and regulation of central sensitization. The analgesic effects of cortistatin in murine arthritic pain were linked to binding of the neuropeptide to somatostatin and ghrelin receptors, activation of the G protein subunit Gαi , impairment of ERK signaling, and decreased production of calcitonin gene-related peptide in primary nociceptors. These findings indicate that cortistatin is an antiinflammatory factor with potent analgesic effects that may offer a new approach to pain therapy in pathologic inflammatory

  6. Sleep Deprivation and Recovery Sleep Prior to a Noxious Inflammatory Insult Influence Characteristics and Duration of Pain.

    Science.gov (United States)

    Vanini, Giancarlo

    2016-01-01

    Insufficient sleep and chronic pain are public health epidemics. Sleep loss worsens pain and predicts the development of chronic pain. Whether previous, acute sleep loss and recovery sleep determine pain levels and duration remains poorly understood. This study tested whether acute sleep deprivation and recovery sleep prior to formalin injection alter post-injection pain levels and duration. Male Sprague-Dawley rats (n = 48) underwent sleep deprivation or ad libitum sleep for 9 hours. Thereafter, rats received a subcutaneous injection of formalin or saline into a hind paw. In the recovery sleep group, rats were allowed 24 h between sleep deprivation and the injection of formalin. Mechanical and thermal nociception were assessed using the von Frey test and Hargreaves' method. Nociceptive measures were performed at 1, 3, 7, 10, 14, 17 and 21 days post-injection. Formalin caused bilateral mechanical hypersensitivity (allodynia) that persisted for up to 21 days post-injection. Sleep deprivation significantly enhanced bilateral allodynia. There was a synergistic interaction when sleep deprivation preceded a formalin injection. Rats allowed a recovery sleep period prior to formalin injection developed allodynia only in the injected limb, with higher mechanical thresholds (less allodynia) and a shorter recovery period. There were no persistent changes in thermal nociception. The data suggest that acute sleep loss preceding an inflammatory insult enhances pain and can contribute to chronic pain. The results encourage studies in a model of surgical pain to test whether enhancing sleep reduces pain levels and duration. © 2016 Associated Professional Sleep Societies, LLC.

  7. Type III Nrg1 back signaling enhances functional TRPV1 along sensory axons contributing to basal and inflammatory thermal pain sensation.

    Science.gov (United States)

    Canetta, Sarah E; Luca, Edlira; Pertot, Elyse; Role, Lorna W; Talmage, David A

    2011-01-01

    Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs). Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling) can acutely activate phosphatidylinositol-3-kinase (PtdIns3K) signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons. Transient receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K, making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function.

  8. Type III Nrg1 back signaling enhances functional TRPV1 along sensory axons contributing to basal and inflammatory thermal pain sensation.

    Directory of Open Access Journals (Sweden)

    Sarah E Canetta

    Full Text Available Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs. Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling can acutely activate phosphatidylinositol-3-kinase (PtdIns3K signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons. Transient receptor potential vanilloid 1 (TRPV1 is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K, making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function.

  9. Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

    Science.gov (United States)

    Hummig, Wagner; Kopruszinski, Caroline Machado; Chichorro, Juliana Geremias

    2014-01-01

    To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

  10. Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2017-01-01

    Full Text Available Chronic inflammatory pain may result from peripheral tissue injury or inflammation, increasing the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines and chemokines. Transient receptor potential vanilloid 1 (TRPV1 is known to be involved in acute to subacute neuropathic and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are not elucidated. Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia were also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG and spinal cord (SC at 3 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB and nociceptive ion channels (Nav1.7 and Nav1.8 were involved in this process. Inflammatory mediators such as GFAP, S100B, and RAGE were also involved. The expression levels of these molecules were reduced in EA and TRPV1−/− mice but not in the sham EA group. Our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

  11. p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats.

    Science.gov (United States)

    Kiyomoto, Masaaki; Shinoda, Masamichi; Honda, Kuniya; Nakaya, Yuka; Dezawa, Ko; Katagiri, Ayano; Kamakura, Satoshi; Inoue, Tomio; Iwata, Koichi

    2015-08-12

    Orofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund's adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain. Mechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1β over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration. These findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation.

  12. Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

    Science.gov (United States)

    Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-08-01

    Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (ppain to chronic low back pain.

  13. Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat

    Directory of Open Access Journals (Sweden)

    Ikeda Hiroshi

    2012-06-01

    Full Text Available Abstract Background The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain. Results In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP. Conclusions These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

  14. Targeted nanoparticles that mimic immune cells in pain control inducing analgesic and anti-inflammatory actions: a potential novel treatment of acute and chronic pain condition.

    Science.gov (United States)

    Hua, Susan; Cabot, Peter J

    2013-01-01

    The peripheral immune-derived opioid analgesic pathway has been well established as a novel target in the clinical pain management of a number of painful pathologies, including acute inflammatory pain, neuropathic pain, and rheumatoid arthritis. Our objective was to engineer targeted nanoparticles that mimic immune cells in peripheral pain control to deliver opioids, in particular loperamide HCl, specifically to peripheral opioid receptors to induce analgesic and anti-inflammatory actions for use in painful inflammatory conditions. This peripheral analgesic system is devoid of central opioid mediated side effects (e.g., respiratory depression, sedation, dependence, tolerance). A randomized, double blind, controlled animal trial. Thirty-six adult male Wistar rats (200 - 250 g) were randomly divided into 6 groups: loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, naloxone methiodide + loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, loperamide HCl-encapsulated liposomes, empty anti-ICAM-1 immunoliposomes, empty liposomes, and loperamide solution. Animals received an intraplantar injection of 150 μL Complete Freund's Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All formulations were administered intravenously via tail vein injection. The dose administered was 200 μL, which equated to 0.8 mg of loperamide HCl for the loperamide HCl treatment groups (sub-therapeutic dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to loperamide-encapsulated anti-ICAM-1 immunoliposomes. An investigator blinded to the treatment administered assessed the time course of the antinociceptive and anti-inflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Biodistribution studies were performed 5 days post-CFA injection with anti-ICAM-1 immunoliposomes and control liposomes via tail vein

  15. Electromagnetic Field Devices and Their Effects on Nociception and Peripheral Inflammatory Pain Mechanisms.

    Science.gov (United States)

    Ross, Christina L; Teli, Thaleia; Harrison, Benjamin S

    2016-03-01

    Context • During cell-communication processes, endogenous and exogenous signaling affects normal and pathological developmental conditions. Exogenous influences, such as extra-low-frequency (ELF) electromagnetic fields (EMFs) have been shown to affect pain and inflammation by modulating G-protein coupling receptors (GPCRs), downregulating cyclooxygenase-2 (Cox-2) activity, and downregulating inflammatory modulators, such as tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) as well as the transcription factor nuclear factor kappa B (NF-κB). EMF devices could help clinicians who seek an alternative or complementary treatment for relief of patients chronic pain and disability. Objective • The research team intended to review the literature on the effects of EMFs on inflammatory pain mechanisms. Design • We used a literature search of articles published in PubMed using the following key words: low-frequency electromagnetic field therapy, inflammatory pain markers, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), opioid receptors, G-protein coupling receptors, and enzymes. Setting • The study took place at the Wake Forest School of Medicine in Winston-Salem, NC, USA. Results • The mechanistic pathway most often considered for the biological effects of EMF is the plasma membrane, across which the EMF signal induces a voltage change. Oscillating EMF exerts forces on free ions that are present on both sides of the plasma membrane and that move across the cell surface through transmembrane proteins. The ions create a forced intracellular vibration that is responsible for phenomena such as the influx of extracellular calcium (Ca2+) and the binding affinity of calmodulin (CaM), which is the primary transduction pathway to the secondary messengers, cAMP and cGMP, which have been found to influence inflammatory pain. Conclusions • An emerging body of evidence indicates the existence of a frequency

  16. Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models

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    Kanako So

    2015-03-01

    Full Text Available Recent evidence suggests a role of transient receptor potential melastatin 2 (TRPM2 in immune and inflammatory responses. We previously reported that TRPM2 deficiency attenuated inflammatory and neuropathic pain in some pain mouse models, including formalin- or carrageenan-induced inflammatory pain, and peripheral nerve injury-induced neuropathic pain models, while it had no effect on the basal mechanical and thermal nociceptive sensitivities. In this study, we further explored the involvement of TRPM2 in various pain models using TRPM2-knockout mice. There were no differences in the chemonociceptive behaviors evoked by intraplantar injection of capsaicin or hydrogen peroxide between wildtype and TRPM2-knockout mice, while acetic acid-induced writhing behavior was significantly attenuated in TRPM2-knockout mice. In the postoperative incisional pain model, no difference in mechanical allodynia was observed between the two genotypes. By contrast, mechanical allodynia in the monosodium iodoacetate-induced osteoarthritis pain model and the experimental autoimmune encephalomyelitis model were significantly attenuated in TRPM2-knockout mice. Furthermore, mechanical allodynia in paclitaxel-induced peripheral neuropathy and streptozotocin-induced painful diabetic neuropathy models were significantly attenuated in TRPM2-knockout mice. Taken together, these results suggest that TRPM2 plays roles in a wide range of pathological pain models based on peripheral and central neuroinflammation, rather than physiological nociceptive pain.

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

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2018-01-01

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

  18. The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain

    OpenAIRE

    Giannini, Elisa; Lattanzi, Roberta; Nicotra, Annalisa; Campese, Antonio F.; Grazioli, Paola; Screpanti, Isabella; Balboni, Gianfranco; Salvadori, Severo; Sacerdote, Paola; Negri, Lucia

    2009-01-01

    Neutrophil migration into injured tissues is invariably accompanied by pain. Bv8/prokineticin 2 (PK2), a chemokine characterized by a unique structural motif comprising five disulfide bonds, is highly expressed in inflamed tissues associated to infiltrating cells. Here, we demonstrate the fundamental role of granulocyte-derived PK2 (GrPK2) in initiating inflammatory pain and driving peripheral sensitization. In animal models of complete Freund's adjuvant-induced paw inflammation the developme...

  19. 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.

  20. Inflammatory spine disease as a cause of back pain

    International Nuclear Information System (INIS)

    Schlossbauer, T.; Panteleon, A.; Becker-Gaab, C.

    2006-01-01

    The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-α antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-α antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI is useful for assessment of the effectiveness of anti-inflammatory therapy. (orig.) [de

  1. Radiological and scintigraphic findings in patients with a clinical history of chronic inflammatory back pain

    International Nuclear Information System (INIS)

    Goei The, H.S.; Lemmens, A.J.; Goedhard, G.; Lokkerbol, H.; Rahmy, A.; Linden, S.M. van der; Cats, A.; Steven, M.M.

    1985-01-01

    The prevalence of radiological abnormalities of the sacroiliac joints, the manubriosternal joint, and the lumbar spine were assessed, and quantitative sacroiliac scintigraphy was performed in 151 patients with a history of chronic inflammatory back pain and in 31 controls with non-inflammatory back pain. Sacroiliitis was found in 124 patients (82%), manubriosternal lesions in 84 patients (56%), and lesions of the lumbar spine in 58 patients (38%). In 19 patients (13%), manubriosternal lesions provided the sole radiological abnormality and in five patients (3%) no radiological abnormality could be demonstrated at any of these sites. Quantitative sacroiliac scintigraphy showed increased values in 69 of 137 patients examined (50%), but also in 10 out of 12 control patients with disc degeneration (83%) and is, therefore, nonspecific for inflammatory lesions. Radiological examination of the manubriosternal joint is recommended in patients with inflammatory back pain without radiographic evidence of sacroiliitis. (orig.)

  2. Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain

    Science.gov (United States)

    2013-01-01

    Background GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a “pain-protective” (PP) haplotype of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH1 gene results in decreased basal GCH1 expression, and is associated with DOPA-responsive dystonia (DRD). So far it is unknown if such mutations affect acute and inflammatory pain. Results In the current study, we examined the involvement of the GCH1 gene in pain models using the hyperphenylalaninemia 1 (hph-1) mouse, a genetic model for DRD, with only 10% basal GTP-CH1 activity compared to wild type mice. The study included assays for determination of acute nociception as well as models for pain after sensitisation. Pain behavioural analysis of the hph-1 mice showed reduced pain-like responses following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in naïve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms. Conclusions In this study, we demonstrate novel evidence that genetic mutations in the GCH1 gene modulate pain-like hypersensitivity. Together, the present data suggest that BH4 is not important for basal heat and mechanical pain, but they support the hypothesis that BH4 plays a role in inflammation-induced hypersensitivity. Our studies suggest that the BH4 pathway could be a therapeutic target for the treatment of inflammatory pain conditions. Moreover, the hph-1 mice provide a valid model to

  3. Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

    Science.gov (United States)

    Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

    2016-01-01

    Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID:26891874

  4. Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers.

    Science.gov (United States)

    Quartana, Phillip J; Finan, Patrick H; Page, Gayle G; Smith, Michael T

    2015-07-01

    Osteoarthritis is the most prevalent arthritic condition. Systemic inflammatory cytokines appear to have an important role in the onset and maintenance of the disease. Sleep disturbances are prevalent in osteoarthritis and associated with alterations in systemic inflammatory cytokines, suggesting a common pathophysiology across these conditions. A comparative investigation of the effects of insomnia disorder and osteoarthritis on pain-evoked cytokine responses has yet to be undertaken. We examined the influence of symptomatic knee osteoarthritis and insomnia disorder on resting C-reactive protein (CRP), interleukin (IL)-6, and IL-10 levels, and pain-evoked IL-6 and IL-10 responses. Participants were N=117 older adults (mean age=59.7years; 61.8% women) rigorously evaluated for knee osteoarthritis and insomnia disorder using established diagnostic guidelines. Results revealed no association of osteoarthritis or insomnia disorder with CRP. Resting IL-6 was greater in osteoarthritis participants versus those without osteoarthritis, although this association was largely attributable to BMI. IL-10 was highest among participants with osteoarthritis or insomnia disorder. Growth curve modeling revealed that participants with insomnia disorder had greater pain-evoked IL-6 responses than participants without insomnia disorder or osteoarthritis. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Moreover, our findings provide evidence for amplified pain-evoked pro-inflammatory cytokine reactivity among older adults with clinically diagnosed insomnia disorder, even after controlling for individual differences in BMI and age. Additional research will be required determine whether an amplified pain-related cytokine response contributes to OA, and possibly other age-related disease, associated with insomnia disorder. Published by Elsevier Inc.

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

    Science.gov (United States)

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

    2008-11-15

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

  6. Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain

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    Busch Melanie

    2009-12-01

    Full Text Available Abstract Background Leukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, anti-bacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC on complete Freund's adjuvant-induced inflammatory pain in rats. Results POMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin. Conclusion Although MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.

  7. Enhanced quantal release of excitatory transmitter in anterior cingulate cortex of adult mice with chronic pain

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    Zhao Ming-Gao

    2009-01-01

    Full Text Available Abstract The anterior cingulate cortex (ACC is a forebrain structure that plays important roles in emotion, learning, memory and persistent pain. Our previous studies have demonstrated that the enhancement of excitatory synaptic transmission was induced by peripheral inflammation and nerve injury in ACC synapses. However, little information is available on their presynaptic mechanisms, since the source of the enhanced synaptic transmission could include the enhanced probability of neurotransmitter release at existing release sites and/or increases in the number of available vesicles. The present study aims to perform quantal analysis of excitatory synapses in the ACC with chronic pain to examine the source of these increases. The quantal analysis revealed that both probability of transmitter release and number of available vesicles were increased in a mouse model of peripheral inflammation, whereas only probability of transmitter release but not number of available vesicles was enhanced in a mouse model of neuropathic pain. In addition, we compared the miniature excitatory postsynaptic potentials (mEPSCs in ACC synapses with those in other pain-related brain areas such as the amygdala and spinal cord. Interestingly, the rate and amplitude of mEPSCs in ACC synapses were significantly lower than those in the amygdala and spinal cord. Our studies provide strong evidences that chronic inflammatory pain increases both probability of transmitter release and number of available vesicles, whereas neuropathic pain increases only probability of transmitter release in the ACC synapses.

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

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    Tayler D Sheahan

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

  9. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

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

    DEFF Research Database (Denmark)

    Ravn, Pernille; Secher, EL; Skram, U

    2013-01-01

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

  11. The Anti-Inflammatory Actions of Auricular Point Acupressure for Chronic Low Back Pain

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    Wei-Chun Lin

    2015-01-01

    Full Text Available Background. Auricular point acupressure (APA is a promising treatment for pain management. Few studies have investigated the physiological mechanisms of APA analgesics. Method. In this pilot randomized clinical trial (RCT, a 4-week APA treatment was used to manage chronic low back pain (CLBP. Sixty-one participants were randomized into a real APA group (n=32 or a sham APA group (n=29. Blood samples, pain intensity, and physical function were collected at baseline and after 4 weeks of treatment. Results. Subjects in the real APA group reported a 56% reduction of pain intensity and a 26% improvement in physical function. Serum blood samples showed (1 a decrease in IL-1β, IL-2, IL-6, and calcitonin gene-related peptide [CGRP] and (2 an increase in IL-4. In contrast, subjects in the sham APA group (1 reported a 9% reduction in pain and a 2% improvement in physical function and (2 exhibited minimal changes of inflammatory cytokines and neuropeptides. Statistically significant differences in IL-4 and CGRP expression between the real and sham APA groups were verified. Conclusion. These findings suggest that APA treatment affects pain intensity through modulation of the immune system, as reflected by APA-induced changes in serum inflammatory cytokine and neuropeptide levels.

  12. Delineating inflammatory and mechanical sub-types of low back pain: a pilot survey of fifty low back pain patients in a chiropractic setting

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    Riksman Janine S

    2011-02-01

    Full Text Available Abstract Background An instrument known as the Mechanical and Inflammatory Low Back Pain (MAIL Scale was drafted using the results of a previous expert opinion study. A pilot survey was conducted to test the feasibility of a larger study designed to determine the MAIL Scale's ability to distinguish two potential subgroups of low back pain: inflammatory and mechanical. Methods Patients with a primary complaint of low back pain (LBP presenting to chiropractic clinics in Perth, Western Australia were asked to fill out the MAIL Scale questionnaire. The instrument's ability to separate patients into inflammatory and mechanical subgroups of LBP was examined using the mean score of each notional subgroup as an arbitrary cut-off point. Results Data were collected from 50 patients. The MAIL Scale did not appear to separate cases of LBP into the two notionally distinct groups of inflammatory (n = 6 or mechanical (n = 5. A larger "mixed symptom" group (n = 39 was revealed. Conclusions In this pilot study the MAIL Scale was unable to clearly discriminate between what is thought to be mechanical and inflammatory LBP in 50 cases seen in a chiropractic setting. However, the small sample size means any conclusions must be viewed with caution. Further research within a larger study population may be warranted and feasible.

  13. Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain.

    Science.gov (United States)

    Chen, Lei; Liu, Jin-cheng; Zhang, Xiao-nan; Guo, Yan-yan; Xu, Zhao-hui; Cao, Wei; Sun, Xiao-li; Sun, Wen-ji; Zhao, Ming-Gao

    2008-06-01

    Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. 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 and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

  14. The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

    Science.gov (United States)

    Offiah, Ifeoma; Didangelos, Athanasios; Dawes, John; Cartwright, Rufus; Khullar, Vik; Bradbury, Elizabeth J; O'Sullivan, Suzanne; Williams, Dic; Chessell, Iain P; Pallas, Kenny; Graham, Gerry; O'Reilly, Barry A; McMahon, Stephen B

    2016-08-01

    Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating

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

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    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. Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis

    DEFF Research Database (Denmark)

    Whittle, Samuel L; Colebatch, Alexandra N; Buchbinder, Rachelle

    2012-01-01

    Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA).Methods. A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process......, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008-09 European League Against Rheumatism (EULAR...... to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty...

  17. EULAR recommendations for the health professional's approach to pain management in inflammatory arthritis and osteoarthritis

    NARCIS (Netherlands)

    Geenen, Rinie; Overman, Cécile L; Christensen, Robin; Åsenlöf, Pernilla; Capela, Susana; Huisinga, Karen L; Husebø, Mai Elin P; Köke, Albère J A; Paskins, Zoe; Pitsillidou, Irene A; Savel, Carine; Austin, Judith; Hassett, Afton L; Severijns, Guy; Stoffer-Marx, Michaela; Vlaeyen, Johan W S; Fernández-de-Las-Peñas, César; Ryan, Sarah J; Bergman, Stefan

    2018-01-01

    Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional's approach to pain management. A multidisciplinary task force including professionals and patient

  18. Long-Term Effects of Neonatal Pain and Stress on Reactivity of the Nociceptive System.

    Science.gov (United States)

    Butkevich, I P; Mikhailenko, V A

    2016-10-01

    The influence of inflammatory pain and/or weaning stress at different terms of neonatal development on functional activity of the nociceptive system during adulthood was studied in rats. Repeated stress in 1-2-day-old rat pups (a premature baby model) enhanced pain sensitivity to peripheral inflammation in both males and females. Repeated inflammatory pain experienced by male pups aged 1-2 or 7-8 days (models of preterm and full-term baby), even in presence of mother, enhanced pain behavior under conditions of repeated inflammatory pain in adulthood. Pain sensitivity in adult animals before (hot plate test) and after formation of the inflammatory focus (formalin test) depended on the age when the animals were subjected to the injury, type of exposure, and on animal sex. The priority data obtained by us will help to understand the mechanisms of long-term effects of early injuries and are important for pediatricians and neonatologists.

  19. Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

    Science.gov (United States)

    Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

    2015-06-01

    Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

  20. Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain.

    Science.gov (United States)

    Fu, Hui; Fang, Peng; Zhou, Hai-Yun; Zhou, Jun; Yu, Xiao-Wei; Ni, Ming; Zheng, Jie-Yan; Jin, You; Chen, Jian-Guo; Wang, Fang; Hu, Zhuang-Li

    2016-02-01

    Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain. © 2016 John Wiley & Sons Australia, Ltd.

  1. 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.

  2. 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.

  3. Pain management in patients with inflammatory bowel disease: insights for the clinician

    Science.gov (United States)

    Srinath, Arvind Iyengar; Walter, Chelsea; Newara, Melissa C.

    2012-01-01

    Abdominal pain is a common symptom in patients with inflammatory bowel disease (IBD) and has a profound negative impact on patients’ lives. There are growing data suggesting that pain is variably related to the degree of active inflammation. Given the multifactorial etiologies underlying the pain, the treatment of abdominal pain in the IBD population is best accomplished by individualized plans. This review covers four clinically relevant categories of abdominal pain in patients with IBD, namely, inflammation, surgical complications, bacterial overgrowth, and neurobiological processes and how pain management can be addressed in each of these cases. The role of genetic factors, psychological factors, and psychosocial stress in pain perception and treatment will also be addressed. Lastly, psychosocial, pharmacological, and procedural pain management techniques will be discussed. An extensive review of the existing literature reveals a paucity of data regarding pain management specific to IBD. In addition, there is growing consensus suggesting a spectrum between IBD and irritable bowel syndrome (IBS) symptoms. Thus, this review for adult and pediatric clinicians also incorporates the literature for the treatment of functional abdominal pain and the clinical consensus from IBD and IBS experts on pharmacological, behavioral, and procedural methods to treat abdominal pain in this population. PMID:22973418

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

    Directory of Open Access Journals (Sweden)

    Bo Hu

    2018-05-01

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

  5. Neural control disturbances of the gastrointestinal tract and visceral pain in inflammatory bowel diseases 

    Directory of Open Access Journals (Sweden)

    Katarzyna Ciesielczyk

    2013-04-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic intestinal inflammatory condition, the etiology of which is composed of factors such as the environment, genetic predisposition, gut dysbiosis and inadequate immune response. The pathologic findings in Crohn’s disease and ulcerative colitis are related to dysfunction of gastrointestinal secretion and motility and also disturbed visceral sensory function, with accompanying intestinal and parenteral complications. The systemic inflammatory response affects neurological control via the gut-brain axis, which modulates the cooperation of the autonomic nervous system (ANS, enteric nervous system (ENS and gut-associated lymphoid tissue (GALT. In chronic inflammation the intestinal neuropathy disrupts peristalsis and intestinal secretion as well as causing unpleasant symptoms of the patients. Pain receptors are stimulated by inflammatory mediators, and due to the intensified activation of the nociceptive system visceral hypersensitivity through central and peripheral sensitization is generated. Chronic visceral pain negatively influences the course of disease and the quality of the patient’s life. The growing knowledge about the neurological control dysfunction of the intestine and immune system dysregulation could provide proper directives for treatment of inflammatory bowel diseases.

  6. Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions

    Science.gov (United States)

    Pezet, Sophie; Marchand, Fabien; D'Mello, Richard; Grist, John; Clark, Anna K.; Malcangio, Marzia; Dickenson, Anthony H.; Williams, Robert J.; McMahon, Stephen B.

    2010-01-01

    Here we show that phosphatidylinositol 3-kinase (PI3K) is a key player in the establishment of central sensitization, the spinal cord phenomenon associated with persistent afferent inputs and contributing to chronic pain states. We demonstrated electrophysiologically that PI3K is required for the full expression of spinal neuronal wind-up. In an inflammatory pain model, intrathecal administration of LY294002, a potent PI3K inhibitor, dose-dependently inhibited pain related behavior. This effect was correlated with a reduction of the phosphorylation of extracellular signal-regulated kinase (ERK) and CaMKinase II. In addition, we observed a significant decrease in the phosphorylation of the NMDA receptor subunit NR2B, decreased translocation to the plasma membrane of the GluR1 AMPA receptor subunit in the spinal cord and a reduction of evoked neuronal activity as measured using c-Fos immunohistochemistry. Our study suggests that PI3K is a major factor in the expression of central sensitization after noxious inflammatory stimuli. PMID:18417706

  7. Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Farshid, Amir-Abbas; Eghdami, Karim; Samadi, Farzad; Erfanparast, Amir

    2013-01-01

    Crocin and safranal are the active substances of saffron and have many biological properties. In the present study, we compared the effects of crocin, safranal and diclofenac on local inflammation and its induced pain in rats. Local inflammation was induced by intraplantar (ipl) injection of carrageenan (100 μl, 2%). Paw thickness was measured before and after carrageenan injection. Inflammatory pain responses including cold allodynia, mechanical allodynia and hyperalgesia were assessed using acetone spray and von Frey filament tests, respectively. The number of neutrophils in inflammatory zone was counted 6.5 h after injection of carrageenan. Carrageenan produced edema, cold allodynia, mechanical allodynia and hyperalgesia and caused neutrophil infiltration in paw tissues. Crocin at doses of 25, 50 and 100 mg/kg, safranal at doses of 0.5, 1 and 2 mg/kg and diclofenac (as a reference drug) at a dose of 10 mg/kg attenuated edema, suppressed inflammatory pain responses and decreased the number of neutrophils. The present study showed anti-inflammatory and antinociceptive activities for crocin, safranal and diclofenac in carrageenan model of local inflammation and inflammatory pain.

  8. A novel model of inflammatory pain in human skin involving topical application of sodium lauryl sulfate.

    Science.gov (United States)

    Petersen, L J; Lyngholm, A M; Arendt-Nielsen, L

    2010-09-01

    Sodium lauryl sulfate (SLS) is a known irritant. It releases pro-inflammatory mediators considered pivotal in inflammatory pain. The sensory effects of SLS in the skin remain largely unexplored. In this study, SLS was evaluated for its effect on skin sensory functions. Eight healthy subjects were recruited for this study. Skin sites were randomized to topical SLS 0.25, 0.5, 1, 2% and vehicle for 24 h. Topical capsaicin 1% was applied for 30 min at 24 h after SLS application. Assessments included laser Doppler imaging of local vasodilation and flare reactions, rating of spontaneous pain, assessment of primary thermal and tactile hyperalgesia, and determination of secondary dynamic and static hyperalgesia. SLS induced significant and dose-dependent local inflammation and primary hyperalgesia to tactile and thermal stimulation at 24 h after application, with SLS 2% treatment eliciting results comparable to those observed following treatment with capsaicin 1%. SLS induced no spontaneous pain, small areas of flare, and minimal secondary hyperalgesia. The primary hyperalgesia vanished within 2-3 days, whereas the skin inflammation persisted and was only partly normalized by Day 6. SLS induces profound perturbations of skin sensory functions lasting 2-3 days. SLS-induced inflammation may be a useful model for studying the mechanisms of inflammatory pain.

  9. Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory pain.

    Science.gov (United States)

    Suardíaz, Margarita; Estivill-Torrús, Guillermo; Goicoechea, Carlos; Bilbao, Ainhoa; Rodríguez de Fonseca, Fernando

    2007-12-15

    Oleoylethanolamide (OEA) is a natural fatty acid amide that mainly modulates feeding and energy homeostasis by binding to peroxisome proliferator-activated receptor-alpha (PPAR-alpha) [Rodríguez de Fonseca F, Navarro M, Gómez R, Escuredo L, Navas F, Fu J, et al. An anorexic lipid mediator regulated by feeding. Nature 2001;414:209-12; Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodríguez de Fonseca F, et al. Oleoylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 2003;425:90-3]. Additionally, it has been proposed that OEA could act via other receptors, including the vanilloid receptor (TRPV1) [Wang X, Miyares RL, Ahern GP. Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1. J Physiol 2005;564:541-7.] or the GPR119 receptor [Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab 2006;3:167-175], suggesting that OEA might subserve other physiological roles, including pain perception. We have evaluated the effect of OEA in two types of nociceptive responses evoked by visceral and inflammatory pain in rodents. Our results suggest that OEA has analgesic properties reducing the nociceptive responses produced by administration of acetic acid and formalin in two experimental animal models. Additional research was performed to investigate the mechanisms underlying this analgesic effect. To this end, we evaluated the actions of OEA in mice null for the PPAR-alpha receptor gene and compared its actions with those of PPAR-alpha receptor wild-type animal. We also compared the effect of MK-801 in order to evaluate the role of NMDA receptor in this analgesia. Our data showed that OEA reduced visceral and inflammatory responses through a PPAR

  10. The role of glia in the spinal cord in neuropathic and inflammatory pain.

    Science.gov (United States)

    Old, Elizabeth Amy; Clark, Anna K; Malcangio, Marzia

    2015-01-01

    Chronic pain, both inflammatory and neuropathic, is a debilitating condition in which the pain experience persists after the painful stimulus has resolved. The efficacy of current treatment strategies using opioids, NSAIDS and anticonvulsants is limited by the extensive side effects observed in patients, underlining the necessity for novel therapeutic targets. Preclinical models of chronic pain have recently provided evidence for a critical role played by glial cells in the mechanisms underlying the chronicity of pain, both at the site of damage in the periphery and in the dorsal horn of the spinal cord. Here microglia and astrocytes respond to the increased input from the periphery and change morphology, increase in number and release pro-nociceptive mediators such as ATP, cytokines and chemokines. These gliotransmitters can sensitise neurons by activation of their cognate receptors thereby contributing to central sensitization which is fundamental for the generation of allodynia, hyperalgesia and spontaneous pain.

  11. VIPER: Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety

    Science.gov (United States)

    2016-10-01

    Whitney U test for evaluating differences in inflammatory mediators between groups (Case vs. Control) and used nonparametric correlations (Spearman’s rho...responses to acute pain. PAIN 2008;140:135–144. [10] Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions...Concentrations in Cases vs. Controls. Mediator Case (n=36) Median (Range) Control (n=40) Median (Range) Mann- Whitney U Test (p value) IFN

  12. TREATMENT OF ACUTE INFLAMMATORY DISEASES ACCOMPANIED BY THROAT IRRITATION AND PAIN

    Directory of Open Access Journals (Sweden)

    M. I. Petrovskaya

    2013-01-01

    Full Text Available Pathogenetically, prescription of local action drugs containing a wide spectrum antiseptic is reasonable for the upper respiratory tract diseases accompanied by throat irritation and pain. It should be noted that such drugs are very popular among parents; however, most of these drugs may have a range of side effects, which considerably complicate their use in children. That is why the right choice of local action drugs for the acute inflammatory diseases accompanied by throat irritation and pain is a guarantee of treatment efficacy and high compliance. This article examines pharmacological qualities of an antiseptic-containing local action drug permitted to use in children over 4 years of age.

  13. Nutmeg oil alleviates chronic inflammatory pain through inhibition of COX-2 expression and substance P release in vivo

    Directory of Open Access Journals (Sweden)

    Wei Kevin Zhang

    2016-04-01

    Full Text Available Background: Chronic pain, or sometimes referred to as persistent pain, reduces the life quality of patients who are suffering from chronic diseases such as inflammatory diseases, cancer and diabetes. Hence, herbal medicines draw many attentions and have been shown effective in the treatment or relief of pain. Methods and Results: Here in this study, we used the CFA-injected rats as a sustainable pain model to test the anti-inflammatory and analgesic effect of nutmeg oil, a spice flavor additive to beverages and baked goods produced from the seed of Myristica fragrans tree. Conclusions: We have demonstrated that nutmeg oil could potentially alleviate the CFA-injection induced joint swelling, mechanical allodynia and heat hyperanalgesia of rats through inhibition of COX-2 expression and blood substance P level, which made it possible for nutmeg oil to be a potential chronic pain reliever.

  14. Systematic review: interventions for abdominal pain management in inflammatory bowel disease.

    Science.gov (United States)

    Norton, C; Czuber-Dochan, W; Artom, M; Sweeney, L; Hart, A

    2017-07-01

    Abdominal pain is frequently reported by people with inflammatory bowel disease (IBD), including in remission. Pain is an under-treated symptom. To systematically review evidence on interventions (excluding disease-modifying interventions) for abdominal pain management in IBD. Databases (MEDLINE, EMBASE, PsycInfo, CINAHL, Scopus, Cochrane Library) were searched (February 2016). Two researchers independently screened references and extracted data. Fifteen papers were included: 13 intervention studies and two cross-sectional surveys. A variety of psychological, dietary and pharmacological interventions were reported. Four of six studies reported pain reduction with psychological intervention including individualised and group-based relaxation, disease anxiety-related Cognitive Behavioural Therapy and stress management. Both psychologist-led and self-directed stress management in inactive Crohn's disease reduced pain compared with controls (symptom frequency reduction index=-26.7, -11.3 and 17.2 at 6-month follow-up, respectively). Two dietary interventions (alcoholic drinks with high sugar content and fermentable carbohydrate with prebiotic properties) had an effect on abdominal pain. Antibiotics (for patients with bacterial overgrowth) and transdermal nicotine patches reduced abdominal pain. Current and past cannabis users report it relieves pain. One controlled trial of cannabis reduced SF-36 and EQ-5D pain scores (1.84 and 0.7, respectively). These results must be treated with caution: data were derived from predominantly small uncontrolled studies of moderate to low quality. Few interventions have been tested for IBD abdominal pain. The limited evidence suggests that relaxation and changing cognitions are promising, possibly with individualised dietary changes. There is a need to develop interventions for abdominal pain management in IBD. © 2017 John Wiley & Sons Ltd.

  15. Role overload, pain and physical dysfunction in early rheumatoid or undifferentiated inflammatory arthritis in Canada.

    Science.gov (United States)

    Mustafa, Sally Sabry; Looper, Karl Julian; Zelkowitz, Phyllis; Purden, Margaret; Baron, Murray

    2012-05-03

    Inflammatory arthritis impairs participation in societal roles. Role overload arises when the demands by a given role set exceed the resources; time and energy, to carry out the required tasks. The present study examines the association between role overload and disease outcomes in early inflammatory arthritis (EIA). Patients (n = 104) of 7.61 months mean duration of inflammatory arthritis completed self-report questionnaires on sociodemographics, disease characteristics and role overload. Pain was assessed using the Short Form McGill Pain Questionnaire (MPQ) and physical functioning was measured with the Medical Outcomes Study Short Form 36 (SF-36) physical functioning score. Role overload was measured by the Role Overload Scale. Patients indicated the number of social roles they occupied from a total of the three typical roles; marital, parental and paid work. Participants' mean age was 56 years and 70.2% were female. Role overload was not correlated to the number of social roles, however, it was positively associated with pain (p = 0.004) and negatively associated with physical functioning (p = 0.001). On multivariate analysis, role overload was negatively associated with physical functioning after controlling for the relevant sociodemographic variables. This study identifies a possible reciprocal relationship between role overload and physical functioning in patients with EIA.

  16. Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain

    DEFF Research Database (Denmark)

    Nasser, A.; Bjerrum, Ole Jannik; Heegaard, A.-M.

    2013-01-01

    following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in naïve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms......Background: GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a " pain-protective" (PP) haplotype...... of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH...

  17. Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain

    Directory of Open Access Journals (Sweden)

    Wei Dong

    2007-06-01

    Full Text Available Abstract Active regulation of gene expression in the nervous system plays an important role in the development and/or maintenance of inflammatory pain. MicroRNA (miRNA negatively regulates gene expression via posttranscriptional or transcriptional inhibition of specific genes. To explore the possible involvement of miRNA in gene regulation during inflammatory pain, we injected complete Freund's adjuvant (CFA unilaterally into the rat masseter muscle and quantified changes in neuron-specific mature miRNAs in the trigeminal ganglion (TG. Real-time reverse-transcription polymerase chain reaction revealed significant, but differential, downregulation of mature miR-10a, -29a, -98, -99a, -124a, -134, and -183 in the ipsilateral mandibular division (V3 of the TG within 4 hr after CFA. In contrast, levels of tested miRNAs did not change significantly in the contralateral V3 or the ipsilateral ophthalmic and maxillary divisions of the TG from inflamed rats, nor in the ipsilateral V3 of saline-injected animals. The downregulated miRNAs recovered differentially to a level equal to or higher than that in naive animals. Full recovery time varied with miRNA species but was at least 4 days. Expression and downregulation of some miRNAs were further confirmed by in situ hybridization of TG neurons that innervate the inflamed muscle. Although neurons of all sizes expressed these miRNAs, their signals varied between neurons. Our results indicate that miRNA species specific to neurons are quickly regulated following inflammatory muscle pain.

  18. Gadolinium-DOTA enhanced MRI of painful osseous crises in children with sickle cell anemia

    International Nuclear Information System (INIS)

    Bonnerot, V.; Sebag, G.; Montalembert, M. de; Wioland, M.; Glorion, C.; Girot, R.; Lallemand, D.

    1994-01-01

    In order to evaluate the role of gadolinium-DOTA enhanced MRI in the management of painful osseous crises in children with sickle cell anemia (SCA), nine children with SCA underwent MRI, bone scans and ultrasonographic studies during 11 osseous crises. Imaging findings were compared with the final diagnosis: three acute osteomyelitis (AO) and 16 acute infarcts (AI). MRI could not differentiate AO from AI. The appearance of severe AI was very misleading and was similar to the usual appearance of AO, including soft tissue changes, periosteal reaction and patterns of enhancement. Gadolinium-DOTA enhanced MRI was useful for determining the anatomic site and extent of AO or AI and for distinguishing between necrotic material, fluid collection and vascularized inflammatory tissue. It can also help to guide the aspiration of intraosseous, subperiosteal and soft tissue fluid collections. (orig.)

  19. Metabotropic glutamate receptor 5 contributes to inflammatory tongue pain via extracellular signal-regulated kinase signaling in the trigeminal spinal subnucleus caudalis and upper cervical spinal cord

    Directory of Open Access Journals (Sweden)

    Liu Ming-Gang

    2012-11-01

    Full Text Available Abstract Background In the orofacial region, limited information is available concerning pathological tongue pain, such as inflammatory pain or neuropathic pain occurring in the tongue. Here, we tried for the first time to establish a novel animal model of inflammatory tongue pain in rats and to investigate the roles of metabotropic glutamate receptor 5 (mGluR5-extracellular signal-regulated kinase (ERK signaling in this process. Methods Complete Freund’s adjuvant (CFA was submucosally injected into the tongue to induce the inflammatory pain phenotype that was confirmed by behavioral testing. Expression of phosphorylated ERK (pERK and mGluR5 in the trigeminal subnucleus caudalis (Vc and upper cervical spinal cord (C1-C2 were detected with immunohistochemical staining and Western blotting. pERK inhibitor, a selective mGluR5 antagonist or agonist was continuously administered for 7 days via an intrathecal (i.t. route. Local inflammatory responses were verified by tongue histology. Results Submucosal injection of CFA into the tongue produced a long-lasting mechanical allodynia and heat hyperalgesia at the inflamed site, concomitant with an increase in the pERK immunoreactivity in the Vc and C1-C2. The distribution of pERK-IR cells was laminar specific, ipsilaterally dominant, somatotopically relevant, and rostrocaudally restricted. Western blot analysis also showed an enhanced activation of ERK in the Vc and C1-C2 following CFA injection. Continuous i.t. administration of the pERK inhibitor and a selective mGluR5 antagonist significantly depressed the mechanical allodynia and heat hyperalgesia in the CFA-injected tongue. In addition, the number of pERK-IR cells in ipsilateral Vc and C1-C2 was also decreased by both drugs. Moreover, continuous i.t. administration of a selective mGluR5 agonist induced mechanical allodynia in naive rats. Conclusions The present study constructed a new animal model of inflammatory tongue pain in rodents, and

  20. Hyperalgesia in a human model of acute inflammatory pain: a methodological study

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    as significant for all variables with fewer than 12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day comparisons demanded up to 25 subjects to detect changes of the same magnitude. The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects (all right-handed) were more......The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection...... thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli...

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

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-08-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

  3. TMJ disorders and pain: Assessment by contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Farina, Davide; Bodin, Christiane; Gandolfi, Silvia; De Gasperi, Werner; Borghesi, Andrea; Maroldi, Roberto

    2009-01-01

    Though magnetic resonance (MRI) is a widely accepted standard for the assessment of patients with temporomandibular joint (TMJ) disorders, efforts to correlate symptoms to MRI findings have often given controversial results. Aim of this study was to investigate the correlation between TMJ pain and findings of contrast-enhanced MRI. Thirty-eight consecutive patients with TMJ dysfunction syndrome (study group) were examined with MRI. Protocol included T2 turbo spin-echo sequence, T1 spin-echo sequence, and T2 gradient-echo (acquired with closed jaw, at intermediate and maximal opening). Post-contrast phase was obtained through a fat sat 3D T1 gradient-echo sequence (VIBE). Post-contrast findings in the study group were matched with those obtained in a control group of 33 patients submitted to MRI of the paranasal sinuses. Statistically significant difference was found between condylar medullary bone enhancement in painful TMJ, in painless TMJ and control group. In addition the average thickness of joint soft tissue enhancement in painful TMJ was superior to painless TMJ (p < 0.0001) and to control group. On multivariate logistic regression analysis, the odds ratio that a painful TMJ showed disk displacement, osteoarthrosis, effusion and JST enhancement were 3.05, 3.18, 1.2 and 11.36, respectively. Though not histologically proven, TMJ enhancement could reflect the presence of inflammation in painful joints. Furthermore, the administration of contrast could be of help for the assessment of patients with orofacial pain, particularly when clinical exploration is insufficient to ascribe the pain to TMJ.

  4. TMJ disorders and pain: Assessment by contrast-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Davide [Department of Radiology (School of Medicine), University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia (Italy); Bodin, Christiane [Division of Gnathology (School of Dentistry), University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia (Italy); Gandolfi, Silvia [Department of Radiology (School of Medicine), University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia (Italy); De Gasperi, Werner [Division of Gnathology (School of Dentistry), University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia (Italy); Borghesi, Andrea; Maroldi, Roberto [Department of Radiology (School of Medicine), University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia (Italy)

    2009-04-15

    Though magnetic resonance (MRI) is a widely accepted standard for the assessment of patients with temporomandibular joint (TMJ) disorders, efforts to correlate symptoms to MRI findings have often given controversial results. Aim of this study was to investigate the correlation between TMJ pain and findings of contrast-enhanced MRI. Thirty-eight consecutive patients with TMJ dysfunction syndrome (study group) were examined with MRI. Protocol included T2 turbo spin-echo sequence, T1 spin-echo sequence, and T2 gradient-echo (acquired with closed jaw, at intermediate and maximal opening). Post-contrast phase was obtained through a fat sat 3D T1 gradient-echo sequence (VIBE). Post-contrast findings in the study group were matched with those obtained in a control group of 33 patients submitted to MRI of the paranasal sinuses. Statistically significant difference was found between condylar medullary bone enhancement in painful TMJ, in painless TMJ and control group. In addition the average thickness of joint soft tissue enhancement in painful TMJ was superior to painless TMJ (p < 0.0001) and to control group. On multivariate logistic regression analysis, the odds ratio that a painful TMJ showed disk displacement, osteoarthrosis, effusion and JST enhancement were 3.05, 3.18, 1.2 and 11.36, respectively. Though not histologically proven, TMJ enhancement could reflect the presence of inflammation in painful joints. Furthermore, the administration of contrast could be of help for the assessment of patients with orofacial pain, particularly when clinical exploration is insufficient to ascribe the pain to TMJ.

  5. CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

    Science.gov (United States)

    Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A.; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L.

    2014-01-01

    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. PMID:24732949

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

    Science.gov (United States)

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

    2015-07-01

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

  7. Pain from Dental Implant Placement, Inflammatory Pulpitis Pain, and Neuropathic Pain Present Different Somatosensory Profiles.

    Science.gov (United States)

    Porporatti, André Luís; Bonjardim, Leonardo Rigoldi; Stuginski-Barbosa, Juliana; Bonfante, Estevam Augusto; Costa, Yuri Martins; Rodrigues Conti, Paulo César

    2017-01-01

    To address the two following questions: (1) What kind of somatosensory abnormalities may be characterized in patients receiving dental implants (IMP), in ongoing inflammatory dental pulpitis (IP) patients, and in neuropathic pain (atypical odontalgia [AO]) patients? and (2) What sort of sensory and neural changes may result from dental implant placement surgery and pulpectomy? A total of 60 subjects were divided into three groups: the IMP (n = 20), IP (n = 20), and AO groups (n = 20). Quantitative sensory testing (QST) was performed preoperatively (baseline) for all three groups and postoperatively at 1 month and 3 months after dental implant placement or pulpectomy (in the IMP group and IP group, respectively). Statistical analyses were completed with one-way and two-way analysis of variance and z score transformations (α = 5%). The main findings of this study indicated that: (1) Elevations in mechanical detection threshold (MDT) and in current perception threshold (CPT) related to C-fiber activation, indicating a loss of function, were found at baseline in IP patients; (2) Somatosensory abnormalities such as allodynia, reduced MDT and mechanical pain threshold (MPT), and impaired pain modulation were found in AO patients; (3) No somatosensory alterations after implant placement were found in the IMP group; and (4) Somatosensory alterations in the form of reduction in the CPT related to C-fiber activation were reported 3 months after pulpectomy in the IP group. This study showed that somatosensory abnormalities were evident in AO and IP patients, and somatosensory alterations were seen in IP patients even 3 months after pulpectomy. However, no somatosensory alterations were seen after implant placement.

  8. 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

    2016-01-01

    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 < 0.05, n = 8) can be alleviated after EA treatment at either ipsilateral (3.91 ± 0.21, p < 0.05, n = 8) or contralateral acupoints (3.79 ± 0.25, p < 0.05, n = 8). EA may also reduce nociceptive Nav sodium currents in dorsal root ganglion (DRG) neurons. The expression of TRPV1 and associated signaling pathways notably increased after the 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. PMID:26906464

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

    OpenAIRE

    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 inc...

  10. Chronic restraint stress exacerbates nociception and inflammatory response induced by bee venom in rats: the role of the P2X7 receptors.

    Science.gov (United States)

    Li, Xiao-Qiu; Li, Man; Zhou, Zhong-He; Liu, Bao-Jun; Chen, Hui-Sheng

    2016-02-01

    Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV). First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV. The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress. Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R.

