WorldWideScience

Sample records for reduces inflammatory pain

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

    Science.gov (United States)

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

    2016-08-17

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

  2. 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.

  3. 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....

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Abolfazl Abbaszadeh

    2018-02-01

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

  6. Benfotiamine relieves inflammatory and neuropathic pain in rats.

    Science.gov (United States)

    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.

  7. 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...

  8. Sigma-1 receptor and inflammatory pain.

    Science.gov (United States)

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

    2015-06-01

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

  9. Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages

    Directory of Open Access Journals (Sweden)

    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.

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

    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.

  11. Peripheral analgesic effects of ketamine in acute inflammatory pain

    DEFF Research Database (Denmark)

    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

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

    Directory of Open Access Journals (Sweden)

    Gui-Lin Jin

    2018-01-01

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

  13. Effect of Probiotic Administration on Acute Inflammatory Pain

    Directory of Open Access Journals (Sweden)

    Shadnoush

    2016-11-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Monocytes/Macrophages Control Resolution of Transient Inflammatory Pain

    Science.gov (United States)

    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

  16. 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.

  17. 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...

  18. 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

  19. Can We Distinguish between Inflammatory and Neuropathic Pain?

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. 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

  2. Slow brushing reduces heat pain in humans.

    Science.gov (United States)

    Liljencrantz, J; Strigo, I; Ellingsen, D M; Krämer, H H; Lundblad, L C; Nagi, S S; Leknes, S; Olausson, H

    2017-08-01

    C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain. Slow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more pronounced for a shorter time interval between brushing and pain. Likewise, the effect was more robust when pain was preceded by a longer duration of brush stimulation. Strong CT-related pain reduction was associated with low anxiety and high calmness scores obtained by a state anxiety questionnaire. Slow brushing - optimal for CT activation - is effective in reducing pain from cutaneous heating. The precise mechanisms for the pain relief are as yet unknown but possible mechanisms include inhibition of nociceptive projection neurons at the level of the dorsal horn as well as analgesia through cortical mechanisms. Slow brushing stimuli - optimal for activation of C-tactile fibres - can reduce pain from cutaneous heating. No such effect was seen with fast brushing or vibration. These observations indicate the role of C-tactile fibres in pain modulation. © 2017 European Pain Federation - EFIC®.

  3. Experimental knee pain reduces muscle strength

    DEFF Research Database (Denmark)

    Henriksen, Marius; Mortensen, Sara Rosager; Aaboe, Jens

    2011-01-01

    Pain is the principal symptom in knee pathologies and reduced muscle strength is a common observation among knee patients. However, the relationship between knee joint pain and muscle strength remains to be clarified. This study aimed at investigating the changes in knee muscle strength following...... experimental knee pain in healthy volunteers, and if these changes were associated with the pain intensities. In a crossover study, 18 healthy subjects were tested on 2 different days. Using an isokinetic dynamometer, maximal muscle strength in knee extension and flexion was measured at angular velocities 0....... Knee pain reduced the muscle strength by 5 to 15% compared to the control conditions (P knee extension and flexion at all angular velocities. The reduction in muscle strength was positively correlated to the pain intensity. Experimental knee pain significantly reduced knee extension...

  4. 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....

  5. 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.

  6. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-04-01

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

  7. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-06-01

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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Warmed local anesthetic reduces pain of infiltration.

    Science.gov (United States)

    Fialkov, J A; McDougall, E P

    1996-01-01

    The effect of warming local anesthetic on the amount of pain experienced during local infiltration was tested by comparing equal volumes of 40 degrees C- and 21 degrees C-infiltrates in each of 26 subjects. Six subjects were patients undergoing excision of two benign asymptomatic nevi in separate locations, and 20 subjects were healthy adult volunteers who were injected in bilateral antebrachial sites. The warmed and room temperature solutions were randomized to each side, so that each subject received both temperature injections in random order. All subjects and the injector were blinded. The rate of injection was time-controlled (0.05 ml/sec). Following both injections, subjects were asked to rate the pain experienced at each site. In addition, the subject was asked if there was no difference, a slight difference, or a substantial difference between the two sites. A two-tailed paired t-test was used to analyze the mean difference in pain scores for all subjects. Paired analysis of the pain scores for each subject eliminated intersubject variance of pain tolerance. The mean difference in pain score between the room temperature and warmed solutions was +1.5 (p < 0.0001). Of the 21 subjects (81%) who found the warmed solution less painful, 11 (52%) found the difference to be significant, while 10 (48%) found the difference to be slight. Two subjects (8%) found no difference between the two, while 3 subjects (11%) found the colder solution slightly less painful. We conclude that warming local anesthetic to 40 degrees C prior to subcutaneous injection is a simple, inexpensive means of reducing the pain of local infiltration.

  13. 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.

  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. 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

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

    NARCIS (Netherlands)

    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

  17. 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.

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

    Science.gov (United States)

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

    2016-02-24

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

  19. 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.

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

    OpenAIRE

    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...

  1. 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....

  2. 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.