  11. Evaluation of clinical and inflammatory profile in opioid addiction patients with comorbid pain: results from a multicenter investigation

    Directory of Open Access Journals (Sweden)

    Dennis BB

    2014-11-01

    Full Text Available Brittany B Dennis,1 M Constantine Samaan,2 Monica Bawor,3 James Paul,4 Carolyn Plater,5 Guillaume Pare,1 Andrew Worster,6 Michael Varenbut,5 Jeff Daiter,5 David C Marsh,5,7 Dipika Desai,8 Lehana Thabane,1,9,10 Zainab Samaan1,8,11 1Department of Clinical Epidemiology and Biostatistics, 2Department of Pediatrics, Division of Pediatric Endocrinology, 3McMaster Integrative Neuroscience Discovery and Study Program, 4Department of Anesthesia, McMaster University, Hamilton, 5Ontario Addiction Treatment Centres, Richmond Hill, 6Department of Medicine, Hamilton General Hospital, Hamilton, 7Northern Ontario School of Medicine, Sudbury, 8Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, 9Centre for Evaluation of Medicine, 10System Linked Research Unit, Hamilton, 11Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada Background: Chronic pain is the most commonly reported comorbidity among patients with opioid addiction receiving methadone maintenance treatment (MMT, with an estimated prevalence ranging between 30% and 55%. Evidence suggests that patients with comorbid pain are at high risk for poor treatment response, including continued illicit substance use. Due to the important relationship between the presence of pain and illicit substance abuse within the MMT setting, it is imperative that we target our efforts toward understanding the characteristics of this patient population.Methods: The primary objective of this study was to explore the clinical and inflammatory profile of MMT patients reporting comorbid pain. This multicenter study enrolled patients (n=235 on MMT for the treatment of opioid dependence. Clinical history and blood and urine data were collected. Blood samples were obtained for estimating the serum levels of inflammatory markers (tumor necrosis factor [TNF]-α, interleukin-1 receptor antagonist [IL-1ra], IL-6, IL-8, IL-10, interferon [IFN]-γ and

  12. Enhancing knowledge and attitudes in pain management: a pain management education program for nursing home staff.

    Science.gov (United States)

    Tse, Mimi Mun Yee; Ho, Suki S K

    2014-03-01

    The aim of the study was to examine the effectiveness of a pain management program (PMP) in enhancing the knowledge and attitudes of health care workers in pain management. Many nursing home residents suffer from pain, and treatment of pain is often inadequate. Failure of health care workers to assess pain and their insufficient knowledge of pain management are barriers to adequate treatment. It was a quasiexperimental pretest and posttest study. Four nursing homes were approached, and 88 staff joined the 8-week PMP. Demographics and the knowledge and attitudes regarding pain were collected with the use of the Nurse's Knowledge and Attitudes Survey Regarding Pain-Chinese version (NKASRP-C) before and after the PMP. A deficit in knowledge and attitudes related to pain management was prominent before the PMP, and there was a significant increase in pain knowledge and attitudes from 7.9 ± SD 3.52 to 19.2 ± SD4.4 (p nursing staff and enable them to provide adequate and appropriate care to older persons in pain. PMPs for nurses and all health care professionals are important in enhancing care for older adults and to inform policy on the provision of pain management. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  13. Effects of mesenchymal stem cells conditioned medium on behavioral aspects of inflammatory arthritic pain induced by CFA adjuvant

    Directory of Open Access Journals (Sweden)

    Vida Nazemian

    2016-07-01

    Full Text Available Background: Rheumatoid arthritis is a type of inflammatory pain and is an autoimmune and chronic inflammatory disease which can lead to hyperalgesia, edema and decreased motor activity in affected area. Mesenchymal stem cells conditioned medium (MSC-CM has anti-inflammatory mediators which can regulate the immune responses, alleviate inflammatory symptoms and has a paracrine effects too. The aim of this study was to evaluate the effects of mesenchymal stem cells conditioned medium on behavioral aspects of inflammatory arthritic pain which induced by CFA adjuvant.Materials and Methods: Complete Freund’s adjuvant (CFA-induced arthritis (AA was caused by single subcutaneous injection of CFA into the rats hind paw on day zero. MSC-CM was administered daily and intraperitoneal during the 21 days of the study after CFA injection. Hyperalgesia and edema were assessed on days 0, 7, 14 and 21 of the study respectively with radian heat and plethysmometer instrument.Results: The results of this study indicated the significant roles of MSC-CM in betterment of inflammatory symptoms such as hyperalgesia and edema during different stages of inflammation caused by CFA. The continuing injection of MSC-CM could reduce the inflammatory symptoms.Conclusion: Long term treatment by MSC-CM can alleviate hyperalgesia and edema and decrease those to the level of the time before induction of inflammation.   

  14. Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.

    Science.gov (United States)

    Volz, Magdalena S; Farmer, Annabelle; Siegmund, Britta

    2016-02-01

    Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.

  15. Lack of effect of chronic pre-treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system

    Science.gov (United States)

    Okine, Bright N; Norris, Leonie M; Woodhams, Stephen; Burston, James; Patel, Annie; Alexander, Stephen PH; Barrett, David A; Kendall, David A; Bennett, Andrew J; Chapman, Victoria

    2012-01-01

    BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day repeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not repeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, PEA and OEA in the spinal cord, compared with those after repeated administration. Single and repeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following repeated administration of low dose URB597 in this model of inflammatory pain. PMID:22595021

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

    Science.gov (United States)

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

    2013-01-01

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

  17. Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

    Directory of Open Access Journals (Sweden)

    Ma Fei

    2012-12-01

    Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

  18. Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain

    Science.gov (United States)

    Krzyzanowska, Agnieszka; Avendaño, Carlos

    2012-01-01

    Orofacial pain conditions are often very debilitating to the patient and difficult to treat. While clinical interest is high, the proportion of studies performed in the orofacial region in laboratory animals is relatively low, compared with other body regions. This is partly due to difficulties in testing freely moving animals and therefore lack of reliable testing methods. Here we present a comprehensive review of the currently used rodent models of inflammatory and neuropathic pain adapted to the orofacial areas, taking into account the difficulties and drawbacks of the existing approaches. We examine the available testing methods and procedures used for assessing the behavioral responses in the face in both mice and rats and provide a summary of some pharmacological agents used in these paradigms to date. The use of these agents in animal models is also compared with outcomes observed in the clinic. PMID:23139912

  19. Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

    Science.gov (United States)

    Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

    2015-06-04

    Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Enhanced presurgical pain temporal summation response predicts post-thoracotomy pain intensity during the acute postoperative phase.

    Science.gov (United States)

    Weissman-Fogel, Irit; Granovsky, Yelena; Crispel, Yonathan; Ben-Nun, Alon; Best, Lael Anson; Yarnitsky, David; Granot, Michal

    2009-06-01

    Recent evidence points to an association between experimental pain measures obtained preoperatively and acute postoperative pain (POP). We hypothesized that pain temporal summation (TS) might be an additional predictor for POP insofar as it represents the neuroplastic changes that occur in the central nervous system following surgery. Therefore, a wide range of psychophysical tests (TS to heat and mechanical repetitive stimuli, pain threshold, and suprathreshold pain estimation) and personality tests (pain catastrophizing and anxiety levels) were administered prior to thoracotomy in 84 patients. POP ratings were evaluated on the 2nd and 5th days after surgery at rest (spontaneous pain) and in response to activity (provoked pain). Linear regression models revealed that among all assessed variables, enhanced TS and higher pain scores for mechanical stimulation were significantly associated with greater provoked POP intensity (overall r2 = 0.225, P = .008). Patients who did not demonstrate TS to both modalities reported lower scores of provoked POP as compared with patients who demonstrated TS in response to at least 1 modality (F = 4.59 P = .013). Despite the moderate association between pain catastrophizing and rest POP, none of the variables predicted the spontaneous POP intensity. These findings suggest that individual susceptibility toward a greater summation response may characterize patients who are potentially vulnerable to augmented POP. This study proposed the role of pain temporal summation assessed preoperatively as a significant psychophysical predictor for acute postoperative pain intensity. The individual profile of enhanced pain summation is associated with the greater likelihood of higher postoperative pain scores.

  1. Current advances in orthodontic pain

    Science.gov (United States)

    Long, Hu; Wang, Yan; Jian, Fan; Liao, Li-Na; Yang, Xin; Lai, Wen-Li

    2016-01-01

    Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons: the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus. Many brain areas participate in the emotion, cognition and memory of orthodontic pain, including the insular cortex, amygdala, hippocampus, locus coeruleus and hypothalamus. A built-in analgesic neural pathway—periaqueductal grey and dorsal raphe—has an important role in alleviating orthodontic pain. Currently, several treatment modalities have been applied for the relief of orthodontic pain, including pharmacological, mechanical and behavioural approaches and low-level laser therapy. The effectiveness of nonsteroidal anti-inflammatory drugs for pain relief has been validated, but its effects on tooth movement are controversial. However, more studies are needed to verify the effectiveness of other modalities. Furthermore, gene therapy is a novel, viable and promising modality for alleviating orthodontic pain in the future. PMID:27341389

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

    Directory of Open Access Journals (Sweden)

    Man-Li Hu

    2017-01-01

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

  3. Neuropathic pain in the orofacial region: The role of pain history. A retrospective study.

    Science.gov (United States)

    Dieb, W; Moreau, N; Chemla, I; Descroix, V; Boucher, Y

    2017-06-01

    Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. The study was performed in the dental department of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n=2) did not report any prior pain and 23% (n=13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n=36) received surgical treatment; 61%, (n=25) endodontic treatment and 22%, (n=9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. 4T1 Murine Mammary Carcinoma Cells Enhance Macrophage-Mediated Innate Inflammatory Responses.

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    Laurence Madera

    Full Text Available Tumor progression and the immune response are intricately linked. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, little is known regarding how cancers affect macrophage-dependent innate host defense. In this study, murine bone-marrow-derived macrophages (BMDM were exposed to murine carcinoma-conditioned media prior to assessment of the macrophage inflammatory response. BMDMs exposed to 4T1 mammary carcinoma-conditioned medium demonstrated enhanced production of pro-inflammatory cytokines tumor necrosis factor α, interleukin-6, and CCL2 in response to lipopolysaccharide (LPS while production of interleukin-10 remained unchanged. The increased LPS-induced production of pro-inflammatory cytokines was transient and correlated with enhanced cytokine production in response to other Toll-like receptor agonists, including peptidoglycan and flagellin. In addition, 4T1-conditioned BMDMs exhibited strengthened LPS-induced nitric oxide production and enhanced phagocytosis of Escherichia coli. 4T1-mediated augmentation of macrophage responses to LPS was partially dependent on the NFκB pathway, macrophage-colony stimulating factor, and actin polymerization, as well as the presence of 4T1-secreted extracellular vesicles. Furthermore, peritoneal macrophages obtained from 4T1 tumor-bearing mice displayed enhanced pro-inflammatory cytokine production in response to LPS. These results suggest that uptake of 4T1-secreted factors and actin-mediated ingestion of 4T1-secreted exosomes by macrophages cause a transient enhancement of innate inflammatory responses. Mammary carcinoma-mediated regulation of innate immunity may have significant implications for our understanding of host defense and cancer progression.

  5. CT differentiation of periappendiceal inflammation with appendicitis and pelvic inflammatory disease in woman with right lower quadrant pain

    International Nuclear Information System (INIS)

    Wang, Hyun Hye; Kim, Mi Young; Kim, Jung Eun; Kim, Youn Jeong; Suh, Chang Hae

    2006-01-01

    We wanted to determine the usefulness of the computed tomography (CT) findings for making the diagnosis between periappendiceal inflammation (PAI) with appendicitis and pelvic inflammatory disease (PID) for the women presenting with right lower quadrant pain. We retrospectively analyzed the CT findings of 83 women with right lower quadrant pain: PAI in 36 and PID in 47 patients. We reviewed the CT images, including the appendiceal diameter and the enhancing wall thickening, the cecal thickening, the location of the appendix, thickening of the right anterior renal fascia, abscess, mesenteric fatty infiltration, ascites, heterogeneous uterine enhancement and paralytic ileus. Statistical analysis was performed by using the t-test for the diameter of appendix, and the x 2 test or Fisher's exact test for the CT findings. The mean diameter of the appendix was 11.0 ± 3.4 mm for the PAI subjects and it was 6.7 ± 2.0 mm for the PID subjects (ρ < 0.0001). Wall thickening of the appendix was more commonly detected in PAI (25 subjects, 69%) than in PID (15 subjects, 32%) (ρ = 0.0007). Thickening of the right anterior renal fascia was more commonly detected in PAI (18 subjects, 50%) than in PID (7 subjects, 15%). Cecal thickening, ascitis, heterogeneous uterine enhancement and paralytic ileus were not significantly different between PAI and PID. Abscess and mesenteric fatty infiltration were more frequently detected in the RLQ and in the abdomen or pelvic cavity in PAI and PID, respectively (ρ < 0.05). There was no significant difference in the distribution of ascites between the diseases. The CT findings of the appendiceal diameter, enhancing wall thickening and thickening of the right anterior renal fascia are useful for making the diagnosis of PAI. The abdominal and pelvic distributions of abscess and mesenteric fatty infiltration are highly suggestive findings of PID

  6. Pain and pain mechanisms in patients with inflammatory arthritis

    DEFF Research Database (Denmark)

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

    2017-01-01

    completed the PDQ (RA: 3,826, PsA: 1,180, SpA: 1,093). 52% of all patients and 63% of PDQ-completers had VAS pain score ≥ 30 mm. The distribution of the PDQ classification-groups (18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More patients with PsA had PDQ score >18....... The objectives were to quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic features) among Danish arthritis patients using the PDQ, and to assess the association with on-going inflammation. METHODS: The PDQ was included onto the DANBIO touch screens at 22 departments of Rheumatology......28-CRP and VAS pain but not with indicators of peripheral inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in mechanism-based pain treatment....

  7. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Park, Thomas J; Lu, Ying; Jüttner, René; Smith, Ewan St J; Hu, Jing; Brand, Antje; Wetzel, Christiane; Milenkovic, Nevena; Erdmann, Bettina; Heppenstall, Paul A; Laurito, Charles E; Wilson, Steven P; Lewin, Gary R

    2008-01-01

    In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P) in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

  8. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber.

    Directory of Open Access Journals (Sweden)

    Thomas J Park

    2008-01-01

    Full Text Available In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

  9. The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

    Science.gov (United States)

    Sakin, Y S; Dogrul, A; Ilkaya, F; Seyrek, M; Ulas, U H; Gulsen, M; Bagci, S

    2015-07-01

    Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on inflammatory and mechanically evoked visceral pain models. Visceral inflammatory and distension-induced pain were assessed with the 0.6% acetic acid writhing test in mice and colorectal distension (CRD) test in rats, respectively. The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL 195, and the cannabis analog CP 55,940 were given systemically 30 min prior to nociceptive testing. PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10, and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195 (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg), JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response (VMR). The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain. © 2015 John Wiley & Sons Ltd.

  10. 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

    2018-02-01

    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.

  11. Inflammatory Mediators and Pain in the First Year After Acute Episode of Low-Back Pain in Elderly Women: Longitudinal Data from Back Complaints in the Elders-Brazil.

    Science.gov (United States)

    Queiroz, Bárbara Zille; Pereira, Daniele Sirineu; Rosa, Nayza Maciel de Britto; Lopes, Renata Antunes; Andrade, André Gustavo Pereira; Felício, Diogo Carvalho; Jardim, Renata Muniz Freire Vinhal Siqueira; Leopoldino, Amanda Aparecida Oliveira; Silva, Juscélio Pereira; Pereira, Leani Souza Máximo

    2017-08-01

    The aims of this study were to determine the course of plasma levels of inflammatory mediators (interleukin 6 [IL-6], tumor necrosis factor α [TNF-α], soluble TNF receptor 1 [sTNF-R1]) and the severity of low-back pain (LBP) over 6 to 12 months after an acute episode of LBP in elderly women and to establish an association between inflammatory mediators and LBP recovery. This was a longitudinal study of a subsample (155 elderly women with acute LBP, aged ≥65 years) of the international Back Complaints in the Elders cohort study. Plasma levels of IL-6, TNF-α, and sTNF-R1 were measured using enzyme-linked immunosorbent assays and pain severity using the numerical pain scale. There was a decrease in the severity of LBP (P = 0.033) and in the levels of IL-6 and TNF-α (P relief at the 12-month follow-up was 2.22 times higher in elderly women who had low levels of IL-6 (<1.58 pg/mL) at baseline. Our findings showed a relationship between inflammation and LBP by establishing that low IL-6 plasma levels preceded outcome (LBP recovery), supporting the concept that proinflammatory cytokines promote pain.

  12. Psychosocial Pain Management Moderation: The Limit, Activate, and Enhance Model.

    Science.gov (United States)

    Day, Melissa A; Ehde, Dawn M; Jensen, Mark P

    2015-10-01

    There is a growing emphasis in the pain literature on understanding the following second-order research questions: Why do psychosocial pain treatments work? For whom do various treatments work? This critical review summarizes research that addresses the latter question and proposes a moderation model to help guide future research. A theoretical moderation framework for matching individuals to specific psychosocial pain interventions has been lacking. However, several such frameworks have been proposed in the broad psychotherapy and implementation science literature. Drawing on these theories and adapting them specifically for psychosocial pain treatment, here we propose a Limit, Activate, and Enhance model of pain treatment moderation. This model is unique in that it includes algorithms not only for matching treatments on the basis of patient weaknesses but also for directing patients to interventions that build on their strengths. Critically, this model provides a basis for specific a priori hypothesis generation, and a selection of the possible hypotheses drawn from the model are proposed and discussed. Future research considerations are presented that could refine and expand the model based on theoretically driven empirical evidence. The Limit, Activate, and Enhance model presented here is a theoretically derived framework that provides an a priori basis for hypothesis generation regarding psychosocial pain treatment moderators. The model will advance moderation research via its unique focus on matching patients to specific treatments that (1) limit maladaptive responses, (2) activate adaptive responses, and (3) enhance treatment outcomes based on patient strengths and resources. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-ibuprofen in experimental animals.

    Science.gov (United States)

    Suthakaran, Chidambarann; Kayalvizhi, Muniyagounder K; Nithya, Karnam; Raja, Thozhudalangudy Ar

    2017-01-01

    Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.

  14. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

    Science.gov (United States)

    Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

    2006-08-24

    Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery

  15. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

    Directory of Open Access Journals (Sweden)

    Mohapatra Shyam S

    2006-08-01

    Full Text Available Abstract Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in

  16. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients

    DEFF Research Database (Denmark)

    Petersen, Susanne G; Beyer, Nina; Hansen, Mette

    2011-01-01

    Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients.......Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients....

  17. The prevalence of radiographic sacroiliitis in patients affected by inflammatory bowel disease with inflammatory low back pain

    Directory of Open Access Journals (Sweden)

    A. Lo Nigro

    2011-09-01

    Full Text Available Inflammatory bowel diseases (IBD, are Crohn’s disease (CD or ulcerative colitis (UC, are frequently complicated by joint complaints with prevalence that varies between 10 and 28 %. The IBD related arthropathy may be expressed as peripheral arthritis or axial one frequently indistinguishable from the classical ankylosing spondylitis (AS. According to ESSG criteria for spondyloarthropathy, the presence of synovitis or the inflammatory back pain (IBP in IBD patients is diagnostic for spondyloarthropathy, but for diagnosis of as also radiological criteria must be fulfilled. There are few studies regarding the radiological prevalence of sacroiliitis in patients with IBD. We examined, by plain film radiograms of pelvis, 100 sacroiliac joints (SJ of 50 IBD patients with IBP. The New York (1984 SJ radiological score with gradation from 0 to 4 was applied. Total sacroiliac score (SJS was summarized between left and right side (from 0 to 8. Fourteen patients fulfilled New York modified criteria for AS and 8 patients had unilateral 2nd grade sacroiliitis. Only 4 of 14 AS patients (28% were HLA B27 positive. Thirty patients had localized IBP, 10 extended to buttock and 4 extended to sacrum. Sixteen patients had sciatica-like extension of back pain. A difference in SJS between left and right side were observed only in CD patients (1,3± 0,8 e 0,8± 0,9 respectively; p<0,05, but not in UC (1,5± 1,2 vs 1,5± 1,3; p=ns nor in total IBD patients (1,4± 1 vs 1,2± 1,2; p=ns. Total SJS was higher in UC respect CD, but not significantly (2,9± 2,3 vs 2,1± 1,5; p=ns. Our data confirm the importance of these symptoms in patients with IBD, who need to be carefully investigated also for these aspects.

  18. Cancer Pain Physiology

    DEFF Research Database (Denmark)

    Falk, Sarah; Bannister, Kirsty; Dickenson, Anthony

    2014-01-01

    Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells....... This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined...... to the mouse femur. This model prompted related approaches and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer induced bone pain results in progressive bone destruction, elevated osteoclast activity...

  19. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex

  20. Surfen is a broad-spectrum calcium channel inhibitor with analgesic properties in mouse models of acute and chronic inflammatory pain

    Czech Academy of Sciences Publication Activity Database

    Rivas-Ramirez, Paula; Gadotti, V. M.; Zamponi, G. W.; Weiss, Norbert

    2017-01-01

    Roč. 469, č. 10 (2017), s. 1325-1334 ISSN 0031-6768 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * pain * inflammatory pain * calcium channel blocker * surfen * DRG neuron Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 3.156, year: 2016

  1. Effect of contrast-enhanced ultrasound on differential diagnosis of intrahepatic cholangiocarcinoma and arterial phase enhanced hepatic inflammatory lesions

    Institute of Scientific and Technical Information of China (English)

    Shanshan Yin; Qiuli Cui; Kun Yan; Wei Yang; Wei Wu; Liping Bao; Minhua Chen

    2017-01-01

    Objective:To investigate differential diagnosis between intrahepatic cholangiocarcinoma (ICC) and arterial phase enhanced hepatic inflammatory lesions in patients without liver cirrhosis using contrast-enhanced ultrasound (CEUS).Methods:ICC and hepatic inflammatory lesions cases with CEUS and pathological diagnosis between Sep 2013 and Oct 2016 were investigated retrospectively.Imaging features of conventional ultrasound and CEUS were analyzed.The parameters of time intensity curve (TIC),including the arrival time,peak intensity (PI) in the lesions,the starting time for washout,and the intensity difference at 3 min (△I3) after contrast agent infection between the lesion and the liver parenchyma,were compared between ICC and hepatic inflammatory lesions.Results:Twenty-five ICC and fifteen inflammatory patients were included in this study.Seventeen ICC (68.0%) and two inflammatory cases (13.3%) showed bile duct dilatation on conventional ultrasound.Using CEUS,three ICC cases (12.0%) were misdiagnosed as inflammatory lesions and three inflammatory lesions (20.0%) as ICC;two ICC (8.0%) and one inflammatory case (6.7%) could not be made definite diagnosis.Washout started at 34.5±3.5 s and 61.5± 12.9 s for ICC and inflammatory lesions respectively (P<0.001).The intensity difference between lesion and liver parenchyma at 3 min after contrast agent injection was 10.8±3.1 dB in ICC and 4.2±2.3 dB in inflammatory group (P<0.00 1).The sensitivity and specificity differentiating ICC and inflammatory lesions were 76% and 87% if the cut-offvalue of the intensity difference was 7.7 dB.Conclusions:Combined with TIC analysis,and particularly with the characteristic of the early-starting and obvious washout in ICC,CEUS can be useful in differential diagnosis between hepatic inflammatory lesions and ICC.

  2. Inflammatory pseudotumor of the liver: ferumoxide-enhanced MR imaging as a tiebreaker.

    Science.gov (United States)

    Kato, Hiroki; Kanematsu, Masayuki; Kondo, Hiroshi; Osada, Shinji; Goshima, Satoshi; Yamada, Tetsuya; Yamada, Yasuhiro; Yokoyama, Ryujiro; Hoshi, Hiroaki; Moriyama, Noriyuki

    2004-09-01

    We examined a 70-year-old male patient with an inflammatory pseudotumor of the liver mimicking a peripheral-type cholangiocellular carcinoma. Ferumoxide-enhanced magnetic resonance (MR) imaging revealed residual Kupffer cell function in liver parenchyma in and surrounding the inflammatory pseudotumor involvement, which suggested the diagnosis of inflammatory pseudotumor of the liver. We correlate the MR imaging and pathologic findings in this report. Copyright 2004 Wiley-Liss, Inc.

  3. Association of Inflammatory Cytokines With the Symptom Cluster of Pain, Fatigue, Depression, and Sleep Disturbance in Chinese Patients With Cancer.

    Science.gov (United States)

    Ji, Yan-Bo; Bo, Chun-Lu; Xue, Xiu-Juan; Weng, En-Ming; Gao, Guang-Chao; Dai, Bei-Bei; Ding, Kai-Wen; Xu, Cui-Ping

    2017-12-01

    Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear. This study aimed to identify subgroups of cluster symptoms, compare demographic and clinical characteristics between subgroups, and examine the associations between inflammatory cytokines and cluster symptoms. Participants were 170 Chinese inpatients with cancer from two tertiary hospitals. Inflammatory markers including interleukin-6 (IL-6), interleukin-1 receptor antagonist, and tumor necrosis factor alpha were measured. Intergroup differences and associations of inflammatory cytokines with the cluster symptoms were examined with one-way analyses of variance and logistic regression. Based on cluster analysis, participants were categorized into Subgroup 1 (all low symptoms), Subgroup 2 (low pain and moderate fatigue), or Subgroup 3 (moderate-to-high on all symptoms). The three subgroups differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, sex, residence, current treatment, education, economic status, and inflammatory cytokines levels (all P cluster symptoms in cancer patients. Clinicians should identify patients at risk for more severe symptoms and formulate novel target interventions to improve symptom management. Copyright © 2017. Published by Elsevier Inc.

  4. Inflammatory pain in experimental burns in man

    DEFF Research Database (Denmark)

    Pedersen, J L

    2000-01-01

    stimuli may be more reproducible. A methodological study also demonstrated that habituation to experimental pain developed as the study proceeded. Habituation is common in experimental pain models, and dividing analgesics and placebo evenly between the study days is one way of eliminating the effects......Human experimental pain models are important tools in pain research. The primary aims of pain research in normal man is 1) to provide insight in pain mechanisms, 2) to provide a rational basis for clinical trials of pain relieving interventions, and 3) to confirm the anti-nociceptive effects...... demonstrated in animal models. Most often clinical pain is due to tissue damage leading to acute inflammation and hyperalgesia, but only few human pain models have examined pain responses in injured tissues. Therefore, models with controlled and reversible tissue trauma are needed. The human burn model...

  5. [Peroral and transdermal application of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of regional musculoskeletal pain syndromes].

    Science.gov (United States)

    Hodinka, László; Bálint, Géza; Budai, Erika; Géher, Pál; Papp, Renáta; Somogyi, Péter; Szántó, Sándor; Vereckei, Edit

    2017-12-01

    In this review the available evidences regarding the most frequently applied medication (peroral and transdermal non-steroidal anti-inflammatory agents) for the most frequent musculoskeletal complaints (regional pain syndromes) have been collected for the appropriate medical professionals who are most frequently faced with these conditions (general practitioners, rheumatologists, orthopedics, occupational and sports medicine experts). The special population at risk (with repeated and high energy overuse because of occupational or sport activities) and the pathology of their syndromes are identified. Mode of action, pharmacological properties of the non-steroidal anti-inflammatory drugs and the unwanted effects of their application especially in infants and elderly are highlighted. Recommendations of the general and specific pain management guidelines have been selected and listed in the review. Orv Hetil. 2017; 158(Suppl. 3): 3-30.

  6. Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain.

    Science.gov (United States)

    Cardoso-Cruz, Helder; Sousa, Mafalda; Vieira, Joana B; Lima, Deolinda; Galhardo, Vasco

    2013-11-01

    The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural circuits that are important for spatial cognition and memory, but it is not known whether the functional connectivity between these areas is affected by the onset of an animal model of inflammatory pain. To address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC and MD of adult rats and recorded local field potential activity during a food-reinforced spatial working memory task. Recordings were performed for 3weeks, before and after the establishment of the pain model. Our results show that inflammatory pain caused an impairment of spatial working memory performance that is associated with changes in the activity of the mPFC-MD circuit; an analysis of partial directed coherence between the areas revealed a global decrease in the connectivity of the circuit. This decrease was observed over a wide frequency range in both the frontothalamic and thalamofrontal directions of the circuit, but was more evident from MD to mPFC. In addition, spectral analysis revealed significant oscillations of power across frequency bands, namely with a strong theta component that oscillated after the onset of the painful condition. Finally, our data revealed that chronic pain induces an increase in theta/gamma phase coherence and a higher level of mPFC-MD coherence, which is partially conserved across frequency bands. The present results demonstrate that functional disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain-related working memory. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  7. The association of fatigue, pain, depression and anxiety with work and activity impairment in immune mediated inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Murray W Enns

    Full Text Available Impairment in work function is a frequent outcome in patients with chronic conditions such as immune-mediated inflammatory diseases (IMID, depression and anxiety disorders. The personal and economic costs of work impairment in these disorders are immense. Symptoms of pain, fatigue, depression and anxiety are potentially remediable forms of distress that may contribute to work impairment in chronic health conditions such as IMID. The present study evaluated the association between pain [Medical Outcomes Study Pain Effects Scale], fatigue [Daily Fatigue Impact Scale], depression and anxiety [Hospital Anxiety and Depression Scale] and work impairment [Work Productivity and Activity Impairment Scale] in four patient populations: multiple sclerosis (n = 255, inflammatory bowel disease (n = 248, rheumatoid arthritis (n = 154 and a depression and anxiety group (n = 307, using quantile regression, controlling for the effects of sociodemographic factors, physical disability, and cognitive deficits. Each of pain, depression symptoms, anxiety symptoms, and fatigue individually showed significant associations with work absenteeism, presenteeism, and general activity impairment (quantile regression standardized estimates ranging from 0.3 to 1.0. When the distress variables were entered concurrently into the regression models, fatigue was a significant predictor of work and activity impairment in all models (quantile regression standardized estimates ranging from 0.2 to 0.5. These findings have important clinical implications for understanding the determinants of work impairment and for improving work-related outcomes in chronic disease.

  8. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS)

    NARCIS (Netherlands)

    Sieper, J.; Van der Heijde, D.M.; Landewe, RB; Brandt, J.; Burgos-Vagas, R.; Collantes-Estevez, E.; Dijkmans, B.A.C.; Dougados, M.; Khan, M.M.; Leirisalo-Repo, M; van der Linden, S.C.; Maksymowych, W.P.; Mielants, H.; Olivieri, I.; Rudwaleit, M.

    2009-01-01

    Objective: Inflammatory back pain (IBP) is an important clinical symptom in patients with axial spondyloarthritis (SpA), and relevant for classification and diagnosis. In the present report, a new approach for the development of IBP classification criteria is discussed. Methods: Rheumatologists (n =

  9. Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats

    Directory of Open Access Journals (Sweden)

    Cao Bing

    2012-06-01

    Full Text Available Abstract Background Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD model with the conditioned place avoidance (CPA paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes. In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK, which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. Results In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593. The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change

  10. Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats.

    Science.gov (United States)

    Cao, Bing; Zhang, Xu; Yan, Ni; Chen, Shengliang; Li, Ying

    2012-06-09

    Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes.In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK), which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change the nociceptive response (visceral pain

  11. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS)

    NARCIS (Netherlands)

    Sieper, J.; van der Heijde, D.; Landewé, R.; Brandt, J.; Burgos-Vagas, R.; Collantes-Estevez, E.; Dijkmans, B.; Dougados, M.; Khan, M. A.; Leirisalo-Repo, M.; van der Linden, S.; Maksymowych, W. P.; Mielants, H.; Olivieri, I.; Rudwaleit, M.

    2009-01-01

    Inflammatory back pain (IBP) is an important clinical symptom in patients with axial spondyloarthritis (SpA), and relevant for classification and diagnosis. In the present report, a new approach for the development of IBP classification criteria is discussed. Rheumatologists (n = 13) who are experts

  12. Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-ibuprofen in experimental animals

    Directory of Open Access Journals (Sweden)

    Chidambarann Suthakaran

    2017-01-01

    Full Text Available Background: Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. Objectives: The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. Animals and Methods: The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Statistical Analysis: Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Results and Conclusion: Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.

  13. Bilobalide, a unique constituent of Ginkgo biloba, inhibits inflammatory pain in rats.

    Science.gov (United States)

    Goldie, Michelle; Dolan, Sharron

    2013-08-01

    Standardized Ginkgo biloba extract EGb 761 has been shown to inhibit inflammatory hyperalgesia in rats; however, the mechanism of action is not known. This study set out to investigate the anti-inflammatory and analgesic potential of bilobalide, a unique G. biloba constituent, in three well-characterized models of acute inflammatory pain. The effect of oral, intraplantar or intrathecal administration of bilobalide or drug-vehicle (0.25% agar; 10% ethanol in H2O) on responses to noxious thermal and mechanical stimulation of the hindpaw, and paw oedema were assessed in adult male Wistar rats before and after intradermal hindpaw injection of carrageenan (3%; 50 μl) or capsaicin (10 μg; 50 μl) or after hindpaw incision (n=6-8/group). Oral administration of bilobalide (10-30 mg/kg) significantly inhibited thermal hyperalgesia in response to carrageenan, capsaicin and paw incision, independent of dose, with an efficacy similar to that of diclofenac. In the carrageenan model, mechanical hypersensitivity and paw oedema were also significantly reduced after treatment with bilobalide (10-30 mg/kg). Intrathecal administration of bilobalide (0.5-1 μg) inhibited carrageenan-induced thermal hyperalgesia, but had no effect on mechanical hypersensitivity or paw oedema (application≥2 μg induced adverse effects, precluding testing of higher doses). Intraplantar administration of bilobalide (30-100 μg) had no effect. These data show that bilobalide is a potent anti-inflammatory and antihyperalgesic agent, the therapeutic effects of which are mediated in part through a central site of action, and may account for the therapeutic action of the whole extract G. biloba.

  14. Medial tibial pain: a dynamic contrast-enhanced MRI study.

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    Mattila, K T; Komu, M E; Dahlström, S; Koskinen, S K; Heikkilä, J

    1999-09-01

    The purpose of this study was to compare the sensitivity of different magnetic resonance imaging (MRI) sequences to depict periosteal edema in patients with medial tibial pain. Additionally, we evaluated the ability of dynamic contrast-enhanced imaging (DCES) to depict possible temporal alterations in muscular perfusion within compartments of the leg. Fifteen patients with medial tibial pain were examined with MRI. T1-, T2-weighted, proton density axial images and dynamic and static phase post-contrast images were compared in ability to depict periosteal edema. STIR was used in seven cases to depict bone marrow edema. Images were analyzed to detect signs of compartment edema. Region-of-interest measurements in compartments were performed during DCES and compared with controls. In detecting periosteal edema, post-contrast T1-weighted images were better than spin echo T2-weighted and proton density images or STIR images, but STIR depicted the bone marrow edema best. DCES best demonstrated the gradually enhancing periostitis. Four subjects with severe periosteal edema had visually detectable pathologic enhancement during DCES in the deep posterior compartment of the leg. Percentage enhancement in the deep posterior compartment of the leg was greater in patients than in controls. The fast enhancement phase in the deep posterior compartment began slightly slower in patients than in controls, but it continued longer. We believe that periosteal edema in bone stress reaction can cause impairment of venous flow in the deep posterior compartment. MRI can depict both these conditions. In patients with medial tibial pain, MR imaging protocol should include axial STIR images (to depict bone pathology) with T1-weighted axial pre and post-contrast images, and dynamic contrast enhanced imaging to show periosteal edema and abnormal contrast enhancement within a compartment.

  15. Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain

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    Ferrari F

    2011-04-01

    Full Text Available Flora Ferrari1, Simonetta Fiorentino1, Laura Mennuni1, Paolo Garofalo1, Ornella Letari1, Stefano Mandelli2, Antonio Giordani3, Marco Lanza1, Gianfranco Caselli11Department of Pharmacology and Toxicology; 2Department of Medicinal Chemistry; 3R&D Chemistry Drug Development and OS, Rottapharm S.p.A., Monza (MB, ItalyAbstract: Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R. However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1ylquinazoline; [CR4056] that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE tissue levels both in the rat cerebral cortex (63.1% ± 4.2%; P<0.05 and lumbar spinal cord (51.3% ± 6.7%; P < 0.05. In the complete Freund's adjuvant (CFA rat model of inflammatory pain, CR4056 was found to be orally active (ED50 = 5.8 mg/kg, by mouth [p.o.]. In the acute capsaicin model, CR4056 completely blocked mechanical hyperalgesia in the injured hind paw (ED50 = 4.1 mg/kg, p.o.; ED100 = 17.9 mg/kg, p.o.. This effect was dose-dependently antagonized by the non-selective imidazoline I2/α2 antagonist idazoxan. In rat models of neuropathic pain, oral administration of CR4056 significantly attenuated mechanical hyperalgesia and allodynia. In summary, the present study suggests a novel

  16. 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.

  17. Peculiarities of Abdominal Pain Syndrome in Patients with Functional and Inflammatory Bowel Diseases and Methods of Its Correction

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    A.E. Dorofeiev

    2014-11-01

    Full Text Available Objective of this study was to evaluate peculiarities of abdominal pain syndrome in patients with irritable bowel syndrome (IBS and inflammatory bowel disease (IBD and to assess efficacy of Enterospasmil in complex therapy of these patients. 120 patients with IBS and 35 patients with IBD were examined. Age of patients varied from 18 to 65 years. Abdominal pain syndrome was detected in all patients with IBS and IBD. In examined patients we have detected predominantly variable, without irradiation, often of blunt, aching nature, lasting more than 3 hours, with moderate intensity. Enterospasmil is an effective drug for abdominal pain relief in patients with IBS and IBD and can be used in complex therapy of these patients.

  18. Effect of nonsteroidal anti-inflammatory drugs on colorectal distension-induced visceral pain

    Science.gov (United States)

    Baskın, Veysel; Bilge, S. Sırrı; Bozkurt, Ayhan; Akyüz, Bahar; Ağrı, Arzu Erdal; Güzel, Hasan; İlkaya, Fatih

    2016-01-01

    Objectives: To investigate nonsteroidal anti-inflammatory drugs effectiveness in colorectal distension (CRD)-induced visceral pain model. Materials and Methods: Male Sprague–Dawley (250–300 g) rats were anesthetized with ketamine (50 mg/kg, intraperitoneally [i.p.]) and chlorpromazine (25 mg/kg, i.p.). Two bipolar Teflon-coated Ni/Cr wire electrodes (80-M diameter) were placed in the abdominal external oblique muscle for the recording of electromyography. Jugular vein catheter was placed for the administration of drugs. CRD method was applied to evaluate of visceral pain. All drugs (paracetamol, meloxicam, metamizole, and dexketoprofen) administered intravenously. Results: Paracetamol 200, 400, and 600 mg/kg did not change the visceromotor response (VMR) when compare with the control group. Meloxicam 2 and 4 mg/kg showed no effect but at doses of 6 mg/kg meloxicam significantly ([51.9 ± 6.4%] [P Dexketoprofen 2 and 4 mg/kg did not cause a change in VMR but 6 mg/kg dose significantly reduced response compared with the control group ([43.9 ± 3.9%, 36.8 ± 2.8%, 34.8 ± 2.5%, 42.1 ± 4.8%, 40.7 ± 3.5%, 36.4 ± 2.7%, and 26.1 ± 2.2%]; from 10 min to 70 min, respectively, [P dexketoprofen and meloxicam show antinociceptive effect with different duration of action on CRD-induced visceral pain model. This condition can be explained due to different chemical structures and different mechanisms which play a role in modulation of pain. PMID:27114637

  19. Mechanisms of Acupuncture-Electroacupuncture on Persistent Pain

    Science.gov (United States)

    Zhang, Ruixin; Lao, Lixing; Ren, Ke; Berman, Brian M.

    2014-01-01

    In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue-injury (inflammatory), nerve-injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2–10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce pro-inflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal n-methyl-d-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management that can forestall the side effects of often-debilitating pharmaceuticals. PMID:24322588

  20. Knowledge of Housewives Regarding Non Steroid Anti Inflammatory Drug Use on Joint Pain in Hegarmanah Village Jatinangor

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    Adi Mulyono Gondopurwanto

    2016-03-01

    Full Text Available Background: Joint pain is frequently found in daily life activities. The prevalence of joint pain increases within the age. One of the medicine used for joint pain is non-steroidal anti-inflammatory drug (NSAID. In connection with inappropriate usage and their side effects, this study aimed to seek the extent ofhousewives’ knowledge on the use of NSAID for joint pain in Hegarmanah village, Jatinangor subdistrict. Methods: This cross-sectional descriptive study was conducted in October 2013 to the housewives resided in Hegarmanah village, Jatinangor subdistrict, West Java. Questionaire sheet was distributed to each of 110 housewives that had been stratifiedly with randomized sample. The questionaire contained identity, age, education level, and knowledge of NSAID in related to joint pain. Results: Based on the data collected, 73 subjects had adequate level of the knowledge and 37 subjects were in a poor level of the knowledge. The proportion of respondents who knew that joint pain was the pain occurs in the joint was 99.1%, the proportion of respondents who knew that the pain relieving drugs are called NSAID group was 40.9%, the proportion of respondents who knew that NSAID had a side-effect was 73.6%, and the proportion of respondents who knew that the side-effect of NSAID is abdominal pain was 61.8%. Conclusions: Most of the housewives in Hegarmanah Subdistrict have adequate knowledge in the use ofNSAID for joint pain relief.

  1. Silencing of FKBP51 alleviates the mechanical pain threshold, inhibits DRG inflammatory factors and pain mediators through the NF-kappaB signaling pathway.

    Science.gov (United States)

    Yu, Hong-Mei; Wang, Qi; Sun, Wen-Bo

    2017-09-05

    Neuropathic pain is chronic pain caused by lesions or diseases of the somatosensory system, currently available analgesics provide only temporal relief. The precise role of FK506 binding protein 51 (FKBP51) in neuropathic pain induced by chronic constriction injury (CCI) is not clear. The purpose of the present study was to investigate the effects and possible mechanisms of FKBP51 in neuropathic pain in the rat model of CCI. Our results showed that FKBP51 was obviously upregulated in a time-dependent manner in the dorsal root ganglion (DRG) of CCI rats. Additionally, silencing of FKBP51 remarkably attenuated mechanical allodynia and thermal hyperalgesia as reflected by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in CCI rats. Moreover, knockdown of FKBP51 reduced the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in the DRG of CCI rats. Furthermore, we revealed that inhibition of FKBP51 greatly suppressed the activation of the NF-kappaB (NF-κB) signaling in the DRG of CCI rats. Interestingly, similar to the FKBP51 siRNA (si-FKBP51), ammonium pyrrolidinedithiocarbamate (PDTC, an inhibitor of NF-κB) also alleviated neuropathic pain and neuro-inflammation, indicating that knockdown of FKBP51 alleviated neuropathic pain development of CCI rats by inhibiting the activation of NF-κB signaling pathway. Taken together, our findings indicate that FKBP51 may serve as a novel therapeutic target for neuropathic pain. Copyright © 2017. Published by Elsevier B.V.

  2. Effect of hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery on the synthesis of pain mediators, inflammatory mediator and oxygen free radicals

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    Liang-Ying Luo

    2017-08-01

    Full Text Available Objective: To explore the effect of hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery on the synthesis of pain mediators, inflammatory mediator and oxygen free radicals. Methods: A total of 120 patients with fracture who underwent operation in the hospital between July 2014 and December 2016 were collected and divided into control group and observation group according to the random number table method, 60 cases in each group. Control group received morphine hydrochloride combined with ropivacaine for analgesia, observation group received hydromorphone hydrochloride combined with ropivacaine for analgesia, and the postoperative analgesia lasted for 48 h. The differences in serum levels of pain mediators, inflammatory mediators and oxidative stress indexes were compared between the two groups. Results: Immediately after operation, the differences in serum levels of pain mediators, inflammatory mediators and oxidative stress indexes were not statistically significant between the two groups. 48 h after operation, serum PGE2, SP, β-EP, IL-6, MCP-1, HMGB-1 and MDA levels of both groups of patients were significantly lower than those immediately after operation while Cu-Zn SOD and GSH-Px levels were significantly higher than those immediately after operation, and serum PGE2, SP, β-EP, IL-6, MCP-1, HMGB-1 and MDA levels of observation group were significantly lower than those of control group while Cu-Zn SOD and GSH-Px levels were significantly higher than those of control group. Conclusion: Hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery is effective in alleviating pain and inhibiting systemic inflammatory response.

  3. Intervertebral Foramen Injection of Ozone Relieves Mechanical Allodynia and Enhances Analgesic Effect of Gabapentin in Animal Model of Neuropathic Pain.

    Science.gov (United States)

    Luo, Wen-Jun; Yang, Fan; Yang, Fei; Sun, Wei; Zheng, Wei; Wang, Xiao-Liang; Wu, Fang-Fang; Wang, Jiang-Lin; Wang, Jia-Shuang; Guan, Su-Min; Chen, Jun

    2017-07-01

    In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. Experimental trial in rats. Institute for Biomedical Sciences of Pain. By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (bee venom, complete Freud's adjuvant.

  4. Purinergic mechanosensory transduction and visceral pain

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    Burnstock Geoffrey

    2009-11-01

    Full Text Available Abstract In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown.

  5. Acute pelvic inflammatory disease: pictorial essay focused on computed tomography and magnetic resonance imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Febronio, Eduardo Miguel; Rosas, George de Queiroz; D' Ippolito, Giuseppe, E-mail: giuseppe_dr@uol.com.br [Department of Imaging Diagnosis, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPMUnifesp), Sao Paulo, SP (Brazil)

    2012-11-15

    The present study was aimed at describing key computed tomography and magnetic resonance imaging findings in patients with acute abdominal pain derived from pelvic inflammatory disease. Two radiologists consensually selected and analyzed computed tomography and magnetic resonance imaging studies performed between January 2010 and December 2011 in patients with proven pelvic inflammatory disease leading to presentation of acute abdomen. Main findings included presence of intracavitary fluid collections, anomalous enhancement of the pelvic excavation and densification of adnexal fat planes. Pelvic inflammatory disease is one of the leading causes of abdominal pain in women of childbearing age and it has been increasingly been diagnosed by means of computed tomography and magnetic resonance imaging supplementing the role of ultrasonography. It is crucial that radiologists become familiar with the main sectional imaging findings in the diagnosis of this common cause of acute abdomen (author)

  6. Pharmacological potential of Maytenus species and isolated constituents, especially tingenone, for treatment of painful inflammatory diseases

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    Clarice C. Veloso

    Full Text Available ABSTRACT Uses of medicinal plants by people around the world significantly contribute and guide biologically active compounds research that can be useful in the combat against various diseases. Due to a great chemical and structural variety found in their vegetal structures it consolidates ethnopharmacology as an important science for the pharmaceutical section. Inserted in the diversity of medicinal plants, is the Maytenus genus, whose research has already revealed lots of isolated substances which are responsible for a great variety of biological activities, among which we cite analgesic and anti-inflammatory, for the treatment of inflammatory diseases such as rheumatoid arthritis, gastritis, ulcers and gastrointestinal disorders. The aim of this review article is to make a compendium of the Maytenus genus and its isolated chemical compounds, among them tingenone. The elucidation of its mechanism of action reveals promising sources for the development of new drugs specially targeted for the treatment of painful inflammatory diseases.

  7. Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.

    Science.gov (United States)

    Eccleston, Christopher; Cooper, Tess E; Fisher, Emma; Anderson, Brian; Wilkinson, Nick Mr

    2017-08-02

    Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain. To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. We searched the Cochrane

  8. Pain management in patients with hidradenitis suppurativa

    NARCIS (Netherlands)

    Horvath, Barbara; Janse, Ineke C.; Sibbald, Gary R.

    Hidradenitis suppurativa (HS) is a chronic, relapsing, and painful inflammatory disease. HS patients' quality of life is severely impaired, and this impairment correlates strongly with their pain. Pain in HS can be acute or chronic and has both inflammatory and noninflammatory origins. The purpose

  9. α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.

    Science.gov (United States)

    Thakkinstian, Ammarin; Attia, John; Anothaisintawee, Thunyarat; Nickel, J Curtis

    2012-10-01

    Study Type - Therapy (systematic review) Level of Evidence 1a. What's known on the subject? and What does the study add? Individual clinical trials evaluating antibiotics, anti-inflammatories and α-blockers for the treatment of chronic prostatitis/chronic pelvic pain syndrome have shown only modest or even no benefits for patients compared with placebo, yet we continue to use these agents in selected patients with some success in clinical practice. This network meta-analysis of current evidence from all available randomized placebo-controlled trials with similar inclusion criteria and outcome measures shows that these '3-As' of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics, anti-inflammatories and α-blockers) do offer benefits to some patients, particularly if we use them strategically in selected individuals. To provide an updated network meta-analysis mapping α-blockers, antibiotics and anti-inflammatories (the 3-As) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). • To use the results of this meta-analysis to comment on the role of the 3-As in clinical practice. We updated a previous review including only randomized controlled studies employing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as one of the outcomes to compare treatment effects in CP/CPPS patients. • A longitudinal mixed regression model (network meta-analysis) was applied to indirectly assess multiple treatment comparisons (i.e. α-blockers, antibiotics, anti-inflammatory/immune modulation therapies, α-blockers plus antibiotics, and placebo). Nineteen studies (1669 subjects) were eligible for analysis. • α-blockers, antibiotics and anti-inflammatory/immune modulation therapies were associated with significant improvement in symptoms when compared with placebo, with mean differences of total CPSI of -10.8 (95% CI -13.2 to -8.3; P antibiotics resulted in the greatest CPSI difference (-13.6, 95% CI -16.7 to -10.6; P

  10. Effects of low energy shock wave therapy on inflammatory moleculars, bladder pain, and bladder function in a rat cystitis model.

    Science.gov (United States)

    Wang, Hung-Jen; Lee, Wei-Chia; Tyagi, Pradeep; Huang, Chao-Cheng; Chuang, Yao-Chi

    2017-08-01

    Low energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. We examined the effects of LESW on the expression of inflammatory molecules, pain behavior, and bladder function in a rat cystitis model. Control and experimental animals were injected with saline or cyclophosphamide (CYP; 75 mg/kg intraperitoneally) on day 1 and 4. After lower midline incision, the bladders were exposed to LESW (300 pulses, 0.12 mJ/mm 2 ) or sham operation on day 2. In study 1 (N = 12, 4 for each group), the nociceptive effects of CYP were evaluated for 30 min by behavioral assessment on day 4 one hour after CYP injection. In study 2 (N = 21, 7 for each group), continuous cystometry (CMG) was performed on day 8. The bladder was harvested after behavioral assessment or CMG for histology and Western blotting. CYP-induced upregulation of COX2 and IL6 expression, caused pain behavior (eye closing and hypolocomotion), and bladder inflammation was noted on days 4 and 8 along with bladder hyperactivity. LESW treatment reduced pain behavior and downregulated the NGF expression (33.3%, P < 0.05) on day 4 and IL6 (40.9%, P < 0.05). LESW treatment suppressed bladder overactivity (intercontraction interval 77.8% increase, P < 0.05) by decreasing inflammation and COX2 (38.6%, P < 0.05) expression and NGF expression (25.2%, P = 0.0812). CYP-induced bladder pain, inflammation, and overactivity involves activation of IL6, NGF, and COX2 expression. These changes are suppressed by LESW, indicating it as a potential candidate for relieving bladder inflammatory conditions and overactivity. © 2016 Wiley Periodicals, Inc.

  11. Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System.

    Science.gov (United States)

    Lochhead, Jeffrey J; Ronaldson, Patrick T; Davis, Thomas P

    2017-07-01

    A functional blood-brain barrier (BBB) is necessary to maintain central nervous system (CNS) homeostasis. Many diseases affecting the CNS, however, alter the functional integrity of the BBB. It has been shown that various diseases and physiological stressors can impact the BBB's ability to selectively restrict passage of substances from the blood to the brain. Modifications of the BBB's permeability properties can potentially contribute to the pathophysiology of CNS diseases and result in altered brain delivery of therapeutic agents. Hypoxia and/or inflammation are central components of a number of diseases affecting the CNS. A number of studies indicate hypoxia or inflammatory pain increase BBB paracellular permeability, induce changes in the expression and/or localization of tight junction proteins, and affect CNS drug uptake. In this review, we look at what is currently known with regard to BBB disruption following a hypoxic or inflammatory insult in vivo. Potential mechanisms involved in altering tight junction components at the BBB are also discussed. A more detailed understanding of the mediators involved in changing BBB functional integrity in response to hypoxia or inflammatory pain could potentially lead to new treatments for CNS diseases with hypoxic or inflammatory components. Additionally, greater insight into the mechanisms involved in TJ rearrangement at the BBB may lead to novel strategies to pharmacologically increase delivery of drugs to the CNS.

  12. Equal pain – Unequal fear response: Enhanced susceptibility of tooth pain to fear conditioning

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    Michael Lukas Meier

    2014-07-01

    Full Text Available Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS applied to the right maxillary canine (UCS-c versus the right tibia (UCS-t. For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+. Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were 1 skin conductance changes and 2 time-dependent brain activity (BOLD responses in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex and medial prefrontal cortex.A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point towards a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.

  13. Effects of neonatal pain, stress and their interrelation on pain sensitivity in later life in male rats.

    Science.gov (United States)

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

    2016-08-31

    Neonatal pain and stress induce long-term changes in pain sensitivity. Therefore their interrelation is a topical subject of clinical and basic research. The present study investigated the effects of inflammatory peripheral pain and stress of maternal deprivation (MD)-isolation in 1-2- and 7-8-day-old Wistar rats (P1,2 and P7,8 respectively, ages comparable to preterm and full-term human babies) on basal pain and pain sensitivity in conditions of inflammatory pain (formalin test) during adolescence. The neonatal impacts were: pain (formalin injection, FOR in the paw), stress (a short 60-min MD), or pain+stress combination (FOR+MD), and appropriate controls. We found that stress of short-term maternal deprivation-isolation and inflammatory pain on P1,2 and P7,8 significantly increased the vulnerability of the nociceptive system to inflammatory pain. Maternal deprivation-isolation on P1,2 as compared with a similar impact on P7,8 had a greater effect on pain sensitivity of the adolescent rats, but the influence of early pain was independent of the injury age. Only adolescent rats with an early combination of pain and maternal deprivation-isolation showed hypoalgesia in the hot plate (HP) test. However licking duration (reflecting pain sensitivity) in these rats did not exceed licking duration in animals exposed only to maternal deprivation-isolation or pain. This study adds new data to the growing body of work demonstrating that early noxious impacts have long-term consequences for the functional activity of the nociceptive system. Our new findings may help to understand the impact of pain and maternal separation in the neonatal intensive care unit.

  14. Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain.

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    Dong, Yingchun; Li, Pengfei; Ni, Yanhong; Zhao, Junjie; Liu, Zhiqiang

    2014-01-01

    Orofacial inflammatory pain is a difficult clinical problem, and the specific molecular mechanisms for this pain remain largely unexplained. The present study aimed to determine the differential expression of microRNAs (miRNAs) and disclose the underlying role of miR-125a-3p in orofacial inflammatory pain induced by complete Freund's adjuvant (CFA). Thirty-two differentially expressed miRNAs were first screened using a microarray chip in ipsilateral trigeminal ganglions (TGs) following CFA injection into the orofacial skin innervated by trigeminal nerve, and a portion of them, including miR-23a*, -24-2*, -26a, -92a, -125a-3p, -183 and -299 were subsequently selected and validated by qPCR. The target genes were predicted based on the miRWalk website and were further analyzed by gene ontology (GO). Further studies revealed miR-125a-3p expression was down-regulated, whereas both the expression of p38 MAPK (mitogen-activated protein kinase) alpha and CGRP (calcitonin gene-related peptide) were up-regulated in ipsilateral TGs at different time points after CFA injection compared with control. Furthermore, mechanistic study revealed that miR-125a-3p negatively regulates p38 alpha gene expression and is positively correlated with the head withdrawal threshold reflecting pain. Luciferase assay showed that binding of miR-125a-3p to the 3'UTR of p38 alpha gene suppressed the transcriptional activity, and overexpression of miR-125a-3p significantly inhibited the p38 alpha mRNA level in ND8/34 cells. Taken together, our results show that miR-125a-3p is negatively correlated with the development and maintenance of orofacial inflammatory pain via regulating p38 MAPK.

  15. Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain.

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    Yingchun Dong

    Full Text Available Orofacial inflammatory pain is a difficult clinical problem, and the specific molecular mechanisms for this pain remain largely unexplained. The present study aimed to determine the differential expression of microRNAs (miRNAs and disclose the underlying role of miR-125a-3p in orofacial inflammatory pain induced by complete Freund's adjuvant (CFA. Thirty-two differentially expressed miRNAs were first screened using a microarray chip in ipsilateral trigeminal ganglions (TGs following CFA injection into the orofacial skin innervated by trigeminal nerve, and a portion of them, including miR-23a*, -24-2*, -26a, -92a, -125a-3p, -183 and -299 were subsequently selected and validated by qPCR. The target genes were predicted based on the miRWalk website and were further analyzed by gene ontology (GO. Further studies revealed miR-125a-3p expression was down-regulated, whereas both the expression of p38 MAPK (mitogen-activated protein kinase alpha and CGRP (calcitonin gene-related peptide were up-regulated in ipsilateral TGs at different time points after CFA injection compared with control. Furthermore, mechanistic study revealed that miR-125a-3p negatively regulates p38 alpha gene expression and is positively correlated with the head withdrawal threshold reflecting pain. Luciferase assay showed that binding of miR-125a-3p to the 3'UTR of p38 alpha gene suppressed the transcriptional activity, and overexpression of miR-125a-3p significantly inhibited the p38 alpha mRNA level in ND8/34 cells. Taken together, our results show that miR-125a-3p is negatively correlated with the development and maintenance of orofacial inflammatory pain via regulating p38 MAPK.

  16. Anti-inflammatory actions of acupuncture

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    Freek J. Zijlstra

    2003-01-01

    Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.

  17. Chronic inflammatory pain: new molecules & mechanisms

    NARCIS (Netherlands)

    Willemen, H.L.D.M.

    2013-01-01

    Pain is an important self-protecting signal. The pain system detects and reacts to (withdrawal reflex) the presence of an acute potentially injurious stimulus such as heat, pressure, tissue damage or inflammation to avoid possible (further) tissue damage. However, after inflammation or tissue damage

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

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    Chao Wang

    2015-01-01

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

  19. Tamsulosin Monotherapy versus Combination Therapy with Antibiotics or Anti-Inflammatory Agents in the Treatment of Chronic Pelvic Pain Syndrome

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    Tae Hyo Kim

    2011-06-01

    Full Text Available Purpose Chronic pelvic pain syndrome (CPPS is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS. Methods Patients (n=107 who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A, tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B or tamsulosin at 0.2 mg plus antibiotics (group C daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI and the International Prostate Symptom Score (IPSS to evaluate 100 patients who were treated for 12 weeks (7 withdrew. Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL. Results All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05. There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01. Conclusions Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.

  20. Effect of Eucalyptus Oil Inhalation on Pain and Inflammatory Responses after Total Knee Replacement: A Randomized Clinical Trial

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    Yang Suk Jun

    2013-01-01

    Full Text Available Eucalyptus oil has been reported effective in reducing pain, swelling, and inflammation. This study aimed to investigate the effects of eucalyptus oil inhalation on pain and inflammatory responses after total knee replacement (TKR surgery. Participants were randomized 1 : 1 to intervention group (eucalyptus inhalation group or control group (almond oil inhalation group. Patients inhaled eucalyptus or almond oil for 30 min of continuous passive motion (CPM on 3 consecutive days. Pain on a visual analog scale (VAS, blood pressure, heart rate, C-reactive protein (CRP concentration, and white blood cell (WBC count were measured before and after inhalation. Pain VAS on all three days (P<.001 and systolic (P<.05 and diastolic (P=.03 blood pressure on the second day were significantly lower in the group inhaling eucalyptus than that inhaling almond oil. Heart rate, CRP, and WBC, however, did not differ significantly in the two groups. In conclusion, inhalation of eucalyptus oil was effective in decreasing patient's pain and blood pressure following TKR, suggesting that eucalyptus oil inhalation may be a nursing intervention for the relief of pain after TKR.

  1. Differential diagnosis of solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomograph

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    Chu, Zhi-gang; Sheng, Bo; Liu, Meng-qi; Lv, Fa-jin; Li, Qi; Ouyang, Yu, E-mail: cyscitg@163.com [Hospital of Chongqing Medical University, Department of Radiology, Chongqing (China)

    2016-10-15

    Objectives: To clarify differences between solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomography. Methods: In total, 64 and 132 patients with solitary pulmonary inflammatory masses/nodules and peripheral lung cancers, respectively, were enrolled in this study. Their computed tomographic findings were summarized and compared retrospectively. Results: Compared with the peripheral lung cancers, the inflammatory lesions were located closer to the pleura (p<0.0001). The majority of the inflammatory lesions were patchy and oval-shaped (82.8%), whereas most of the tumors were lobulated (82.6%). Almost all the inflammatory cases were unclear (93.8%), whereas most of the tumors had speculated margins (72.7%). Computed tomography values were significantly higher for the inflammatory lesions than for the cancers (p<0.0001). More than half of the inflammatory lesions had defined necrosis (59.3%). Furthermore, 49.2% of the cancers enhanced inhomogeneously, but only 24.6% had ill-defined necrosis or cavities. The peripheral zones of 98.4% of the inflammatory lesions and 72.7% of the tumors were unclear, with peripheral scattered patches (92.2%) and beam-shaped opacity (66.7%) being the most common findings, respectively. Adjacent pleural thickening was more frequent for the inflammatory lesions than the cancers (95.3% vs. 21.1%, p<0.0001), whereas pleural indentation was found in 67.4% of the subjects with cancer. In addition, hilar (p=0.034) and mediastinal (p=0.003) lymphadenopathy were more commonly detected in the cancers than in the inflammatory cases. Conclusions: Contrast-enhanced computed tomography findings for pulmonary inflammatory lesions and peripheral lung cancers were significantly different in many aspects. Developing a comprehensive understanding of these differences is helpful for directing their management. (author)

  2. Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models.

    Science.gov (United States)

    Teodoro, Fernanda C; Tronco Júnior, Marcos F; Zampronio, Aleksander R; Martini, Alessandra C; Rae, Giles A; Chichorro, Juliana G

    2013-06-01

    There is accumulating evidence that substance P released from peripheral sensory neurons participates in inflammatory and neuropathic pain. In this study it was investigated the ability of substance P to induce orofacial nociception and thermal and mechanical hyperalgesia, as well as the role of NK1 receptors on models of orofacial inflammatory and neuropathic pain. Substance P injected into the upper lip at 1, 10 and 100 μg/50 μL failed to induce nociceptive behavior. Also, substance P (0.1-10 μg/50 μL) injected into the upper lip did not evoke orofacial cold hyperalgesia and when injected at 1 μg/50 μL did not induce mechanical hyperalgesia. However, substance P at this latter dose induced orofacial heat hyperalgesia, which was reduced by the pre-treatment of rats with a non-peptide NK1 receptor antagonist (SR140333B, 3mg/kg). Systemic treatment with SR140333B (3 mg/kg) also reduced carrageenan-induced heat hyperalgesia, but did not exert any influence on carrageenan-induced cold hyperalgesia. Blockade of NK1 receptors with SR140333B also reduced by about 50% both phases of the formalin response evaluated in the orofacial region. Moreover, heat, but not cold or mechanical, hyperalgesia induced by constriction of the infraorbital nerve, a model of trigeminal neuropathic pain, was abolished by pretreatment with SR140333B. Considering that substance P was peripherally injected (i.e. upper lip) and the NK1 antagonist used lacks the ability to cross the blood-brain-barrier, our results demonstrate that the peripheral SP/NK1 system participates in the heat hyperalgesia associated with inflammation or nerve injury and in the persistent pain evoked by formalin in the orofacial region. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Anti-Inflammatory and Immune Regulatory Actions of Naja naja atra Venom

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    Shu-Zhi Wang

    2018-02-01

    Full Text Available Naja naja atra venom (NNAV is composed of various proteins, peptides, and enzymes with different biological and pharmacological functions. A number of previous studies have reported that NNAV exerts potent analgesic effects on various animal models of pain. The clinical studies using whole venom or active components have confirmed that NNAV is an effective and safe medicine for treatment of chronic pain. Furthermore, recent studies have demonstrated that NNAV has anti-inflammatory and immune regulatory actions in vitro and in vivo. In this review article, we summarize recent studies of NNAV and its components on inflammation and immunity. The main new findings in NNAV research show that it may enhance innate and humoral immune responses while suppressing T lymphocytes-mediated cellular immunity, thus suggesting that NNAV and its active components may have therapeutic values in the treatment of inflammatory and autoimmune diseases.

  4. The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms.

    Science.gov (United States)

    Alsalem, Mohammad; Wong, Amy; Millns, Paul; Arya, Pallavi Huma; Chan, Michael Siang Liang; Bennett, Andrew; Barrett, David A; Chapman, Victoria; Kendall, David A

    2013-04-01

    The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9- and 13- hydroxyoctadecadienoic acid (HODE)] to TRPV1-mediated noxious responses and inflammatory pain responses. 9- and 13-HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan-inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9-HODE- and 13-HODE-evoked responses, and the contribution of 15-lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9- and 13-HODE and 15-lipoxygenase to inflammatory pain behaviour. 9-HODE (35 ± 7 pmol g(-1)) and 13-HODE (32 ± 6 pmol g(-1)) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9- and 13-HODE were detected in DRGs and TRPV1 antagonist-sensitive calcium responses evoked, which were blocked by the 15-lipoxygenase inhibitor PD146176 and an anti-13-HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan-inflamed hindpaw (P PD146176 significantly (P < 0.01) attenuated carrageenan-induced hyperalgesia. This study demonstrates that, although 9- and 13-HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  5. Systemic Inflammatory and Th17 Immune Activation among Patients Treated for Lumbar Radiculopathy Exceeds that of Patients Treated for Persistent Postoperative Neuropathic Pain.

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    Shamji, Mohammed F; Guha, Daipayan; Paul, Darcia; Shcharinsky, Alina

    2017-09-01

    The pathophysiology of lumbar radiculopathy includes both mechanical compression and biochemical irritation of apposed neural elements. Inflammatory and immune cytokines have been implicated, induced by systemic exposure of immune-privileged intervertebral disc tissue. Surgical intervention provides improved symptoms and quality of life, but persistent postoperative neuropathic pain (PPNP) afflicts a significant fraction of patients. To compare the inflammatory and immune phenotypes among patients undergoing structural surgery for lumbar radiculopathy and spinal cord stimulation for neuropathic pain. Consecutive patients undergoing surgical intervention for lumbar radiculopathy or neuropathic pain were studied. Demographic data included age, gender, and VAS and neuropathic pain scores. Serum was evaluated for cytokine levels (IL-6, Il-17, TNF-α) and cellular content [white blood cell (WBC)/differential, lymphocyte subtypes]. The primary analysis differentiated molecular and cellular profiles between radiculopathy and neuropathic pain patients. Subgroup analysis within the surgical radiculopathy population compared those patients achieving relief of symptoms and those with PPNP. Heightened IL-6, Il-17, and TNF-α levels were observed for the lumbar radiculopathy group compared with the neuropathic pain group. This was complemented by higher WBC count and a greater fraction of Th17 lymphocytes among radiculopathy patients. In the lumbar discectomy subgroup, pain relief was seen among patients with preoperatively elevated IL-17 levels. Those patients with PPNP refractory to surgical discectomy exhibited normal cytokine levels. Differences in Th17 immune activation are seen among radiculopathy and neuropathic pain patients. These cellular and molecular profiles may be translated into biomarkers to improve patient selection for structural spine surgery. Copyright © 2017 by the Congress of Neurological Surgeons

  6. Using e-learning to enhance nursing students' pain management education.

    Science.gov (United States)

    Keefe, Gemma; Wharrad, Heather J

    2012-11-01

    Absence of standardised pain curricula has led to wide diversity in the understanding and awareness of pain by healthcare students. Indeed pain management is frequently under-prioritised in nursing education, providing potential to negatively impact upon patient care. Yet the recent addition of Pain to the UK National Health Service's Essence of Care Benchmarks has highlighted the need to address this issue, and in response pain educators have called for the development of high quality, globally accessible e-learning resources in pain management. This study will determine the effectiveness of an e-learning intervention on pain management developed for nursing students. Two variants of an e-learning resource on pain management were developed, each containing the same core content but one with a section focusing on pain assessment and the other on pharmacological management. Nursing students (n=42) were randomly assigned to trial one resource, after which they undertook a questionnaire adapted (to ensure alignment with the content of the e-learning resources) from Ferrell and McCaffrey's Nurses Knowledge and Attitudes Towards Pain Survey. Scores were analysed for each resource and year of study, and compared with scores from a standard non-intervention group completing the questionnaire only (n=164). Scores averaged 19.2% higher for students undertaking the e-learning resources (pe-learning has substantial benefit to enhance pain education in nursing. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode-the good, the bad, and the ugly.

    Science.gov (United States)

    Klyne, David M; Barbe, Mary F; van den Hoorn, Wolbert; Hodges, Paul W

    2018-04-01

    Prospective longitudinal study. To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery. Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related. Individuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months. CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory/poor sleep") or less ("high TNF/depression") recovery. This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific

  8. Association of chest pain and risk of cardiovascular disease with coronary atherosclerosis in patients with inflammatory joint diseases

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    Silvia eRollefstad

    2015-11-01

    Full Text Available Objectives: The relation between chest pain and coronary atherosclerosis (CA in patients with inflammatory joint diseases (IJD has not been explored previously. Our aim was to evaluate the associations of the presence of chest pain and the predicted 10-year risk of cardiovascular disease (CVD by use of several CVD risk algorithms, with multi-detector computer tomography (MDCT coronary angiography verified CA. Methods: Detailed information concerning chest pain and CVD risk factors was obtained in 335 patients with rheumatoid arthritis (RA and ankylosing spondylitis (AS. In addition, 119 of these patients underwent MDCT coronary angiography.Results: Thirty-one percent of the patients (104/335 reported chest pain. Only 6 patients (1.8% had atypical angina pectoris (pricking pain at rest. In 69 patients without chest pain, two thirds had CA, while in those who reported chest pain (n=50, CA was present in 48.0%. In a logistic regression analysis, chest pain was not associated with CA (dependent variable (p=0.43. About 30% (Nagelkerke R2 of CA was explained by any of the CVD risk calculators: SCORE, Framingham Risk Score or Reynolds Risk Score.Conclusion: The presence of chest pain was surprisingly infrequently reported in patients with IJD who were referred for a CVD risk evaluation. However, when present, chest pain was weakly associated with CA, in contrast to the predicted CVD risk by several risk calculators which was highly associated with the presence of CA. These findings suggest that clinicians treating patients with IJD should be alert of coronary atherosclerotic disease also in absence of chest pain symptoms.

  9. Enhanced MR imaging of tenosynovitis of hand and wrist in inflammatory arthritis

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    Tehranzadeh, J.; Ashilyan, O.; Anavim, A.; Tramma, S. [Univ. of California, Orange (United States). Dept. of Radiological Sciences

    2006-11-15

    The purpose of this study is to describe the appearance of tenosynovitis in various tendon groups in the wrist and hand and to compare MR enhanced and non-enhanced imaging evaluation of tenosynovitis of hand and wrist in inflammatory arthritis. We reviewed 72 MRI studies of hands and wrists, including coronal, axial and sagittal images in 30 consecutive patients with inflammatory arthritis and tenosynovitis. We compared the degree of synovitis on T2-weighted vs contrast-enhanced T1-weighted images, using a predetermined scale. We also measured the extent of tenosynovitis in three dimensions. The tendons were assigned to volar, dorsal, ulnar and radial groups in the wrist and to extensor, flexor and thumb groups in the hand. Degree of tenosynovitis (graded 0-3), cross-sectional area and volume of the inflamed synovium in various tendon groups were then compared by statistical analysis. Review of the medical records revealed the following diagnoses in our patient population: rheumatoid arthritis (n=16), unspecified inflammatory polyarthritis (n=9), psoriatic arthritis (n=2), CREST syndrome (n=1), systemic lupus erythematosus (n=1), paraneoplastic syndrome with arthritis (n=1). The average T2 brightness scores and post-gadolinium enhancement scores were 1.0 and 1.7 respectively (P<0.001) in the wrist studies. The average T2 brightness scores and post-gadolinium enhancement scores were 0.7 and 1.4, respectively (P<0.001) in the hand studies. The average sensitivity of T2-weighted imaging for detection of tenosynovitis was 40% in the hand and 67% in the wrist tendons, when contrast-enhanced images were used as a reference. Carpal tunnel flexor tendons were the most frequently affected tendons of the wrist. The most frequently affected tendons of the hand were second and third flexor tendons. The hand flexors demonstrated higher degrees of enhancement and larger volumes of the inflamed tenosynovium than did the hand extensors and tendons of the thumb.

  10. Enhanced MR imaging of tenosynovitis of hand and wrist in inflammatory arthritis

    International Nuclear Information System (INIS)

    Tehranzadeh, J.; Ashilyan, O.; Anavim, A.; Tramma, S.

    2006-01-01

    The purpose of this study is to describe the appearance of tenosynovitis in various tendon groups in the wrist and hand and to compare MR enhanced and non-enhanced imaging evaluation of tenosynovitis of hand and wrist in inflammatory arthritis. We reviewed 72 MRI studies of hands and wrists, including coronal, axial and sagittal images in 30 consecutive patients with inflammatory arthritis and tenosynovitis. We compared the degree of synovitis on T2-weighted vs contrast-enhanced T1-weighted images, using a predetermined scale. We also measured the extent of tenosynovitis in three dimensions. The tendons were assigned to volar, dorsal, ulnar and radial groups in the wrist and to extensor, flexor and thumb groups in the hand. Degree of tenosynovitis (graded 0-3), cross-sectional area and volume of the inflamed synovium in various tendon groups were then compared by statistical analysis. Review of the medical records revealed the following diagnoses in our patient population: rheumatoid arthritis (n=16), unspecified inflammatory polyarthritis (n=9), psoriatic arthritis (n=2), CREST syndrome (n=1), systemic lupus erythematosus (n=1), paraneoplastic syndrome with arthritis (n=1). The average T2 brightness scores and post-gadolinium enhancement scores were 1.0 and 1.7 respectively (P<0.001) in the wrist studies. The average T2 brightness scores and post-gadolinium enhancement scores were 0.7 and 1.4, respectively (P<0.001) in the hand studies. The average sensitivity of T2-weighted imaging for detection of tenosynovitis was 40% in the hand and 67% in the wrist tendons, when contrast-enhanced images were used as a reference. Carpal tunnel flexor tendons were the most frequently affected tendons of the wrist. The most frequently affected tendons of the hand were second and third flexor tendons. The hand flexors demonstrated higher degrees of enhancement and larger volumes of the inflamed tenosynovium than did the hand extensors and tendons of the thumb

  11. Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

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    Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P

    1981-12-01

    PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

  12. Pain and microcrystalline arthritis

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    R. Ramonda

    2014-06-01

    Full Text Available Microcrystals are responsible for some of the most common and complex arthropathies which are often accompanied by intense, severe pain and inflammatory reactions. The main pathogens are crystals of monosodium urate (MSU, responsible for the gout, calcium pyrophosphate (CPP, which deposits also in various clinical forms of arthopathies, and basic calcium phosphate associated with osteoarthritis. In this context, the microcrystal arthritis is characterized by multiple, acute attacks followed by chronic pain, disability, impaired quality of life, and increased mortality. Given their chronic nature, they represent an ever more urgent public health problem. MSU and CPP crystals are also able to activate nociceptors. The pain in mycrocrystalline arthritis (MCA is an expression of the inflammatory process. In the course of these diseases there is an abundant release of inflammatory molecules, including prostaglandins 2 and kinins. Interleukin-1 represents the most important cytokine released during the crystal-induced inflammatory process. Therefore, clinically, pain is the most important component of MCA, which lead to functional impairment and disability in a large proportion of the population. It is fundamental to diagnose these diseases as early as possible, and to this aim, to identify appropriate and specific targets for a timely therapeutic intervention.

  13. Plasma IL-8 signature correlates with pain and depressive symptomatology in patients with burning mouth syndrome: Results from a pilot study.

    Science.gov (United States)

    Barry, Alison; O'Halloran, Ken D; McKenna, Joseph P; McCreary, Christine; Downer, Eric J

    2018-02-01

    Burning mouth syndrome (BMS) is a neuropathic orofacial pain condition of unknown aetiology that encompasses intra-oral burning pain without abnormal clinical findings. Psychological, neural and inflammatory processes are associated with BMS pathogenesis. Currently, studies characterising plasma cytokine/chemokine profiles with pain and depression in patients with BMS are lacking. Considering that inflammation is associated with the pathophysiology of BMS, and that inflammation is closely associated with pain and depression, we aimed to correlate depressive symptomatology and oral cavity pain with plasma cytokine/chemokine signatures in a cohort of patients with BMS. In this study, plasma protein levels of Th1 cytokines (IFN-γ, IL-2, IL-12p70, TNF-α), Th2 cytokines (IL-4, IL-10, IL-6, IL-13) and the chemokine IL-8 were assessed in patients with BMS (n = 10) and healthy volunteers (n = 10), using pro-inflammatory-10-plex assays. Clinical histories, alongside self-rated oral cavity pain intensities and depressive symptomatology were assessed using a visual analogue scale and the 16-item Quick Inventory of Depressive Symptomatology questionnaires, respectively. We present evidence that BMS is associated with increased depressive symptomatology and enhanced oral cavity pain. Plasma isolated from BMS patients display enhanced expression of the pro-inflammatory chemokine IL-8, when compared to plasma from healthy individuals. Plasma IL-8 signature correlates with pain and depressive symptomatology in the study cohort. Overall, these findings indicate that plasma IL-8 profiles are dysregulated in BMS and that modulation of IL-8 production in the disorder may be a tool in the management of BMS symptomatology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. 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.

  15. Analgesic and anti-inflammatory effects of Cyphostemma vogelii (Hook

    African Journals Online (AJOL)

    Rita

    2013-04-24

    Apr 24, 2013 ... Key words: Analgesic, anti-inflammatory, mice, Cyphostemma vogelii, nociception. ... steroidal anti- inflammatory drugs (NSAIDs) are considered the drugs of ..... 44-55. Hughes H, Lang M (1983). Control of pain in dogs and cats In: Kitchell. R, Erickson H (eds.) Animal pain. Baltimore Waverly press. pp. 207-.

  16. 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.

  17. Prediction of pain sensitivity in healthy volunteers

    DEFF Research Database (Denmark)

    Ravn, Pernille; Frederiksen, R; Skovsen, AP

    2012-01-01

    The primary objective of the present study was to evaluate predictive parameters of the acute pain score during induction of an inflammatory heat injury.......The primary objective of the present study was to evaluate predictive parameters of the acute pain score during induction of an inflammatory heat injury....

  18. Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

    Science.gov (United States)

    Mert, Tufan; Kurt, Akif Hakan; Altun, İdiris; Celik, Ahmet; Baran, Furkan; Gunay, Ismail

    2017-05-01

    Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Diagnostic Accuracy of Quantitative Sensory Testing to Discriminate Inflammatory Toothache and Intraoral Neuropathic Pain.

    Science.gov (United States)

    Porporatti, André Luís; Costa, Yuri Martins; Stuginski-Barbosa, Juliana; Bonjardim, Leonardo Rigoldi; Duarte, Marco Antônio Hungaro; Conti, Paulo César Rodrigues

    2015-10-01

    A differential diagnosis between inflammatory toothache (IT) and intraoral neuropathic pain is challenging. The aim of this diagnostic study was to quantify somatosensory function of subjects with IT (acute pulpitis) and atypical odontalgia (AO, intraoral neuropathic pain) and healthy volunteers and to quantify how accurately quantitative sensory testing (QST) discriminates an IT or AO diagnosis. The sample consisted of 60 subjects equally divided (n = 20) into 3 groups: (1) IT, (2) AO, and (3) control. A sequence of 4 QST methods was performed over the dentoalveolar mucosa in the apical maxillar or mandibular area: mechanical detection threshold, pain detection threshold (PDT), dynamic mechanical allodynia, and temporal summation. One-way analysis of variance, Tukey post hoc analyses, and z score transformation were applied to the data. In addition, the receiver operating characteristic curve analysis, diagnostic accuracy, sensitivity, specificity, likelihood ratios, and diagnostic odds ratio of the QST methods were calculated (α = 5%). Somatosensory abnormalities were found for the AO group, which is consistent with a low detection threshold to touch and pain and the presence of mechanical allodynia. For the IT group, no somatosensory abnormality was observed when compared with the control group. The most accurate QST to discriminate the diagnostic differences between IT and healthy individuals is the PDT. The diagnostic differences between AO and healthy individuals and between IT and AO are best discriminated with the mechanical detection threshold, PDT, and dynamic mechanical allodynia. The proposed QST methods may aid in the differential diagnosis between IT and AO with strong accuracy and may be used as complementary diagnostic tests. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  20. Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

    Science.gov (United States)

    Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey; Han, Dingfen; Haywood, Carlton; Lanzkron, Sophie; Swedberg, Lauren; Edwards, Robert R; Page, Gayle G; Haythornthwaite, Jennifer A

    2016-04-01

    Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

  1. 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.

  2. Chronic widespread pain in spondyloarthritis

    Directory of Open Access Journals (Sweden)

    F. Atzeni

    2014-06-01

    Full Text Available The pain associated with spondyloarthritis (SpA can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP that characterises fibromyalgia (FM. The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs.

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

    Science.gov (United States)

    Lev, Rina; Granovsky, Yelena; Yarnitsky, David

    2013-01-01

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

  4. Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain

    Directory of Open Access Journals (Sweden)

    Yul Huh

    2017-08-01

    Full Text Available Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain, and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL-1β, IL-6, CCL2, and CXCL1]. Recent studies suggest that bone marrow stem cells or bone marrow stromal cells (BMSCs produce powerful analgesic effects in animal models of inflammatory pain, neuropathic pain, and cancer pain. We recently demonstrated that intrathecal injection of BMSCs resulted in a long-term relief of neuropathic pain for several weeks after peripheral nerve injury. Strikingly, this analgesic effect is mediated by the anti-inflammatory cytokine transforming growth factor beta secreted from BMSCs. Additionally, BMSCs exhibit potent modulation of neuroinflammation, by inhibiting monocyte infiltration, glial activation, and cytokine/chemokine production in the DRG and spinal cord. Thus, BMSCs control chronic pain by regulation of neuroinflammation in the PNS and CNS via paracrine signaling. In this review, we discuss the similar results from different laboratories of remarkable anti-nociceptive efficacy of BMSCs in animal and clinical studies. We also discuss the mechanisms by which BMSCs control neuroinflammation and chronic pain and how these cells specifically migrate to damaged tissues.

  5. Detection of systemic inflammation in severely impaired chronic pain patients, and effects of a CBT-ACT-based multi-modal pain rehabilitation program.

    Science.gov (United States)

    Hysing, E-B; Smith, L; Thulin, M; Karlsten, R; Gordh, T

    2017-12-29

    Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear signs of increased inflammatory activity were detected in the pain patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43 of the 92 inflammatory biomarkers. The expression of 8 biomarkers were 4 times higher in patients compared to controls. Three biomarkers, CXCL5, SIRT2, AXIN1 were more than 8 times higher. The conventional marker for inflammation, CRP, did not differ. Of the 28 patients available for follow up one year after the intervention, all showed lower levels of the inflammatory biomarker initially raised. Conclusions The results indicate that CPP suffer from a low grade of chronic systemic inflammation, not detectable by CRP analysis. This may have implications for the general pain hypersensitivity, and other symptoms, often described in this group of patients. We conclude that inflammatory plasma proteins may be measureable molecular markers to distinguishes CPP from pain free controls, and that a CBT-ACT pain rehab program seem to

  6. Fatigue, Pain, Anxiety and Depression in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

    Science.gov (United States)

    Merkies, Ingemar S J; Kieseier, Bernd C

    2016-01-01

    In the clinical evaluation of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), scant attention is paid to symptoms such as fatigue, pain and anxiety/depression. We aimed at addressing seminal studies that focused on the burden of these symptoms and their impact on quality of life (QoL) in these conditions. Fatigue, pain, and anxiety/depression are increasingly being recognized in patients with GBS and CIDP, although their pathophysiological provenance remains unknown. Fatigue and pain are significant in terms of prevalence and intensity, may be a presenting symptom, and can persist for years after apparent functional recovery, suggesting residual injury. Anxiety/depression has also been examined although studies are limited. Despite their negative impact on QoL, the long-term dynamics of these symptoms in patients with GBS and particularly CIDP receiving therapy in routine clinical practice have not been systematically evaluated. Such observations formed the basis for the ongoing (GAMEDIS) studies evaluating the effect of Gamunex on fatigue and depression in patients with CIDP, of which some preliminary data are presented. Strength and sensory deficits are the main areas of focus in patients with GBS and CIDP, but they do not explain the total reduction in QoL, suggesting the possible role of other complaints. A more comprehensive approach to patient care demands that factors such as pain, fatigue and anxiety/depression receive greater attention. The non-interventional GAMEDIS studies are expected to provide valuable insight into the long-term effectiveness of Gamunex in everyday practice. © 2016 S. Karger AG, Basel.

  7. Melittin, the Major Pain-Producing Substance of Bee Venom.

    Science.gov (United States)

    Chen, Jun; Guan, Su-Min; Sun, Wei; Fu, Han

    2016-06-01

    Melittin is a basic 26-amino-acid polypeptide that constitutes 40-60% of dry honeybee (Apis mellifera) venom. Although much is known about its strong surface activity on lipid membranes, less is known about its pain-producing effects in the nervous system. In this review, we provide lines of accumulating evidence to support the hypothesis that melittin is the major pain-producing substance of bee venom. At the psychophysical and behavioral levels, subcutaneous injection of melittin causes tonic pain sensation and pain-related behaviors in both humans and animals. At the cellular level, melittin activates primary nociceptor cells through direct and indirect effects. On one hand, melittin can selectively open thermal nociceptor transient receptor potential vanilloid receptor channels via phospholipase A2-lipoxygenase/cyclooxygenase metabolites, leading to depolarization of primary nociceptor cells. On the other hand, algogens and inflammatory/pro-inflammatory mediators released from the tissue matrix by melittin's pore-forming effects can activate primary nociceptor cells through both ligand-gated receptor channels and the G-protein-coupled receptor-mediated opening of transient receptor potential canonical channels. Moreover, subcutaneous melittin up-regulates Nav1.8 and Nav1.9 subunits, resulting in the enhancement of tetrodotoxin-resistant Na(+) currents and the generation of long-term action potential firing. These nociceptive responses in the periphery finally activate and sensitize the spinal dorsal horn pain-signaling neurons, resulting in spontaneous nociceptive paw flinches and pain hypersensitivity to thermal and mechanical stimuli. Taken together, it is concluded that melittin is the major pain-producing substance of bee venom, by which peripheral persistent pain and hyperalgesia (or allodynia), primary nociceptive neuronal sensitization, and CNS synaptic plasticity (or metaplasticity) can be readily induced and the molecular and cellular mechanisms

  8. Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

    Science.gov (United States)

    Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

    2014-06-01

    Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation

  9. Contemporary views on inflammatory pain mechanisms: TRPing over innate and microglial pathways [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Zhonghui Guan

    2016-09-01

    Full Text Available Tissue injury, whether by trauma, surgical intervention, metabolic dysfunction, ischemia, or infection, evokes a complex cellular response (inflammation that is associated with painful hyperalgesic states. Although in the acute stages it is necessary for protective reflexes and wound healing, inflammation may persist well beyond the need for tissue repair or survival. Prolonged inflammation may well represent the greatest challenge mammalian organisms face, as it can lead to chronic painful conditions, organ dysfunction, morbidity, and death. The complexity of the inflammatory response reflects not only the inciting event (infection, trauma, surgery, cancer, or autoimmune but also the involvement of heterogeneous cell types including neuronal (primary afferents, sensory ganglion, and spinal cord, non-neuronal (endothelial, keratinocytes, epithelial, and fibroblasts, and immune cells. In this commentary, we will examine 1. the expression and regulation of two members of the transient receptor potential family in primary afferent nociceptors and their activation/regulation by products of inflammation, 2. the role of innate immune pathways that drive inflammation, and 3. the central nervous system’s response to injury with a focus on the activation of spinal microglia driving painful hyperalgesic states.

  10. Activated microglia in the spinal cord underlies diabetic neuropathic pain.

    Science.gov (United States)

    Wang, Dongmei; Couture, Réjean; Hong, Yanguo

    2014-04-05

    Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  12. Learned helplessness predicts functional disability, pain and fatigue in patients with recent-onset inflammatory polyarthritis.

    Science.gov (United States)

    Camacho, Elizabeth M; Verstappen, Suzanne M M; Chipping, Jacqueline; Symmons, Deborah P M

    2013-07-01

    Cross-sectional studies have found that learned helplessness (LH) is associated with disease outcome in patients with RA. However, little is known about the longitudinal impact of LH. The aim of this study was to investigate whether LH is associated with future disease outcome (disability, pain and fatigue) and to investigate whether LH changes over time in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. Patients included in this investigation had been recruited to the Norfolk Arthritis Register, a primary-care-based inception cohort. LH was measured at baseline as patients' total score on the Rheumatology Attitudes Index (RAI). A total of 443 patients completed the HAQ and visual analogue scales of pain and fatigue at baseline and after 2 years of follow-up. Greater feelings of LH at baseline were associated with higher HAQ scores at follow-up [difference in HAQ score per 1-point increase in RAI score (β-coefficient) 0.02; 95% CI 0.01, 0.04]. Greater baseline LH was also associated with more pain (β-coefficient 1.0; 95% CI 0.4, 1.5) and more fatigue (β-coefficient 1.0; 95% CI 0.2, 1.4) at follow-up. LH was highly changeable during follow-up, with 87% of patients showing any change and 50% improving. Baseline LH independently predicted disability, pain and fatigue at follow-up. Half of patients reported fewer feelings of helplessness after 2 years of follow-up, suggesting that LH may potentially be a modifiable risk factor for disease outcome in IP and a target for intervention.

  13. 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.

  14. Can the painDETECT Questionnaire score and MRI help predict treatment outcome in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Rifbjerg-Madsen, Signe; Christensen, Anton Wulf; Boesen, Mikael

    2014-01-01

    contrast-enhanced MRI (DCE-MRI) is performed. METHOD AND ANALYSIS: The painDETECT Questionnaire (PDQ), originally developed to screen for a neuropathic pain component, is applied to indicate the presence of central sensitisation. Adults diagnosed with RA are included when either (A) initiating disease......-inflammatory treatment, to explore the prognostic value of a screening questionnaire for central sensitisation, hand inflammation assessed by conventional MRI, and the interaction between them regarding treatment outcome evaluated by clinical status (DAS28-CRP). For the purpose of further exploratory analyses, dynamic...

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

    Directory of Open Access Journals (Sweden)

    Ravn P

    2013-01-01

    Full Text Available Pernille Ravn,1 Erik L Secher,2 Ulrik Skram,3 Trine Therkildsen,1 Lona L Christrup,1 Mads U Werner41Department of Drug Design and Pharmacology, University of Copenhagen, 2Department of Anesthesiology, Juliane Marie Center, Rigshospitalet, Copenhagen University Hospitals, 3Department of Intensive Care, Gentofte Hospital, Copenhagen University Hospitals, 4Multidisciplinary Pain Center, Neuroscience Center, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, DenmarkPurpose: Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than µ-opioid receptor agonists. The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending pain modulation.Subjects and methods: Twenty-eight healthy subjects were included. The study was a double-blind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg, buprenorphine (0.3/0.6 mg, or placebo (normal saline were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm2, and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist.Results: For nearly all tested variables, significant dose-dependent analgesic effects were demonstrated. The median antihyperalgesia/analgesia ratio (secondary hyperalgesia

  16. Pain following double-bundle anterior cruciate ligament reconstruction: Correlation with morphological graft findings and dynamic contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Lin, Y.-C.; Mhuircheartaigh, J.N.; Cheung, Y.-C.; Juan, Y.-H.; Chiu, C.-H.; Yeh, W.-L.; Wu, J.S.

    2014-01-01

    Aim: To determine the relationship between knee pain following anterior cruciate ligament (ACL) graft placement with morphological graft findings and dynamic contrast enhancement as assessed at MRI. Material and methods: Following institutional review board approval, 37 consecutive patients with double-bundle ACL reconstruction were enrolled. Thirteen patients had pain and 24 were asymptomatic. Imaging was performed using a 1.5 T MRI machine an average of 7.6 months after surgery. Graft-related (increase signal intensity, abnormal orientation, discontinuity, cystic degeneration, anterior translation of lateral tibia, arthrofibrosis), and non-graft related causes of knee pain (meniscal tear, cartilage injury, loose bodies, and synovitis) were evaluated. During dynamic contrast enhancement analysis, peak enhancement (ePeak) was calculated by placing a region of interest at the osteoligamentous interface of each bundle. Student's t-test was used for continuous variables analysis and chi-square or Fisher's exact test was used for categorical variables analysis. Results: There was no difference between symptomatic and asymptomatic patients regarding morphological graft-related or non-graft-related causes of knee pain. For dynamic contrast enhancement analysis, symptomatic patients had significantly lower ePeak values than asymptomatic patients in the anteromedial (p = 0.008) and posterolateral (p = 0.001) bundles or when using the higher ePeak value in either bundle (p = 0.003). Conclusion: Morphological ACL graft findings as assessed at MRI could not be used to distinguish between symptomatic and asymptomatic patients. However, lower ePeak values had a significant association with knee pain. This may indicate poor neovascularization of the graft, potentially leading to graft failure. - Highlights: • Morphologic graft findings of MRI are poorly associated with knee pain. • Lower contrast enhancement values are significantly associated with knee pain

  17. Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study

    Directory of Open Access Journals (Sweden)

    Jian Kong

    Full Text Available Objectives: Expectation can significantly modulate pain and treatment effects. This study aims to investigate if boosting patients' expectancy can enhance the treatment of knee osteoarthritis (KOA, and its underlying brain mechanism. Methods: Seventy-four KOA patients were recruited and randomized to three groups: boosted acupuncture (with a manipulation to enhance expectation, standard acupuncture, or treatment as usual (TAU. Each patient underwent six treatments before being debriefed, and four additional treatments after being debriefed. The fMRI scans were applied during the first and sixth treatment sessions. Results: We found significantly decreased knee pain in the boosted acupuncture group compared to the standard acupuncture or TAU groups after both six and ten treatments. Resting state functional connectivity (rsFC analyses using the nucleus accumbens (NAc as the seed showed rsFC increases between the NAc and the medial prefrontal cortex (MPFC/rostral anterior cingulate cortex (rACC and dorsolateral prefrontal cortex in the boosted group as compared to the standard acupuncture group after multiple treatments. Expectancy scores after the first treatment were significantly associated with increased NAc-rACC/MPFC rsFC and decreased knee pain following treatment. Conclusions: Our study provides a novel method and mechanism for boosting the treatment of pain in patients with KOA. Our findings may shed light on enhancing outcomes of pharmacological and integrative medicines in clinical settings. Keywords: Knee osteoarthritis, Expectancy, Acupuncture, Reward, Resting state functional connectivity

  18. Inflammatory aortic arch syndrome: contrast-enhanced, three-dimensional MR - angiography in stenotic lesions

    International Nuclear Information System (INIS)

    Both, M.; Mueller-Huelsbeck, S.; Biederer, J.; Heller, M.; Reuter, M.

    2004-01-01

    Purpose: To determine the value of contrast-enhanced, three-dimensional MR angiography for the evaluation of stenotic and occlusive vascular lesions in inflammatory aortic arch syndrome. Materials and Methods: 14 patients with inflammatory aortic arch syndrome (giant cell arteritis: n = 8, Takayasu arteritis: n = 4, ankylosing spondylitis: n = 1 sarcoidosis: n = 1) underwent MR angiography of the aortic arch and the supra-aortic vessels (n = 15,2 patients were examined twice) and of the abdominal aorta (n = 2). MRA was performed using a 3D-FLASH sequence (TR/TE 4.6/1.8 ms, flip angle 30 ) on a 1.5T system. MRA imaging was compared with the findings of DSA, which served as gold standard. Results: In a total of 467 examined vascular territories, DSA revealed 50 stenoses and 35 occlusions. All lesions were detected by MRA. In 23 segments, the degree of stenosis was overestimated by MRA. Sensitivity and specificity of MRA were 100% and 94,3%, positive and negative predictive values were 73.6 and 100%, and the accuracy was 95,1%. Conclusions: Despite a tendency to overestimate stenoses, contrast-enhanced three-dimensional MR angiography is a valid, non-invasive technique in the assessment of inflammatory aortic arch syndrome. (orig.) [de

  19. Temporomandibular joint (TMJ) pain revisited with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)

    International Nuclear Information System (INIS)

    Tasali, N.; Cubuk, R.; Aricak, M.; Ozarar, M.; Saydam, B.; Nur, H.; Tuncbilek, N.

    2012-01-01

    Purpose: We aimed to assess the contrast enhancement patterns of the retrodiscal tissue with dynamic contrast-enhanced MR imaging (DCE-MRI) with respect to different temporomandibular joint disc pathologies. Additionally, we questioned the relationship between the temporomandibular joint (TMJ) pain and the contrast enhancement pattern of the retrodiscal tissue regardless of the TMJ disc position. Materials and methods: 52 joints of 26 patients (4 males and 22 females) who have pain in at least at one of their TMJ were included in this study. For the qualitative analysis, the joints were divided into four groups in terms of their disc positions: normal (1), partially displaced with or without reduction (2), totally dislocated with reduction (3) and totally dislocated without reduction (4). Besides, two different joint groups were constituted, namely the painful group and painless group according to the clinical findings without taking the TMJ disc positions into account. Quantitative analyses were made by means of measuring signal intensity ratios (SI) ratio at the retrodiscal tissue (from internal side and external side of the each joint) using DCE-MRI and these measurements were analyzed with paired samples t test to define the difference between the measurements. At the second stage, the time-dependent arithmetical mean values of the SI ratios were calculated for each joint group and significant differences between the groups were questioned using analysis of variance (ANOVA) test. Besides, painful and painless groups which were classified on the basis of the clinical data were compared according to the mean SI ratios found for each joint and the significant differences between these two groups were assessed by means of Student's T test. The results were assessed in 95% confidence interval where the significance level was p < 0.05. Results: A significant difference was observed between the internal and external contrast enhancement of the joints with partial

  20. Attitudes of farmers and veterinarians towards pain and the use of pain relief in pigs.

    Science.gov (United States)

    Ison, S H; Rutherford, K M D

    2014-12-01

    A survey of UK-based pig farmers and veterinarians was conducted, in order to investigate attitudes to pain and the use of pain relief in pigs. Survey respondents were asked to indicate which anti-inflammatory drugs they used or prescribed for pigs, how often these were administered, and the level of pain they associated with particular conditions. The survey found that veterinarians used a range of anti-inflammatory products to treat pigs with lameness. While both farmers and veterinarians gave similar pain scores overall, farmers rated gastrointestinal disease as more painful and conversely veterinarians scored lameness higher. Female and younger respondents gave higher pain scores than males and older respondents. Overall, farmers and veterinarians had a positive attitude towards pain relief in pigs with the majority agreeing that animals recovered more promptly when pain relief was administered. Most farmers agreed that the recognition and management of pain is an important part of pig husbandry, and many expressed an interest in finding out more about identifying pain in this species as well as the treatment options available. The study highlighted potential barriers to the increased application of pain relief in pigs in that almost one-third of veterinarians and two-thirds of farmers did not agree that they discussed pain management with each other, while other respondents indicated that they found it difficult to recognise pain in pigs, and did not know how to treat it appropriately. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Enhanced pain and autonomic responses to ambiguous visual stimuli in chronic Complex Regional Pain Syndrome (CRPS) type I.

    Science.gov (United States)

    Cohen, H E; Hall, J; Harris, N; McCabe, C S; Blake, D R; Jänig, W

    2012-02-01

    Cortical reorganisation of sensory, motor and autonomic systems can lead to dysfunctional central integrative control. This may contribute to signs and symptoms of Complex Regional Pain Syndrome (CRPS), including pain. It has been hypothesised that central neuroplastic changes may cause afferent sensory feedback conflicts and produce pain. We investigated autonomic responses produced by ambiguous visual stimuli (AVS) in CRPS, and their relationship to pain. Thirty CRPS patients with upper limb involvement and 30 age and sex matched healthy controls had sympathetic autonomic function assessed using laser Doppler flowmetry of the finger pulp at baseline and while viewing a control figure or AVS. Compared to controls, there were diminished vasoconstrictor responses and a significant difference in the ratio of response between affected and unaffected limbs (symmetry ratio) to a deep breath and viewing AVS. While viewing visual stimuli, 33.5% of patients had asymmetric vasomotor responses and all healthy controls had a homologous symmetric pattern of response. Nineteen (61%) CRPS patients had enhanced pain within seconds of viewing the AVS. All the asymmetric vasomotor responses were in this group, and were not predictable from baseline autonomic function. Ten patients had accompanying dystonic reactions in their affected limb: 50% were in the asymmetric sub-group. In conclusion, there is a group of CRPS patients that demonstrate abnormal pain networks interacting with central somatomotor and autonomic integrational pathways. © 2011 European Federation of International Association for the Study of Pain Chapters.

  2. Adiponectin and adiponectin receptor 1 overexpression enhance inflammatory bowel disease.

    Science.gov (United States)

    Peng, Yu-Ju; Shen, Tang-Long; Chen, Yu-Shan; Mersmann, Harry John; Liu, Bing-Hsien; Ding, Shih-Torng

    2018-03-14

    Adiponectin (ADN) is an adipokine derived from adipocytes. It binds to adiponectin receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils. We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease. We also treated a THP-1 macrophage and a HT-29 colon epithelial cell line with ADN recombinant protein to study the effects of ADN on inflammation. After inducing murine colitis, pAdipoR1 mice developed more severe symptoms than wild-type (WT) mice. Treatment with ADN increased the expression of pro-inflammatory factors in THP-1 and HT-29 cells. Moreover, we also observed that the expression of cyclooxygenase2 (cox2), neutrophil chemokines (CXCL1, CXCL2 and CXCL5), and the infiltration of neutrophils were increased in the colon of pAdipoR1 mice. Our study showed that ADN-AdipoR1 signaling exacerbated colonic inflammation through two possible mechanisms. First, ADN-AdipoR1 signaling increased pro-inflammatory factors. Second, AdipoR1 enhanced neutrophil chemokine expression and recruited neutrophils into the colonic tissue to increase inflammation.

  3. Flank pain

    Science.gov (United States)

    ... how to do these exercises at home. Nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy may be prescribed for flank pain caused by spinal arthritis. Antibiotics are used to treat most kidney infections. You ...

  4. Synovitis assessed on static and dynamic contrast-enhanced magnetic resonance imaging and its association with pain in knee osteoarthritis

    DEFF Research Database (Denmark)

    Riis, Robert Gabriel Coumine; Gudbergsen, Henrik; Henriksen, Marius

    2016-01-01

    OBJECTIVES: To investigate the association between pain and peripatellar-synovitis on static and dynamic contrast-enhanced MRI in knee osteoarthritis. METHODS: In a cross-sectional setting, knee synovitis was assessed using 3-Tesla MRI and correlated with pain using the knee injury and osteoarthr......OBJECTIVES: To investigate the association between pain and peripatellar-synovitis on static and dynamic contrast-enhanced MRI in knee osteoarthritis. METHODS: In a cross-sectional setting, knee synovitis was assessed using 3-Tesla MRI and correlated with pain using the knee injury...

  5. Enhancing the Safe and Effective Management of Chronic Pain in Accountable Care Organization Primary Care Practices in Kentucky.

    Science.gov (United States)

    Wubu, Selam; Hall, Laura Lee; Straub, Paula; Bair, Matthew J; Marsteller, Jill A; Hsu, Yea-Jen; Schneider, Doron; Hood, Gregory A

    Chronic pain is a prevalent chronic condition with significant burden and economic impact in the United States. Chronic pain is particularly abundant in primary care, with an estimated 52% of chronic pain patients obtaining care from primary care physicians (PCPs). However, PCPs often lack adequate training and have limited time and resources to effectively manage chronic pain. Chronic pain management is complex in nature because of high co-occurrence of psychiatric disorders and other medical comorbidities in patients. This article describes a quality improvement initiative conducted by the American College of Physicians (ACP), in collaboration with the Kentucky ACP Chapter, and the Center for Health Services and Outcomes Research at the Johns Hopkins Bloomberg School of Public Health, to enhance chronic pain management in 8 primary care practices participating in Accountable Care Organizations in Kentucky, with a goal of enhancing the screening, diagnosis, and treatment of patients with chronic pain.

  6. Pain, power and patience - A narrative study of general practitioners' relations with chronic pain patients

    OpenAIRE

    Hemborg Kristiansson, Mia; Brorsson, Annika; Wachtler, Caroline; Troein, Margareta

    2011-01-01

    Abstract Background Chronic pain patients are common in general practice. In this study "chronic pain" is defined as diffuse musculoskeletal pain not due to inflammatory diseases or cancer. Effective patient-physician relations improve treatment results. The relationship between doctors and chronic pain patients is often dysfunctional. Consultation training for physicians and medical students can improve the professional ability to build effective relations, but this demands a thorough unders...

  7. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch.

    Science.gov (United States)

    Lionberger, David R; Brennan, Michael J

    2010-11-10

    The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978-2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5-1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical-chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions.

  8. Osteoarthritis: the genesis of pain.

    Science.gov (United States)

    Fu, Kai; Robbins, Sarah R; McDougall, Jason J

    2018-05-01

    OA is a painful joint disease that predominantly affects the elderly. Pain is the primary symptom of OA, and it can present as either intermittent or constant. OA pain mechanisms are complex and have only recently been determined. Both peripheral and central processes are involved in creating the OA pain experience, making targeted therapy problematic. Nociceptive, inflammatory and neuropathic pains are all known to occur in OA, but to varying degrees in a patient- and time-specific manner. A better understanding of these multifactorial components of OA pain will lead to the development of more effective and safer pain treatments.

  9. Anti-inflammatory management for tendon injuries - friends or foes?

    Directory of Open Access Journals (Sweden)

    Chan Kai-Ming

    2009-10-01

    Full Text Available Abstract Acute and chronic tendon injuries are very common among athletes and in sedentary population. Most physicians prescribe anti-inflammatory managements to relieve the worst symptoms of swelling and pain, including non-steroidal anti-inflammatory drugs, corticosteroids and physical therapies. However, experimental research shows that pro-inflammatory mediators such as prostaglandins may play important regulatory roles in tendon healing. Noticeably nearly all cases of chronic tendon injuries we treat as specialists have received non-steroidal anti-inflammatory drugs by their physician, suggesting that there might be a potential interaction in some of these cases turning a mild inflammatory tendon injury into chronic tendinopathy in predisposed individuals. We are aware of the fact that non-steroidal anti-inflammatory drugs and corticosteroids may well have a positive effect on the pain control in the clinical situation whilst negatively affect the structural healing. It follows that a comprehensive evaluation of anti-inflammatory management for tendon injuries is needed and any such data would have profound clinical and health economic importance.

  10. Ketamine analgesia for inflammatory pain in neonatal rats: a factorial randomized trial examining long-term effects

    Directory of Open Access Journals (Sweden)

    Bhutta Adnan T

    2008-08-01

    Full Text Available Abstract Background Neonatal rats exposed to repetitive inflammatory pain have altered behaviors in young adulthood, partly ameliorated by Ketamine analgesia. We examined the relationships between protein expression, neuronal survival and plasticity in the neonatal rat brain, and correlated these changes with adult cognitive behavior. Methods Using Western immunoblot techniques, homogenates of cortical tissue were analyzed from neonatal rats 18–20 hours following repeated exposure to 4% formalin injections (F, N = 9, Ketamine (K, 2.5 mg/kg × 2, N = 9, Ketamine prior to formalin (KF, N = 9, or undisturbed controls (C, N = 9. Brain tissues from another cohort of rat pups (F = 11, K = 12, KF = 10, C = 15 were used for cellular staining with Fos immunohistochemistry or FluoroJade-B (FJB, followed by cell counting in eleven cortical and three hippocampal areas. Long-term cognitive testing using a delayed non-match to sample (DNMS paradigm in the 8-arm radial maze was performed in adult rats receiving the same treatments (F = 20, K = 24, KF = 21, C = 27 in the neonatal period. Results Greater cell death occurred in F vs. C, K, KF in parietal and retrosplenial areas, vs. K, KF in piriform, temporal, and occipital areas, vs. C, K in frontal and hindlimb areas. In retrosplenial cortex, less Fos expression occurred in F vs. C, KF. Cell death correlated inversely with Fos expression in piriform, retrosplenial, and occipital areas, but only in F. Cortical expression of glial fibrillary acidic protein (GFAP was elevated in F, K and KF vs. C. No significant differences occurred in Caspase-3, Bax, and Bcl-2 expression between groups, but cellular changes in cortical areas were significantly correlated with protein expression patterns. Cluster analysis of the frequencies and durations of behaviors grouped them as exploratory, learning, preparatory, consumptive, and foraging behaviors. Neonatal inflammatory pain exposure reduced exploratory behaviors in adult

  11. Localized scleroderma and regional inflammatory myopathy.

    Science.gov (United States)

    Zivković, Saša A; Freiberg, William; Lacomis, David; Domsic, Robyn T; Medsger, Thomas A

    2014-05-01

    Inflammatory myopathy is rare in localized scleroderma. We report 2 new cases of regional inflammatory myopathy associated with localized scleroderma and review 10 reported cases of localized scleroderma associated with an inflammatory myopathy with regional muscle involvement, more often in the upper extremities. Serum creatine kinase was mildly elevated or normal. Histopathology often showed perimysial inflammation and plasma cell infiltration. These cases demonstrate that inflammatory myopathy should be considered in patients with localized scleroderma and regional muscle weakness, pain or atrophy. Muscle biopsy can confirm the diagnosis of myositis, which if identified, will require anti-inflammatory and/or immunosuppressive therapy. Published by Elsevier B.V.

  12. Pain – Part I. Pharmaco-therapeutic management (ro.

    Directory of Open Access Journals (Sweden)

    Tuns, C. I.,

    2011-12-01

    Full Text Available The complexity of pain mechanisms require different treatments that address to the different stages of pain production, transmission, modulation and control and at the same time can be individualized according to each patient. In this respect several substances with specific anti-inflammatory, analgesic, antipyretic activity,tranquilizers, etc. are successfully used in pain, they are supplemented by physical and chemical means. Treatment of pain is achieved by removing the cause that produced it. Elimination of inflammation, ischemia control, of infection or nerve compression, many times can lead to complete disappearance of pain. In thepresent referate groups of substances with implications in pain are presented. Are presented sintheticaly:amines, antihistamines group, anti-inflammatory nonsteroidic drugs (classic and modern, anesthetics and tranquilizers groups etc. Are also presented other means of pain therapy (analgesic electrotherapy: low frequency effect analgesic currents: diadynamic, Trabert, stochastic, transcutaneous electrical nerve stimulation (TENS, pain stimulation by galvanic current.

  13. [Cholinergic anti-inflammatory pathway of some non-pharmacological therapies of complementary medicine: possible implications for treatment of rheumatic and autoimmune diseases].

    Science.gov (United States)

    Gamus, Dorit

    2011-08-01

    Rheumatologic and autoimmune diseases are among foremost diseases for which patients seek complementary and integrative medicine options. Therefore, physicians should be informed on the advances in research of these therapies, in order to be able to discuss possible indications and contraindications for these treatment modalities with their patients. This review summarizes several therapeutic modalities of complementary medicine that may be involved in the cholinergic anti-inflammatory pathway. The analysis of systematic reviews of acupuncture for rheumatic conditions has concluded that the evidence is sufficiently sound to warrant positive recommendations of this therapy for osteoarthritis, low back pain and lateral elbow pain. There is relatively strong evidence to support the use of hypnosis in pain treatment, such as in cases of fibromyalgia. A recent controlled study that evaLuated tai-chi in fibromyalgia has reported reductions in pain, improvements in mood, quality of Life, self efficacy and exercise capacity. There is also cumulative evidence that acupuncture, hypnosis and tai-chi may decrease the high frequency of heart rate variability, suggesting enhancement of vagus nerve activity. Hence, it has been hypothesized that these modalities might impact the cholinergic anti-inflammatory pathway to modulate inflammation. Further clinical and basic research to confirm this hypothesis should be performed in order to validate integration of these therapies in comprehensive treatment for some inflammatory and autoimmune diseases.

  14. Resistin Enhances Inflammatory Cytokine Production in Coronary Artery Tissues by Activating the NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Fang Gao

    2016-01-01

    Full Text Available Purpose. Kawasaki disease (KD is a systemic vasculitis and is a leading cause of coronary artery lesions (CALs in childhood. Our previous study has shown higher levels of serum Resistin in KD patients with coronary aneurysm. This study aimed at examining the association of Resistin with inflammatory cytokine expression in mouse model of coronary arteritis and determining the potential mechanisms. Methods. C57BL/6 mice were injected with Lactobacillus cell wall extract (LCWE to induce coronary arteritis. The relative levels of Resistin, TNF-α, IL-1β, and MMP-9 expression and inflammatory infiltrates in the coronary arteries were determined longitudinally by quantitative RT-PCR, ELISA, and histology. The effect of TLR4 and NF-κB activation on Resistin-induced TNF-α and IL-1β expression in human coronary artery endothelium cells (HCAECs was examined by quantitative RT-PCR. Results. Higher levels of Resistin, TNF-α, IL-1β, and MMP-9 expression were associated with the degrees of inflammatory infiltrates in the coronary artery walls of the LCWE-injected mice. Resistin enhanced TNF-α and IL-1β expression in HCAECs at 18 or 24 hours after stimulation. Pretreatment with anti-TLR4 attenuated Resistin-enhanced IL-1β, but not TNF-α, expression and pretreatment with parthenolide or QNZ demolished Resistin-enhanced TNF-α expression in HACECs. Pretreatment with parthenolide, but not QNZ, blocked Resistin-enhanced IL-1β expression in HCAECs. Conclusion. Resistin may enhance inflammation by cross-talking with TLR4/NF-κB signaling during the development of coronary arteritis in mice.

  15. Investigating the Burden of Chronic Pain: An Inflammatory and Metabolic Composite

    Directory of Open Access Journals (Sweden)

    Kimberly T. Sibille

    2016-01-01

    Full Text Available Background. Chronic pain is associated with increased morbidity and mortality, predominated by cardiovascular disease and cancer. Investigating related risk factor measures may elucidate the biological burden of chronic pain. Objectives. We hypothesized that chronic pain severity would be positively associated with the risk factor composite. Methods. Data from 12,982 participants in the 6th Tromsø study were analyzed. Questionnaires included demographics, health behaviors, medical comorbidities, and chronic pain symptoms. The risk factor composite was comprised of body mass index, fibrinogen, C-reactive protein, and triglycerides. Chronic pain severity was characterized by frequency, intensity, time/duration, and total number of pain sites. Results. Individuals with chronic pain had a greater risk factor composite than individuals without chronic pain controlling for covariates and after excluding inflammation-related health conditions (p<0.001. A significant “dose-response” relationship was demonstrated with pain severity (p<0.001. In individuals with chronic pain, the risk factor composite varied by health behavior, exercise, lower levels and smoking, and higher levels. Discussion. The risk factor composite was higher in individuals with chronic pain, greater with increasing pain severity, and influenced by health behaviors. Conclusions. Identification of a biological composite sensitive to pain severity and adaptive/maladaptive behaviors would have significant clinical and research utility.

  16. Controlling pain during orthodontic fixed appliance therapy with non-steroidal anti-inflammatory drugs (NSAID): a randomized, double-blinded, placebo-controlled study.

    Science.gov (United States)

    Gupta, Mudit; Kandula, Srinivas; Laxmikanth, Sarala M; Vyavahare, Shreyas S; Reddy, Satheesha B H; Ramachandra, Chanila S

    2014-11-01

    Despite all the technological advances in orthodontics, orthodontic treatment still seems to involve some degree of discomfort and/or pain. Pain control during orthodontic therapy is of great concern to both orthodontists and patients. However, there has been limited research into controlling such pain. The purpose of this work was to assess patient-perceived pain following fixed orthodontic treatment and to evaluate the comparative analgesic efficacy of non-steroidal anti-inflammatory drugs for controlling pain. A total of 45 patients about to undergo fixed appliance orthodontic treatment were enrolled in this double-blind prospective study. Patients were evenly and randomly distributed in a blinded manner to one of three groups as follows: paracetamol/acetaminophen 500 mg thrice daily; placebo in the form of empty capsules; and etoricoxib 60 mg once daily. Drug administration began 1 h before initiating the bonding procedure and archwire placement, and given until the day 3. The pain perceived was recorded by the patients on a linear and graded Visual Analogue Scale at time intervals of 2 h after insertion of the appliance; 6 h thereafter and again at nighttime of the same day of the appointment; 24 h later and on the 2nd day at nighttime; 48 h after the appointment and on day 3 at nighttime. Our results revealed that moderately intense pain is associated with routine orthodontic treatment, and that the amount of pain individuals perceive varies widely. We observed statistically significant differences in the pain control among the three groups, and that etoricoxib 60 mg proved most efficient. Etoricoxib 60 mg is highly efficacious for controlling pain during fixed orthodontic appliance therapy.

  17. The role of tramadol in pain management in Latin America: a report by the Change Pain Latin America Advisory Panel.

    Science.gov (United States)

    Santos Garcia, Joäo Batista; Lech, Osvandré; Campos Kraychete, Durval; Rico, María Antonieta; Hernández-Castro, John Jairo; Colimon, Frantz; Guerrero, Carlos; Sempértegui Gallegos, Manuel; Lara-Solares, Argelia; Flores Cantisani, José Alberto; Amescua-Garcia, César; Guillén Núñez, María Del Rocío; Berenguel Cook, María Del Rosario; Jreige Iskandar, Aziza; Bonilla Sierra, Patricia

    2017-09-01

    Change Pain Latin America (CPLA) was created to enhance chronic pain understanding and develop pain management improving strategies in this region. During its seventh meeting (August 2016), the main objective was to discuss tramadol's role in treating pain in Latin America. Furthermore, potential pain management consequences were considered, if tramadol was to become more stringently controlled. Key topics discussed were: main indications for prescribing tramadol, its pharmacological characteristics, safety and tolerability, effects of restrictions on its availability and use, and consequent impact on pain care quality. The experts agreed that tramadol is used to treat a wide spectrum of non-oncological pain conditions (e.g. post-surgical, musculoskeletal, post-traumatic, neuropathic, fibromyalgia), as well as cancer pain. Its relevance when treating special patient groups (e.g. the elderly) is recognized. The main reasons for tramadol's high significance as a treatment option are: its broad efficacy, an inconspicuous safety profile and its availability, considering that access to strong analgesics - mainly controlled drugs (classical opioids) - is highly restricted in some countries. The CPLA also agreed that tramadol is well tolerated, without the safety issues associated with long-term nonsteroidal anti-inflammatory drug (NSAID) use, with fewer opioid-like side effects than classical opioids and lower abuse risk. In Latin America, tramadol is a valuable and frequently used medication for treating moderate to severe pain. More stringent regulations would have significant impact on its availability, especially for outpatients. This could cause regression to older and frequently inadequate pain management methods, resulting in unnecessary suffering for many Latin American patients.

  18. Effects of Preoperative Non-Steroidal Anti-Inflammatory Drugs on Pain Mitigation and Patients’ Shoulder Performance Following Rotator Cuff Repair

    Directory of Open Access Journals (Sweden)

    Alireza Rouhani

    2014-12-01

    Full Text Available Purpose: Pain is one of the most important factors adversely affecting clinical outcomes of operated patients. The present study aims at evaluating effects of preoperative COX2 non-steroidal anti-inflammatory inhibitors on pain mitigation and performance of patients with shoulder rotator cuff tear. Methods: This case-control study was conducted on 60 patients suffering from rotator cuff injury candidate for arthroscopic repair. The patients were classified in two parallel and matched groups. One group (case group was treated using Celecoxib (200mg/12h started 48 hours before surgery and continued for 10 days after operation. In the control group, the placebo was prescribed in the same way. Postoperative pain, side effects, sleep disturbance, and short-term outcomes were compared between two groups using DASH questionnaire. Results: Postoperative pain in the Celecoxib group significantly decreased in comparison with the control one. The difference was statistically meaningful (P<0.001. Well motion ability was seen in 80% of patients of the Celecoxib group. It was 26.6% in the placebo group since pain inhibited them from exercising more motions. In this regard, there was a statistically meaningful difference between these two groups (P=0.02. Sleep disturbance was meaningfully at higher levels in the placebo group (P=0.001. Following up the patients for three months, it was made clear that performance of the Celecoxib group was better than that of the placebo one. Conclusion: COX2 inhibitors are well efficient in patients’ pain management after arthroscopic rotator cuff repair surgery. It results in less life complications, less sleep disturbances, improvement of patients’ short-term clinical outcome, and more quick recovery.

  19. The roles of special proresolving mediators in pain relief.

    Science.gov (United States)

    Zhang, Lan-Yu; Jia, Ming-Rui; Sun, Tao

    2018-02-08

    The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders. Due to the potent proresolving and anti-inflammatory effects, SPMs are also used for pain relief. This review focuses on the mechanisms by which SPMs act on their respective G-protein-coupled receptors in immune cells and nerve cells to normalize pain via regulating inflammatory mediators, transient receptor potential ion channels, and central sensitization. SPMs may offer novel therapeutic approaches for preventing and treating pain conditions associated with inflammation.

  20. Endogenous Opioid-Masked Latent Pain Sensitization

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  1. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS).

    Science.gov (United States)

    Sieper, J; van der Heijde, D; Landewé, R; Brandt, J; Burgos-Vagas, R; Collantes-Estevez, E; Dijkmans, B; Dougados, M; Khan, M A; Leirisalo-Repo, M; van der Linden, S; Maksymowych, W P; Mielants, H; Olivieri, I; Rudwaleit, M

    2009-06-01

    Inflammatory back pain (IBP) is an important clinical symptom in patients with axial spondyloarthritis (SpA), and relevant for classification and diagnosis. In the present report, a new approach for the development of IBP classification criteria is discussed. Rheumatologists (n = 13) who are experts in SpA took part in a 2-day international workshop to investigate 20 patients with back pain and possible SpA. Each expert documented the presence/absence of clinical parameters typical for IBP, and judged whether IBP was considered present or absent based on the received information. This expert judgement was used as the dependent variable in a logistic regression analysis in order to identify those individual IBP parameters that contributed best to a diagnosis of IBP. The new set of IBP criteria was validated in a separate cohort of patients (n = 648). Five parameters best explained IBP according to the experts. These were: (1) improvement with exercise (odds ratio (OR) 23.1); (2) pain at night (OR 20.4); (3) insidious onset (OR 12.7); (4) age at onset validation cohort. This new approach with real patients defines a set of IBP definition criteria using overall expert judgement on IBP as the gold standard. The IBP experts' criteria are robust, easy to apply and have good face validity.

  2. Overlap between functional abdominal pain disorders and organic diseases in children.

    Science.gov (United States)

    Langshaw, A H; Rosen, J M; Pensabene, L; Borrelli, O; Salvatore, S; Thapar, N; Concolino, D; Saps, M

    2018-04-02

    Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  3. Arthroscopic treatment of impingement of the ankle reduces pain and enhances function

    DEFF Research Database (Denmark)

    Rasmussen, S; Hjorth Jensen, C

    2002-01-01

    A consecutive series of 105 patients with a median age of 35 (16-62) years who were operated on with arthroscopic resection for impingement of the ankle using standardized technique without distraction is presented. All patients complained of painful dorsiflexion and had failed to respond to cons...... synovectomy and intravenous antibiotics. In one patient persistent symptoms were recorded. Ankle arthroscopy yielded good results in the treatment of anterior impingement of the ankle as it effectively reduced pain and enhanced function....... of pain. Gait was improved in 30/41 patients and 22 resumed sporting activities. The results were graded excellent in 67, good in 25, fair in six and poor in seven patients. There were four deep infections and one synovial fistula in this series. The deep infections all responded well to arthroscopic...

  4. Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

    DEFF Research Database (Denmark)

    Pedersen, J L; Rung, G W; Kehlet, H

    1997-01-01

    BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers....... The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds...... between sympathetic block and placebo for pain or mechanical allodynia during injury, or pain thresholds, pain responses to heat, or areas of secondary hyperalgesia after the injury. The comparisons were done for the period when the block was effective. CONCLUSION: Sympathetic nerve block did not change...

  5. [Complex regional pain syndrome (CRPS) : An update].

    Science.gov (United States)

    Dimova, V; Birklein, F

    2018-04-17

    The acute phase of complex regional pain syndrome (CRPS) is pathophysiologically characterized by an activation of the immune system and its associated inflammatory response. During the course of CRPS, central nervous symptoms like mechanical hyperalgesia, loss of sensation, and body perception disorders develop. Psychological factors such as pain-related anxiety and traumatic events might have a negative effect on the treatment outcome. While the visible inflammatory symptoms improve, the pain often persists. A stage adapted, targeted treatment could improve the prognosis. Effective multidisciplinary treatment includes the following: pharmacotherapy with steroids, bisphosphonates, or dimethylsulfoxide cream (acute phase), and antineuropathic analgesics (all phases); physiotherapy and behavioral therapy for pain-related anxiety and avoidance of movement; and interventional treatment like spinal cord or dorsal root ganglion stimulation if noninvasive options failed.

  6. Inflammatory spine disease as a cause of back pain; Entzuendliche Wirbelsaeulenerkrankungen als Ursache fuer Rueckenschmerzen

    Energy Technology Data Exchange (ETDEWEB)

    Schlossbauer, T.; Panteleon, A.; Becker-Gaab, C. [Klinikum Innenstadt der Ludwig-Maximilians-Universitaet, Institut fuer Klinische Radiologe, Muenchen (Germany)

    2006-06-15

    The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-{alpha} antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-{alpha} antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI is useful for assessment of the effectiveness of anti-inflammatory therapy. (orig.) [German] Ziel der Arbeit ist, die Bedeutung inflammatorischer Wirbelsaeulenerkrankungen fuer das Leitsymptom Rueckenschmerz zu eroertern. Die Aussagekraft der verschiedenen radiologischen Verfahren wird diskutiert. Basierend auf der Einteilung der seronegativen Spondylarthropathien (SpA) sowie der rheumatoiden Arthritis (RA), erfolgte eine systematische Literaturrecherche. Die Ergebnisse dieser Recherche und die eigenen Erfahrungen mit einem grossen rheumatologischen Krankengut werden analysiert. Die Praevalenz der RA (1-2%) und der Gruppe der SpA (1,9%) ist vergleichbar, wobei die Aetiologie letztlich bei keiner der genannten Erkrankungen bekannt ist. Die bildmorphologische Kriterien koennen sich ueberlappen. Die MRT wird zunehmend bei Frueherkennung und Verlaufsbeurteilung der immunmodulatorischen Therapien (TNF-{alpha}-Antagonisten) eingesetzt. Ein Oedem im Knochen, das nur mit der MRT nachweisbar ist, zeigt die Aktivitaet der Entzuendung

  7. Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

    Science.gov (United States)

    Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

    2017-06-09

    Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection.

    Science.gov (United States)

    Jhang, Jia-Fong; Kuo, Hann-Chorng

    2015-06-18

    Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months' duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.

  9. BACK PAIN ASSOCIATED WITH INTERVERTEBRAL DISK DEGENERATION: MORPHOLOGICAL, GENETIC AND CLINICO-INSTRUMENTAL ASPECTS

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2014-07-01

    Full Text Available Degenerative spine disease is one of the causes of back pain. Clinical types of pain and severity of inflammatory changes in the vertebral bodies depend on the activity of pro-inflammatory cytokines. Rate of development and progression of degenerative changes in the spine structures is genetically determined. Therapy of pain syndrome associated with a degenerative disc disease may include use of methods to restore damaged intervertebral disc structures, and also use of different combinations of anti-inflammatory and analgesics therapy.

  10. BACK PAIN ASSOCIATED WITH INTERVERTEBRAL DISK DEGENERATION: MORPHOLOGICAL, GENETIC AND CLINICO-INSTRUMENTAL ASPECTS

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2011-01-01

    Full Text Available Degenerative spine disease is one of the causes of back pain. Clinical types of pain and severity of inflammatory changes in the vertebral bodies depend on the activity of pro-inflammatory cytokines. Rate of development and progression of degenerative changes in the spine structures is genetically determined. Therapy of pain syndrome associated with a degenerative disc disease may include use of methods to restore damaged intervertebral disc structures, and also use of different combinations of anti-inflammatory and analgesics therapy.

  11. Enhancement of inflammatory protein expression and nuclear factor Κb (NF-Κb) activity by trichostatin A (TSA) in OP9 preadipocytes.

    Science.gov (United States)

    Sato, Taiki; Kotake, Daisuke; Hiratsuka, Masahiro; Hirasawa, Noriyasu

    2013-01-01

    The production of inflammatory proteins such as interleukin-6 (IL-6) by preadipocytes and mature adipocytes is closely associated with the impairment of systemic glucose homeostasis. However, precisely how the production is regulated and the roles of histone deacetylases (HDACs) remain largely unknown. The aim of this study was to establish whether HDAC inhibitors affect the expression of inflammatory proteins in pre/mature adipocytes, and, if so, to determine the mechanism involved. Trichostatin A (TSA), an HDAC inhibitor, enhanced lipopolysaccharide (LPS)-induced production of IL-6 in OP9 preadipocytes but not the mature adipocytes. Moreover, TSA also enhanced palmitic acid-induced IL-6 production and the expression of inflammatory genes induced by LPS in preadipocytes. Although TSA did not affect TLR4 mRNA expression or the activation of MAPKs, a reporter gene assay revealed that the LPS-induced increase in nuclear factor κB (NF-κB) activity was enhanced by TSA. Moreover, TSA increased the level of NF-κB p65 acetylation at lysine 310 and duration of its translocation into the nucleus, which leads to enhancement of NF-κB activity and subsequently expression of inflammatory genes. These findings shed new light on the regulatory roles of HDACs in preadipocytes in the production of inflammatory proteins.

  12. Vitamin D in Pain Management.

    Science.gov (United States)

    Helde-Frankling, Maria; Björkhem-Bergman, Linda

    2017-10-18

    Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like other hormones, vitamin D plays a role in a wide range of processes in the body. Here we review the possible role of vitamin D in nociceptive and inflammatory pain. In observational studies, low vitamin D levels have been associated with increased pain and higher opioid doses. Recent interventional studies have shown promising effects of vitamin D supplementation on cancer pain and muscular pain-but only in patients with insufficient levels of vitamin D when starting intervention. Possible mechanisms for vitamin D in pain management are the anti-inflammatory effects mediated by reduced cytokine and prostaglandin release and effects on T-cell responses. The recent finding of vitamin D-mediated inhibition of Prostaglandin E2 (PGE2) is especially interesting and exhibits a credible mechanistic explanation. Having reviewed current literature, we suggest that patients with deficient levels defined as 25-hydroxyvitamin D (25-OHD) levels 50 nmol/L probably have little benefit from supplementation. Our conclusion is that vitamin D may constitute a safe, simple and potentially beneficial way to reduce pain among patients with vitamin D deficiency, but that more randomized and placebo-controlled studies are needed before any firm conclusions can be drawn.

  13. Prostatic acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine

    Science.gov (United States)

    Zylka, Mark J.; Sowa, Nathaniel A.; Taylor-Blake, Bonnie; Twomey, Margaret A.; Herrala, Annakaisa; Voikar, Vootele; Vihko, Pirkko

    2008-01-01

    SUMMARY Thiamine monophosphatase (TMPase, also known as Fluoride-Resistant Acid Phosphatase) is a classic histochemical marker of small-diameter dorsal root ganglia neurons. The molecular identity of TMPase is currently unknown. We found that TMPase is identical to the transmembrane isoform of Prostatic Acid Phosphatase (PAP), an enzyme with unknown molecular and physiological functions. We then found that PAP knockout mice have normal acute pain sensitivity but enhanced sensitivity in chronic inflammatory and neuropathic pain models. In gain-of-function studies, intraspinal injection of PAP protein has potent anti-nociceptive, anti-hyperalgesic and anti-allodynic effects that last longer than the opioid analgesic morphine. PAP suppresses pain by functioning as an ecto-5’-nucleotidase. Specifically, PAP dephosphorylates extracellular adenosine monophosphate (AMP) to adenosine and activates A1-adenosine receptors in dorsal spinal cord. Our studies reveal molecular and physiological functions for PAP in purine nucleotide metabolism and nociception and suggest a novel use for PAP in the treatment of chronic pain. PMID:18940592

  14. Enhanced barrier functions and anti-inflammatory effect of cultured coconut extract on human skin.

    Science.gov (United States)

    Kim, Soomin; Jang, Ji Eun; Kim, Jihee; Lee, Young In; Lee, Dong Won; Song, Seung Yong; Lee, Ju Hee

    2017-08-01

    Natural plant oils have been used as a translational alternative to modern medicine. Particularly, virgin coconut oil (VCO) has gained popularity because of its potential benefits in pharmaceutical, nutritional, and cosmetic applications. Cultured coconut extract (CCE) is an alternative end product of VCO, which undergoes a further bacterial fermentation process. This study aimed to investigate the effects of CCE on human skin. We analyzed the expression of skin barrier molecules and collagens after applying CCE on human explanted skin. To evaluate the anti-inflammatory properties of CCE, the expression of inflammatory markers was analyzed after ultraviolet B (UVB) irradiation. The CCE-treated group showed increased expression of cornified cell envelope components, which contribute to protective barrier functions of the stratum corneum. Further, the expression of inflammatory markers was lower in the CCE-treated group after exposure to UVB radiation. These results suggest an anti-inflammatory effect of CCE against UVB irradiation-induced inflammation. Additionally, the CCE-treated group showed increased collagen and hyaluronan synthase-3 expression. In our study, CCE showed a barrier-enhancing effect and anti-inflammatory properties against ex vivo UVB irradiation-induced inflammation. The promising effect of CCE may be attributed to its high levels of polyphenols and fatty acid components. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

    Science.gov (United States)

    Schinkel, Christian; Scherens, A; Köller, M; Roellecke, G; Muhr, G; Maier, C

    2009-03-17

    The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory

  16. Systemic inflammatory mediators in post-traumatic Complex Regional Pain Syndrome (CRPS I - longitudinal investigations and differences to control groups

    Directory of Open Access Journals (Sweden)

    Schinkel Ch

    2009-03-01

    Full Text Available Abstract Objectives The Complex Regional Pain Syndrome I (CRPS I is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. Methods To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP, White Blood Cell Count (WBC, Interleukins 4, 6, 8, 10, 11, 12 (p70, Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-α and its soluble Receptors I/II, soluble Selectins (E, L, P, Substance-P (SP, and Calcitonin Gene-Related Peptide (CGRP at different time points in venous blood from patients with acute (AC and chronic (CC CRPS I, patients with forearm fractures (FR, with neuralgia (NE, and from healthy volunteers (C. Results No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007, FR/C (CGRP p = 0.048 and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049. High interindividual variations were observed. No intra-or interindividual correlation of parameters with clinical course (e.g. chronification or outcome was detectable. Conclusion Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this

  17. Anti-inflammatory, anti-nociceptive and antipyretic potential of ...

    African Journals Online (AJOL)

    Materials and Methods: Extracts of Terminalia citrina fruits were evaluated at doses of 200mg/kg, 400mg/kg and 600mg/kg in albino mice for preventive effect in inflammatory edema, peripheral pain sensation and pyrexia. Carrageenan induced paw edema method was utilized to evaluate anti-inflammatory activity.

  18. An Autologous Anti-Inflammatory Protein Solution Yielded a Favorable Safety Profile and Significant Pain Relief in an Open-Label Pilot Study of Patients with Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Jason Hix

    2017-12-01

    Full Text Available Osteoarthritis (OA is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient's own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs were experienced by seven subjects (63.6%. There was one serious AE (diverticulitis unrelated to the device or procedure. One subject experienced AEs that were judged “likely” to be procedure related (arthralgia/musculoskeletal discomfort and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC pain scores improved significantly over time (ANOVA, p < 0.0001, 12.0 ± 1.2 preinjection, 3.3 ± 2.9 one year postinjection, and 72.5% WOMAC pain improvement. There was significant positive correlation between white blood cell concentration in APS and improvement in WOMAC pain scores.

  19. An Autologous Anti-Inflammatory Protein Solution Yielded a Favorable Safety Profile and Significant Pain Relief in an Open-Label Pilot Study of Patients with Osteoarthritis

    Science.gov (United States)

    Hix, Jason; Klaassen, Mark; Foreman, Ryan; Cullen, Edith; Toler, Krista; King, William; Woodell-May, Jennifer

    2017-01-01

    Abstract Osteoarthritis (OA) is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS) Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient's own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs) were experienced by seven subjects (63.6%). There was one serious AE (diverticulitis) unrelated to the device or procedure. One subject experienced AEs that were judged “likely” to be procedure related (arthralgia/musculoskeletal discomfort) and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores improved significantly over time (ANOVA, p < 0.0001, 12.0 ± 1.2 preinjection, 3.3 ± 2.9 one year postinjection, and 72.5% WOMAC pain improvement). There was significant positive correlation between white blood cell concentration in APS and improvement in WOMAC pain scores. PMID:29279807

  20. Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

    Directory of Open Access Journals (Sweden)

    David R Lionberger

    2010-11-01

    Full Text Available David R Lionberger1, Michael J Brennan21Southwest Orthopedic Group, Houston, TX, USA; 2Department of Medicine, Bridgeport Hospital, Bridgeport, CT, USAAbstract: The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs, diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9. In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs. The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Inflammatory pseudotumor of the spleen: report of a case in a child

    International Nuclear Information System (INIS)

    Dardanelli, Esteban; Cermeno, Claudia; Rizzi, Ana Maria; Felipe, Laura; Goldberg, Alberto; Moguillansky, Silvia

    2003-01-01

    We report a case of inflammatory pseudotumor of the spleen in a 4 years old child. Clinical findings were limited to diffuse abdominal pain and a palpable mass at the left hypochondrium. Ultrasonography and CT revealed a solid homogeneous mass in the lower pole of the spleen, with irregular enhancement with IV contrast. Laparoscopic splenectomy was performed. The diagnosis was histological. The pseudotumor of the spleen is extremely rare, especially in children, with only 4 cases (including our own) reported in the literature. Our patient constitutes the youngest case ever reported. (author)

  3. [Evaluation of anti-inflammatory activity of extracts from Siberian plants].

    Science.gov (United States)

    Nesterova, Iu V; Povet'eva, T N; Aksinenko, S G; Suslov, N I; Gaĭdamovich, N N; Nagorniak, Iu G; Popova, E V; Kravtsova, S S; Andreeva, T I

    2009-01-01

    Experimental investigations have shown that water-alcohol extracts from plants containing alkaloids (Aconitum baikalense, Aconitum septentrionale, Delphinium elatum L., Conium maculatum) and salicylic acid (Filipendula ulmaria, Salix viminalis, Fragaria vesca, Rubus idaeus) inhibited the development of main symptoms of inflammation, viz. exudation, pain, fever, to the same extent as non-steroidal anti-inflammatory agents. The substances studied in this work may be used to develop new efficient pharmacological preparations for the treatment of different inflammatory conditions associated with severe pain syndrome.

  4. Survey of Thai Physicians Regarding Recognition and Management of Inflammatory Back Pain and Spondyloarthritis.

    Science.gov (United States)

    Tangrungruengkit, Mintra; Srinonprasert, Varalak; Chiowchanwisawakit, Praveena

    2016-01-01

    To assess recognition and management of inflammatory back pain (IBP) and spondyloarthritis (SpA) among non-rheumatologists (NRs) and rheumatologists in Thailand. A cross-sectional survey was conducted among physicians in Thailand A questionnaire designed to evaluate knowledge regarding IBP and SpA was sent to 1,336 NRs. A different questionnaire regarding SpA management in practice was sent to 112 rheumatologists. Of 1,448 questionnaires distributed, 367 (25.3%) questionnaires were returned (NRs: 321 [24.0%] and included rheumatologists, 46 [41.1%]). Among NRs, 26.6%, 20.9%, and 9.4% recognized all features of IBP according to Calin, Assessment of SpondyloArthritis International Society, and Berlin criteria, respectively. In the presence of typical features of ankylosing spondylitis, 57.8% of NRs made the correct diagnosis. Regarding related clinical skills and involvement, 43.8%, 53.6%, and 37.3% of NRs lacked confidence in distinguishing IBP from mechanical back pain, performing musculoskeletal examination, and interpretation of plain radiography, respectively. Expensive biologic agents (31.2%) and advanced disease stage at diagnosis (27.1%) were the main problems reported by rheumatologists. Problems in diagnosis and management of SpA patients among NRs in Thailand included lack of knowledge and lack of associated clinical skills. Issues reported by rheumatologists centered on case management limitations. In order to improve overall quality of care for SpA patients, focused strategies should be implemented for both NRs and rheumatologists that consider the needs of patients, clinicians, and policy makers.

  5. Postpartum Inflammatory Sacroiliitis-A Case Report

    Directory of Open Access Journals (Sweden)

    Seniz Akcay Yalbuzdag

    2013-08-01

    Full Text Available During the pregnancy several changes occur in sacroiliac joint and pelvis which may predispose for sacroiliac joint strain and septic sacroiliitis. We describe a case of acute inflammatory sacroiliitis in a patient with HLA B27 positivity during postpartum period, and diagnosed psoriatic arthritis during the follow up period. We aimed to emphasize that inflammatory sacroiliitis should take place whithin differantial diagnose of postpartum low back pain.

  6. HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Mudan Lu

    2015-01-01

    Full Text Available Background/Purpose. HMGB1, which may act as a proinflammatory mediator, has been proposed to contribute to the pathogenesis of multiple chronic inflammatory and autoimmune diseases including systemic lupus erythematosus (SLE; however, the precise mechanism of HMGB1 in the pathogenic process of SLE remains obscure. Method. The expression of HMGB1 was measured by ELISA and western blot. The ELISA was also applied to detect proinflammatory cytokines levels. Furthermore, nephritic pathology was evaluated by H&E staining of renal tissues. Results. In this study, we found that HMGB1 levels were significantly increased and correlated with SLE disease activity in both clinical patients and murine model. Furthermore, gain- and loss-of-function analysis showed that HMGB1 exacerbated the severity of SLE. Of note, the HMGB1 levels were found to be associated with the levels of proinflammatory cytokines such as TNF-α and IL-6 in SLE patients. Further study demonstrated that increased HMGB1 expression deteriorated the severity of SLE via enhancing macrophage inflammatory response. Moreover, we found that receptor of advanced glycation end products played a critical role in HMGB1-mediated macrophage inflammatory response. Conclusion. These findings suggested that HMGB1 might be a risk factor for SLE, and manipulation of HMGB1 signaling might provide a therapeutic strategy for SLE.

  7. Enhanced Brain Responses to Pain-Related Words in Chronic Back Pain Patients and Their Modulation by Current Pain.

    Science.gov (United States)

    Ritter, Alexander; Franz, Marcel; Puta, Christian; Dietrich, Caroline; Miltner, Wolfgang H R; Weiss, Thomas

    2016-08-10

    Previous functional magnetic resonance imaging (fMRI) studies in healthy controls (HC) and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP) patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain activations induced by pain-related adjectives. Subjects viewed pain-related, negative, positive, and neutral words; subjects were asked to generate mental images related to these words during fMRI scanning. Brain activation was compared between CBP patients and HC in response to the different word categories and examined in relation to current pain in CBP patients. Pain-related words vs. neutral words activated a network of brain regions including cingulate cortex and insula in subjects and patients. There was stronger activation in medial and dorsolateral prefrontal cortex (DLPFC) and anterior midcingulate cortex in CPB patients than in HC. The magnitude of activation for pain-related vs. negative words showed a negative linear relationship to CBP patients' current pain. Our findings confirm earlier observations showing that pain-related words activate brain networks similar to noxious stimulation. Importantly, CBP patients show even stronger activation of these structures while merely processing pain-related words. Current pain directly influences on this activation.

  8. Psychological Characteristics of Chronic Pain: a Review of Current Evidence and Assessment Tools to Enhance Treatment.

    Science.gov (United States)

    Miller, Rhondene M; Kaiser, Ronald S

    2018-03-14

    The complicated nature of chronic pain involves an interplay between psychological and physical factors, often resulting in increased emotional distress and reduced quality of life. This review is designed to help the medical practitioner who is working with chronic pain patients to be aware of psychological assessment techniques that can add to comprehensive patient understanding and more effectively guide treatment. Enhanced ability to assess and understand the emotional life of the chronic pain patient provides a basis for intervening and treating more successfully. There are a broad range of assessment techniques, some of which require a background in psychology and some that do not, that can identify psychological differences in chronic pain patients and serve to guide intervention strategies. Chronic pain is often comorbid with depression, anxiety, catastrophizing, and various ineffective coping strategies. Some patients, however, have demonstrated more adaptive and effective strategies for cognitively and behaviorally coping with pain and normalizing their lives. Proper assessment enables the individualization of treatment to overcome and/or build upon each patient's psychological frame of mind to maximize the potential for effective functioning. The use of standardized and documented psychological assessment techniques can lead to a better understanding of chronic pain patients and contribute in ways that can enhance response to medical treatment and improve quality of life. It is recommended that certain psychological tools be included to supplement the medical assessment of patients who have chronic pain. A basic assessment can include a short psychological-based clinical interview along with brief measures of depression, anxiety, and coping strategies. It is also recommended that the pain physician have access to professional psychological practitioners as a resource for more complicated assessments and psychological intervention services.

  9. A systematic review assessing non-pharmacological conservative treatment studies for people with non-inflammatory multi-joint pain: clinical outcomes and research design considerations.

    Science.gov (United States)

    Comer, C; Smith, T O; Drew, B; Raja, R; Kingsbury, S R; Conaghan, Philip G

    2018-03-01

    To systematically review the evidence to determine the clinical outcomes and the important methodological quality features of interventional studies on adults with non-inflammatory multi-joint pain (MJP). Systematic search of published and unpublished literature using the databases: AMED, CINAHL, MEDLINE, EMBASE, psycINFO, SPORTDiscus, PEDro, OpenGrey, the EU Clinical Trials Register, World Health Organization International Clinical Trial Registry Platform, ClinicalTrials.gov and the ISRCTN registry (search: inception to 19th October 2017). All papers reporting the clinical outcomes of non-pharmacological interventions for people with non-inflammatory MJP were included. Studies were critically appraised using the Downs and Black Critical Appraisal and the TIDieR reporting checklists. Data were analysed using a Best Evidence Synthesis approach. From 3824 citations, four papers satisfied the eligibility criteria. Three studies reported outcomes from multidisciplinary rehabilitation programmes and one study reported the findings of a spa therapy intervention. All interventions significantly improved pain, function and quality of life in the short-term. There was limited reporting of measures for absenteeism, presenteeism and psychosocial outcomes. The evidence was 'weak', and due to a lack of controlled trials, there is limited evidence to ascertain treatment effectiveness. Design consideration for future trials surround improved reporting of participant characteristics, interventions and the standardisation of core outcome measures. There is insufficient high-quality trial data to determine the effectiveness of treatments for non-inflammatory MJP. Given the significant health burden which this condition presents on both individuals and wider society, developing and testing interventions and accurately reporting these, should be a research priority. Registration PROSPERO (CRD42013005888).

  10. Non-Steroidal Anti Inflammatory Drugs Usage In Orthopaedics And ...

    African Journals Online (AJOL)

    Background: Non steroidal anti-inflammatory drugs NSAIDs) are a group of heterogeneous compounds with nti inflammatory, analgesic and often times anti pyretic roperties. They are weak organic acids and are the most commonly used drugs in Orthopaedic/Trauma practice. hey provide mild to moderate pain relief.

  11. Enhanced Brain Responses to Pain-Related Words in Chronic Back Pain Patients and Their Modulation by Current Pain

    OpenAIRE

    Ritter, Alexander; Franz, Marcel; Puta, Christian; Dietrich, Caroline; Miltner, Wolfgang H. R.; Weiss, Thomas

    2016-01-01

    Previous functional magnetic resonance imaging (fMRI) studies in healthy controls (HC) and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP) patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain acti...

  12. Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Can Zhang

    Full Text Available Painful neuropathy (PN is a prevalent condition in patients with metabolic syndrome (MetS. However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN remain unclear. In the current study, high-fat-fed mice (HF mice were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF mice. Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 wk of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin. To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of proinflammatory cytokines, including tumor necrosis factor (TNF-α, and interleukin (IL-6, IL-1β as well as reduced anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG of HF mice. Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.

  13. Dehydration enhances pain-evoked activation in the human brain compared with rehydration.

    Science.gov (United States)

    Ogino, Yuichi; Kakeda, Takahiro; Nakamura, Koji; Saito, Shigeru

    2014-06-01

    Negative effects of dehydration on the human brain and cognitive function have been reported. In this study, we examined the effects of dehydration on pain thresholds and cortical activations in response to pain, compared with rehydration with an oral rehydration solution (ORS) by functional magnetic resonance imaging. Five healthy adult men were subjected to dehydration and rehydration on 2 different days. The condition on the first day was randomly assigned to each subject. They completed a 40-minute exercise protocol using a walking machine after 12 hours of fasting under both conditions. For rehydration, the subjects consumed up to 3000 mL ORS starting from the night before the test day. After exercise, a painful stimulus (cold pressor test) was applied to the subjects' medial forearm in a magnetic resonance imaging scanning gantry, and pain-evoked brain activation was analyzed. On the rehydration day, each of the subjects consumed an average of 2040 mL (range; 1800-2500 mL) ORS. Physiological data revealed that subjects when dehydrated lost more weight from exercise than subjects when rehydrated had a larger heart rate increase, a higher tympanic temperature, and a higher urine osmolality. Subjective data revealed that the subjects reported significantly stronger thirst while dehydrated than while rehydrated with ORS, although the levels of hunger and anxiety and mood did not significantly differ between conditions. The cold pressor test robustly activated the pain-related neural network, notably the anterior cingulate cortex, insula, and thalamus. Such activations in the dehydrated subjects were greater than those in the rehydrated subjects in terms of peak and cluster, accompanied by a decrease in pain threshold (P = 0.001). Our findings suggest that dehydration brings about increased brain activity related to painful stimuli together with enhanced thirst, whereas rehydration with ORS alleviates thirst and decreases brain activity related to painful stimuli.

  14. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat

    DEFF Research Database (Denmark)

    Munro, G; Hansen, Rikke Rie; Erichsen, Hk

    2012-01-01

    BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators. Increasin......BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators...

  15. Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling

    Directory of Open Access Journals (Sweden)

    Sidra Khalid

    2018-03-01

    Full Text Available The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p. honokiol: a phenolic compound originally isolated from Magnolia officinalis, in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p. with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity. To elucidate the effect of honokiol on various cytokines and antioxidant enzymes, quantitative real-time-PCR was performed to determine the expression levels of pro-inflammatory cytokines and antioxidant enzymes. It is demonstrated that honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, and vascular endothelial growth factor (VEGF. Similarly, honokiol was also found to potentiate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2, superoxide dismutase 2 (SOD2, and heme oxygenase-1 (HO-1 levels. Additionally, honokiol significantly reduced plasma nitrite levels as compared to complete Freund’s adjuvant (CFA induced group. X-ray analysis and hematoxylin and eosin (H&E staining of inflamed and treated paws showed that honokiol reduced the inflammation with significantly less leukocyte infiltration and soft tissue inflammation. In order to explore the possible mechanism of action of honokiol, agonists [piroxicam (5 mg/kg, tramadol (50 mg/kg, and gabapentin (5 mg/kg i.p.] as well as antagonists [naloxone (4 mg/kg, olanzapine (10 mg/kg, and flumazenil (0.2 mg/kg i.p.] were used to study involvement of various receptors on the anti-nociceptive effect of honokiol. The potential side effects of honokiol on muscle activity were assessed. An adverse effect testing of honokiol by

  16. Neuropathic pain, depressive symptoms, and C-reactive protein in sciatica patients.

    Science.gov (United States)

    Uher, Tomas; Bob, Petr

    2013-03-01

    There is evidence that neuropathic pain component in low back pain (LBP) patients is associated with higher ratings of comorbidities such as depression and anxiety disorders. In line with current findings, the purpose of this clinical study is to examine a hypothesis regarding a relationship of neuropathic pain component, depression, and other psychopathological symptoms in a specific group of LBP patients with sciatica pain. With respect to findings that depression is related to inflammatory changes, and inflammatory mediators may play a role in neuropathic pain generation, we have assessed also serum C-reactive protein (CRP). Results of the present study show that increased neuropathic pain component in sciatica patients is associated with elevated levels of depression, anxiety, alexithymia, and serum CRP levels. In conclusion, results of this study indicate that CRP levels in sciatica patients are closely associated with neuropathic pain.

  17. Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

    Directory of Open Access Journals (Sweden)

    Marco Sisignano

    Full Text Available Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs. However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18∶1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18∶1, 9-and 13-HODE and HETEs.

  18. Pain management in lung cancer.

    Science.gov (United States)

    Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

    2016-01-01

    Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.

  19. Control of pain with topical plant medicines

    Directory of Open Access Journals (Sweden)

    James David Adams Jr.

    2015-04-01

    Full Text Available Pain is normally treated with oral nonsteroidal anti-inflammatory agents and opioids. These drugs are dangerous and are responsible for many hospitalizations and deaths. It is much safer to use topical preparations made from plants to treat pain, even severe pain. Topical preparations must contain compounds that penetrate the skin, inhibit pain receptors such as transient receptor potential cation channels and cyclooxygenase-2, to relieve pain. Inhibition of pain in the skin disrupts the pain cycle and avoids exposure of internal organs to large amounts of toxic compounds. Use of topical pain relievers has the potential to save many lives, decrease medical costs and improve therapy.

  20. Rheumatoid arthritis of the craniocervical region: assessment and characterization of inflammatory soft tissue proliferations with unenhanced and contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Czerny, C.; Grampp, S.; Henk, C.B. [University Hospital Vienna (Austria). Dept. of Radiology; Neuhold, A. [Institute for Diagnostic Imaging, Hospital Rudolfinerhaus, Vienna (Austria); Stiskal, M. [Institute for Diagnostic Imaging, Hospital Lainz, Vienna (Austria); Smolen, J. [Department of Rheumatology, University Hospital Vienna (Austria)

    2000-09-01

    The aim of this study was to depict and characterize inflammatory soft tissue proliferations caused by rheumatoid arthritis (RA) in the craniocervical region by unenhanced and contrast-enhanced CT. Computed tomography of the craniocervical region was performed in 35 patients in the axial plane before and after the i. v. administration of contrast material. According to the densities and contrast enhancement of the inflammatory soft tissue proliferations, four groups were classified. Ancillary findings, such as a compression of the dural sac or spinal cord, erosions of the bony structures, and atlantoaxial subluxation, were also evaluated. Inflammatory soft tissue proliferations were depicted in 28 of 35 patients and could be differentiated by unenhanced and contrast-enhanced CT according to the above defined criteria: effusion in 6 patients (17 %); hypervascular pannus in 8 (23 %); hypovascular pannus in 5 (14 %); and fibrous tissue in 9 patients (26 %). A compression of the dural sac was seen in 11 (31 %) patients; 3 of these had neurological symptoms. Erosions of the odontoid process were found in 20 (57 %) patients; 16 (80 %) of these also showed erosions of the atlas. Atlantoaxial subluxation was seen in 11 (31 %) patients. Inflammatory soft tissue proliferations in the craniocervical region caused by RA can be reliably demonstrated and classified by unenhanced and contrast-enhanced CT, which can differentiate between joint effusion and various forms of pannus and depict ancillary findings. Computed tomography is an alternative method for patients unable to undergo an MRI examination. (orig.)

  1. Rheumatoid arthritis of the craniocervical region: assessment and characterization of inflammatory soft tissue proliferations with unenhanced and contrast-enhanced CT

    International Nuclear Information System (INIS)

    Czerny, C.; Grampp, S.; Henk, C.B.; Stiskal, M.; Smolen, J.

    2000-01-01

    The aim of this study was to depict and characterize inflammatory soft tissue proliferations caused by rheumatoid arthritis (RA) in the craniocervical region by unenhanced and contrast-enhanced CT. Computed tomography of the craniocervical region was performed in 35 patients in the axial plane before and after the i. v. administration of contrast material. According to the densities and contrast enhancement of the inflammatory soft tissue proliferations, four groups were classified. Ancillary findings, such as a compression of the dural sac or spinal cord, erosions of the bony structures, and atlantoaxial subluxation, were also evaluated. Inflammatory soft tissue proliferations were depicted in 28 of 35 patients and could be differentiated by unenhanced and contrast-enhanced CT according to the above defined criteria: effusion in 6 patients (17 %); hypervascular pannus in 8 (23 %); hypovascular pannus in 5 (14 %); and fibrous tissue in 9 patients (26 %). A compression of the dural sac was seen in 11 (31 %) patients; 3 of these had neurological symptoms. Erosions of the odontoid process were found in 20 (57 %) patients; 16 (80 %) of these also showed erosions of the atlas. Atlantoaxial subluxation was seen in 11 (31 %) patients. Inflammatory soft tissue proliferations in the craniocervical region caused by RA can be reliably demonstrated and classified by unenhanced and contrast-enhanced CT, which can differentiate between joint effusion and various forms of pannus and depict ancillary findings. Computed tomography is an alternative method for patients unable to undergo an MRI examination. (orig.)

  2. Effects of Astaxanthin from Litopenaeus Vannamei on Carrageenan-Induced Edema and Pain Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Zulkiflee Kuedo

    2016-03-01

    Full Text Available Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from astaxanthin treatment in mice: an inhibition of paw edema induced in hind paw, an increase in mechanical paw withdrawal threshold and thermal paw withdrawal latency, and a reduction in the amount of myeloperoxidase enzyme and lipid peroxidation products in the paw. Furthermore the effect was comparable to indomethacin, a standard treatment for inflammation symptoms. Due to adverse effects of indomethacin on cardiovascular and gastrointestinal systems, our study suggests promising prospect of astaxanthin extract as an anti-inflammatory alternative against carrageenan-induced paw edema and pain behavior.

  3. A novel selective prostaglandin E2 synthesis inhibitor relieves pyrexia and arthritis in Guinea pigs inflammatory models

    Directory of Open Access Journals (Sweden)

    Ryusuke Sugita

    2016-02-01

    Full Text Available Prostaglandin E2 (PGE2, one of the terminal products in the cyclooxygenase pathway, plays an important role in various inflammatory responses. To determine whether selective inhibition of PGE2 may relieve these inflammatory symptoms, we synthesized a selective PGE2 synthesis inhibitor, compound A [1-(6-fluoro-5,7-dimethyl-1,3-benzothiazol-2-yl-N-[(1S,2R-2-(hydroxymethylcyclohexyl]piperidine-4-carboxamide], then investigated the effects on pyrexia, arthritis and inflammatory pain in guinea pigs. In LPS-stimulated guinea pig macrophages, compound A selectively inhibited inducible PGE2 biosynthesis in a dose-dependent manner whereas enhanced the formation of thromboxane B2 (TXB2. Compound A suppressed yeast-evoked PGE2 production selectively and enhanced the production of TXB2 and 6-keto PGF1α in vivo. In addition, compound A relieved yeast-induced pyrexia and also suppressed paw swelling in an adjuvant-induced arthritis model. The effect on gastrointestinal (GI ulcer formation was also evaluated and compound A showed a lower GI adverse effect than indomethacin. However, compound A failed to relieve yeast-induced thermal hyperalgesia. These results suggest that selective inhibition of PGE2 synthesis may have anti-pyretic and anti-inflammatory properties without GI side effect, but lack the analgesic efficacy.

  4. [Correlation analysis of bone marrow edema degree and serum inflammatory factors change with knee joint pain symptoms in patients with bone contusion around the knee joint].

    Science.gov (United States)

    Li, Songiun; An, Rongze; Wang, Zhaojie; Kuang, Lipeng; Tan, Weiyuan; Fang, Cunxun

    2014-05-01

    To explore the correlation between the degree of bone marrow edema (BME) and the content change of tumor necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 3 (MMP-3) and the knee pain symptoms in patients with bone contusion around the knee joint. Thirty patients (30 knees) of bone contusion around the knee joint were chosen as the trial group between October 2009 and April 2012. According to visual analogue scale (VAS), 30 patients were divided into mild group (10 cases), moderate group (10 cases), and severe group (10 cases); according to MRI morphological changes, the patients were divided into type I group (12 cases), type II group (11 cases), and type III group (7 cases). Ten patients (10 knees) with soft tissue injury of the knee were chosen as control group. No significant difference was found (P > 0.05) in gender, age, causes, side, and admission time after injury between 2 groups. The serum contents of MMP-3 and TNF-alpha were detected and statistically analysed between different degrees of pain groups and between different degrees of BME groups. Correlation was analysed between BME and inflammatory factor changes and VAS score. The MMP-3 and TNF-alpha contents in trial group [(29.580 +/- 6.870) (microg/L and (23.750 +/- 7.096) ng/L] were significantly higher than those in control group [(8.219 +/- 1.355) microg/L and (6.485 +/- 1.168) ng/L] (t = 9.686, P = 0.000; t = 7.596, P =0.000). The MMP-3 and TNF-alpha contents in patients with different degrees of pain and BME were significantly higher than those in patients of control group (P pain (P 0.05). Multiple linear regression analysis showed that TNF-alpha content was significantly correlated with VAS score (P = 0.000). Knee pain symptoms are not related to the degree of BME in patients with bone contusion around the knee joint. Inflammatory factor TNF-alpha content is the main influence factor of knee joint pain symptoms.

  5. N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes

    Directory of Open Access Journals (Sweden)

    Erica Hoffer

    2002-01-01

    Full Text Available The anti-inflammatory effect of non-steroidal anti-inflammatory drugs (NSAIDs is associated with inhibition of cyclooxygenase (COX, the rate-limiting enzyme responsible for the synthesis of prostaglandins. Since oxygen free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract, it seems plausible that antioxidants might affect the production of prostaglandin by activated cells. This research is focused on the effect of the antioxidant N-acetylcysteine (NAC on the inhibition of prostaglandin E2 formation in activated monocytes by specific and non-specific COX inhibitors. We found that lipopolysaccharide-induced prostaglandin E2 formation was significantly reduced by rofecoxib and by diclofenac, two NSAIDs. Addition of NAC to each of these drugs enhanced the effect of the NSAIDs. These results suggest that one might expect either a potentiation of the anti-inflammatory effect of COX inhibitors by their simultaneous administration with NAC, or obtaining the same anti-inflammatory at lower drug levels.

  6. Radiologic imaging of degenerative and inflammatory joint disorders in women

    International Nuclear Information System (INIS)

    Krestan, C.R.; Grampp, S.; Kainberger . christian.krestan@univie.ac.at

    2001-01-01

    Pain in joints and other structures of the musculoskeletal system is a common complaint in women. It may occur as functional pain, in many cases as inflammatory episode of arthrosis or of metabolic joint disease, sometimes as early manifestation of rheumatoid disease. With conventional radiography, high resolution sonography, and MR imaging it is possible to classify many of these clinical syndromes. A semiquantitative assessment of inflammatory activity can be made by analysing the degree of joint effusion, the thickness of the synovium and the extent of hypervascularization. (author)

  7. Complex Regional Pain Syndrome: An inflammatory disease

    NARCIS (Netherlands)

    M. Dirckx (Maaike)

    2015-01-01

    markdownabstractThe pathophysiology of Complex Regional Pain Syndrome (CRPS) is complex and still not completely understood. In addition to a convincing role of inflammation, there are a number of arguments why an involvement of the immune system has been suggested in the pathophysiology of CRPS.

  8. Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain

    Science.gov (United States)

    Kandasamy, Ram; Lee, Andrea T.; Morgan, Michael M.

    2017-01-01

    Opioid withdrawal in humans is often subtle and almost always spontaneous. In contrast, most preclinical studies precipitate withdrawal by administration of an opioid receptor antagonist such as naloxone. These animal studies rely on measurement of physiological symptoms (e.g., wet dog shakes) in the period immediately following naloxone administration. To more closely model the human condition, we tested the hypothesis that depression of home cage wheel running will provide an objective method to measure the magnitude and duration of spontaneous morphine withdrawal. Rats were allowed access to a running wheel in their home cage for 8 days prior to implantation of two 75 mg morphine or placebo pellets. The pellets were removed 3 or 5 days later to induce spontaneous withdrawal. In normal pain-free rats, removal of the morphine pellets depressed wheel running for 48 hours compared to rats that had placebo pellets removed. Morphine withdrawal-induced depression of wheel running was greatly enhanced in rats with persistent inflammatory pain induced by injection of Complete Freund’s Adjuvant (CFA) into the hindpaw. Removal of the morphine pellets following 3 days of treatment depressed wheel running in these rats for over 6 days. These data demonstrate that home cage wheel running provides an objective and more clinically relevant method to assess spontaneous morphine withdrawal compared to precipitated withdrawal in laboratory rats. Moreover, the enhanced withdrawal in rats with persistent inflammatory pain suggests that pain patients may be especially susceptible to opioid withdrawal. PMID:28366799

  9. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

  10. Chronic pelvic pain

    African Journals Online (AJOL)

    misdiagnoses, inappropriate or inadequate treatment strategies, and poor patient compliance .... excitation tenderness implies an active pelvic inflammatory process. Pain localising to ... neoplastic process, particularly cervical cancer, must be excluded. .... The dosage should be started at 10 mg at night, and increased by 5 ...

  11. Antinociceptive and anti-exudative synergism between dexketoprofen and tramadol in a model of inflammatory pain in mice.

    Science.gov (United States)

    Miranda, Hugo F; Romero, Maria Asunción; Puig, Margarita M

    2012-06-01

    Preclinical studies have demonstrated antinociceptive synergism between dexketoprofen (DEX) and tramadol (TRM) in acute animal models of nociception. The aim of the present study was to investigate the type of interaction between DEX and TRM in a chronic musculoskeletal pain model in mice, which fairly replicates the characteristics of chronic osteoarticular pain in humans. Inflammation was induced by a subplantar injection of complete Freund's adjuvant (CFA) in male CF1 mice. Nociceptive thresholds were evaluated using the hot plate, the nocifensive spontaneous behavior and the acetone tests, while plasma extravasation (PE) was assessed with Evan's blue. We used the following experimental groups: control (no inflammation), acute (1 day after CFA injection), and chronic inflammation (7 days after CFA). Dose-response curves for DEX and TRM, individually and combined in a 1 : 1 proportion based on their potency were obtained, and the doses that produced a 50% inhibition calculated. The isobolographic analysis revealed that in all groups of study (no inflammation, acute, and chronic inflammation), the combination of DEX : TRM was synergistic, for both the inhibition of nociception and the PE. The results suggest that the DEX : TRM (1 : 1) combination could be useful in the management of acute and chronic inflammatory musculoskeletal pains in humans; in addition, the synergistic interaction between the drugs observed both during acute and chronic inflammation suggests that less doses would be required of each drug to obtain effective analgesia. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

  12. Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats

    Directory of Open Access Journals (Sweden)

    Xu Wen

    2010-08-01

    Full Text Available Abstract Background Temporomandibular disorders (TMDs are characterized by persistent orofacial pain and have diverse etiologic factors that are not well understood. It is thought that central sensitization leads to neuronal hyperexcitability and contributes to hyperalgesia and spontaneous pain. Nonsteroidal anti-inflammatory drugs (NSAIDs are currently the first choice of drug to relieve TMD pain. NSAIDS were shown to exhibit anticonvulsant properties and suppress cortical neuron activities by enhancing neuronal voltage-gated potassium KCNQ/Kv7 channels (M-current, suggesting that specific activation of M-current might be beneficial for TMD pain. Results In this study, we selected a new anticonvulsant drug retigabine that specifically activates M-current, and investigated the effect of retigabine on inflammation of the temporomandibular joint (TMJ induced by complete Freund's adjuvant (CFA in rats. The results show that the head withdrawal threshold for escape from mechanical stimulation applied to facial skin over the TMJ in inflamed rats was significantly lower than that in control rats. Administration of centrally acting M-channel opener retigabine (2.5 and 7.5 mg/kg can dose-dependently raise the head withdrawal threshold of mechanical allodynia, and this analgesic effect can be reversed by the specific KCNQ channel blocker XE991 (3 mg/kg. Food intake is known to be negatively associated with TMJ inflammation. Food intake was increased significantly by the administration of retigabine (2.5 and 7.5 mg/kg, and this effect was reversed by XE991 (3 mg/kg. Furthermore, intracerebralventricular injection of retigabine further confirmed the analgesic effect of central retigabine on inflammatory TMJ. Conclusions Our findings indicate that central sensitization is involved in inflammatory TMJ pain and pharmacological intervention for controlling central hyperexcitability by activation of neuronal KCNQ/M-channels may have therapeutic potential for

  13. Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative

    NARCIS (Netherlands)

    Whittle, Samuel L.; Colebatch, Alexandra N.; Buchbinder, Rachelle; Edwards, Christopher J.; Adams, Karen; Englbrecht, Matthias; Hazlewood, Glen; Marks, Jonathan L.; Radner, Helga; Ramiro, Sofia; Richards, Bethan L.; Tarner, Ingo H.; Aletaha, Daniel; Bombardier, Claire; Landewé, Robert B.; Müller-Ladner, Ulf; Bijlsma, Johannes W. J.; Branco, Jaime C.; Bykerk, Vivian P.; da Rocha Castelar Pinheiro, Geraldo; Catrina, Anca I.; Hannonen, Pekka; Kiely, Patrick; Leeb, Burkhard; Lie, Elisabeth; Martinez-Osuna, Píndaro; Montecucco, Carlomaurizio; Ostergaard, Mikkel; Westhovens, Rene; Zochling, Jane; van der Heijde, Désirée

    2012-01-01

    To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA). A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists

  14. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

    Science.gov (United States)

    Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

    2014-09-01

    Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

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

    Directory of Open Access Journals (Sweden)

    Terrighena EL

    2017-07-01

    Full Text Available Esslin L Terrighena,1,2 Ge Lu,1 Wai Ping Yuen,1 Tatia M C Lee,1–4 Kati Keuper1,2,5 1Department of Psychology, Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong; 2Laboratory of Social Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong; 3The State Key Laboratory of Brain and Cognitive Sciences, Hong Kong; 4Institute of Clinical Neuropsychology, The University of Hong Kong, Hong Kong; 5Institute for Biomagnetism and Biosignalanalysis, University of Münster, Münster, Germany Abstract: The observation of pain in others may enhance or reduce self-pain, yet the boundary conditions and factors that determine the direction of such effects are poorly understood. The current study set out to show that visual stimulus awareness plays a crucial role in ­determining whether vicarious pain primarily activates behavioral defense systems that enhance pain sensitivity and stimulate withdrawal or appetitive systems that attenuate pain sensitivity and stimulate approach. We employed a mixed factorial design with the between-subject factors exposure time (subliminal vs optimal and vicarious pain (pain vs no pain images, and the within-subject factor session (baseline vs trial to investigate how visual awareness of vicarious pain images affects subsequent self-pain in the cold-pressor test. Self-pain tolerance, intensity and unpleasantness were evaluated in a sample of 77 healthy participants. Results revealed ­significant interactions of exposure time and vicarious pain in all three dependent measures. In the presence of visual awareness (optimal condition, vicarious pain compared to no-pain elicited overall enhanced self-pain sensitivity, indexed by reduced pain tolerance and enhanced ratings of pain intensity and unpleasantness. Conversely, in the absence of visual awareness (subliminal condition, vicarious pain evoked decreased self-pain intensity and unpleasantness while pain tolerance remained unaffected. These

  16. Quality of life considerations and pain management in hidradenitis suppurativa

    DEFF Research Database (Denmark)

    Jemec, Gregor Be

    2017-01-01

    perceived as unclean and stigmatizing by the patients, but also cause pain and scarring making this inflammatory skin disorder unique. It is obvious that the disease has a significant negative impact on the patients' quality of life (QOL). The impact is influenced not only by the pain which is a significant...... independent contributor to the patients' life quality, but by the clinically significant comorbidity associated with HS. In particular, the psychological comorbidities of depression and anxiety both further compound QOL impairment and pain. It is strongly recommended that these factors be taken into account...... when planning a treatment strategy for patients with HS, and that specific steps are taken to manage pain and comorbidities associated with the reduced QOL generally experienced by this group of patients. Basic pain management includes anti-inflammatory treatments as well as local- and central...

  17. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages.

    Science.gov (United States)

    Chiong, Hoe Siong; Yong, Yoke Keong; Ahmad, Zuraini; Sulaiman, Mohd Roslan; Zakaria, Zainul Amiruddin; Yuen, Kah Hay; Hakim, Muhammad Nazrul

    2013-01-01

    Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug. Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7. Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2) than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine. This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.

  18. Nociception and role of immune system in pain.

    Science.gov (United States)

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

    2015-09-01

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

  19. Traditional Uses of Medicinal Plants from the Canadian Boreal Forest for the Management of Chronic Pain Syndromes.

    Science.gov (United States)

    Uprety, Yadav; Lacasse, Anaïs; Asselin, Hugo

    2016-04-01

    Chronic pain is more prevalent in indigenous populations who often prefer traditional remedies over allopathic drugs. Our objective was to investigate the traditional uses of medicinal plants from the Canadian boreal forest for the management of chronic pain syndromes. We reviewed the most extensive database on medicinal plants used by aboriginal people of the Canadian boreal forest to investigate the plants used in the management of 3 of the most common chronic pain syndromes: arthritis/rheumatism; back pain; and headache/migraine. We also reviewed the pharmacology and phytochemistry literature to investigate concordance with indigenous knowledge. A total of 114 medicinal plant species were reported, of which 27 (23.5%) were used to treat more than 1 chronic pain syndrome. Pharmacological or phytochemical evidence to explain plant function as chronic pain remedy was available in the literature for only 38 species (33%), with several species reported to have anti-inflammatory and analgesic properties effective in treating chronic pain syndromes. Our study showed the potential of boreal plants as alternative and complementary medicines for the treatment of chronic pain syndromes that could be enhanced by further research on efficacy and safety issues. © 2015 World Institute of Pain.

  20. Diagnostic performance of contrast-enhanced MR for acute appendicitis and alternative causes of abdominal pain in children

    Energy Technology Data Exchange (ETDEWEB)

    Koning, Jeffrey L. [University of California San Diego, Department of Radiology, San Diego, CA (United States); Naheedy, John H.; Kruk, Peter G. [University of California San Diego, Department of Radiology, San Diego, CA (United States); Rady Children' s Hospital, Department of Radiology, San Diego, CA (United States)

    2014-08-15

    Unenhanced MRI has emerged as a useful tool for diagnosing pediatric acute appendicitis. The use of contrast-enhanced MRI for diagnosing pediatric appendicitis has not been documented. The purpose of this study is to examine the diagnostic performance of contrast-enhanced MRI for acute appendicitis and alternative entities in the pediatric population presenting with acute abdominal pain. A retrospective review was conducted of 364 consecutive pediatric patients undergoing contrast-enhanced MRI for the evaluation of possible appendicitis at a single institution between November 2012 and September 2013. There were 132 cases of pathologically confirmed appendicitis out of 364 pediatric patients (36.3%) included in the study. Overall sensitivity and specificity were 96.2% (95% CI [91.4-98.4%]) and 95.7% (95% CI [92.3-97.6%]), respectively. Positive predictive value and negative predictive value were 92.7% (95% CI [86.6-96.3%]) and 97.8% (95% CI [94.7-99.1%]), respectively. The appendix was visualized in 243 cases (66.8%). Imaging confirmed alternative diagnoses in 75 patients, including most commonly colitis, enteritis or terminal ileitis (n = 25, 6.9%), adnexal cysts (n = 25, 6.9%) and mesenteric adenitis (n = 7, 1.9%). Contrast-enhanced MRI is capable of accurately diagnosing acute appendicitis while detecting many alternative entities of abdominal pain, and it allows good visualization of the appendix. Further evaluation is needed to determine whether contrast-enhanced MRI provides an advantage over non-enhanced MRI for imaging evaluation of acute abdominal pain in the pediatric population. (orig.)

  1. Diagnostic performance of contrast-enhanced MR for acute appendicitis and alternative causes of abdominal pain in children

    International Nuclear Information System (INIS)

    Koning, Jeffrey L.; Naheedy, John H.; Kruk, Peter G.

    2014-01-01

    Unenhanced MRI has emerged as a useful tool for diagnosing pediatric acute appendicitis. The use of contrast-enhanced MRI for diagnosing pediatric appendicitis has not been documented. The purpose of this study is to examine the diagnostic performance of contrast-enhanced MRI for acute appendicitis and alternative entities in the pediatric population presenting with acute abdominal pain. A retrospective review was conducted of 364 consecutive pediatric patients undergoing contrast-enhanced MRI for the evaluation of possible appendicitis at a single institution between November 2012 and September 2013. There were 132 cases of pathologically confirmed appendicitis out of 364 pediatric patients (36.3%) included in the study. Overall sensitivity and specificity were 96.2% (95% CI [91.4-98.4%]) and 95.7% (95% CI [92.3-97.6%]), respectively. Positive predictive value and negative predictive value were 92.7% (95% CI [86.6-96.3%]) and 97.8% (95% CI [94.7-99.1%]), respectively. The appendix was visualized in 243 cases (66.8%). Imaging confirmed alternative diagnoses in 75 patients, including most commonly colitis, enteritis or terminal ileitis (n = 25, 6.9%), adnexal cysts (n = 25, 6.9%) and mesenteric adenitis (n = 7, 1.9%). Contrast-enhanced MRI is capable of accurately diagnosing acute appendicitis while detecting many alternative entities of abdominal pain, and it allows good visualization of the appendix. Further evaluation is needed to determine whether contrast-enhanced MRI provides an advantage over non-enhanced MRI for imaging evaluation of acute abdominal pain in the pediatric population. (orig.)

  2. Functional abdominal pain.

    Science.gov (United States)

    Grover, Madhusudan; Drossman, Douglas A

    2010-10-01

    Functional abdominal pain syndrome (FAPS) is a relatively less common functional gastrointestinal (GI) disorder defined by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods (Drossman Gastroenterology 130:1377-1390, 2006), which points to a more centrally targeted (spinal and supraspinal) basis for the symptoms. However, FAPS is frequently confused with irritable bowel syndrome and other functional GI disorders in which abdominal pain is associated with eating and bowel movements. FAPS also differs from chronic abdominal pain associated with entities such as chronic pancreatitis or chronic inflammatory bowel disease, in which the pain is associated with peripherally acting factors (eg, gut inflammation or injury). Given the central contribution to the pain experience, concomitant psychosocial disturbances are common and strongly influence the clinical expression of FAPS, which also by definition is associated with loss of daily functioning. These factors make it critical to use a biopsychosocial construct to understand and manage FAPS, because gut-directed treatments are usually not successful in managing this condition.

  3. Analgesic and Anti-inflammatory Activity of Teucrium chamaedrys Leaves Aqueous Extract in Male Rats

    Directory of Open Access Journals (Sweden)

    Ali Pourmotabbed

    2010-06-01

    Full Text Available Objective(sCurrent study was undertaken to investigate the analgesic and anti-inflammatory effects of the aqueous extract of Teucrium chamaedrys in mice and rats. Materials and MethodsFor evaluating of analgesic and anti-inflammatory activity, we used the carrageenan- and dextran-induced paw oedema, acetic acid-induced writhing, tail flick and formalin pain tests.ResultsThe extract of T. chamaedrys (50–200 mg/kg and acetylsalicylic acid (100 mg/kg produced a significant (P< 0.01 inhibition of the second phase response in the formalin pain model, while only the high dose (200 mg/kg of the extract showed an analgesic effect in the first phase. The extract also inhibited acetic acid-induced abdominal writhes in a dose-dependent manner. The tail flick latency was dose dependently enhanced by the extract but this was significantly (P< 0.05 lower than that produced by morphine (10 mg/kg. The extract (25–250 mg/kg administered 1 hr before carrageenan-induced paw swelling produced a dose dependent inhibition of the oedema. No effect was observed with the dextran-induced oedema model. Results of the phytochemical screening show the presence of alkaloids, flavonoids and triterpenoids in the extract.ConclusionThe data obtained also suggest that the anti-inflammatory and analgesic effects of the extract may be mediated via both peripheral and central mechanisms. The role of alkaloids, flavonoids and triterpenoids will evaluate in future studies.

  4. Joint pain epidemiology and analgesic usage in Madagascar.

    Science.gov (United States)

    Samison, Luc Hervé; Randriatsarafara, Fidiniaina Mamy; Ralandison, Stéphane

    2017-01-01

    To describe the epidemiology of joint pains and document analgesics usage in an African context. Patients suffering from joint pain were recruited from nine sites located in Antananarivo, Madagascar, including 6 hospital services and 3 clinics. Doctors collected information on the etiology and characteristics of the patients' pain. Analgesics prescribed by these doctors were also documented. In total, 400 patients were enrolled in the study (52.5% women, mean age of 42.34 years ± 17.7 [4-86]). Pain of mechanical type was found in 260 participants, 65%; 95% CI [60.1% to 69.6%] and inflammatory type pains in 128 cases 32%; 95% CI [27.5% to 36.9%]. Mixed pains were found in 12 patients (3%). The median duration of pain prior to the consultation was 6.5 days. The average pain intensity was 57.9 ± 19.9 mm of a total of 100 mm maximum on a visual analogue scale, VAS. The etiologies of mechanical type pains were dominated by fracture, common low back pain and tendonitis. Arthrosis was the dominant cause of inflammatory type pain, followed by rheumatoid arthritis and gout. NSAIDs (74.5%) were the most frequently prescribed analgesics followed by paracetamol (49.5%), weak opioids (23%) and corticosteroids (12.25%). Two-thirds of medical prescriptions (65.3%) were of combined analgesics. These findings demonstrated that mechanical type pains were the main reason for consultations for joint pain in these situations in Antananarivo, Madagascar. The most frequently prescribed pain-relieving medications were NSAIDs, paracetamol, weak opioids and corticosteroids. This descriptive study may be a useful starting point for further epidemiological studies of pain in the African context.

  5. The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain.

    Science.gov (United States)

    Vucković, Sonja M; Tomić, Maja A; Stepanović-Petrović, Radica M; Ugresić, Nenad; Prostran, Milica S; Bosković, Bogdan

    2006-11-01

    In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.

  6. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    Science.gov (United States)

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The Profile of Anti-inflammatory Activity of Syzigium Aromaticum Volatile Oil in Lotion with Variation Composition of Oleic Acid and Propylene Glycol as Enhancer

    Directory of Open Access Journals (Sweden)

    Fitriah Ardiawijianti Iriani

    2017-08-01

    Full Text Available Essential oil of clove (Syzygium aromaticum containing eugenol has an anti-inflammatory activity. The study was aimed to develop the formulation of lotion by adding of oleic acid and propylene glycol as penetration enhancer. The effect of enhancer composition was also studied. Lotion was prepared with the composition of oleic acid (AO and propylene glycol (PG as follow: 1:0 (FI, 0,5:0,5 (FII, 0:1 (FIII. Capacity an anti-inflammatory of formulation based on parameters of the amount of cells with COX-2 expression, the number of inflammatory cells and the epidermis thickness was evaluated using male mouse strain BALb/C induced by crotton oil as inflammatory agents. The results showed that the increasing composition propylene glycol caused the decreasing of the amount of cells with COX-2 expression (p <0.05, the inflammatory cells (P <0.05 and the epidermis thickness (p <0.05

  8. Psychological resilience, pain catastrophizing, and positive emotions: perspectives on comprehensive modeling of individual pain adaptation.

    Science.gov (United States)

    Sturgeon, John A; Zautra, Alex J

    2013-03-01

    Pain is a complex construct that contributes to profound physical and psychological dysfunction, particularly in individuals coping with chronic pain. The current paper builds upon previous research, describes a balanced conceptual model that integrates aspects of both psychological vulnerability and resilience to pain, and reviews protective and exacerbating psychosocial factors to the process of adaptation to chronic pain, including pain catastrophizing, pain acceptance, and positive psychological resources predictive of enhanced pain coping. The current paper identifies future directions for research that will further enrich the understanding of pain adaptation and espouses an approach that will enhance the ecological validity of psychological pain coping models, including introduction of advanced statistical and conceptual models that integrate behavioral, cognitive, information processing, motivational and affective theories of pain.

  9. Utilization of Samarium-153 in bone pain and bone tumours in dog

    International Nuclear Information System (INIS)

    Martin, V. de; Marques, F.L.N.; Okamoto, M.; Guimaraes, M.I.C.C.; Dias-Neto, A.; Fonseca, A.C.

    1997-01-01

    Full text: The experimental unit of of Centro de Medicina Nuclear of the University of Sao Paulo is working on the utilization of Sm-153-EDTMP, produced by IPEN/CNEN-SP (Brazil), for the treatment of bone pain due either inflammatory process or bone tumours spontaneously developed in dogs. The effect of the injection of the radiopharmaceutical (37 MBq/kg) were analysed by observing the animal behavior against the pain and the evolution of the clinical picture of the inflammatory process. The cases where tumours were diagnosed, bone scintigraphy was performed to follow-up the evolution of those tumours. Preliminary observations indicated that, especially in inflammatory process due to disc spondylitis, there was an improvement concerning pain and consequently a better condition of the life for those animals. Bone tumours even being more difficult to evaluate, have shown a favorable evolution concerning the reduction of pain and consequently the increase in the life span of the animals

  10. 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

  11. 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

  12. Increased wind-up to heat pain in women with a childhood history of functional abdominal pain.

    Science.gov (United States)

    Dengler-Crish, Christine M; Bruehl, Stephen; Walker, Lynn S

    2011-04-01

    Idiopathic or functional abdominal pain (FAP) is common in school-age children and typically reflects a functional gastrointestinal disorder (FGID). FGIDs in adults have been distinguished by enhanced responses of the central nervous system to pain stimuli, known as central sensitization. This study investigated whether adolescents and young adults with a history of pediatric FAP (n=144), compared with well control subjects (n=78), showed enhanced central sensitization demonstrated by greater temporal summation (wind-up) to brief, repetitive heat pulses. We also assessed the role of gender and trait anxiety in wind-up to heat pain. Women with a history of FAP showed greater wind-up to heat pain than men with a history of FAP (Ppain was ongoing at follow-up and those whose pain had resolved. Although anxiety was significantly higher in the FAP group compared with control subjects (Ppain associated with enhanced central nervous system responses to pain stimuli. Young women with a childhood history of functional abdominal pain may have a long-term vulnerability to pain that is associated with enhanced responses of the central nervous system to pain stimuli. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  13. Enhanced biocompatibility of neural probes by integrating microstructures and delivering anti-inflammatory agents via microfluidic channels

    Science.gov (United States)

    Liu, Bin; Kim, Eric; Meggo, Anika; Gandhi, Sachin; Luo, Hao; Kallakuri, Srinivas; Xu, Yong; Zhang, Jinsheng

    2017-04-01

    Objective. Biocompatibility is a major issue for chronic neural implants, involving inflammatory and wound healing responses of neurons and glial cells. To enhance biocompatibility, we developed silicon-parylene hybrid neural probes with open architecture electrodes, microfluidic channels and a reservoir for drug delivery to suppress tissue responses. Approach. We chronically implanted our neural probes in the rat auditory cortex and investigated (1) whether open architecture electrode reduces inflammatory reaction by measuring glial responses; and (2) whether delivery of antibiotic minocycline reduces inflammatory and tissue reaction. Four weeks after implantation, immunostaining for glial fibrillary acid protein (astrocyte marker) and ionizing calcium-binding adaptor molecule 1 (macrophages/microglia cell marker) were conducted to identify immunoreactive astrocyte and microglial cells, and to determine the extent of astrocytes and microglial cell reaction/activation. A comparison was made between using traditional solid-surface electrodes and newly-designed electrodes with open architecture, as well as between deliveries of minocycline and artificial cerebral-spinal fluid diffused through microfluidic channels. Main results. The new probes with integrated micro-structures induced minimal tissue reaction compared to traditional electrodes at 4 weeks after implantation. Microcycline delivered through integrated microfluidic channels reduced tissue response as indicated by decreased microglial reaction around the neural probes implanted. Significance. The new design will help enhance the long-term stability of the implantable devices.

  14. Consistent inhibition of cyclooxygenase drives macrophages towards the inflammatory phenotype.

    Directory of Open Access Journals (Sweden)

    Yi Rang Na

    Full Text Available Macrophages play important roles in defense against infection, as well as in homeostasis maintenance. Thus alterations of macrophage function can have unexpected pathological results. Cyclooxygenase (COX inhibitors are widely used to relieve pain, but the effects of long-term usage on macrophage function remain to be elucidated. Using bone marrow-derived macrophage culture and long-term COX inhibitor treatments in BALB/c mice and zebrafish, we showed that chronic COX inhibition drives macrophages into an inflammatory state. Macrophages differentiated in the presence of SC-560 (COX-1 inhibitor, NS-398 (COX-2 inhibitor or indomethacin (COX-1/2 inhibitor for 7 days produced more TNFα or IL-12p70 with enhanced p65/IκB phosphoylation. YmI and IRF4 expression was reduced significantly, indicative of a more inflammatory phenotype. We further observed that indomethacin or NS-398 delivery accelerated zebrafish death rates during LPS induced sepsis. When COX inhibitors were released over 30 days from an osmotic pump implant in mice, macrophages from peritoneal cavities and adipose tissue produced more TNFα in both the basal state and under LPS stimulation. Consequently, indomethacin-exposed mice showed accelerated systemic inflammation after LPS injection. Our findings suggest that macrophages exhibit a more inflammatory phenotype when COX activities are chronically inhibited.

  15. Post-photorefractive keratectomy pain and corneal sub-basal nerve density

    Directory of Open Access Journals (Sweden)

    Masoumeh Mohebbi

    2017-01-01

    Conclusion: Crude density of corneal nerves may not be a good predictor of post-PRK pain while wearing bandage contact lenses. The predominant pain mechanism appears to be of an inflammatory nature (not nociceptive or neuropathic.

  16. 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

    Excessive N-Methyl-d-aspartate receptor (NMDAR)-dependent production of nitric oxide (NO) is involved in the development and maintenance of chronic pain states, and is mediated by postsynaptic density protein-95 (PSD-95). By binding to both the NMDAR and neuronal NO synthase (nNOS), PSD-95 mediates...... a specific coupling between NMDAR activation and NO production. NMDAR antagonism shows anti-nociceptive action in humans and animal models of chronic pain but is associated with severe disturbances of cognitive and motor functions. An alternative approach to modulate the NMDAR-related activity is to perturb......'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...

  17. Ossificans myositis: inflammatory changes and contrast enhancement of adjacent bone shown by MR imaging

    International Nuclear Information System (INIS)

    David, H.; Jolles, E.; Le Friant, G.; Silvestre, A.; Sarrazin, J.L.; Gordoliani, Y.S.

    1995-01-01

    The authors report a case of ossificans myositis, in which magnetic resonance imaging (MRI) showed inflammatory changes of the adjacent bone. T 1 weighted fat saturation sequence with gadolinium injection showed enhancement of medullary and cortical bone. This potentially mistaking pattern must be known, to avoid mis diagnosing with malignant osseous tumor, specially before achievement of the characteristic pattern of zonal maturation and its calcified rim. (authors). 15 refs., 6 figs

  18. Spontaneous inflammatory pain model from a mouse line with N-ethyl-N-nitrosourea mutagenesis

    Directory of Open Access Journals (Sweden)

    Chen Tsung-Chieh

    2012-05-01

    in pstpip2 causes autoinflammatory disease in an N-ethyl-N-nitrosourea mutagenesis mouse model. Thus, our pstpip2 mutant mice provide a new model for investigating the potential mechanisms of inflammatory pain.

  19. Anterior cingulate cortex is crucial for contra- but not ipsi-lateral electro-acupuncture in the formalin-induced inflammatory pain model of rats

    Directory of Open Access Journals (Sweden)

    Xing Guo-Gang

    2011-08-01

    Full Text Available Abstract Acupuncture and electro-acupuncture (EA are now widely used to treat disorders like pain. We and others have shown previously that current frequency, intensity and treatment duration all significantly influence the anti-nociceptive effects of EA. There is evidence that stimulating sites also affect the antinociception, with EA applied ipsilaterally to the pain site being more effective under some pain states but contralateral EA under others. It was recently reported that local adenosine A1 receptors were responsible for ipsilateral acupuncture, but what mechanisms specifically mediate the anti-nociceptive effects of contralateral acupuncture or EA remains unclear. In the present study, we applied 100 Hz EA on the ipsi- or contra-lateral side of rats with inflammatory pain induced by intra-plantar injection of formalin, and reported distinct anti-nociceptive effects and mechanisms between them. Both ipsi- and contra-lateral EA reduced the paw lifting time in the second phase of the formalin test and attenuated formalin-induced conditioned place aversion. Contralateral EA had an additional effect of reducing paw licking time, suggesting a supraspinal mechanism. Lesions of rostral anterior cingulate cortex (ACC completely abolished the anti-nociceptive effects of contra- but not ipsi-lateral EA. These findings were not lateralized effects, since injection of formalin into the left or right hind paws produced similar results. Overall, these results demonstrated distinct anti-nociceptive effects and mechanisms between different stimulating sides and implied the necessity of finding the best stimulating protocols for different pain states.

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

    Directory of Open Access Journals (Sweden)

    Adriana Banozic

    2017-01-01

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

  1. Inflammatory pseudotumor of the liver: CT findings

    International Nuclear Information System (INIS)

    Lee, Kang Mo; Yoon, Kwon Ha; Rho, Ji Young; Park, Ki Han; Yun, Ki Jung; Kim, Chang Keun; Won, Jong Jin; Ha, Hyun Kwon; Suh, Jae Hee; Auh, Yong Ho

    1998-01-01

    To evaluate the CT features of inflammatory pseudotumor of the liver with histopathologic correlation. The CT features of 14 cases (ten patients) with pathologically proven inflammatory hepatic pseudotumor were retrospectively analyzed and correlated with resected and biopsy specimens. The size of lesions ranged between 2.0 and 7.0cm (mean, 3.7 cm); On unenhanced CT, the masses were seen as ill-defined hypodense lesions, while on contrast-enhanced CT they were heterogeneous and multiseptated, with enhancement of internal septa and peripheral wall (n=3D10). In four lesions, central low density and peripheral homogeneous enhancement were seen. On histopathological correlation, the central hypoattenuated area corresponded to chronic inflammatory cell infiltrates with foamy histiocytes, plasmacytes, and lymphocytes, while the hyperattenuated peripheral wall and internal septa represented dense fibrosis. In patients in whon CT shows a heterogeneous enhancing mass, inflammatory pseudotumor of the liver should be included in differential diagnosis

  2. Social learning contributions to the etiology and treatment of functional abdominal pain and inflammatory bowel disease in children and adults

    Institute of Scientific and Technical Information of China (English)

    Rona L Levy; Shelby L Langer; William E Whitehead

    2007-01-01

    This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular emphasis is placed on randomized controlled trials,the majority of which are multi-modal in orientation,incorporating elements of cognitive behavioral therapy,social learning, and relaxation. Based on this review,we offer methodological and clinical suggestions: (1)Research investigations should include adequate sample sizes, long-term follow-up assessments, and a credible,active control group. (2) Standard gastrointestinal practice should include, when appropriate, learning opportunities for patients and family members, for example, instruction regarding the encouragement of wellness behavior.

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

    Directory of Open Access Journals (Sweden)

    Xianbo Zhuang

    2016-07-01

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

  4. Pain after earthquake

    Directory of Open Access Journals (Sweden)

    Angeletti Chiara

    2012-06-01

    Full Text Available Abstract Introduction On 6 April 2009, at 03:32 local time, an Mw 6.3 earthquake hit the Abruzzi region of central Italy causing widespread damage in the City of L Aquila and its nearby villages. The earthquake caused 308 casualties and over 1,500 injuries, displaced more than 25,000 people and induced significant damage to more than 10,000 buildings in the L'Aquila region. Objectives This observational retrospective study evaluated the prevalence and drug treatment of pain in the five weeks following the L'Aquila earthquake (April 6, 2009. Methods 958 triage documents were analysed for patients pain severity, pain type, and treatment efficacy. Results A third of pain patients reported pain with a prevalence of 34.6%. More than half of pain patients reported severe pain (58.8%. Analgesic agents were limited to available drugs: anti-inflammatory agents, paracetamol, and weak opioids. Reduction in verbal numerical pain scores within the first 24 hours after treatment was achieved with the medications at hand. Pain prevalence and characterization exhibited a biphasic pattern with acute pain syndromes owing to trauma occurring in the first 15 days after the earthquake; traumatic pain then decreased and re-surged at around week five, owing to rebuilding efforts. In the second through fourth week, reports of pain occurred mainly owing to relapses of chronic conditions. Conclusions This study indicates that pain is prevalent during natural disasters, may exhibit a discernible pattern over the weeks following the event, and current drug treatments in this region may be adequate for emergency situations.

  5. Anti-inflammatory and antinociceptive activities of Solenostemon monostachyus aerial part extract in mice

    Directory of Open Access Journals (Sweden)

    Jude Fiom Okokon

    2016-04-01

    Full Text Available Objective: Solenostemon monostachyus is used in traditional medicine for the treatment of various ailments such as ulcer, hypertension, pains and inflammatory diseases. Evaluation of anti-inflammatory and analgesic activities of S. monostachyus aerial parts was carried out to ascertain its uses in traditional medicine. Materials and Methods: The aerial parts of S. monostachyus was cold extracted by soaking the dried powdered material in ethanol. The aerial parts crude extract (75 –225 mg/kg of  S. monostachyus was investigated for analgesic and anti-inflammatory activities using various experimental models; acetic acid, formalin and thermal- induced pains models for analgesic study and carrageenin, egg albumin and xylene – induced edema models for anti-inflammatory investigation. Results: The extract caused a significant (pConclusion: The anti-inflammatory and analgesic effects of this plant may in part be mediated through the chemical constituents of the plant and the results of the analgesic action suggest central and peripheral mechanisms. The findings of this work confirm the ethno medical use of this plant to treat inflammatory conditions.

  6. P2X7 receptor-mediated analgesia in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; D. Schwab, Samantha; Frøsig-Jørgensen, Majbrit

    2015-01-01

    Pain is a common and debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of molecular events, including mechanisms observed in inflammatory and neuropathic pain states, but also changes unique for ca...

  7. Exercise in fibromyalgia and related inflammatory disorders: known effects and unknown chances.

    Science.gov (United States)

    Ortega, E; García, J J; Bote, M E; Martín-Cordero, L; Escalante, Y; Saavedra, J M; Northoff, H; Giraldo, E

    2009-01-01

    Fibromyalgia (FM) is characterised by chronic widespread pain and allodynia (pain from stimuli which are not normally painful with pain that may occur other than in the area stimulated) of more than 3 months duration. The current hypothesis of the aetiology of FM includes inflammatory and neuroendocrine disorders. The biophysiology of this syndrome, however; remains still widely elusive, and there are no formally approved therapies. Non-pharmacological interventions in FM patients include habitual exercise programs which improve physical function and quality of life of patients and may even reduce pain. However the mechanisms through which exercise benefits FM symptoms needs to be elucidated. In this article we firstly review the main topics and characteristics of the FM syndrome, while focusing our attention on the inflammatory hypothesis of FM, as well as on the beneficial effects of habitual exercise as a co-therapy for FM patients. In this context, the latest developments in research on anti-inflammatory effects of exercise are also reviewed and discussed. To find out what is known about the connection between benefits of exercise for FM and anti-inflammatory effects of exercise, we carried out a PubMed search using the term "fibromyalgia" and "exercise" together with "inflammation", and no more than ten published articles were found (six of them reviews), which are also discussed. In the second part of the article we present a pilot investigation on a group of 14 female FM patients with a diagnosis of FM by a rheumatologist. They took part in a pool-aquatic program in warm water over a period of fourth months (three weekly 60-min sessions). Circulating inflammatory (IL-1beta, IL-2, IFNgamma, TNFalpha, IL-8, IL-6, IL-4, IL-10 and CRP) and neuroendocrine (NA and cortisol) markers were determined. FM patients showed higher circulating levels of IL-8, IFNgamma and CRP as well as cortisol and NA than age-matched healthy control women. After the exercise program, a

  8. Modifying tetramethyl–nitrophenyl–imidazoline with amino acids: design, synthesis, and 3D-QSAR for improving inflammatory pain therapy

    Directory of Open Access Journals (Sweden)

    Jiang X

    2015-04-01

    Full Text Available Xueyun Jiang,1 Yuji Wang,1 Haimei Zhu,1 Yaonan Wang,1 Ming Zhao,1,2 Shurui Zhao,1 Jianhui Wu,1 Shan Li,1 Shiqi Peng11Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, TaiwanAbstract: With the help of pharmacophore analysis and docking investigation, 15 novel 1-(4,4,5,5-tetramethyl-2-(3-nitrophenyl-4,5-dihydroimidazol-1-yl-oxyacetyl-L-amino acids (6a–o were designed, synthesized, and assayed. On tail-flick and xylene-induced ear edema models, 10 µmol/kg 6a–o exhibited excellent oral anti-inflammation and analgesic activity. The dose-dependent assay of their representative 6f indicates that the effective dose should be 3.3 µmol/kg. The correlation of the three-dimensional quantitative structure–activity relationship with the docking analysis provides a basis for the rational design of drugs to treat inflammatory pain.Keywords: tetramethylimidazoline, analgesic, anti-inflammatory, 3D-QSAR

  9. Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

    Science.gov (United States)

    Owoyele, Bamidele Victor; Oladejo, Rasheed Olajiire; Ajomale, Kayode; Ahmed, Rasheedat Omotayo; Mustapha, Abdulrasheed

    2014-03-01

    The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

  10. Pain and Its Management in Animals | Mogoa | Kenya Veterinarian

    African Journals Online (AJOL)

    Although the selection and techniques of administration of individual analgesic drugs vary, local and opioid analgesics, non-steroidal anti-inflammatory drugs, tranquilizers and other combination therapies when used appropriately can control pain and alleviate suffering in animals experiencing pain. This paper looks at ...

  11. Craniofacial Pain: Brainstem Mechanisms

    Directory of Open Access Journals (Sweden)

    Barry J Sessle

    1996-01-01

    Full Text Available This article reviews recent research advances in animals that have identified critical neural elements in the brainstem receiving and transmitting craniofacial nociceptive inputs, as well as some of the mechanisms involved in the modulation and plasticity of nociceptive transmission. Nociceptive neurones in the trigeminal (V brainstem sensory nuclear complex can be classified as nociceptive-specific (NS or wide dynamic range (WDR. Some of these neurones respond exclusively to sensory inputs evoked by stimulation of facial skin or oral mucosa and have features suggesting that they are critical neural elements involved in the ability to localize an acute superficial pain and sense its intensity and duration. Many of the V brainstem nociceptive neurones, however, receive convergent inputs from afferents supplying deep craniofacial tissues (eg, dural vessel, muscle and skin or mucosa. These neurones are likely involved in deep pain, including headache, because few nociceptive neurones receive inputs exclusively from afferents supplying these tissues. These extensive convergent input patterns also appear to be important factors in pain spread and referral, and in central mechanisms underlying neuroplastic changes in V neuronal properties that may occur with injury and inflammation. For example, application of the small fibre excitant and inflammatory irritant mustard oil into the temporomandibular joint, masseter or tongue musculature induces a prolonged but reversible enhancement of responses to cutaneous and deep afferent inputs of most WDR and NS neurones. These effects may be accompanied by increased electromyographic activity reflexly induced in the masticatory muscles by mustard oil, and involve endogenous N-methyl-D-aspartate and opioid neurochemical mechanisms. Such peripherally induced modulation of brainstem nociceptive neuronal properties reflects the functional plasticity of the central V system, and may be involved in the development of

  12. Quantitative analysis of contrast enhanced MRI of the inferior alveolar nerve in inflammatory changes of the mandible

    International Nuclear Information System (INIS)

    Gottschalk, G.; Gerber, S.; Solbach, T.; Baehren, W.; Anders, L.; Kress, B.

    2003-01-01

    Purpose: To evaluate the role of contrast enhanced MRI in quantifying signal changes of the inferior alveolar nerve following inflammatory changes of the mandible. Material and methods: 30 patients with inflammatory changes of the mandible underwent MRI of the face. Both sides of the mandible, the affected as well as the unaffected healthy side were evaluated retrospectively. Regions of interest were placed at 5 defined placed on both sides to assess signal intensity before and after intravenous application of paramagnetic contrast agent. The results of the measurements were compared between the healthy and the affected side (t-test, p [de

  13. MRI appearances of inflammatory vertebral osteitis in early ankylosing spondylitis

    Energy Technology Data Exchange (ETDEWEB)

    Kurugoglu, Sebuh; Kanberoglu, Kaya; Mihmanli, Ismail; Cokyuksel, Oktay [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University (Turkey); Kanberoglu, Ayfer [Department of Physical Medicine, SSK Istanbul Hospital, Istanbul (Turkey)

    2002-03-01

    Background: Undiagnosed and early ankylosing spondylitis (AS), especially in adolescent patients suffering from back pain, may present with the finding of vertebral osteitis on MRI. Aims: To identify the early MRI changes of vertebral osteitis in AS. Patients and methods: Five patients (three boys, two girls) aged 11-20 years (mean 15.4 years) suffering from back pain underwent MRI of the thoracolumbar spine. There was no initial diagnosis of AS. After clinical and radiological suspicion of AS, MRI of the sacroiliac (SI) joints was performed. Results: During the course of AS, destructive and reactive changes affect the discovertebral junctions that are initially seen in the thoracolumbar area. At this stage plain radiography of the spinal column may be normal. On MR images, inflammatory osteitis of the vertebrae is seen as hypointense areas on T1-weighted images and hyperintense areas on T2-W images. The lesions enhance homogenously with contrast material. Conclusions: Awareness of the MRI appearances of vertebral osteitis is helpful in suspecting AS. Radiological examination of the SI facilitates the diagnosis and unnecessary further imaging can be avoided. (orig.)

  14. Acute dental pain II

    DEFF Research Database (Denmark)

    Jonasson, Peter; Kirkevang, Lise-Lotte; Rosen, Annika

    2016-01-01

    Acute dental pain most often occurs in relation to inflammatory conditions in the dental pulp or in the periradicular tissues surrounding a tooth, but it is not always easy to reach a diagnose and determine what treatment to perform. The anamnesis and the clinical examination provide valuable...

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

    Science.gov (United States)

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

    2018-06-01

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

  16. Thermal grill-evoked sensations of heat correlate with cold pain threshold and are enhanced by menthol and cinnamaldehyde.

    Science.gov (United States)

    Averbeck, B; Rucker, F; Laubender, R P; Carr, R W

    2013-05-01

    Thunberg's thermal grill produces a sensation of strong heat upon skin contact with spatially interlaced innocuous warm and cool stimuli. To examine the classes of peripheral axons that might contribute to this illusion, the effects of topical l-menthol, an activator of TRPM8, and cinnamaldehyde, a TRPA1 agonist, on the magnitude of thermal sensations were examined during grill stimulation in healthy volunteers. Under control conditions, cutaneous grill stimulation (interlaced 20/40 °C) evoked a sensation of heat, and for individual subjects, the magnitude of this heat sensation was positively correlated with cold pain threshold (CPT). Menthol increased the CPT and enhanced the magnitude of grill-evoked heat. Cinnamaldehyde intensified warm sensations, reduced heat pain threshold and also enhanced grill-evoked heat. Both TRPM8-expressing and TRPA1-expressing afferent axons can affect grill-evoked thermal sensations. The enhancement of grill-evoked sensations of temperature with menthol and cinnamaldehyde may provide an additional clinically relevant means of testing altered thermal sensitivity, which is often affected in neuropathic patient groups. © 2012 European Federation of International Association for the Study of Pain Chapters.

  17. A selective role for α3 subunit glycine receptors in inflammatory pain

    Directory of Open Access Journals (Sweden)

    Victoria L Harvey

    2009-11-01

    Full Text Available GlyR α3 has previously been found to play a critical role in pain hypersensitivity following spinal PGE2 injection, complete Freund’s adjuvant (CFA and zymosan induced peripheral inflammation. In this study, although all models displayed typical phenotypic behaviours, no significant differences were observed when comparing the pain behaviours of Glra3-/- and wild-type littermates following the injection of capsaicin, carrageenan, kaolin/ carrageenan or monosodium iodoacetate, models of rheumatoid and osteoarthritis, respectively. However, clear differences were observed following CFA injection (p < 0.01. No significant differences were observed in the pain behaviours of Glra3-/- and wild-type littermates following experimentally induced neuropathic pain (partial sciatic nerve ligation. Similarly, Glra3-/- and wild-type littermates displayed indistinguishable visceromotor responses to colorectal distension (a model of visceral pain and in vivo spinal cord dorsal horn electrophysiology revealed no differences in responses to multimodal suprathreshold stimuli, intensities which equate to higher pain scores such as those reported in the clinic. These data suggest that apart from its clear role in CFA- and zymosan-induced pain sensitisation, hypersensitivity associated with other models of inflammation, neuropathy and visceral disturbances involves mechanisms other than the EP2 receptor - GlyR α3 pathway.

  18. Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

    Science.gov (United States)

    Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

    2018-01-15

    Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats

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    Miroslav Dinić

    2018-01-01

    Full Text Available The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11 to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1β and iNOS mRNAs in rat’s paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1β, TNF-α and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.

  20. Synthesis, Analgesic, Anti-inflammatory and Antimicrobial Activities ...

    African Journals Online (AJOL)

    Purpose: Microbial infections often produce pain and inflammation. Chemotherapeutic, analgesic and anti-inflammatory drugs are prescribed simultaneously in normal practice. The compound possessing all three activities is not common.The purpose of the present study was to examine whether molecular modification ...

  1. The anti-inflammatory effects of venlafaxine in the rat model of carrageenan-induced paw edema

    Directory of Open Access Journals (Sweden)

    Valiollah Hajhashemi

    2015-07-01

    Full Text Available Objective(s:Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin norepinephrine reuptake inhibition property. The pain alleviating properties of venlafaxine in different pain models such as neurogenic pain, diabetic neuropathy, and fibromyalgia have been demonstrated. Anti-inflammatory effects of venlafaxine and also its underlying mechanisms remain unclear. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine and determine possible underlying mechanisms. Materials and Methods: We examined the anti-inflammatory effects of intraperitoneal (IP and intracerebroventricular (ICV administration of venlafaxine in the rat model of carrageenan-induced paw edema. Results: Our results showed that both IP (50 and 100 mg/kg and ICV (50 and 100 μg/rat injection of venlafaxine inhibited carrageenan-induced paw edema. Also IP and ICV administration of venlafaxine significantly decreased myeloperoxidase (MPO activity and interleukin (IL-1β and tumor necrosis factor (TNF-α production. Finally, we tried to reverse the anti-inflammatory effect of venlafaxine by yohimbine (5 mg/kg, IP, an alpha2-adrenergic antagonist. Our results showed that applied antagonist failed to change the anti-inflammatory effect of venlafaxine. Conclusion: These results demonstrated that venlafaxine has potent anti-inflammatory effect which is related to the peripheral and central effects of this drug. Also we have shown that anti-inflammatory effect of venlafaxine is mediated mostly through the inhibition of IL-1β and TNF-α production and decreases MPO activity in the site of inflammation.

  2. Investigation on the anti- inflammatory and analgesic effects of Olea europaea L. metanolic extract on male NMRI mouse

    Directory of Open Access Journals (Sweden)

    Elaheh Tekye

    2012-04-01

    Full Text Available Background: Different mediators are involved in pain and edema induction during different stages of inflammation. Then, treatment of them encounters some difficulties. Medicinal plants are an important source of substances which are claimed to induce anti-inflammatory effects. This study was aimed to investigate anti-inflammatory and analgesic effects of Olea europaea L.methanolic extract on male NMRI mouse. Methods: Methanolic extraction was done for leaf of Olea europaea L. and different doses (200, 300 and 400 mg/kg were intraperitoneally (i.p. adminstered to male NMRI mice. Analgesic and anti-inflammatory effects of extract was measured during both phases of Formalin test, Acetic acid induced visceral pain and xylene inflammation tests. A standard analgesic and anti-inflammatory drug such as indomethacin, dexamethasone and morphine were administered in positive control groups where appropriates. Results: Results indicated significant dose-dependent analgesic and anti-inflammatory effects of methanolic extract of Olea europaea L. leaf on pain which induced by formalin (both phase and acetic acid, and inflammation caused by xylene. Conclusion: Our findings Showed that administration of methanolic extract of Olea europaea L.leaf can suppress pain and inflammation dose dependently which, may mediate via different components of extract. However, more investigations need to be done.

  3. Does catastrophic thinking enhance oesophageal pain sensitivity?

    DEFF Research Database (Denmark)

    Martel, M O; Olesen, A E; Jørgensen, D

    2016-01-01

    that catastrophic thinking exerts an influence on oesophageal pain sensitivity, but not necessarily on the magnitude of acid-induced oesophageal sensitization. WHAT DOES THIS STUDY ADD?: Catastrophizing is associated with heightened pain sensitivity in the oesophagus. This was substantiated by assessing responses...

  4. A Review of Select Centralized Pain Syndromes

    Directory of Open Access Journals (Sweden)

    David R. Spiegel

    2015-01-01

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

  5. Aspects of dentinal and pulpal pain. Pain of dentinal and pulpal origin--a review for the clinician.

    Science.gov (United States)

    Figdor, D

    1994-04-01

    Recent advances in understanding the mechanisms of pain arising from the dental pulp serve to benefit patients by improving the clinician's ability to diagnose and treat pain. There are two types of pain arising from the pulp which are mediated by entirely different nerve fibres, each with their own individual characteristics. One is a short, sharp fast pain which is induced by stimuli which cause a rapid fluid flow within the dentinal tubules. Such stimuli include cold, heat, air, drilling, and osmotic stimuli. Once the affected teeth are identified, they can often be treated by sealing the open, exposed dentine. The second type of pain is experienced as a slow, dull, aching, poorly localized pain which is mediated by pain fibres activated by stimuli which are noxious to the pulp, such as prolonged damaging heat and inflammatory mediators. Pain of this character can be difficult to diagnose and often indicates serious pulp damage necessitating removal of the offending pulp by endodontic therapy.

  6. Anti-inflammatory and Analgesic Activities of Amorphophallus bulbifer

    African Journals Online (AJOL)

    HP

    time of the animals treated with either standard or extract. Pentazocin ... standard. Results: The extract showed significant anti-inflammatory and analgesic activities at the two test dose ..... effectiveness of analgesic agents in the tail- flick pain ...

  7. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Zhang, Yong, E-mail: zhangyong1956@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100, Shaanxi (China); Gao, Ming-Qing, E-mail: gaomingqing@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100, Shaanxi (China)

    2016-11-15

    Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.

  8. Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis

    International Nuclear Information System (INIS)

    Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

    2016-01-01

    Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.

  9. Evolutionary considerations in the development of chronic pelvic pain.

    Science.gov (United States)

    Jarrell, John; Arendt-Nielsen, Lars

    2016-08-01

    Chronic pelvic pain is common among women of reproductive age and is associated with significant morbidity and comorbidities. In this Viewpoint, we explore the evolutionary cause of pelvic pain and summarize evidence that supports a menstruation-related evolutionary cause of chronic visceral pelvic pain: (1) lifetime menstruation has increased; (2) severe dysmenorrhea is common in the chronic pelvic pain population, particularly among those with pain sensitization; and (3) a potential biological mechanism can be identified. Thus, chronic pelvic pain may arise from the mismatch between the slow pace of biological evolution in our bodies and the relatively rapid pace of cultural changes that have resulted in increased menstrual frequency due to earlier menarche, later mortality, and lower fecundity. One possible mechanism that explains the development of persistent pain from repeated episodes of intermittent pain is hyperalgesic priming, a physiological process defined as a long-lasting latent hyperresponsiveness of nociceptors to inflammatory mediators after an inflammatory or neuropathic insult. The repetitive severely painful menstrual episodes may play such a role. From an evolutionary perspective the relatively rapid increase in lifetime menstruation experience in contemporary society may contribute to a mismatch between lifetime menstruation and the physiological pain processes, leading to a maladaptive state of chronic visceral pelvic pain. Our current physiology does not conform to current human needs. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Francesco Rossi

    2010-08-01

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

  11. Tramadol hydrochloride/acetaminophen combination versus non-steroidal anti-inflammatory drug for the treatment of perioperative pain after total knee arthroplasty: A prospective, randomized, open-label clinical trial.

    Science.gov (United States)

    Mochizuki, Takeshi; Yano, Koichiro; Ikari, Katsunori; Hiroshima, Ryo; Takaoka, Hiromitsu; Kawakami, Kosei; Koenuma, Naoko; Ishibashi, Mina; Shirahata, Toshikatsu; Momohara, Shigeki

    2016-09-01

    While many of the commonly used treatments for perioperative pain after total knee arthroplasty (TKA) have been recognized as effective, there is still insufficient evidence for oral medication. In orthopedics, non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used for perioperative pain; however, serious adverse events have been reported. Conversely, tramadol hydrochloride/acetaminophen combination (TRAM/APAP) therapy has been shown to reduce pain, particularly for chronic pain in Japan. This study aimed to determine TRAM/APAP efficacy in comparison with NSAIDs for perioperative pain after TKA. Two hundred eighty patients were enrolled in this study; 137 patients were treated with TRAM/APAP, and 143 patients were treated with NSAID from postoperative (PO) day 2. The primary endpoint was a comparison between the pain visual analog scale (VAS) change from baseline (PO day 2) and PO day 4, day 7, day 10, and day 14. The second endpoint was the number of days until the patient achieved independence from cane walking. Analysis of endpoints included 130 and 139 patients in the TRAM/APAP and NSAID groups, respectively. The pain VAS change in the TRAM/APAP group on any of the measurement days was significantly improved compared with the NSAID group (P pain management after TKA of TRAM/APAP was shown to be superior to that of NSAID; TRAM/APAP was also effective in improving the progress of rehabilitation. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  12. Pain management in older adults.

    Science.gov (United States)

    Tracy, Bridget; Sean Morrison, R

    2013-11-01

    Chronic pain is prevalent among older adults but is underrecognized and undertreated. The approach to pain assessment and management in older adults requires an understanding of the physiology of aging, validated assessment tools, and common pain presentations among older adults. To identify the overall principles of pain management in older adults with a specific focus on common painful conditions and approaches to pharmacologic treatment. We searched PubMed for common pain presentations in older adults with heart failure, end-stage renal disease, dementia, frailty, and cancer. We also reviewed guidelines for pain management. Our review encompassed 2 guidelines, 10 original studies, and 22 review articles published from 2000 to the present. This review does not discuss nonpharmacologic treatments of pain. Clinical guidelines support the use of opioids in persistent nonmalignant pain. Opioids should be used in patients with moderate or severe pain or pain not otherwise controlled but with careful attention to potential toxic effects and half-life. In addition, clinical practice guidelines recommend use of oral nonsteroidal anti-inflammatory drugs with extreme caution and for defined, limited periods. An understanding of the basics of pain pathophysiology, assessment, pharmacologic management, and a familiarity with common pain presentations will allow clinicians to effectively manage pain for older adults. © 2013 Elsevier HS Journals, Inc. All rights reserved.

  13. Dental Pulp Cells Isolated from Teeth with Superficial Caries Retain an Inflammatory Phenotype and Display an Enhanced Matrix Mineralization Potential

    Directory of Open Access Journals (Sweden)

    Reem El-Gendy

    2017-04-01

    Full Text Available We have isolated dental pulp cells (DPCs from three healthy (hDPCs and three carious (cDPCs donors and shown that compared to hDPCs cells isolated from superficial carious lesions show higher clonogenic potential; show an equivalent proportion of cells with putative stem cell surface markers; show enhanced matrix mineralization capability; have enhanced angiogenic marker expression and retain the inflammatory phenotype in vitro characteristic of superficial caries lesions in vivo. Our findings suggest that cDPCs may be used for further investigation of the cross talk between inflammatory, angiogenic and mineralization pathways in repair of carious pulp. In addition cells derived from carious pulps (almost always discarded may have potential for future applications in mineralized tissue repair and regeneration.

  14. Kinin B1 receptors contributes to acute pain following minor surgery in humans

    Directory of Open Access Journals (Sweden)

    Brahim Jaime S

    2010-02-01

    Full Text Available Abstract Background Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Results Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. Conclusions These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the

  15. Assessment of inflammatory activity in Crohn's disease by means of dynamic contrast-enhanced MRI.

    Science.gov (United States)

    Pupillo, V A; Di Cesare, E; Frieri, G; Limbucci, N; Tanga, M; Masciocchi, C

    2007-09-01

    Our aim was to perform a dynamic study of contrast enhancement of the intestinal wall in patients with Crohn's disease to quantitatively assess local inflammatory activity. We studied a population of 50 patients with histologically proven Crohn's disease. Magnetic resonance imaging (MRI) was performed using a 1.5-T magnet with a phased-array coil and acquisition of T2-weighted single-shot fast spin echo (SSFSE) half Fourier sequences before intravenous administration of gadolinium, and T1-weighted fast spoiled gradient (FSPGR) fat-saturated sequences before and after contrast administration. Before the examination, patents received oral polyethylene glycol (PEG) (1,000 ml for adults; 10 ml/Kg of body weight for children). Regions of interest (ROI) were placed on the normal and diseased intestinal wall to assess signal intensity and rate of increase in contrast enhancement over time. Data were compared with the Crohn's Disease Activity Index (CDAI). The diseased bowel wall showed early and intense uptake of contrast that increases over time until a plateau is reached. In patients in the remission phase after treatment, signal intensity was only slightly higher in diseased bowel loops than in healthy loops. There was a significant correlation between the peak of contrast uptake and CDAI. Dynamic MRI is a good technique for quantifying local inflammatory activity of bowel wall in patients with Crohn's disease.

  16. Anti-inflammatory, antinociceptive activity of an essential oil recipe consisting of the supercritical fluid CO2 extract of white pepper, long pepper, cinnamon, saffron and myrrh in vivo.

    Science.gov (United States)

    Zhang, Yuanbin; Wang, Xinfang; Ma, Ling; Dong, Lin; Zhang, Xinhui; Chen, Jing; Fu, Xueyan

    2014-01-01

    This study was designed to investigate the anti-inflammatory and antinociceptive activities of essential oil recipe (OR) in rodents. The anti-inflammatory activity was evaluated by inflammatory models of dimethylbenzene (DMB)-induced ear vasodilatation and acetic acid-induced capillary permeability enhancement in mice whereas the antinociceptive activity was evaluated using acetic acid-induced writhes and hot plate test methods in mice. Additionally, the chemical composition of OR has been also analyzed by gas chromatography and mass spectrometry (GC/MS). 37 compounds, representing 74.42% of the total oil content, were identified. β-Selinene (7.38%), aromadendrene (5.30%), β-elemene (5.22%), cis-piperitol (5.21%), cis-β-guaiene (4.67%), ylangene (3.70%), 3-heptadecene (3.55%), δ-cadinene (3%) and β-cadinene (2.87%) were found to be the major constituents of the oil. Oral pretreatment with OR (62.5-1000 mg/kg) not only decreased the DMB-induced ear vasodilatation but also attenuated capillary permeability under acetic acid challenge in mice. OR significantly reduced the writhing number evoked by acetic acid injection. All test samples showed no significant analgesic activity on the hot plate pain threshold in mice. These data demonstrated that the OR inhibits inflammatory and peripheral inflammatory pain. These results may support the fact that the essential oil of traditional Hui prescription played a role in the inflammation of stroke.

  17. Tramadol plus metamizole combined or not with anti-inflammatory drugs is clinically effective for moderate to severe chronic pain treatment in cancer patients.

    Science.gov (United States)

    Flôr, Patrícia B; Yazbek, Karina V B; Ida, Keila K; Fantoni, Denise T

    2013-05-01

    To test the effectiveness and safety of tramadol plus metamizole combined or not with a non-steroidal anti-inflammatory drug (NSAID) for treating moderate to severe chronic neoplastic pain in dogs, and its impact on quality of life (QL). Prospective, uncontrolled, open-label, clinical study. Sixty nine client-owned dogs with multiple forms of cancer and visual analog scale (VAS) pain score ≥ 40 after receiving NSAIDs for at least 7 days. The MN group received metamizole + NSAID, MNT group received metamizole + NSAID + tramadol and MT group received metamizole + tramadol. Pain was scored by the 0 to 100 mm VAS (0 = no pain, 100 = worst pain) and analgesic therapy was considered effective if 25 mm differences in VAS scores were observed between day 0 and the follow ups. The QL was evaluated according to a 0 to 36 scoring method for dogs (0 = worst, 36 = best) and side effects were recorded. Data were registered at day 0 (baseline) and at the first and second follow ups (7 and 14 days after day 0, respectively). The MN group had less analgesia at day 7 (25%) and day 14 (42%) than MNT (59%, p = 0.0274; 76%, p = 0.0251, respectively) and MT groups (69%, p = 0.0151; 81%, p = 0.0341, respectively). The QL scores were lower in the MN group at the first (score 23) and second follow up (score 26) than in MNT (27, p = 0.0847; 30, p = 0.0002) and MT (28, p = 0.0384; 31, p = 0.0001) groups. Side effects were more commonly observed in the MN group (87%) than in MNT (24%, p pain in dogs with cancer and improved QL. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  18. The role of the blood–brain barrier in the development and treatment of migraine and other pain disorders

    Science.gov (United States)

    DosSantos, Marcos F.; Holanda-Afonso, Rosenilde C.; Lima, Rodrigo L.; DaSilva, Alexandre F.; Moura-Neto, Vivaldo

    2014-01-01

    The function of the blood–brain barrier (BBB) related to chronic pain has been explored for its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as opioid analgesics (e.g., morphine) and non-steroidal anti-inflammatory drugs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. Furthermore, inflammatory pain produces structural changes in the P-glycoprotein, the major efflux transporter at the BBB. One possible explanation for these findings is the action of substances typically released at the site of peripheral injuries that could lead to changes in the brain endothelial permeability, including substance P, calcitonin gene-related peptide, and interleukin-1 beta. Interestingly, inflammatory pain also results in microglial activation, which potentiates the BBB damage. In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood–spinal cord barrier and blood–nerve barrier, and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine. PMID:25339863

  19. The role of the blood-brain barrier in the development and treatment of migraine and other pain disorders

    Directory of Open Access Journals (Sweden)

    Marcos Fabio DosSantos

    2014-10-01

    Full Text Available The function of the blood-brain barrier (BBB related to chronic pain has been explored by its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as the opioid analgesics (e.g., morphine and non-steroidal anti-inflammatory drugs (NSAIDs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. Furthermore, inflammatory pain produces structural changes in the P-glycoprotein (P-gp, the major efflux transporter at the BBB. One possible explanation for these findings is the action of substances typically released at the site of peripheral injuries that could lead to changes in the brain endothelial permeability, including: substance P, calcitonin gene related peptide (CGRP and IL- 1β. Interestingly, inflammatory pain also results in microglial activation, which potentiates the BBB damage. In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood-spinal cord barrier (BSCB and blood-nerve barrier (BNB and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine.

  20. HLA-B27 and gender independently determine the likelihood of a positive MRI of the sacroiliac joints in patients with early inflammatory back pain: a 2-year MRI follow-up study

    NARCIS (Netherlands)

    van Onna, M.; Jurik, A. G.; van der Heijde, D.; van Tubergen, A.; Heuft-Dorenbosch, L.; Landewé, R.

    2011-01-01

    To describe how inflammation on MRI of the sacroiliac joints in patients with recent-onset inflammatory back pain (IBP) evolves over time, and to study determinants of activity on MRI of the sacroiliac joint. A 2-year follow-up study with annual MRI of the sacroiliac joints was conducted in patients

  1. Evaluation of reward from pain relief

    Science.gov (United States)

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

    2014-01-01

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

  2. Cognitive and Physical Fatigue Tasks Enhance Pain, Cognitive Fatigue and Physical Fatigue in People with Fibromyalgia

    Science.gov (United States)

    Dailey, Dana L; Keffala, Valerie J; Sluka, Kathleen A

    2014-01-01

    Objective Fibromyalgia is a condition characterized by chronic widespread muscle pain and fatigue. The primary objective of this study was to determine if pain, perceived cognitive fatigue, and perceived physical fatigue were enhanced in participants with fibromyalgia compared to healthy controls during a cognitive fatigue task, a physical fatigue task and a dual fatigue task. Methods Twenty four people with fibromyalgia and 33 healthy controls completed pain, fatigue and function measures. A cognitive fatigue task (Controlled Oral Word Association Test) and physical fatigue task (Valpar peg test) were done individually and combined for a dual fatigue task. Resting pain, perceived cognitive fatigue and perceived physical fatigue were assessed during each task using visual analogue scales. Function was assessed with shoulder range of motion and grip. Results People with fibromyalgia had significantly higher increases in pain, cognitive fatigue and physical fatigue when compared to healthy controls after completion of a cognitive fatigue task, a physical fatigue task, or a dual fatigue task (pfatigue tasks, respectively. Conclusions These data show that people with fibromyalgia show larger increases in pain, perceived cognitive fatigue and perceived physical fatigue to both cognitive and physical fatigue tasks compared to healthy controls. The increases in pain and fatigue during cognitive and physical fatigue tasks could influence subject participation in daily activities and rehabilitation. PMID:25074583

  3. Pain Management in Functional Gastrointestinal Disorders

    Directory of Open Access Journals (Sweden)

    Antonio Vigano

    1995-01-01

    Full Text Available Pain is a common feature in functional gastrointestinal disorders (FGID. An abnormally low visceral sensory threshold, as well as a number of central, spinal and peripheral pain-modulating abnormalities, have been proposed for this syndrome. Clinical aspects of pain associated with irritable esophagus, functional dyspepsia, biliary dysmotility, inflammatory bowel syndrome and proctalgia fugax are reviewed. Because of its unclear pathophysiology, pain expression is the main target for the successful assessment and management of symptomatic FGID. The sensory, cognitive and affective components of pain intensity expression need to be addressed in the context of a good physician-patient rapport. A multidisciplinary team approach is ideal for the smaller subset of patients with severe and disabling symptoms. Although pharmacotherapy may target specific functional disorders, the role of behavioural techniques and psychotherapy appears much more important for pain management in FGID. Functional performance and quality of life improvement, rather than pain intensity, are the main therapeutic goals in these patients.

  4. Antibacterial and Anti-Inflammatory Activities of Anacardium ...

    African Journals Online (AJOL)

    ABSTRACT: Anacardium occidentale is a local medicinal plant used in ethno medicine for the treatment of diarrhea, constipation,pain and inflammation. The aqueous and ethanolic extracts of this plant parts were assessed for anti- inflammatory and antibacterial activities using experimental animal model and agar disc ...

  5. Testing a path-analytic mediation model of how motivational enhancement physiotherapy improves physical functioning in pain patients.

    Science.gov (United States)

    Cheing, Gladys; Vong, Sinfia; Chan, Fong; Ditchman, Nicole; Brooks, Jessica; Chan, Chetwyn

    2014-12-01

    Pain is a complex phenomenon not easily discerned from psychological, social, and environmental characteristics and is an oft cited barrier to return to work for people experiencing low back pain (LBP). The purpose of this study was to evaluate a path-analytic mediation model to examine how motivational enhancement physiotherapy, which incorporates tenets of motivational interviewing, improves physical functioning of patients with chronic LBP. Seventy-six patients with chronic LBP were recruited from the outpatient physiotherapy department of a government hospital in Hong Kong. The re-specified path-analytic model fit the data very well, χ (2)(3, N = 76) = 3.86, p = .57; comparative fit index = 1.00; and the root mean square error of approximation = 0.00. Specifically, results indicated that (a) using motivational interviewing techniques in physiotherapy was associated with increased working alliance with patients, (b) working alliance increased patients' outcome expectancy and (c) greater outcome expectancy resulted in a reduction of subjective pain intensity and improvement in physical functioning. Change in pain intensity also directly influenced improvement in physical functioning. The effect of motivational enhancement therapy on physical functioning can be explained by social-cognitive factors such as motivation, outcome expectancy, and working alliance. The use of motivational interviewing techniques to increase outcome expectancy of patients and improve working alliance could further strengthen the impact of physiotherapy on rehabilitation outcomes of patients with chronic LBP.

  6. The efficacy of tramadol/acetaminophen combination tablets (Ultracet®) as add-on and maintenance therapy in knee osteoarthritis pain inadequately controlled by nonsteroidal anti-inflammatory drug (NSAID).

    Science.gov (United States)

    Park, Kyung-Su; Choi, Jin-Jung; Kim, Wan-Uk; Min, June-Ki; Park, Sung-Hwan; Cho, Chul-Soo

    2012-02-01

    The purpose of this study is to compare the efficacy of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (tramadol/APAP) with that of nonsteroidal anti-inflammatory drugs (NSAIDs) as maintenance therapy following tramadol/APAP and NSAID combination therapy in knee osteoarthritis (OA) pain which was inadequately controlled by NSAIDs. Subjects with knee OA for over 1 year and moderate pain (numerical rating scale [NRS] ≥5) despite at least 4 weeks' NSAID therapy (meloxicam 7.5 mg or 15 mg qd or aceclofenac 100 mg bid) received tramadol/APAP add-on (combination with NSAID) for 4 weeks. Thereafter, subjects with significant pain improvement (NRS pain intensity (NRS), pain relief score, and subjects' and investigators' overall medication assessments. Of 143 subjects enrolled, 112 completed the 4-week tramadol/APAP and NSAID combination phase and 97 (67.8%) experienced significant pain improvement. Of the 97 subjects randomized, 36 in tramadol/APAP group and 47 in NSAID group completed the 8-week comparator study. On days 29 and 57, WOMAC scores and pain intensities did not increase in both groups compared to measurements immediately after the combination therapy. At these two time points, there were no significant differences in WOMAC scores, pain intensities, and other secondary measures between the two groups. Overall adverse event rates were similar in both groups. Tramadol/APAP add-on significantly improved knee OA pain which had been inadequately controlled by NSAIDs. In those subjects who showed favorable response to tramadol/APAP and NSAID combination therapy, both tramadol/APAP and NSAIDs were effective at maintaining the pain-reduced state and there was no significant difference in efficacy between tramadol/APAP and NSAIDs.

  7. Immune Reconstitution Inflammatory Syndrome and Shingles ...

    African Journals Online (AJOL)

    Immune Reconstitution Inflammatory Syndrome and Shingles Associated with a Combined Paralysis of Three Oculomotor Nerves: A Case Report. ... CASE DETAILS: A 40 years old patient was seen for a pain of the right side of the face and a complete immobility of the eyeball. The diagnosis of V1 shingles with a pan uveitis ...

  8. Infected aortic aneurysm and inflammatory aortic aneurysm. In search of an optimal differential diagnosis

    International Nuclear Information System (INIS)

    Ishizaka, Nobukazu; Sohmiya, Koichi; Miyamura, Masatoshi; Umeda, Tatsuya; Tsuji, Motomu; Katsumata, Takahiro; Miyata, Tetsuro

    2012-01-01

    Infected aortic aneurysm and inflammatory aortic aneurysm each account for a minor fraction of the total incidence of aortic aneurysm and are associated with periaortic inflammation. Despite the similarity, infected aortic aneurysm generally shows a more rapid change in clinical condition, leading to a fatal outcome; in addition, delayed diagnosis and misuse of corticosteroid or immunosuppressing drugs may lead to uncontrolled growth of microorganisms. Therefore, it is mandatory that detection of aortic aneurysm is followed by accurate differential diagnosis. In general, infected aortic aneurysm appears usually as a saccular form aneurysm with nodularity, irregular configuration; however, the differential diagnosis may not be easy sometimes for the following reasons: symptoms, such as abdominal and/or back pain and fever, and blood test abnormalities, such as elevated C-reactive protein and enhanced erythrocyte sedimentation rate, are common in infected aortic aneurysm, but they are not found infrequently in inflammatory aortic aneurysm; some inflammatory aortic aneurysms are immunoglobulin (Ig) G4-related, but not all of them; the prevalence of IgG4 positivity in infected aortic aneurysm has not been well investigated; enhanced uptake of 18F-fluorodeoxyglucose (FDG) by 18F-FDG-positron emission tomography may not distinguish between inflammation mediated by autoimmunity and that mediated by microorganism infection. Here we discuss the characteristics of these two forms of aortic aneurysm and the points of which we have to be aware before reaching a final diagnosis. (author)

  9. Imaging study of the painful heel syndrome

    International Nuclear Information System (INIS)

    Williams, P.L.; Smibert, J.G.; Cox, R.; Mitchell, R.; Klenerman, L.

    1987-01-01

    A total of 45 patients with the painful heel syndrome without evidence of an associated inflammatory arthritis, seven of whom had pain in both heels, were studied using technetium-99 isotope bone scans and lateral and 45 degrees medial oblique radiographs of both feet. Of the 52 painful heels 31 (59.6%) showed increased uptake of tracer at the calcaneum. Patients with scans showing increased uptake tended to have more severe heel pain and responded more frequently to a local hydrocortisone injection. On plain x-ray, 39 of 52 painful heels (75%) and 24 of the 38 opposite nonpainful heels (63%) showed plantar spurs, compared with five of 63 (7.9%) heels in 59 age- and sex-matched controls. No evidence of stress fractures was seen

  10. In vivo immune signatures of healthy human pregnancy: Inherently inflammatory or anti-inflammatory?

    Directory of Open Access Journals (Sweden)

    Caroline Graham

    Full Text Available Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an inflammatory phenotype (transiently enhancing host defense or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops. Women were examined during pregnancy and again, one and/or three years postpartum. Most pro-inflammatory cytokine expression, including CCL2, CXCL10, IL-18 and TNFα, was reduced in vivo during pregnancy (20-57%, p<0.0001. Anti-inflammatory biomarkers (sTNF-RI, sTNF-RII, and IL-1Ra were elevated by ~50-100% (p<0.0001. Systemic IL-10 levels were unaltered during vs. post-pregnancy. Kinetic studies demonstrate that while decreased pro-inflammatory biomarker expression (CCL2, CXCL10, IL-18, and TNFα was constant, anti-inflammatory expression increased progressively with increasing gestational age (p<0.0001. We conclude that healthy resting maternal immune status is characterized by an increasingly pronounced bias towards a systemic anti-inflammatory innate phenotype during the last two trimesters of pregnancy. This is resolved by one year postpartum in the absence of repeat pregnancy. The findings provide enhanced understanding of immunological changes that occur in vivo during healthy human pregnancy.

  11. Sacroiliac pain in a dialysis patient

    Science.gov (United States)

    Tristano, Antonio G

    2009-01-01

    The case is reported of a 47-year-old man with a history of chronic renal failure, treated with peritoneal dialysis, who presented with acute sacroiliac joint pain secondary to a pelvic abscess. Initially a diagnosis of infectious sacroiliitis of the left sacroiliac joint was suspected, but following investigation a pain referable to the sacroiliac joint was suspected. The patient recovered with a combination of antibiotics for the pelvic abscess and non-steroidal anti-inflammatory drugs. PMID:21994518

  12. Depression: An Immuno-Inflammatory Cascade

    Directory of Open Access Journals (Sweden)

    Vivek Sharma

    2016-06-01

    Full Text Available Major depressive disorder also known as clinical depression, unipolar depression or depression is associated with significant morbidity, mortality, high suicidal tendencies and deaths. Preclinical and clinical studies suggest that psychiatric illnesses like MDD, are associated with inflammatory processes. While it is unlikely that major depressive disorder is a primary and lsquo;inflammatory' disorder, there is now evidence to suggest that inflammation play a subtle role in the pathophysiology of major depressive disorder. The inflammation in depression cascade pin points to the origin from immune hyperactivity and thus a new theory that explains role of immune system mediated inflammation has been accepted and researched upon. widely. This theory states that depression is accompanied by altered immune function and activation of the inflammatory response system. This theory is strengthened form the fact that the current therapeutic options which mainly target neurotransmitters, are not effective in many patients and these patients has been found to be associated with elevated levels of inflammatory mediators specifically cytokines. It is reported more recently that other risk factors for depression, including psychosocial stress, psychological trauma, sleep disturbance and pain, also increases inflammatory processes. Thus the intervention in the immune system originated from inflammatory cytokines seems a therapeutically viable option in the field of depression research. [Archives Medical Review Journal 2016; 25(2.000: 223-240

  13. Caregivers' attentional bias to pain : does it affect caregiver accuracy in detecting patient pain behaviors?

    NARCIS (Netherlands)

    Mohammadi, Somayyeh; Dehghani, Mohsen; Khatibi, Ali; Sanderman, Robbert; Hagedoorn, Mariet

    Attentional bias to pain among family caregivers of patients with pain may enhance the detection of pain behaviors in patients. However, both relatively high and low levels of attentional bias may increase disagreement between patients and caregivers in reporting pain behaviors. This study aims to

  14. An Unusual Case of Systemic Inflammatory Myofibroblastic Tumor with Successful Treatment with ALK-Inhibitor

    Directory of Open Access Journals (Sweden)

    Sanjivini V. Jacob

    2014-01-01

    Full Text Available Systemic inflammatory myofibroblastic tumor is an exceedingly rare entity. A 45-year-old Hispanic female presented with a 6-month history of left-sided thigh pain, low back pain, and generalized weakness. PET/CT scan revealed abnormal activity in the liver, adrenal gland, and pancreas. MRI of the abdomen demonstrated two 6-7 cm masses in the liver. MRI of the lumbar spine demonstrated lesions in the L2 to L4 spinous processes, paraspinal muscles, and subcutaneous tissues, as well as an 8 mm enhancing intradural lesion at T11, all thought to be metastatic disease. A biopsy of the liver showed portal tract expansion by a spindle cell proliferation rich in inflammation. Tumor cells showed immunoreactivity for smooth muscle actin and anaplastic lymphoma kinase 1 (ALK1. Tissue from the L5 vertebra showed a process histologically identical to that seen in the liver. FISH analysis of these lesions demonstrated an ALK (2p23 gene rearrangement. The patient was successfully treated with an ALK-inhibitor, Crizotinib, and is now in complete remission. We present the first reported case, to our knowledge, of inflammatory myofibroblastic tumor with systemic manifestations and ALK translocation. This case is a prime example of how personalized medicine has vastly improved patient care through the use of molecular-targeted therapy.

  15. Back/joint pain, illness perceptions and coping are important predictors of quality of life and work productivity in patients with inflammatory bowel disease: a 12-month longitudinal study.

    Science.gov (United States)

    van der Have, Mike; Brakenhoff, Lianne K P M; van Erp, Sanne J H; Kaptein, Ad A; Leenders, Max; Scharloo, Margreet; Veenendaal, Roeland A; van der Heijde, Désirée M F M; van der Meulen-de Jong, Andrea E; Hommes, Daan W; Fidder, Herma H

    2015-03-01

    Back and joint pain are the most common extraintestinal symptoms reported by patients with inflammatory bowel disease (IBD). We assessed the impact of back/joint pain, illness perceptions, and coping on quality of life (QOL) and work productivity in patients with IBD. Our cohort included 155 IBD patients with and 100 without arthropathy. Arthropathy was defined as daily back pain for ≥3 months and/or peripheral joint pain and/or joint swelling over the last year. At baseline and at 12 months, patients completed questionnaires on the extent of back/joint pain, IBD disease activity, illness perceptions, coping, QOL, and work productivity. The impact of back/joint pain, illness perceptions and coping on QOL and work productivity was determined, using linear mixed models. In total, 204 IBD patients (72% Crohn's disease, 40% male, mean age 44 ± 14 years) completed questionnaires at both time points. At both time points, IBD patients with back/joint pain reported a significantly lower QOL and work productivity compared with IBD patients without back/joint pain. Predictors of low QOL were back/joint pain (β = -1.04, 95% confidence interval [CI] -1.40, -0.68), stronger beliefs about the illness consequences (β = -0.39, 95% CI -0.59, -0.18) and emotional impact of IBD (β = -0.47, 95% CI -0.66, -0.28), and the coping strategy 'decreasing activity' (β = -0.26, 95% CI -0.48, -0.03). Predictors of work productivity were back/joint pain (β = 0.22, 95% CI 0.07, 0.37) and illness consequences (β = 0.14, 95% CI 0.06, 0.22). Back/joint pain, illness perceptions, and coping are significant predictors of QOL and work productivity, after controlling for disease activity. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. The peritoneum--an important factor for pathogenesis and pain generation in endometriosis.

    Science.gov (United States)

    Barcena de Arellano, Maria-Luisa; Mechsner, Sylvia

    2014-06-01

    Endometriosis (EM) is an oestrogen-dependent disease affecting 10-15 % of women during reproductive age. It is characterised by the presence of endometrial glands, stromal- and smooth muscle-like cells outside of the uterine cavity. Fifty to sixty per cent of women and teenage girls with pelvic pain suffer from EM. EM causes disability and compromises the quality of life in women and young girls significantly. Pain generation in EM is an intricate interplay of several factors such as the endometriotic lesions themselves and the pain-mediating substances, nerve fibres and cytokine-releasing immune cells such as macrophages. These interactions seem to induce a neurogenic inflammatory process. Recently published data demonstrated an increased peptidergic and decreased noradrenergic nerve fibre density in peritoneal lesions. These data could be substantiated by in vitro analyses demonstrating that the peritoneal fluids of patients suffering from EM induced an enhanced sprouting of sensory neurites from chicken dorsal root ganglia and decreased neurite outgrowth from sympathetic ganglia. These findings might be directly involved in the perpetuation of inflammation and pain. Furthermore, the evidence of EM-associated smooth muscle-like cells seems another important factor in pain generation. The peritoneal endometriotic lesion leads to reactions in the surrounding tissue and, therefore, is larger than generally believed. The identification of EM-associated nerve fibres and smooth muscle-like cells fuel discussions on the mechanisms of pain generation in EM, and may present new targets for innovative treatments.

  17. Footwear characteristics in people with inflammatory arthritis in Singapore.

    Science.gov (United States)

    Carter, K; Lahiri, M; Cheung, P P; Santosa, A; Rome, K

    2016-01-01

    Foot problems are common in people with inflammatory arthritis. Despite suitable footwear having the potential to alleviate pain, improve mobility and maintain independence, previous studies have found many people with inflammatory arthritis wearing poorly fitting and inappropriate footwear. Footwear styles and characteristics have not been reported in a Singapore inflammatory arthritis population. The objective of this study was to identify current footwear styles and characteristics of footwear worn by people with inflammatory arthritis in Singapore. One-hundred-and-one participants with inflammatory arthritis were recruited from the rheumatology outpatient clinic of a large public hospital in Singapore. Disease and clinical characteristics were recorded. A patient-reported outcome included current foot pain. An objective footwear assessment of style, age of shoe, fit and construction was conducted. The majority of participants were Chinese women with a mean (SD) age was 52.0 (15.0) years old and a mean (SD) disease duration of 9.3 (0.3) years. We found 50 % of participants (n = 51) reported footwear problems. Sandals (n = 27, 26 %), flip-flops (n = 19, 19 %) and moccasin type (n = 19, 19 %) was the most common footwear choice. Evaluation of footwear characteristics found that there was a lack of motion control features. Only 32 (32 %) participants had correctly fitting footwear with regard to length, width and depth. No participant was wearing therapeutic footwear. This study provides the first insight into footwear preferences of people with inflammatory arthritis in Singapore. Use of slip-on and poorly fitting footwear was found to be common in people with inflammatory arthritis. Further research on footwear preferences in Southeast-Asian communities needs to take into account cultural habit and preference, socio-economic status, footwear options and affordability.

  18. Reduction of inflammatory responses and enhancement of extracellular matrix formation by vanillin-incorporated poly(lactic-co-glycolic acid) scaffolds.

    Science.gov (United States)

    Lee, Yujung; Kwon, Jeongil; Khang, Gilson; Lee, Dongwon

    2012-10-01

    Vanillin is one of the major components of vanilla, a commonly used flavoring agent and preservative and is known to exert potent antioxidant and anti-inflammatory activities. In this work, vanillin-incorporated poly(lactic-co-glycolic acid) (PLGA) films and scaffolds were fabricated to evaluate the effects of vanillin on the inflammatory responses and extracellular matrix (ECM) formation in vitro and in vivo. The incorporation of vanillin to PLGA films induced hydrophilic nature, resulting in the higher cell attachment and proliferation than the pure PLGA film. Vanillin also reduced the generation of reactive oxygen species (ROS) in cells cultured on the pure PLGA film and significantly inhibited the PLGA-induced inflammatory responses in vivo, evidenced by the reduced accumulation of inflammatory cells and thinner fibrous capsules. The effects of vanillin on the ECM formation were evaluated using annulus fibrous (AF) cell-seeded porous PLGA/vanillin scaffolds. PLGA/vanillin scaffolds elicited the more production of glycosaminoglycan and collagen than the pure PLGA scaffold, in a concentration-dependent manner. Based on the low level of inflammatory responses and enhanced ECM formation, vanillin-incorporated PLGA constructs make them promising candidates in the future biomedical applications.

  19. Reduction of Inflammatory Responses and Enhancement of Extracellular Matrix Formation by Vanillin-Incorporated Poly(Lactic-co-Glycolic Acid) Scaffolds

    Science.gov (United States)

    Lee, Yujung; Kwon, Jeongil; Khang, Gilson

    2012-01-01

    Vanillin is one of the major components of vanilla, a commonly used flavoring agent and preservative and is known to exert potent antioxidant and anti-inflammatory activities. In this work, vanillin-incorporated poly(lactic-co-glycolic acid) (PLGA) films and scaffolds were fabricated to evaluate the effects of vanillin on the inflammatory responses and extracellular matrix (ECM) formation in vitro and in vivo. The incorporation of vanillin to PLGA films induced hydrophilic nature, resulting in the higher cell attachment and proliferation than the pure PLGA film. Vanillin also reduced the generation of reactive oxygen species (ROS) in cells cultured on the pure PLGA film and significantly inhibited the PLGA-induced inflammatory responses in vivo, evidenced by the reduced accumulation of inflammatory cells and thinner fibrous capsules. The effects of vanillin on the ECM formation were evaluated using annulus fibrous (AF) cell-seeded porous PLGA/vanillin scaffolds. PLGA/vanillin scaffolds elicited the more production of glycosaminoglycan and collagen than the pure PLGA scaffold, in a concentration-dependent manner. Based on the low level of inflammatory responses and enhanced ECM formation, vanillin-incorporated PLGA constructs make them promising candidates in the future biomedical applications. PMID:22551555

  20. Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

    Science.gov (United States)

    Zhang, Le; Wang, Gongming; Ma, Jinben; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

    2016-10-01

    The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Anti-Inflammatory and Antinociceptive Activities of Untreated, Germinated, and Fermented Mung Bean Aqueous Extract

    Directory of Open Access Journals (Sweden)

    Norlaily Mohd Ali

    2014-01-01

    Full Text Available Evaluation of anti-inflammatory and antinociceptive activities of untreated mung bean (MB, germinated mung bean (GMB, and fermented mung bean (FMB was performed on both in vitro (inhibition of inflammatory mediator, nitric oxide(NO and in vivo (inhibition of ear oedema and reduction of response to pain stimulus studies. Results showed that both GMB and FMB aqueous extract exhibited potent anti-inflammatory and antinociceptive activities in a dose-dependent manner. In vitro results showed that GMB and FMB were potent inflammatory mediator (NO inhibitors at both 2.5 and 5 mg/mL. Further in vivo studies showed that GMB and FMB aqueous extract at 1000 mg/kg can significantly reduce ear oedema in mice caused by arachidonic acid. Besides, both 200 mg/kg and 1000 mg/kg concentrations of GMB and FMB were found to exhibit potent antinociceptive effects towards hotplate induced pain. With these, it can be concluded that GMB and FMB aqueous extract exhibited potential anti-inflammatory and antinociceptive effects.

  2. Antinociceptive and anti-inflammatory activities of the methanol ...

    African Journals Online (AJOL)

    This study was aimed at screening the methanol tuber extract of Chlorophytum alismifolium for antinociceptive and anti-inflammatory activities using experimental animal models. The antinociceptive activity was tested using acetic acid-induced writhing response in Swiss albino mice and formalininduced pain in Wistar rats, ...

  3. Neural tissue engineering scaffold with sustained RAPA release relieves neuropathic pain in rats.

    Science.gov (United States)

    Ding, Tan; Zhu, Chao; Kou, Zhen-Zhen; Yin, Jun-Bin; Zhang, Ting; Lu, Ya-Cheng; Wang, Li-Ying; Luo, Zhuo-Jing; Li, Yun-Qing

    2014-09-01

    To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1.3 (Nav1.3), 1.7 (Nav1.7), and 1.8 (Nav1.8) through immunohistochemistry (IHC) and Western Blot, along with the observation of postsurgical pathological pain in rats by pain-related behavior approaches. Relatively small upregulation of DRG sodium channels was observed in the experimental group (RAPA+poly(lactic-co-glycolic acid) (PLGA)+stent) after surgery, along with low degrees of neuropathic pain and anxiety, which were similar to those in the Autologous nerve graft group. Autoimmune inflammatory response plays a leading role in the occurrence of post-traumatic neuropathic pain, and that RAPA significantly inhibits the abnormal upregulation of sodium channels to reduce pain by alleviating inflammatory response. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. The effects of coping style on virtual reality enhanced videogame distraction in children undergoing cold pressor pain.

    Science.gov (United States)

    Sil, Soumitri; Dahlquist, Lynnda M; Thompson, Caitlin; Hahn, Amy; Herbert, Linda; Wohlheiter, Karen; Horn, Susan

    2014-02-01

    This study sought to evaluate the effectiveness of virtual reality (VR) enhanced interactive videogame distraction for children undergoing experimentally induced cold pressor pain and examined the role of avoidant and approach coping style as a moderator of VR distraction effectiveness. Sixty-two children (6-13 years old) underwent a baseline cold pressor trial followed by two cold pressor trials in which interactive videogame distraction was delivered both with and without a VR helmet in counterbalanced order. As predicted, children demonstrated significant improvement in pain tolerance during both interactive videogame distraction conditions. However, a differential response to videogame distraction with or without the enhancement of VR technology was not found. Children's coping style did not moderate their response to distraction. Rather, interactive videogame distraction with and without VR technology was equally effective for children who utilized avoidant or approach coping styles.

  5. Molecular Signatures of Chronic Pain Subtypes

    Science.gov (United States)

    2015-03-01

    inflammatory cytokines in human articular chondrocytes. Arthritis Rheum 2009;60(11):3303–13. 100 Su RC, Becker AB, Kozyrskyj AL, Hayglass KT. Epi...Korzets A. Reflex sympathetic dystrophy of the stump in below-knee amputees. Clin J Pain 1992;8(3):270–5. 31. Sherman RA, Sherman CJ, Parker L. Chronic...sympathetic dystrophy of the stump in below-knee amputees. The Clinical journal of pain. Sep 1992;8(3):270-275. 4. Lindsay DR, Pyati S, Buchheit TE

  6. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

    Directory of Open Access Journals (Sweden)

    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  7. Osteoarthritis guidelines: a progressive role for topical nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Stanos SP

    2013-04-01

    Full Text Available Steven P Stanos Rehabilitation Institute of Chicago, Center for Pain Management, Chicago, IL, USA Abstract: Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events. Keywords: osteoarthritis, nonsteroidal anti-inflammatory drugs, guidelines, topical analgesics, diclofenac

  8. Cancer Health Empowerment for Living without Pain (Ca-HELP: study design and rationale for a tailored education and coaching intervention to enhance care of cancer-related pain

    Directory of Open Access Journals (Sweden)

    Slee Christina

    2009-09-01

    Full Text Available Abstract Background Cancer-related pain is common and under-treated. This article describes a study designed to test the effectiveness of a theory-driven, patient-centered coaching intervention to improve cancer pain processes and outcomes. Methods/Design The Cancer Health Empowerment for Living without Pain (Ca-HELP Study is an American Cancer Society sponsored randomized trial conducted in Sacramento, California. A total of 265 cancer patients with at least moderate pain severity (Worst Pain Numerical Analog Score >=4 out of 10 or pain-related impairment (Likert score >= 3 out of 5 were randomly assigned to receive tailored education and coaching (TEC or educationally-enhanced usual care (EUC; 258 received at least one follow-up assessment. The TEC intervention is based on social-cognitive theory and consists of 6 components (assess, correct, teach, prepare, rehearse, portray. Both interventions were delivered over approximately 30 minutes just prior to a scheduled oncology visit. The majority of visits (56% were audio-recorded for later communication coding. Follow-up data including outcomes related to pain severity and impairment, self-efficacy for pain control and for patient-physician communication, functional status and well-being, and anxiety were collected at 2, 6, and 12 weeks. Discussion Building on social cognitive theory and pilot work, this study aims to test the hypothesis that a brief, tailored patient activation intervention will promote better cancer pain care and outcomes. Analyses will focus on the effects of the experimental intervention on pain severity and impairment (primary outcomes; self-efficacy and quality of life (secondary outcomes; and relationships among processes and outcomes of cancer pain care. If this model of coaching by lay health educators proves successful, it could potentially be implemented widely at modest cost. Trial Registration [Clinical Trials Identifier: NCT00283166

  9. Neurovascular Unit in Chronic Pain

    Directory of Open Access Journals (Sweden)

    Beatrice Mihaela Radu

    2013-01-01

    Full Text Available Chronic pain is a debilitating condition with major socioeconomic impact, whose neurobiological basis is still not clear. An involvement of the neurovascular unit (NVU has been recently proposed. In particular, the blood-brain barrier (BBB and blood-spinal cord barrier (BSCB, two NVU key players, may be affected during the development of chronic pain; in particular, transient permeabilization of the barrier is suggested by several inflammatory- and nerve-injury-based pain models, and we argue that the clarification of molecular BBB/BSCB permeabilization events will shed new light in understanding chronic pain mechanisms. Possible biases in experiments supporting this theory and its translational potentials are discussed. Moving beyond an exclusive focus on the role of the endothelium, we propose that our understanding of the mechanisms subserving chronic pain will benefit from the extension of research efforts to the NVU as a whole. In this view, the available evidence on the interaction between analgesic drugs and the NVU is here reviewed. Chronic pain comorbidities, such as neuroinflammatory and neurodegenerative diseases, are also discussed in view of NVU changes, together with innovative pharmacological solutions targeting NVU components in chronic pain treatment.

  10. Experimental integrative muscular movement technique enhances cervical range of motion in patients with chronic neck pain: a pilot study.

    Science.gov (United States)

    Rohe, Benjamin G; Carter, Ronald; Thompson, William R; Duncan, Randall L; Cooper, Carlton R

    2015-04-01

    Neck pain presents a tremendous physical and financial burden. This study compared the efficacy of the complementary and alternative medical treatments of integrative muscular movement technique (IMMT) and Swedish massage on neck pain in women of occupation age, the largest demographic group with neck pain. A total of 38 women were assigned to IMMT (n=28) or Swedish massage (n=10) in a blinded manner. Both groups received eight 30-minute treatments over 4 weeks. Cervical range of motion (ROM) in flexion, extension, sidebending, and rotation was measured before and after treatment. Each patient's pain was assessed by using an analogue pain scale of 0-10. Compared with the Swedish massage group, patients receiving IMMT experienced a significant increase in ROM in cervical flexion (ppain for IMMT was -1.75 units compared with -0.3 units for Swedish massage (pcervical ROM in every movement measured compared with Swedish massage. Inclusion of the IMMT in a treatment regimen for chronic neck pain may lead to decreased pain and increased cervical ROM. These positive effects of the IMMT intervention may have a role in enhancing functional outcomes in patients with neck pain.

  11. Spinal pain

    International Nuclear Information System (INIS)

    Izzo, R.; Popolizio, T.; D’Aprile, P.; Muto, M.

    2015-01-01

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  12. 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

  13. Nonsteroidal anti-inflammatory drugs for treatment of acute gout

    NARCIS (Netherlands)

    van Durme, Caroline M. P. G.; Wechalekar, Mihir D.; Landewé, Robert B. M.

    2015-01-01

    Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with better outcomes than cyclooxygenase inhibitors, glucocorticoids, IL-1 inhibitors or placebo in the treatment of acute gout? NSAIDs are not significantly associated with a difference in pain reduction compared with cyclooxygenase

  14. Mechanism involved in the anti-inflammatory effect of Spiranthera odoratissima (Manacá

    Directory of Open Access Journals (Sweden)

    Daniela B. M. Barbosa

    2012-02-01

    Full Text Available Acetic acid-induced writhing, hot-plate, carrageenan-induced pleurisy, formalin-induced pain, croton oil-induced ear edema, vascular permeability tests and phospholipase A2 activity assay were used to study the analgesic and/or anti-inflammatory activity of the hydromethanolic fraction of ethanolic extract from Spiranthera odoratissima A. St.-Hil., Rutaceae, leaves (HMF and its subfraction (sub-Fr10-28. HMF and sub-Fr10-28 reduced the leukocyte migration on the carrageenan-induced pleurisy test; sub-Fr10-28 reduced the pain reaction time in the second phase of formalin-induced pain, as well as the ear edema and vascular permeability. Both HMF and sub-Fr10-28 inhibited the phospholipase A2 activity. These results suggest that the analgesic effect of this plant could be, in part, due to an anti-inflammatory action produced by the inhibition of phospholipase A2 activity.

  15. Antinociceptive and anti-inflammatory activities of a pomegranate (Punica granatum L.) extract rich in ellagitannins.

    Science.gov (United States)

    González-Trujano, María Eva; Pellicer, Francisco; Mena, Pedro; Moreno, Diego A; García-Viguera, Cristina

    2015-01-01

    Pomegranate (Punica granatum L.) has been used for centuries for the treatment of inflammatory diseases. However, there is a lack of comprehensive information focused on the properties of a certain pomegranate (poly)phenolic profile to cure pain and gastric injury induced by anti-inflammatory drugs. This study investigated the systemic effects of different doses of a HPLC-characterized pomegranate extract on the formalin-induced nociceptive behavior in mice. The effect of the extract against gastric injury caused by non-steroidal anti-inflammatory drugs and ethanol was also assessed. Pomegranate reduced nociception in both phases of the formalin test, suggesting central and peripheral activities to inhibit nociception. Indomethacin-induced gastric injury was not produced in the presence of pomegranate, which also protected against ethanol-induced gastric lesions. The present results reinforce the benefits of pomegranate (poly)phenolics in the treatment of pain as well as their anti-inflammatory properties.

  16. Increased spinal prodynorphin gene expression in reinflammation-associated hyperalgesia after neonatal inflammatory insult

    Directory of Open Access Journals (Sweden)

    Wen Yeong-Ray

    2010-10-01

    Full Text Available Abstract Background Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood. Results A decrease in paw withdrawal latency (PWL after a heat stimulus was documented in rats that received inflammatory injections in their left hind paws on postnatal day one (P1 and a reinflammation stimulus at postnatal 6-8 weeks of age, compared with normal rats. An increase in the expression of the prodynorphin (proDYN gene was noted after reinflammation in the spinal cord ipsilateral to the afferents of the neonatally treated hind paw. The involvement of the activation of extracellular signal-regulated kinases (ERK in peripheral inflammatory pain hypersensitivity was evidenced evident by the increase in phospho-ERK (pERK activity after reinflammation. Conclusions Our results indicate that peripheral inflammation in neonates can permanently alter the pain processing pathway during the subsequent sensory stimulation of the region. Elucidation of the mechanism underlying the developing pain circuitry will provide new insights into the understanding of the early pain behaviours and the subsequent adaptation to pain.

  17. Diagnosis and treatment of abnormal dental pain.

    Science.gov (United States)

    Fukuda, Ken-Ichi

    2016-03-01

    Most dental pain is caused by an organic problem such as dental caries, periodontitis, pulpitis, or trauma. Diagnosis and treatment of these symptoms are relatively straightforward. However, patients often also complain of abnormal dental pain that has a non-dental origin, whose diagnosis is challenging. Such abnormal dental pain can be categorized on the basis of its cause as referred pain, neuromodulatory pain, and neuropathic pain. When it is difficult to diagnose a patient's dental pain, these potential alternate causes should be considered. In this clinical review, we have presented a case of referred pain from the digastric muscle (Patient 1), of pulpectomized (Patient 2), and of pulpectomized pain (Patient 3) to illustrate referred, neuromodulatory, and neuropathic pain, respectively. The Patient 1 was advised muscle stretching and gentle massage of the trigger points, as well as pain relief using a nonsteroidal anti-inflammatory and the tricyclic antidepressant amitriptyline. The pain in Patient 2 was relieved completely by the tricyclic antidepressant amitriptyline. In Patient 3, the pain was controlled using either a continuous drip infusion of adenosine triphosphate or intravenous Mg2+ and lidocaine administered every 2 weeks. In each case of abnormal dental pain, the patient's diagnostic chart was used (Fig.2 and 3). Pain was satisfactorily relieved in all cases.

  18. Involvement of AMPA receptor GluR2 and GluR3 trafficking in trigeminal spinal subnucleus caudalis and C1/C2 neurons in acute-facial inflammatory pain.

    Directory of Open Access Journals (Sweden)

    Makiko Miyamoto

    Full Text Available To evaluate the involvement of trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR GluR2 and GluR3 subunits in an acute inflammatory orofacial pain, we analyzed nocifensive behavior, phosphorylated extracellular signal-regulated kinase (pERK and Fos expression in Vi/Vc, Vc and C1/C2 in GluR2 delta7 knock-in (KI, GluR3 delta7 KI mice and wild-type mice. We also studied Vc neuronal activity to address the hypothesis that trafficking of GluR2 and GluR3 subunits plays an important role in Vi/Vc, Vc and C1/C2 neuronal activity associated with orofacial inflammation in these mice. Late nocifensive behavior was significantly depressed in GluR2 delta7 KI and GluR3 delta7 KI mice. In addition, the number of pERK-immunoreactive (IR cells was significantly decreased bilaterally in the Vi/Vc, Vc and C1/C2 in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice at 40 min after formalin injection, and was also significantly smaller in GluR3 delta7 KI compared to GluR2 delta7 KI mice. The number of Fos protein-IR cells in the ipsilateral Vi/Vc, Vc and C1/C2 was also significantly smaller in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice 40 min after formalin injection. Nociceptive neurons functionally identified as wide dynamic range neurons in the Vc, where pERK- and Fos protein-IR cell expression was prominent, showed significantly lower spontaneous activity in GluR2 delta7 KI and GluR3 delta7 KI mice than wild-type mice following formalin injection. These findings suggest that GluR2 and GluR3 trafficking is involved in the enhancement of Vi/Vc, Vc and C1/C2 nociceptive neuronal excitabilities at 16-60 min following formalin injection, resulting in orofacial inflammatory pain.

  19. Topical Niosome Gel of Zingiber cassumunar Roxb. Extract for Anti-inflammatory Activity Enhanced Skin Permeation and Stability of Compound D.

    Science.gov (United States)

    Priprem, Aroonsri; Janpim, Khwanhatai; Nualkaew, Somsak; Mahakunakorn, Pramote

    2016-06-01

    An extract of Zingiber cassumunar Roxb. (ZC) was encapsulated in niosomes of which a topical gel was formed. (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol or compound D detected by a gradient HPLC was employed as the marker and its degradation determined to follow zero-order kinetics. Niosomes significantly retarded thermal-accelerated decomposition of compound D in the gel (p D. Niosomes enhanced in vitro permeation rate of compound D from the gel. Topical applications of ZC noisome gel gave a faster change in tail flick latency than piroxicam gel and hydrocortisone cream (p anti-inflammatory activity up to 6 h using croton oil-induced ear edema model in mice (p > 0.05). Thus, encapsulation of ZC extract in niosomes enhanced chemical stability and skin permeation with comparable topical anti-inflammatory effects to steroid and NSAID.

  20. Spinal interleukin-10 therapy to treat peripheral neuropathic pain.

    Science.gov (United States)

    Milligan, Erin D; Penzkover, Kathryn R; Soderquist, Ryan G; Mahoney, Melissa J

    2012-01-01

      Current research indicates that chronic peripheral neuropathic pain includes a role for glia and the actions of proinflammatory factors. This review briefly discusses the glial and cytokine responses that occur following peripheral nerve damage in support of utilizing anti-inflammatory cytokine interleukin-10 (IL-10) therapy to suppress chronic peripheral neuropathic pain. SPINAL NONVIRAL INTERLEUKIN-10 GENE THERAPY:  IL-10 is one of the most powerful endogenous counter-regulators of proinflammatory cytokine function that acts in the nervous system. Subarachnoid (intrathecal) spinal injection of the gene encoding IL-10 delivered by nonviral vectors has several advantages over virally mediated gene transfer methods and leads to profound pain relief in several animal models. NONVIRAL GENE DELIVERY:  Lastly, data are reviewed that nonviral deoxyribonucleic acid (DNA) encapsulated by a biologically safe copolymer, poly(lactic-co-glycolic) acid (PLGA), thought to protect DNA, leads to significantly improved therapeutic gene transfer in animal models, which additionally and significantly extends pain relief.   The impact of these early studies exploring anti-inflammatory genes emphasizes the exceptional therapeutic potential of new biocompatible intrathecal nonviral gene delivery approaches such as PLGA microparticles. Ultimately, ongoing expression of therapeutic genes is a viable option to treat chronic neuropathic pain in the clinic. © 2012 International Neuromodulation Society.

  1. Mast cell-neural interactions contribute to pain and itch.

    Science.gov (United States)

    Gupta, Kalpna; Harvima, Ilkka T

    2018-03-01

    Mast cells are best recognized for their role in allergy and anaphylaxis, but increasing evidence supports their role in neurogenic inflammation leading to pain and itch. Mast cells act as a "power house" by releasing algogenic and pruritogenic mediators, which initiate a reciprocal communication with specific nociceptors on sensory nerve fibers. Consequently, nerve fibers release inflammatory and vasoactive neuropeptides, which in turn activate mast cells in a feedback mechanism, thus promoting a vicious cycle of mast cell and nociceptor activation leading to neurogenic inflammation and pain/pruritus. Mechanisms underlying mast cell differentiation, activation, and intercellular interactions with inflammatory, vascular, and neural systems are deeply influenced by their microenvironment, imparting enormous heterogeneity and complexity in understanding their contribution to pain and pruritus. Neurogenic inflammation is central to both pain and pruritus, but specific mediators released by mast cells to promote this process may vary depending upon their location, stimuli, underlying pathology, gender, and species. Therefore, in this review, we present the contribution of mast cells in pathological conditions, including distressing pruritus exacerbated by psychologic stress and experienced by the majority of patients with psoriasis and atopic dermatitis and in different pain syndromes due to mastocytosis, sickle cell disease, and cancer. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Diagnostic value of inflammatory markers (complete blood count ...

    African Journals Online (AJOL)

    Objective The aim of the study was to evaluate the diagnostic value of inflammatory markers [complete blood cell count (CBC), erythrocyte sedimentation rate (ESR),. C-reactive protein (CRP)] for the differentiation of acute appendicitis from nonspecific abdominal pain in children. Patients and methods In this prospective ...

  3. Diagnostic value of inflammatory markers (complete blood count ...

    African Journals Online (AJOL)

    Objective The aim of the study was to evaluate the diagnostic value of inflammatory markers [complete blood cell count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] for the differentiation of acute appendicitis from nonspecific abdominal pain in children. Patients and methods In this prospective ...

  4. Pelvic pain in a young patient: Sclerosing stromal tumor

    Directory of Open Access Journals (Sweden)

    Huriye Ayşe Parlakgümüş

    2013-03-01

    Full Text Available Introduction: Sclerosing stromal tumors are rare, benign sex chord stromal tumors. They are usually unilateral and are seen in second or third decades. The complaint at admission may be menstrual irregularity, pelvic pain, palpable pelvic mass, precocious puberty and postmenopausal bleeding. Because the complaint at admission and radiological findings are not specific to SSTs preoperative diagnosis is challenging. Herein we present the sonographical, intraoperative and histopathological findings of a SST diagnosed during laparoscopy in a patient who admitted with chronic pelvic pain and received pelvic inflammatory disease and endometriosis treatment and differential diagnosis of SSTs with the other ovarian tumors. Case report: 24 years old nulliparous patient first admitted to the gynecology department with the complaint of foul smelling vaginal discharge and pelvic pain. The diagnosis was pelvic inflammatory disease and the patient received antibiotics. The pelvic examination was normal except the mass in the right ovary which had similar echogenity to the ovary. Because of the pelvic pain the mass was assumed to be an endometrioma and the patient was prescribed an oral contraceptive treatment for 3 months. Because of the persistent pelvic pain a diagnostic laparoscopy was performed which revealed a 2 cm, pinkish- white, exophytic lesion originating from the right ovary. Pathological examination reported the mass to be a sclerosing stromal tumor. After the treatment the patient no longer complained of vaginal discharge but pelvic pain still persisted. After the operation the patient no longer complained of pelvic pain. Conclusion: Although SSTs are rare, they should be kept in mind when a young patient admits with menstrual irregularity, pelvic pain and hirsutism, particularly if the pain is refractory to treatment.

  5. Measuring Emotional Intelligence Enhances the Psychological Evaluation of Chronic Pain.

    Science.gov (United States)

    Doherty, Eva M; Walsh, Rosemary; Andrews, Leanne; McPherson, Susan

    2017-12-01

    The assessment of emotional factors, in addition to other psychosocial factors, has been recommended as a means of identifying individuals with chronic pain who may not respond to certain pain treatments. Systematic reviews of the evidence regarding the prediction of responsiveness to a treatment called the spinal cord stimulator (SCS) have yielded inconclusive results. Emotional intelligence is a term which refers to the ability to identify and manage emotions in oneself and others and has been shown to be inversely associated with emotional distress and acute pain. This study aims to investigate the relationship between emotional intelligence, chronic pain, and the more established psychosocial factors usually used for SCS evaluations by clinical psychologists in medical settings. A sample of 112 patients with chronic pain on an acute hospital waiting list for SCS procedures in a pain medicine service were recruited. Psychological measures were completed including: a novel measure of emotional intelligence; usual measures of emotional distress and catastrophizing; and a numerical rating scale designed to assess pain intensity, pain-related distress, and interference. As predicted, findings revealed significant associations between most of the measures analyzed and current pain intensity. When entered into a simultaneous regression analysis, emotional intelligence scores remained the only significant predictor of current pain intensity. There are potential clinical, ethical, and organizational implications of emotional intelligence processes partially predicting pain in patients on a waiting list for a medical procedure. These results may offer new insight, understanding, and evaluation targets for clinical psychologists in the field of pain management.

  6. Role of Prophylactic Antibiotics in the Management of Postoperative Endodontic Pain.

    Science.gov (United States)

    Alsomadi, Leena; Al Habahbeh, Riyad

    2015-12-01

    To investigate the efficacy of using antibiotics in post endodontic treatment as a method to alleviate post-treatment pain. After completion of endodontic treatment 129 patients were randomly divided into two groups: Group A (65 patients) received Ibuprofen 400 mg one tablet before procedure and one tablet every 8 hours for the first day, then one tablet once indicated by pain. Group B (64 patients) received the same regimen as group A in addition to amoxicillin, clavulanic acid tablets (one tablet before the procedure, and then one tablet twice daily for a total of 3 days). Intensity of pain at 8 hours interval using visual analog scale (VAS) and total number of Ibuprofen tablets used was recorded by patients. Peak postoperative pain occurred at 16 hours post-treatment in both groups, there was a significant difference in the pain scale between the two groups in favor for group B over group A (3.8 vs 2.1 respectively). Pain scale was significantly lower in group B at 24, 32, 40, and 48 hours post-treatment with a p-value of Antibiotic prescription to manage post endodontic treatment pain results in less pain with less consumption of Ibuprofens. Pain management in endodontics is a real challenge, nonsteroidal anti-inflammatory drugs (NSAIDS) are used effectively in many patients to alleviate post endodontic pain. Nonsteroidal anti-inflammatory drugs may have adverse reactions or may be contraindicated. Short-term use of antibiotics to alleviate pain can be of clinical benefits in these patients.

  7. The association of mast cells and serotonin in children with chronic abdominal pain of unknown etiology

    Directory of Open Access Journals (Sweden)

    Shankar Ravi

    2010-10-01

    Full Text Available Abstract Background Abdominal pain of unknown origin affects up to 20% of school-aged children. Evaluation of children is symptom-based without clear guidelines to investigate molecular mechanisms of abdominal pain. Aberrant molecular mechanisms may increase intestinal permeability leading to interactions between the immune and nervous systems, subclinical inflammation, and visceral pain. This study evaluated the association between interleukin-6 (IL-6, mast cell infiltrates, and serotonin (5-HT levels in gastrointestinal (GI biopsies, with perceived abdominal pain in a pediatric cohort. Methods Clinical data and biopsy samples from pediatric patients (n = 48 with chronic abdominal pain, with and without inflammation were included. Formalin-fixed paraffin-embedded GI biopsies were sectioned and immunohistochemistry performed for IL-6 and 5-HT; mast cells were identified with toluidine blue stain. Histological findings were compared to self-reported abdominal pain between groups. Results There was significantly greater IL-6 immunoreactivity in biopsies with confirmed histologic inflammation (p = 0.004. There was a greater number of mast cells per HPF in non-inflammatory biopsies (3.5 ± 2.9 compared to the inflammatory biopsies (2.6 ± 1.8 p = 0.049. The non-inflammatory biopsy group was significantly less likely to respond to standard treatment as evidenced by higher pain reports (p = .018. Mast cells (p = .022 and 5-HT (p = .02 were significantly related to abdominal pain scores. Conclusions A potential association between self-reported abdominal pain, number of mast cells, and 5-HT levels, which may contribute to perceived GI pain in pediatric patients may exist.

  8. Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain

    Science.gov (United States)

    Pergolizzi, Joseph V; van de Laar, Mart; Langford, Richard; Mellinghoff, Hans-Ulrich; Merchante, Ignacio Morón; Nalamachu, Srinivas; O’Brien, Joanne; Perrot, Serge; Raffa, Robert B

    2012-01-01

    Pain is the most common reason patients seek medical attention and pain relief has been put forward as an ethical obligation of clinicians and a fundamental human right. However, pain management is challenging because the pathophysiology of pain is complex and not completely understood. Widely used analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen) have been associated with adverse events. Adverse event rates are of concern, especially in long-term treatment or at high doses. Paracetamol and NSAIDs are available by prescription, over the counter, and in combination preparations. Patients may be unaware of the risk associated with high dosages or long-term use of paracetamol and NSAIDs. Clinicians should encourage patients to disclose all medications they take in a “do ask, do tell” approach that includes patient education about the risks and benefits of common pain relievers. The ideal pain reliever would have few risks and enhanced analgesic efficacy. Fixed-dose combination analgesics with two or more agents may offer additive or synergistic benefits to treat the multiple mechanisms of pain. Therefore, pain may be effectively treated while toxicity is reduced due to lower doses. One recent fixed-dose combination analgesic product combines tramadol, a centrally acting weak opioid analgesic, with low-dose paracetamol. Evidence-based guidelines recognize the potential value of combination analgesics in specific situations. The current guideline-based paradigm for pain treatment recommends NSAIDs for ongoing use with analgesics such as opioids to manage flares. However, the treatment model should evolve how to use low-dose combination products to manage pain with occasional use of NSAIDs for flares to avoid long-term and high-dose treatment with these analgesics. A next step in pain management guidelines should be targeted therapy when possible, or low-dose combination therapy or both, to achieve maximal efficacy with

  9. Effects of “Danzhi Decoction” on Chronic Pelvic Pain, Hemodynamics, and Proinflammatory Factors in the Murine Model of Sequelae of Pelvic Inflammatory Disease

    Directory of Open Access Journals (Sweden)

    Xiaoling Bu

    2015-01-01

    Full Text Available Objective. To evaluate the effect of Danzhi decoction (DZD on chronic pelvic pain (CPP, hemodynamics, and proinflammatory factors of sequelae of pelvic inflammatory diseases (SPID in murine model. Methods. SPID mice were randomly treated with high-dose DZD, mid-dose DZD, low-dose DZD, aspirin, and vehicle for 3 estrous circles. The Mouse Grimace Scale (MGS was performed to evaluate CPP; blood flows of the upper genital tract, pelvic wall, and mesentery were used to assess hemodynamics in SPID mice; expressions of vascular endothelial growth factor (VEGF, angiopoietin-2 (Ang-2, and osteopontin (OPN were measured by Western blot and immunochemistry. Results. Treatment with dose-dependent DZD significantly decreased the MGS scores, accelerated blood flows of the pelvis, and reduced expressions of VEGF, Ang-2, and OPN in the upper genital tract. Conclusions and Discussions. DZD was effective in relieving CPP and improving hemodynamics of the pelvic blood-stasis microenvironment in SPID mice. There was a relationship between CPP and the pelvic blood-stasis microenvironment. Furthermore, DZD might play a positive role in the anti-inflammatory process.

  10. Modeling subjective well-being in individuals with chronic pain and a physical disability: the role of pain control and pain catastrophizing.

    Science.gov (United States)

    Furrer, Angela; Michel, Gisela; Terrill, Alexandra L; Jensen, Mark P; Müller, Rachel

    2017-10-23

    To investigate the associations between subjective well-being and pain intensity, pain interference, and depression in individuals with physical disabilities. We hypothesized that (1) pain control and (2) pain catastrophizing mediate the effects of subjective well-being on pain intensity, pain interference, and depression. Analyses of cross-sectional data from 96 individuals diagnosed with spinal cord injury, multiple sclerosis, neuromuscular disease, or post-polio syndrome, with average pain intensity of ≥4 (0-10) on at least half the days in the past month. Two models tested study hypotheses using structural equation. Both models showed acceptable model fit. Pain catastrophizing significantly mediated the effect of subjective well-being on pain intensity and pain interference, but not on depression. Pain control did not significantly mediate the effect of subjective well-being on pain intensity, pain interference, or depression. Path coefficients showed significant direct effects of subjective well-being on pain control (β = 0.39), pain catastrophizing (β = -0.61), pain interference (β = -0.48; -0.42), and depression (β = -0.75; -0.78). This study supports the potential of enhancing subjective well-being and lowering pain catastrophizing for reducing pain intensity, pain interference, and depressive symptoms in individuals with chronic pain and a physical disability. The findings indicate that true experiments to test for causal associations are warranted. Implications for rehabilitation The majority of individuals with physical disabilities report having persistent moderate-to-severe pain that may negatively limit daily activities and quality of life. The present cross-sectional study indicates that individuals who reported greater subjective well-being showed significantly lower pain intensity via the mediating effect of lower pain catastrophizing. Since sample size and respective power are low, these findings should be taken as first

  11. Rethinking the Psychogenic Model of Complex Regional Pain Syndrome: Somatoform Disorders and Complex Regional Pain Syndrome

    Science.gov (United States)

    Hill, Renee J.; Chopra, Pradeep; Richardi, Toni

    2012-01-01

    Abstract Explaining the etiology of Complex Regional Pain Syndrome (CRPS) from the psychogenic model is exceedingly unsophisticated, because neurocognitive deficits, neuroanatomical abnormalities, and distortions in cognitive mapping are features of CRPS pathology. More importantly, many people who have developed CRPS have no history of mental illness. The psychogenic model offers comfort to physicians and mental health practitioners (MHPs) who have difficulty understanding pain maintained by newly uncovered neuro inflammatory processes. With increased education about CRPS through a biopsychosocial perspective, both physicians and MHPs can better diagnose, treat, and manage CRPS symptomatology. PMID:24223338

  12. Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents

    OpenAIRE

    Eccleston, Christopher; Cooper, Tess E.; Fisher, Emma; Anderson, Brian; Wilkinson, Nick M. R.

    2017-01-01

    Background Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pai...

  13. Anorectal and Pelvic Pain.

    Science.gov (United States)

    Bharucha, Adil E; Lee, Tae Hee

    2016-10-01

    Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  14. Infection of human monocyte-derived dendritic cells by ANDES Hantavirus enhances pro-inflammatory state, the secretion of active MMP-9 and indirectly enhances endothelial permeability

    Directory of Open Access Journals (Sweden)

    Lopez-Lastra Marcelo

    2011-05-01

    Full Text Available Abstract Background Andes virus (ANDV, a rodent-borne Hantavirus, is the major etiological agent of Hantavirus cardiopulmonary syndrome (HCPS in South America, which is mainly characterized by a vascular leakage with high rate of fatal outcomes for infected patients. Currently, neither specific therapy nor vaccines are available against this pathogen. ANDV infects both dendritic and epithelial cells, but in despite that the severity of the disease directly correlates with the viral RNA load, considerable evidence suggests that immune mechanisms rather than direct viral cytopathology are responsible for plasma leakage in HCPS. Here, we assessed the possible effect of soluble factors, induced in viral-activated DCs, on endothelial permeability. Activated immune cells, including DC, secrete gelatinolytic matrix metalloproteases (gMMP-2 and -9 that modulate the vascular permeability for their trafficking. Methods A clinical ANDES isolate was used to infect DC derived from primary PBMC. Maturation and pro-inflammatory phenotypes of ANDES-infected DC were assessed by studying the expression of receptors, cytokines and active gMMP-9, as well as some of their functional status. The ANDES-infected DC supernatants were assessed for their capacity to enhance a monolayer endothelial permeability using primary human vascular endothelial cells (HUVEC. Results Here, we show that in vitro primary DCs infected by a clinical isolate of ANDV shed virus RNA and proteins, suggesting a competent viral replication in these cells. Moreover, this infection induces an enhanced expression of soluble pro-inflammatory factors, including TNF-α and the active gMMP-9, as well as a decreased expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. These viral activated cells are less sensitive to apoptosis. Moreover, supernatants from ANDV-infected DCs were able to indirectly enhance the permeability of a monolayer of primary HUVEC. Conclusions Primary human DCs

  15. Neuropathic pain: targeting the melatonin MT receptor

    African Journals Online (AJOL)

    inflammatory drugs (NSAIDs) and opioids is highly effective in ... to drug treatment. .... effects in chronic neuropathic pain, which are mediated by the .... Reiter R, Tan D, Kim S, Cruz M. Delivery of pineal melatonin to the brain and SCN:.

  16. Inflammatory Profile of Awake Function-Controlled Craniotomy and Craniotomy under General Anesthesia

    Science.gov (United States)

    Klimek, Markus; Hol, Jaap W.; Wens, Stephan; Heijmans-Antonissen, Claudia; Niehof, Sjoerd; Vincent, Arnaud J.; Klein, Jan; Zijlstra, Freek J.

    2009-01-01

    Background. Surgical stress triggers an inflammatory response and releases mediators into human plasma such as interleukins (ILs). Awake craniotomy and craniotomy performed under general anesthesia may be associated with different levels of stress. Our aim was to investigate whether those procedures cause different inflammatory responses. Methods. Twenty patients undergoing craniotomy under general anesthesia and 20 patients undergoing awake function-controlled craniotomy were included in this prospective, observational, two-armed study. Circulating levels of IL-6, IL-8, and IL-10 were determined pre-, peri-, and postoperatively in both patient groups. VAS scores for pain, anxiety, and stress were taken at four moments pre- and postoperatively to evaluate physical pain and mental duress. Results. Plasma IL-6 level significantly increased with time similarly in both groups. No significant plasma IL-8 and IL-10 change was observed in both experimental groups. The VAS pain score was significantly lower in the awake group compared to the anesthesia group at 12 hours postoperative. Postoperative anxiety and stress declined similarly in both groups. Conclusion. This study suggests that awake function-controlled craniotomy does not cause a significantly different inflammatory response than craniotomy performed under general anesthesia. It is also likely that function-controlled craniotomy does not cause a greater emotional challenge than tumor resection under general anesthesia. PMID:19536349

  17. [Use of alpha-lipoic acid and omega-3 in postpartum pain treatment].

    Science.gov (United States)

    Costantino, D; Guaraldi, C; Costantino, M; Bounous, V E

    2015-10-01

    Postpartum pain is a frequent condition that negatively affects women's quality of life, interferring with everyday life. Analgesic drugs and surgery are often contraindicated in pregnancy and during breast feeding. This review of the literature aims to evaluate the rational of the association of lipoic acid and omega-3 employ in the management of postpartum pain. Lipoic acid is a cofactor essential in mitochondrial metabolism with antioxidant and anti-inflammatory activity. Lipoic acid has been shown to be effective in neuropatic pain treatment in patients with sciatica, carpal tunnel syndrome and diabetic neuropathy. Omega-3 are known for their anti-inflammatory and neurotrophic activity. The peripheral and central activity of both substances allows to act on neuroinflammation mechanisms thus reducing cronicization of pain and also determining a potential improvement of women's emotional status. The preliminary data here presented confirm the positive effect of this association on the treatment of postpartum perineal pain. The supplementation of lipoic acid in association with omega-3 seems effective and safe for the treatment of chronic postpartum pain, allowing a pathogenetic approach to neuroinflammation, thus reducing the consumption of analgesic drugs, often contraindicated during breast-feeding.

  18. Spinal neuronal correlates of tapentadol analgesia in cancer pain: A back-translational approach

    DEFF Research Database (Denmark)

    Falk, Sarah; Patel, Ryan; Heegaard, Anne-Marie

    2015-01-01

    Background Pain is a common and highly debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of multiple mechanisms including both inflammatory and neuropathic processes and also some unique changes. S...

  19. Anti-inflammatory effect as a mechanism of effectiveness underlying the clinical benefits of pelotherapy in osteoarthritis patients: regulation of the altered inflammatory and stress feedback response

    Science.gov (United States)

    Ortega, E.; Gálvez, I.; Hinchado, M. D.; Guerrero, J.; Martín-Cordero, L.; Torres-Piles, S.

    2017-10-01

    The purpose of the present investigation was to evaluate whether an anti-inflammatory effect together with an improvement of the regulation of the interaction between the inflammatory and stress responses underlies the clinical benefits of pelotherapy in osteoarthritis (OA) patients. This study evaluated the effects of a 10-day cycle of pelotherapy at the spa centre `El Raposo' (Spain) in a group of 21 OA patients diagnosed with primary knee OA. Clinical assessments included pain intensity using a visual analog scale; pain, stiffness and physical function using the Western Ontario and McMaster Universities Arthritis Index; and health-related quality of life using the EuroQol-5D questionnaire. Serum inflammatory cytokine levels (IL-1β, TNF-α, IL-8, IL-6, IL-10 and TGF-β) were evaluated using the Bio-Plex® Luminex® system. Circulating neuroendocrine-stress biomarkers, such as cortisol and extracellular 72 kDa heat shock protein (eHsp72), were measured by ELISA. After the cycle of mud therapy, OA patients improved the knee flexion angle and OA-related pain, stiffness and physical function, and they reported a better health-related quality of life. Serum concentrations of IL-1β, TNF-α, IL-8, IL-6 and TGF-β, as well as eHsp72, were markedly decreased. Besides, systemic levels of cortisol increased significantly. These results confirm that the clinical benefits of mud therapy may well be mediated, at least in part, by its systemic anti-inflammatory effects and neuroendocrine-immune regulation in OA patients. Thus, mud therapy could be an effective alternative treatment in the management of OA.

  20. Personalized pain medicine: the clinical value of psychophysical assessment of pain modulation profile.

    Science.gov (United States)

    Granovsky, Yelena; Yarnitsky, David

    2013-01-01

    Experimental pain stimuli can be used to simulate patients' pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests-conditioned pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.

  1. Analgesic and Anti-Inflammatory Activities of Resveratrol through Classic Models in Mice and Rats

    Directory of Open Access Journals (Sweden)

    Guangxi Wang

    2017-01-01

    Full Text Available Background. Inflammation and pain are closely related to humans’ and animals’ health. Resveratrol (RSV is a natural compound with various biological activities. The current study is aimed to evaluate the analgesic and anti-inflammatory activities of RSV in vivo. Materials and Methods. The analgesic effects were assessed by the acetic acid-induced writhing and hot plate tests. The anti-inflammatory effects were determined using the xylene-induced mouse ear oedema, the acetic acid-induced rat pleurisy, and carrageenan-induced rat synovitis tests, respectively. Results. The analgesic results showed that RSV could significantly inhibit the number of writhes and improve the time and pain threshold of mice standing on hot plate. The anti-inflammatory results showed that RSV could inhibit the ear oedema of mice. In acetic acid-induced pleurisy test, RSV could significantly inhibit the WBC and pleurisy exudates, could decrease the production of NO, and elevate the activity of SOD in serum. In carrageenan-induced synovitis test, RSV could reduce the content of MDA and elevate the T-SOD activity in serum; RSV could inhibit the expressions of TP, PGE2, NO, and MDA. Conclusion. Shortly, these results indicated that RSV had potent analgesic and anti-inflammatory activities and could be a potential new drug candidate for the treatment of inflammation and pain.

  2. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Chiong HS

    2013-03-01

    Full Text Available Hoe Siong Chiong,1 Yoke Keong Yong,1 Zuraini Ahmad,1 Mohd Roslan Sulaiman,1 Zainul Amiruddin Zakaria,1 Kah Hay Yuen,2 Muhammad Nazrul Hakim1,31Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia; 3Sports Academy, Universiti Putra Malaysia, Serdang, MalaysiaBackground: Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug.Methods: Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7.Results: Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine.Conclusion: This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.Keywords: liposomes, nitric oxide, cytokines, prostaglandin E2, interleukin-1β, piroxicam

  3. Enhanced recovery pathways in thoracic surgery from Italian VATS Group: perioperative analgesia protocols.

    Science.gov (United States)

    Piccioni, Federico; Segat, Matteo; Falini, Stefano; Umari, Marzia; Putina, Olga; Cavaliere, Lucio; Ragazzi, Riccardo; Massullo, Domenico; Taurchini, Marco; Del Naja, Carlo; Droghetti, Andrea

    2018-03-01

    Video-assisted thoracoscopic surgery (VATS) is a minimally invasive technique that allows a faster recovery after thoracic surgery. Although enhanced recovery after surgery (ERAS) principles seem reasonably applicable to thoracic surgery, there is little literature on the application of such a strategy in this context. In regard to pain management, ERAS pathways promote the adoption of a multimodal strategy, tailored to the patients. This approach is based on combining systemic and loco-regional analgesia to favour opioid-sparing strategies. Thoracic paravertebral block is considered the first-line loco-regional technique for VATS. Other techniques include intercostal nerve block and serratus anterior plane block. Nonsteroidal anti-inflammatory drugs and paracetamol are essential part of the multimodal treatment of pain. Also, adjuvant drugs can be useful as opioid-sparing agents. Nevertheless, the treatment of postoperative pain must take into account opioid agents too, if necessary. All above is useful for careful planning and execution of a multimodal analgesic treatment to enhance the recovery of patients. This article summarizes the most recent evidences from literature and authors' experiences on perioperative multimodal analgesia principles for implementing an ERAS program after VATS lobectomy.

  4. Synthesis and Study of Analgesic and Anti-inflammatory Activities of Amide Derivatives of Ibuprofen.

    Science.gov (United States)

    Ahmadi, Abbas; Khalili, Mohsen; Olama, Zahra; Karami, Shirin; Nahri-Niknafs, Babak

    2017-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide and represent a mainstay in the therapy of acute and chronic pain and inflammation. The traditional NSAIDs like ibuprofen (I) contain free carboxylic acid group which can produce gastrointestinal (GI) damage for long-term use. In order to obtain the novel NSAIDs with less side effects; carboxylic acid moiety has been modified into various amide groups which is the most active area of research in this family. In this research, synthesis of various pharmacological heterocyclic amides of ibuprofen is described. All the new compounds were tested for their analgesic and anti-inflammatory activities in mice and compared with standard (Ibuprofen) and control (saline) groups. The results revealed that all the synthesized compounds (III-VI) exhibited more analgesic and anti-inflammatory activities in tail immersion (as a model of acute thermal pain), formalin (as a model of acute chemical and chronic pain) and paw edema (as a model of acute inflammation) tests when compared with standard and control animals. These pharmacological activities were significant for VI compared to other new compounds (III-V) which may be concern to more effective role of morpholin for the reduction of pain and inflammation compared to other used heterocyclic amines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Pelvic inflammatory disease: diagnosis and treatment in the emergency department [digest].

    Science.gov (United States)

    Bugg, Charles Walter; Taira, Taku; Zaurova, Milana

    2016-12-22

    Pelvic inflammatory disease is a common disease that is associated with significant complications including infertility, chronic pelvic pain, ruptured tubo-ovarian abscess, and ectopic pregnancy. The diagnosis may be delayed when the presentation has nonspecific signs and symptoms. Even when it is properly identified, pelvic inflammatory disease is often treated suboptimally. This review provides evidence-based recommendations for the diagnosis, treatment, disposition, and follow-up of patients with pelvic inflammatory disease. Arranging follow-up of patients within 48 to 72 hours and providing clear patient education are fundamental to ensuring good patient outcomes. Emerging issues, including new pathogens and evolving resistance patterns among pelvic inflammatory disease pathogens are reviewed. [Points & Pearls is a digest of Emergency Medicine Practice].

  6. Copaiba oil enhances in vitro/in vivo cutaneous permeability and in vivo anti-inflammatory effect of celecoxib.

    Science.gov (United States)

    Quiñones, Oliesia Gonzalez; Hossy, Bryan Hudson; Padua, Tatiana Almeida; Miguel, Nádia Campos de Oliveira; Rosas, Elaine Cruz; Ramos, Mônica Freiman de Souza; Pierre, Maria Bernadete Riemma

    2018-03-29

    The aim of this article was to use copaiba oil (C.O) to improve skin permeability and topical anti-inflammatory activity of celecoxib (Cxb). Formulations containing C.O (1-50%) were associated with Cxb (2%). In vitro skin permeability studies were conducted using porcine ear skin. Histological analysis of the hairless mice skin samples after application of formulations was achieved with the routine haematoxylin/eosin technique. The anti-inflammatory activity was assessed using the AA-induced ear oedema mice model. The formulation containing 25% C.O promoted the highest levels of in vitro Cxb permeation through pig ear skin, retention in the stratum corneum (SC) and epidermis/dermis of pig ear skin in vitro (~5-fold) and hairless mice skin in vivo (~2.0-fold), as compared with the control formulation. At 25%, C.O caused SC disorganization and increased cell infiltration and induced angiogenesis without clear signs of skin irritation. The formulation added to 25% C.O as adjuvant inhibited ear oedema and protein extravasation by 77.51 and 89.7%, respectively, and that it was, respectively, 2.0- and 3.4-fold more efficient than the commercial diethylammonium diclofenac cream gel to suppress these inflammatory parameters. 25% C.O is a potential penetration enhancer for lipophilic drugs like Cxb that can improve cutaneous drug penetration and its anti-inflammatory activity. © 2018 Royal Pharmaceutical Society.

  7. Topical nonsteroidal anti-inflammatory drugs for management of osteoarthritis in long-term care patients

    Directory of Open Access Journals (Sweden)

    Argoff CE

    2011-09-01

    Full Text Available Charles E Argoff1, F Michael Gloth2 1Albany Medical College and Comprehensive Pain Center, Albany Medical Center, Albany, NY, USA; 2Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Osteoarthritis is common in patients ≥65 years of age. Although nonsteroidal anti-inflammatory drugs (NSAIDs are often prescribed for osteoarthritis pain, they pose age-related cardiovascular, renal, and gastrointestinal risks. Two topical NSAIDs, diclofenac sodium 1% gel (DSG and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution (D-DMSO, are approved in the US for the treatment of osteoarthritis pain. Topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO and hand (DSG osteoarthritis. Analyses of data from randomized controlled trials of DSG in hand and knee osteoarthritis demonstrate significant improvement of pain and function in both younger patients (<65 years and older patients (≥65 years and suggest good safety and tolerability. However, long-term safety data in older patients are limited. Topical NSAIDs can ease medication administration and help address barriers to pain management in older patients, such as taking multiple medications and inability to swallow, and are a valuable option for long-term care providers. Keywords: nonsteroidal anti-inflammatory drugs, long-term care, nursing homes, chronic pain, topical analgesics

  8. Ceftriaxone and clavulanic acid induce antiallodynia and anti-inflammatory effects in rats using the carrageenan model

    Directory of Open Access Journals (Sweden)

    Ochoa-Aguilar A

    2018-05-01

    Full Text Available Abraham Ochoa-Aguilar,1,2 Rosa Ventura-Martinez,1 Marco Antonio Sotomayor-Sobrino,1 Ruth Jaimez,1 Ulises Coffeen,3 Ariadna Jiménez-González,2 Luis Gerardo Balcázar-Ochoa,1 Rafael Pérez-Medina-Carballo,2 Rodolfo Rodriguez,1 Ricardo Plancarte-Sánchez4 1Pharmacology Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, México; 2Research Department, Mexican Faculty of Medicine, La Salle University, Mexico City, México; 3Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, México; 4Pain Clinic, National Cancer Institute of Mexico, Mexico City, México Introduction: Ceftriaxone (CFX and clavulanic acid (CA are 2 β-lactam molecules widely used as antibiotics. However, several reports of their antiallodynic properties have been published in recent years. Although this effect has been considered mostly due to a GLT1 overexpression, these molecules have also been proven to induce direct immunomodulation. In this work, we determine the acute analgesic effect of CFX and CA in an inflammatory pain model and assess if their administration may induce anti-inflammatory effects. Methods: The carrageenan (Carr test was used as an inflammatory pain model. Both mechanical and thermal responses were analyzed after CFX and CA administration at different times. A plethysmometer was used to determine inflammation. Also, TNF-α and IL-10 serum concentrations were determined by enzyme-linked immunosorbent assay. Results: Both CFX and CA induced a significant thermal antiallodynic effect 3 and 24 h after administration. Furthermore, CA induced a mechanical antiallodynic effect 30, 60, and 90 min after administration. Moreover, a significant anti-inflammatory effect was found for both molecules 24 h after Carr injection. Also, both CA and CFX modulated TNF-α and IL-10 serum concentrations at different times. Conclusion: Our results provide evidence that both CFX and CA cause an analgesic effect on a Carr

  9. Parenting disability, parenting stress and child behaviour in early inflammatory arthritis.

    Science.gov (United States)

    Zelkowitz, P; Looper, K J; Mustafa, S S; Purden, M; Baron, M

    2013-03-01

    Our study examines the association between the disease characteristics of inflammatory arthritis and patients' self-perception of mental health, parenting disability, parenting stress and child behaviour in early inflammatory arthritis (EIA). Patients in the early phase (more than 6 weeks, less than 18 months) of inflammatory arthritis were recruited from a larger EIA registry that recorded sociodemographic data and measures of pain, physical functioning and disease activity. Patient-perceived parenting disability, parenting stress, depression and children's behaviour problems were assessed using the Parenting Disability Index, Parenting Stress Index, Center for Epidemiologic Studies--Depression Mood Scale and Child Behavior Checklist, respectively. Pain, physical dysfunction, number of tender joints and physician global assessment of disease activity were associated with parenting disability. Self-report measures of parenting disability were associated with those of depression and parenting stress. Parenting stress was associated with children internalizing and externalizing behaviour problems while parenting disability was associated with children externalizing behaviour problems. This study suggests a possible reciprocal relationship among physical aspects of disease activity, parenting disability and parent and child distress in EIA.

  10. Metallothionein as an Anti-Inflammatory Mediator

    Directory of Open Access Journals (Sweden)

    Ken-ichiro Inoue

    2009-01-01

    Full Text Available The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions.

  11. Modulation of oral heat and cold pain by irritant chemicals.

    Science.gov (United States)

    Albin, Kelly C; Carstens, Mirela Iodi; Carstens, E

    2008-01-01

    Common food irritants elicit oral heat or cool sensations via actions at thermosensitive transient receptor potential (TRP) channels. We used a half-tongue, 2-alternative forced-choice procedure coupled with bilateral pain intensity ratings to investigate irritant effects on heat and cold pain. The method was validated in a bilateral thermal difference detection task. Capsaicin, mustard oil, and cinnamaldehyde enhanced lingual heat pain elicited by a 49 degrees C stimulus. Mustard oil and cinnamaldehyde weakly enhanced lingual cold pain (9.5 degrees C), whereas capsaicin had no effect. Menthol significantly enhanced cold pain and weakly reduced heat pain. To address if capsaicin's effect was due to summation of perceptually similar thermal and chemical sensations, one-half of the tongue was desensitized by application of capsaicin. Upon reapplication, capsaicin elicited little or no irritant sensation yet still significantly enhanced heat pain on the capsaicin-treated side, ruling out summation. In a third experiment, capsaicin significantly enhanced pain ratings to graded heat stimuli (47 degrees C to 50 degrees C) resulting in an upward shift of the stimulus-response function. Menthol may induce cold hyperalgesia via enhanced thermal gating of TRPM8 in peripheral fibers. Capsaicin, mustard oil, and cinnamaldehyde may induce heat hyperalgesia via enhanced thermal gating of TRPV1 that is coexpressed with TRPA1 in peripheral nociceptors.

  12. Effects of gabapentin in acute inflammatory pain in humans

    DEFF Research Database (Denmark)

    Werner, M U; Perkins, F M; Holte, Kathrine

    2001-01-01

    ,200 mg or placebo was given on 2 separate study days. Three hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm(2), 47 degrees C for 7 minutes). Quantitative sensory testing (QST) included pain ratings to thermal and mechanical...

  13. Antinociceptive and Anti-Inflammatory Activities of Teucrium persicum Boiss. Extract in Mice

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    Abdolhossein Miri

    2015-01-01

    Full Text Available Background. Therapeutic properties of Teucrium species as antioxidant, antibacterial, analgesic, anticancer, diuretic, and tonic compounds have been proved earlier. Materials and Methods. In this study, the antinociceptive and anti-inflammatory effects of the aqueous extract of Teucrium persicum on chronic pain, sciatic nerve ligation as a model of neuropathic pain, and inflammatory models were investigated by formalin, hot-plate, and cotton pellet-induced granuloma models in mice, respectively. T. persicum aqueous extracts (100, 200, and 400 mg/kg were orally gavaged for one week. On 8th day, the time spent and the number of lickings were recorded in formalin test. Morphine and Diclofenac were used intraperitoneally as positive controls. In sciatic nerve ligated animals, as a model of neuropathic pain, doses (100, 200, and 400 mg/kg of T. persicum extract (TPE were orally gavaged for 14 consecutive days. The analgesic effect of this extract was examined 14 days after sciatic nerve ligation using the hot-plate test. Controls received saline and Imipramine (40 mg/kg, i.p. was used a positive control for neuropathic pain model. Results. In the formalin test, a week oral gavage of all TPE doses (100, 200, and 400 mg/kg caused a significant decrease on the licking response compared to the control negative animals. In the hot-plate test, doses of 200 and 400 mg/kg showed significant analgesic effects in sciatic nerve ligated animals. Oral gavaged of TPE revealed significant analgesic effect on chronic pain in both formalin test and sciatic nerve ligated animals. The TPEs did not have any significant anti-inflammatory effects in cotton pellet-induced granuloma formation in mice. Conclusions. These results suggest that the aqueous extract from T. persicum Boiss. produced antinociceptive effects. Its exact mechanism of action still remains indistinct.

  14. Weight cycling enhances adipose tissue inflammatory responses in male mice.

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    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  15. Topical herbal remedies for treatment of joint pain according to Iranian Traditional Medicine

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    A. Ziaei

    2016-07-01

    Full Text Available Joint pain is one of the most common complaints with many possible causes.Some medicines used for joint pain relief such as NSAIDs have substantial and frequent side effects. Topical route possibly reduces adverse reactions by maximizing local delivery and minimizing systemic toxicity. Throughout history, plants have been the most important sources of medicines for human health and Iranian Traditional Medicine (ITM is well known for its extensive use of herbal medicines to treat diseases accompanied with joint pain for centuries. In the present study, the plants used topically for relieving joint pain in ITM were searched. Moreover, their pharmacological effectiveness in modern medicine was reviewed. The terms “Waja mafasil” (joint pain, “Waja-ol-mafasil” (joint pain, “Irq-on-nasa” (sciatica, “Waja-ol-warik” (coxalgia, ‘Waja-ol-zahr” (back pain, “Waja-ol-rakbah” (knee pain and “Niqris” (gout were searched in three important Iranian traditional books including “Canon”, “Al-Hawi” and “Tohfat al-mu’minin” and topical preparations introduced as “Tela” and “Zemad” were selected. The scientific literatures were searched for their effectiveness related to the analgesic and anti-inflammatory activities. Thirty five plants were selected on the basis of their topical use to relief joint pain. Among these plants, 22 species have been found to exhibit anti-inflammatory and analgesic activities.

  16. Quality of Life in Arthritis Patients Using Nonsteroidal Anti-Inflammatory Drugs

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    Ingela Wiklund

    1999-01-01

    Full Text Available Arthritis is a painful and disabling condition. To suppress the pain and the inflammatory process, patients are often chronic nonsteroidal anti-inflammatory drug (NSAID users. Chronic use of NSAIDs may induce peptic ulcer, dyspeptic problems and heartburn. Therefore, these patients are often provided with treatment to relieve and/or protect against gastrointestinal problems. Rheumatic disorders also affect a range of health-related quality of life domains. In one study, patients with NSAID-associated gastroduodenal lesions complained about lack of energy, sleep disturbances, emotional distress and social isolation in addition to pain and mobility limitations. The degree of distress and dysfunction differed markedly from scores in an unselected population. Clinical trial data suggest that acid-suppressing therapy with omeprazole is superior to therapy with misoprostol and ranitidine in healing gastroduodenal lesions and preventing abdominal pain, heartburn and indigestion symptoms during continued NSAID treatment. Because arthritic patients are severely incapacitated by their condition regarding most aspects of health-related quality of life, it is important to offer a treatment that is effective in healing and preventing NSAID-induced ulcers and gastrointestinal symptoms during continued NSAID treatment without further compromising the patients’ quality of life. Treatment with omeprazole once daily has been shown to be superior to that with ranitidine and misoprostol in this respect.

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

    Directory of Open Access Journals (Sweden)

    Norbert Mair

    2011-02-01

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

  18. Analgesic Microneedle Patch for Neuropathic Pain Therapy.

    Science.gov (United States)

    Xie, Xi; Pascual, Conrado; Lieu, Christopher; Oh, Seajin; Wang, Ji; Zou, Bende; Xie, Julian; Li, Zhaohui; Xie, James; Yeomans, David C; Wu, Mei X; Xie, Xinmin Simon

    2017-01-24

    Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

  19. Personalized Pain Medicine: The Clinical Value of Psychophysical Assessment of Pain Modulation Profile

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    Yelena Granovsky

    2013-10-01

    Full Text Available Experimental pain stimuli can be used to simulate patients’ pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests—conditioned pain modulation (CPM and temporal summation (TS. Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.

  20. Inflammatory Response in Islet Transplantation

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    Mazhar A. Kanak

    2014-01-01

    Full Text Available Islet cell transplantation is a promising beta cell replacement therapy for patients with brittle type 1 diabetes as well as refractory chronic pancreatitis. Despite the vast advancements made in this field, challenges still remain in achieving high frequency and long-term successful transplant outcomes. Here we review recent advances in understanding the role of inflammation in islet transplantation and development of strategies to prevent damage to islets from inflammation. The inflammatory response associated with islets has been recognized as the primary cause of early damage to islets and graft loss after transplantation. Details on cell signaling pathways in islets triggered by cytokines and harmful inflammatory events during pancreas procurement, pancreas preservation, islet isolation, and islet infusion are presented. Robust control of pre- and peritransplant islet inflammation could improve posttransplant islet survival and in turn enhance the benefits of islet cell transplantation for patients who are insulin dependent. We discuss several potent anti-inflammatory strategies that show promise for improving islet engraftment. Further understanding of molecular mechanisms involved in the inflammatory response will provide the basis for developing potent therapeutic strategies for enhancing the quality and success of islet transplantation.

  1. Inflammatory Response in Islet Transplantation

    Science.gov (United States)

    Kanak, Mazhar A.; Kunnathodi, Faisal; Lawrence, Michael C.; Levy, Marlon F.

    2014-01-01

    Islet cell transplantation is a promising beta cell replacement therapy for patients with brittle type 1 diabetes as well as refractory chronic pancreatitis. Despite the vast advancements made in this field, challenges still remain in achieving high frequency and long-term successful transplant outcomes. Here we review recent advances in understanding the role of inflammation in islet transplantation and development of strategies to prevent damage to islets from inflammation. The inflammatory response associated with islets has been recognized as the primary cause of early damage to islets and graft loss after transplantation. Details on cell signaling pathways in islets triggered by cytokines and harmful inflammatory events during pancreas procurement, pancreas preservation, islet isolation, and islet infusion are presented. Robust control of pre- and peritransplant islet inflammation could improve posttransplant islet survival and in turn enhance the benefits of islet cell transplantation for patients who are insulin dependent. We discuss several potent anti-inflammatory strategies that show promise for improving islet engraftment. Further understanding of molecular mechanisms involved in the inflammatory response will provide the basis for developing potent therapeutic strategies for enhancing the quality and success of islet transplantation. PMID:24883060

  2. Management of inflammatory complications in third molar surgery: A ...

    African Journals Online (AJOL)

    Background: Pain, swelling and trismus are common complications associated with third molar surgery. These complications have been reported to have an adverse effect on the quality of life of patients undergoing third molar surgery. Objective: To review the different modalities of minimizing inflammatory complications in ...

  3. Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions.

    Science.gov (United States)

    Singh, Ajeet Kumar; Kumar, Sanjay; Vinayak, Manjula

    2018-05-16

    Pain is an unpleasant sensation triggered by noxious stimulation. It is one of the most prevalent conditions, limiting productivity and diminishing quality of life. Non steroidal anti inflammatory drugs (NSAIDs) are widely used as pain relievers in present day practice as pain is mostly initiated due to inflammation. However, due to potentially serious side effects, long term use of these antihyperalgesic drugs raises concern. Therefore there is a demand to search novel medicines with least side effects. Herbal products have been used for centuries to reduce pain and inflammation, and phytochemicals are known to cause fewer side effects. However, identification of active phytochemicals of herbal medicines and clear understanding of the molecular mechanism of their action is needed for clinical acceptance. In this review, we have briefly discussed the cellular and molecular changes during hyperalgesia via inflammatory mediators and neuro-modulatory action involved therein. The review includes 54 recently reported phytochemicals with antihyperalgesic action, as per the literature available with PubMed, Google Scholar and Scopus. Compounds of high interest as potential antihyperalgesic agents are: curcumin, resveratrol, capsaicin, quercetin, eugenol, naringenin and epigallocatechin gallate (EGCG). Current knowledge about molecular targets of pain and their regulation by these phytochemicals is elaborated and the scope of further research is discussed.

  4. Intravenous lignocaine infusion for intractable pain in Ewing's sarcoma

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    Nivedita Page

    2018-01-01

    Full Text Available A 23-year-old female presented to our palliative care center with Ewing's sarcoma of the humerus with lung metastases. Pain in her arm was unrelieved by nonsteroidal anti-inflammatory drugs, neuropathic medication as well as morphine. She could not tolerate any further increase in opioid dose but was so distraught due to the pain that she wanted to die. An intravenous lignocaine infusion in a dose of 2 mg/kg was given over an hour for three successive days. This successfully relieved her pain after which she was settled with her original medication. We feel that in palliative care settings, where intractable pain and tolerance to morphine are so common, intravenous lignocaine infusions could provide a safe and effective tool for pain relief.

  5. Scaling Up Cortical Control Inhibits Pain

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    Jahrane Dale

    2018-05-01

    Full Text Available Summary: Acute pain evokes protective neural and behavioral responses. Chronic pain, however, disrupts normal nociceptive processing. The prefrontal cortex (PFC is known to exert top-down regulation of sensory inputs; unfortunately, how individual PFC neurons respond to an acute pain signal is not well characterized. We found that neurons in the prelimbic region of the PFC increased firing rates of the neurons after noxious stimulations in free-moving rats. Chronic pain, however, suppressed both basal spontaneous and pain-evoked firing rates. Furthermore, we identified a linear correlation between basal and evoked firing rates of PFC neurons, whereby a decrease in basal firing leads to a nearly 2-fold reduction in pain-evoked response in chronic pain states. In contrast, enhancing basal PFC activity with low-frequency optogenetic stimulation scaled up prefrontal outputs to inhibit pain. These results demonstrate a cortical gain control system for nociceptive regulation and establish scaling up prefrontal outputs as an effective neuromodulation strategy to inhibit pain. : Dale et al. find that acute pain increases activity levels in the prefrontal cortex. Chronic pain reduces both basal spontaneous and pain-evoked activity in this region, whereas neurostimulation to restore basal activities can in turn enhance nociception-evoked prefrontal activities to inhibit pain. Keywords: chronic pain, neuromodulation, prefrontal cortex, PFC, cortical gain control

  6. Electroacupuncture Alleviates Pain Responses and Inflammation in a Rat Model of Acute Gout Arthritis

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    Wenxin Chai

    2018-01-01

    Full Text Available Acute gout arthritis is one of the most painful inflammatory conditions. Treatments for gout pain are limited to colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids, which oftentimes result in severe adverse effects. Electroacupuncture (EA has been proved to be effective in relieving many inflammatory pain conditions with few side effects. Here, we aim to investigate the therapeutic potentials of EA on pain and inflammation of a rat model of acute gout arthritis and underlying mechanisms. We found that 2/100 Hz EA produced the most robust analgesic effect on mechanical hyperalgesia of acute gout arthritis rat model compared with 2 and 100 Hz. EA produced similar analgesic effect compared with indomethacin. 2/100 Hz EA also significantly alleviates the ongoing pain behavior, thermal hyperalgesia, and ankle edema. Locally applied μ and κ-opioid receptor antagonists but not adenosine A1 receptor antagonist significantly abolished the analgesic effect of EA. Locally applied μ and κ-opioid receptor agonists produced significant antiallodynia on acute gout arthritis rats, mimicking EA. Furthermore, 2/100 Hz EA upregulated β-endorphin expression in inflamed ankle skin tissue. Our results demonstrated, for the first time, that EA can be used for relieving acute gout arthritis with effect dependent on peripheral opioid system and comparable with the one obtained with indomethacin.

  7. Pain Intensity and Its Objective Determinants Following Implant ...

    African Journals Online (AJOL)

    2017-10-26

    Oct 26, 2017 ... has been shown to result with a lower pain score than the conventional techniques. ..... Effect of age, impaction types and operative time on inflammatory tissue reactions following lower third molar surgery. Head Face Med ...

  8. The involvement of peripheral alpha 2-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain.

    Science.gov (United States)

    Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Paranos, Sonja Lj; Prostran, Milica S; Bosković, Bogdan

    2007-11-01

    We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.pl.), BRL 44408 (100 and 200 nmol/paw; i.pl.) and MK-912 (10 and 20 nmol/paw; i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/paw; i.pl.) in a dose-dependent manner. The effects of antagonists were due to local effects since they were not observed after administration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED(50) (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. Isobolographic analysis revealed an additive antihyperalgesic effect. Our results indicate that the peripheral alpha2A and alpha2C adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia.

  9. Enhancement of Antioxidative and Intestinal Anti-inflammatory Activities of Glycated Milk Casein after Fermentation with Lactobacillus rhamnosus 4B15.

    Science.gov (United States)

    Oh, Nam Su; Joung, Jae Yeon; Lee, Ji Young; Kim, Younghoon; Kim, Sae Hun

    2017-06-14

    In this study, we investigated the glycoproteomics of glycated milk casein (GMC) and GMC fermented by Lactobacillus rhamnosus 4B15 (FGMC) and determined their biological implications. There was a significant increase in the antioxidative and anti-inflammatory activities of GMC with galactose, which were higher than those of GMC with glucose (GMC-glc). Furthermore, the fermentation of GMC by L. rhamnosus 4B15 synergistically enhanced the above activities compared to those of unfermented GMC. Especially, fermented GMC-glc (FGMC-glc) possessed remarkably improved reducing power and radical scavenging activities. Moreover, FGMC-glc ameliorated the inflammatory response and tight junction-related intestinal epithelial dysfunction. Additionally, hexose-derived glycation and modification sites in protein sequences of GMC were identified. In particular, glycosylation and sulfation of serine and threonine residues were observed, and distinct modification sites were detected after fermentation. Therefore, these results indicated that glycation-induced modification of casein and fermentation correlated strongly with the enhanced functional properties.

  10. Pharmacogenetic guidance: individualized medicine promotes enhanced pain outcomes

    Directory of Open Access Journals (Sweden)

    Dragic LL

    2017-12-01

    Full Text Available Lisa Lynn Dragic,1 Erica L Wegrzyn,2 Michael E Schatman,3–5 Jeffrey Fudin2,6 1Central Arkansas Veterans Healthcare System, Little Rock, AR, USA; 2Department of Pharmacy, Albany Stratton VA Medical Center, Albany, NY, USA; 3Research and Network Development, Boston Pain Care, Waltham, MA, USA; 4Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 5Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 6Scientific and Clinical Affairs, Remitigate, LLC, Delmar, NY, USA Abstract: The use of pharmacogenomics has become more prevalent over the past several years in treating many disease states. Several cytochrome P450 enzymes play a role in the metabolism of many pain medications including opioids and antidepressants. Noncytochrome P450 enzymes such as methylenetetrahydrofolate reductase (MTHFR and catechol-O-methyl transferase (COMT also play a role in the explanation of opioid dosage requirements as well as in response to certain antidepressants. We present the case of a patient with reduced COMT and MTHFR expression treated with leucovorin 10 mg daily for the management of chronic pain. The use of leucovorin in this patient decreased pain scores, which were clinically significant and increased functionality. This case demonstrates the importance of pharmacogenetics testing in patients, as this can help direct providers to better therapeutic options for their patients. Keywords: pharmacogenetic, depression, pain, MTHFR, COMT, methyl tetrahydrofolate reductase, catechol-O-methyltransferase

  11. Can New Inflammatory Markers Improve the Diagnosis of Acute Appendicitis?

    DEFF Research Database (Denmark)

    Andersson, Manne; Rubér, Marie; Ekerfelt, Christina

    2014-01-01

    BACKGROUND: The diagnosis of appendicitis is difficult and resource consuming. New inflammatory markers have been proposed for the diagnosis of appendicitis, but their utility in combination with traditional diagnostic variables has not been tested. Our objective is to explore the potential of new...... inflammatory markers for improving the diagnosis of appendicitis.METHODS: The diagnostic properties of the six most promising out of 21 new inflammatory markers (interleukin [IL]-6, chemokine ligand [CXCL]-8, chemokine C-C motif ligand [CCL]-2, serum amyloid A [SAA], matrix metalloproteinase [MMP]-9......, and myeloperoxidase [MPO]) were compared with traditional diagnostic variables included in the Appendicitis Inflammatory Response (AIR) score (right iliac fossa pain, vomiting, rebound tenderness, guarding, white blood cell [WBC] count, proportion neutrophils, C-reactive protein and body temperature) in 432 patients...

  12. Ethnopharmacological survey of medicinal plants with hallucinogenic effect and plants used against pain, inflammatory diseases, diabetes and urinary lithiasis in Zagora “Morocco”.

    Directory of Open Access Journals (Sweden)

    Hicham Boufous

    2017-12-01

    Full Text Available Aim: The aim of this study was to identify different plants used in folk medicine for treating pain, inflammatory diseases, diabetes and kidney stones by the population of Zagora province, in southern east of Morocco. This investigation was undertaken during more than 2 years started in 2013 and ended in 2015. Methods: A total of 1400 person with different ages between 20 and 80 years, in twelve areas, was included in this survey; 348 were diabetes, 292 were suffering from kidney stones and 760 are healthy. Data collected was separated in two parts. The first part concerned interviewee information’s (age, sex and level of education and a second part was designed for plants uses (vernacular names, uses, parts used and mode of preparation.Use value (UV, fidelity level (FL and family use value (FUV were calculated. Results: We inventoried 83 plants species belonging to 40 families that were used, Ranunculaceae family family showed the highest significance (FUV= 0.36. Six species with the highest UV were Zygophyllum gaetulum L. (0.44, Nigella sativa (0.36, Rosmarinus officinalis L (0.36, Trigonella foenum-graecum L (0.35 and Thymus satureioides L (0.35. We identified 50 species used for treating or managing pain, 45 for diabetes, 19 for kidney stone, 7 for treating inflammatory diseases and only 3 species that were recognized with hallucinogenic effects. Conclusions: This study shows that folk medicine in Zagora still occupies a high level in primary health care. Data collected may help to preserve knowledge about different plants used and their mode of preparation. [J Complement Med Res 2017; 6(4.000: 342-350

  13. Alginate micro-encapsulation of mesenchymal stromal cells enhances modulation of the neuro-inflammatory response.

    Science.gov (United States)

    Stucky, Elizabeth C; Schloss, Rene S; Yarmush, Martin L; Shreiber, David I

    2015-10-01

    Modulation of inflammation after brain trauma is a key therapeutic goal aimed at limiting the consequences of the subsequent injury cascade. Mesenchymal stromal cells (MSCs) have been demonstrated to dynamically regulate the inflammatory environment in several tissue systems, including the central nervous system. There has been limited success, however, with the use of direct implantation of cells in the brain caused by low viability and engraftment at the injury site. To circumvent this, we encapsulated MSCs in alginate microspheres and evaluated the ability of these encapsulated MSCs to attenuate inflammation in rat organotypic hippocampal slice cultures (OHSC). OHSC were administered lipopolysaccharide to induce inflammation and immediately co-cultured with encapsulated or monolayer human MSCs. After 24 h, culture media was assayed for the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) produced by OHSC, as well as MSC-produced trophic mediators. Encapsulated MSCs reduced TNF-α more effectively than did monolayer MSCs. Additionally, there was a strong correlation between increased prostaglandin E2 (PGE2) and reduction of TNF-α. In contrast to monolayer MSCs, inflammatory signals were not required to stimulate PGE2 production by encapsulated MSCs. Further encapsulation-stimulated changes were revealed in a multiplex panel analyzing 27 MSC-produced cytokines and growth factors, from which additional mediators with strong correlations to TNF-α levels were identified. These results suggest that alginate encapsulation of MSCs may not only provide an improved delivery vehicle for transplantation but may also enhance MSC therapeutic benefit for treating neuro-inflammation. Copyright © 2015. Published by Elsevier Inc.

  14. Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection.

    Science.gov (United States)

    Martini, Alessandra Cadete; Berta, Temugin; Forner, Stefânia; Chen, Gang; Bento, Allisson Freire; Ji, Ru-Rong; Rae, Giles Alexander

    2016-04-08

    Spinal cord injury (SCI) is a severe neurological disorder with many disabling consequences, including persistent neuropathic pain, which develops in about 40 % of SCI patients and is induced and sustained by excessive and uncontrolled spinal neuroinflammation. Here, we have evaluated the effects of lipoxin A4 (LXA4), a member of a unique class of endogenous lipid mediators with both anti-inflammatory and analgesic properties, on spinal neuroinflammation and chronic pain in an experimental model of SCI. Spinal hemisection at T10 was carried out in adult male CD1 mice and Wistar rats. To test if LXA4 can reduce neuroinflammation and neuropathic pain, each animal received two intrathecal injections of LXA4 (300 pmol) or vehicle at 4 and 24 h after SCI. Sensitivity to mechanical stimulation of the hind paws was evaluated using von Frey monofilaments, and neuroinflammation was tested by measuring the mRNA and/or protein expression levels of glial markers and cytokines in the spinal cord samples after SCI. Also, microglia cultures prepared from murine cortical tissue were used to assess the direct effects of LXA4 on microglial activation and release of pro-inflammatory TNF-α. LXA4 treatment caused significant reductions in the intensity of mechanical pain hypersensitivity and spinal expression levels of microglial markers and pro-inflammatory cytokines induced by SCI, when compared to rodents receiving control vehicle injections. Notably, the increased expressions of the microglial marker IBA-1 and of the pro-inflammatory cytokine TNF-α were the most affected by the LXA4 treatment. Furthermore, cortical microglial cultures expressed ALX/FPR2 receptors for LXA4 and displayed potentially anti-inflammatory responses upon challenge with LXA4. Collectively, our results suggest that LXA4 can effectively modulate microglial activation and TNF-α release through ALX/FPR2 receptors, ultimately reducing neuropathic pain in rodents after spinal cord hemisection. The dual anti-inflammatory

  15. Chronic female pelvic pain

    Directory of Open Access Journals (Sweden)

    Gaurab Maitra

    2013-01-01

    Full Text Available Chronic pelvic pain (CPP is defined as nonmalignant pain perceived in the structures related to the pelvis that has been present for more than 6 months or a non acute pain mechanism of shorter duration. Pain in the pelvic region can arise from musculoskeletal, gynaecological, urologic, gastrointestinal and or neurologic conditions. Key gynaecological conditions that contribute to CPP include pelvic inflammatory disease (PID, endometriosis, adnexa pathologies (ovarian cysts, ovarian remnant syndrome, uterine pathologies (leiomyoma, adenomyosis and pelvic girdle pain associated with pregnancy. Several major and minor sexually transmitted diseases (STD can cause pelvic and vulvar pain. A common painful condition of the urinary system is Interstitial cystitis(IC. A second urologic condition that can lead to development of CPP is urethral syndrome. Irritable bowel syndrome (IBS is associated with dysmenorrhoea in 60% of cases. Other bowel conditions contributing to pelvic pain include diverticular disease,Crohn′s disease ulcerative colitis and chronic appendicitis. Musculoskeletal pathologies that can cause pelvic pain include sacroiliac joint (SIJ dysfunction, symphysis pubis and sacro-coccygeal joint dysfunction, coccyx injury or malposition and neuropathic structures in the lower thoracic, lumbar and sacral plexus. Prolonged pelvic girdle pain, lasting more than 6 months postpartum is estimated in 3% to 30% of women. Nerve irritation or entrapment as a cause of pelvic pain can be related to injury of the upper lumbar segments giving rise to irritation of the sensory nerves to the ventral trunk or from direct trauma from abdominal incisions or retractors used during abdominal surgical procedures. Afflictions of the iliohypogastric, ilioinguinal, genitofemoral, pudendal and obturator nerves are of greatest concern in patients with pelvic pain. Patient education about the disease and treatment involved is paramount. A knowledge of the differential

  16. Cannabis use amongst patients with inflammatory bowel disease.

    Science.gov (United States)

    Lal, Simon; Prasad, Neeraj; Ryan, Manijeh; Tangri, Sabrena; Silverberg, Mark S; Gordon, Allan; Steinhart, Hillary

    2011-10-01

    Experimental evidence suggests the endogenous cannabinoid system may protect against colonic inflammation, leading to the possibility that activation of this system may have a therapeutic role in inflammatory bowel disease (IBD). Medicinal use of cannabis for chronic pain and other symptoms has been reported in a number of medical conditions. We aimed to evaluate cannabis use in patients with IBD. One hundred patients with ulcerative colitis (UC) and 191 patients with Crohn's disease (CD) attending a tertiary-care outpatient clinic completed a questionnaire regarding current and previous cannabis use, socioeconomic factors, disease history and medication use, including complimentary alternative medicines. Quality of life was assessed using the short-inflammatory bowel disease questionnaire. A comparable proportion of UC and CD patients reported lifetime [48/95 (51%) UC vs. 91/189 (48%) CD] or current [11/95 (12%) UC vs. 30/189 (16%) CD] cannabis use. Of lifetime users, 14/43 (33%) UC and 40/80 (50%) CD patients have used it to relieve IBD-related symptoms, including abdominal pain, diarrhoea and reduced appetite. Patients were more likely to use cannabis for symptom relief if they had a history of abdominal surgery [29/48 (60%) vs. 24/74 (32%); P=0.002], chronic analgesic use [29/41 (71%) vs. 25/81 (31%); Pmedicine use [36/66 (55%) vs. 18/56 (32%); P=0.01] and a lower short inflammatory bowel disease questionnaire score (45.1±2.1 vs. 50.3±1.5; P=0.03). Patients who had used cannabis [60/139 (43%)] were more likely than nonusers [13/133 (10%); Pcannabis for IBD. Cannabis use is common amongst patients with IBD for symptom relief, particularly amongst those with a history of abdominal surgery, chronic abdominal pain and/or a low quality of life index. The therapeutic benefits of cannabinoid derivatives in IBD may warrant further exploration.

  17. Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function

    DEFF Research Database (Denmark)

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis

    2013-01-01

    antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic...... of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r...... dermatitis), topical H1/2r agonists aggravated, whereas H1/2r antagonists improved, inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased...

  18. Pregabalin for Opioid-Refractory Pain in a Patient with Ankylosing Spondylitis

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    Konstantinos A. Kontoangelos

    2013-01-01

    Full Text Available Background. Ankylosing spondylitis (AS is a systemic inflammatory disease with chronic back pain as the most common presenting symptom. We present a case of a male patient with AS reporting symptoms of severe low back pain, buttock pain, and limited spinal mobility. After chronic treatment with opioids, we administered pregabalin at a dose of 300 mg as an analgesic agent while opioids were discontinued. Findings. Pain symptoms improved progressively, and opioids were gradually discontinued without any withdrawal symptoms reported. Conclusions. Pregabalin is potentially useful in the management of pain in patients with AS while effectively managing the discontinuation of opioid treatment.

  19. Ketamine for chronic pain: risks and benefits

    Science.gov (United States)

    Niesters, Marieke; Martini, Christian; Dahan, Albert

    2014-01-01

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