  3. 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.   

  4. 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...

  5. 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.

  6. [Ice application for reducing pain associated with goserelin acetate injection].

    Science.gov (United States)

    Ishii, Kaname; Nagata, Chika; Koshizaki, Eiko; Nishiuchi, Satoko

    2013-10-01

    We investigated the effectiveness of using an ice pack for reducing the pain associated with goserelin acetate injection. In this study, 39 patients with prostate cancer and 1 patient with breast cancer receiving hormonal therapy with goserelin acetate were enrolled. All patients completed a questionnaire regarding the use of ice application. We used the numerical rating scale (NRS) to assess the pain associated with injection. The NRS scores indicated that the pain was significantly less with ice application than with the usual method (p application could decrease the duration of pain sensation. Ice application at the injection site is safe and effective for reducing pain.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2013-03-22

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

  11. 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.)

  12. Acute psychosocial stress reduces pain modulation capabilities in healthy men.

    Science.gov (United States)

    Geva, Nirit; Pruessner, Jens; Defrin, Ruth

    2014-11-01

    Anecdotes on the ability of individuals to continue to function under stressful conditions despite injuries causing excruciating pain suggest that acute stress may induce analgesia. However, studies exploring the effect of acute experimental stress on pain perception show inconsistent results, possibly due to methodological differences. Our aim was to systematically study the effect of acute stress on pain perception using static and dynamic, state-of-the-art pain measurements. Participants were 29 healthy men who underwent the measurement of heat-pain threshold, heat-pain intolerance, temporal summation of pain, and conditioned pain modulation (CPM). Testing was conducted before and during exposure to the Montreal Imaging Stress Task (MIST), inducing acute psychosocial stress. Stress levels were evaluated using perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol. The MIST induced a significant stress reaction. Although pain threshold and pain intolerance were unaffected by stress, an increase in temporal summation of pain and a decrease in CPM were observed. These changes were significantly more robust among individuals with stronger reaction to stress ("high responders"), with a significant correlation between the perception of stress and the performance in the pain measurements. We conclude that acute psychosocial stress seems not to affect the sensitivity to pain, however, it significantly reduces the ability to modulate pain in a dose-response manner. Considering the diverse effects of stress in this and other studies, it appears that the type of stress and the magnitude of its appraisal determine its interactions with the pain system. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  13. Home Cervical Traction to Reduce Neck Pain in Fighter Pilots.

    Science.gov (United States)

    Chumbley, Eric M; O'Hair, Nicole; Stolfi, Adrienne; Lienesch, Christopher; McEachen, James C; Wright, Bruce A

    2016-12-01

    Most fighter pilots report cervical pain during their careers. Recommendations for remediation lack evidence. We sought to determine whether regular use of a home cervical traction device could decrease reported cervical pain in F-15C pilots. An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, controlled crossover study was undertaken with 21 male F-15C fighter pilots between February and June 2015. Of the 21 subjects, 12 completed 6 wk each of traction and control, while logging morning, postflying, and post-traction pain. Pain was compared with paired t-tests between the periods, from initial pain scores to postflying, and postflying to post-traction. In the traction phase, initial pain levels increased postflight, from 1.2 (0.7) to 1.6 (1.0) Subsequent post-traction pain levels decreased to 1.3 (0.9), with a corresponding linear decrease in pain relative to pain reported postflight. The difference in pain levels after traction compared to initial levels was not significant, indicating that cervical traction was effective in alleviating flying-related pain. Control pain increased postflight from 1.4 (0.9) to 1.9 (1.3). Daily traction phase pain was lower than the control, but insignificant. To our knowledge, this is the first study of home cervical traction to address fighter pilots' cervical pain. We found a small but meaningful improvement in daily pain rating when using cervical traction after flying. These results help inform countermeasure development for pilots flying high-performance aircraft. Further study should clarify the optimal traction dose and timing in relation to flying.Chumbley EM, O'Hair N, Stolfi A, Lienesch C, McEachen JC, Wright BA. Home cervical traction to reduce neck pain in fighter pilots. Aerosp Med Hum Perform. 2016; 87(12):1010-1015.

  14. 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...

  15. 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.

  16. 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

  17. 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....

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

    Science.gov (United States)

    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.

  19. 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

  20. Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

    Science.gov (United States)

    Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

    2015-12-01

    Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway. Copyright © 2015 by Daedalus Enterprises.

  1. Listening to music does not reduce pain during sigmoidoscopy.

    Science.gov (United States)

    Meeuse, Jan J; Koornstra, Jan Jacob; Reyners, An K L

    2010-08-01

    Up to 40% of the sigmoidoscopies are considered painful by patients. Nonpharmacological intervention would be attractive, as sedation and analgesia carry the risk of side-effects and increase procedure-related costs. Music might have the potential of pain reduction, but its effect during sigmoidoscopy has not been established yet. To study whether listening to music reduces experienced pain during sigmoidoscopy. Consecutive patients, above 18 years of age, undergoing sigmoidoscopy without sedation or analgesia and who gave their informed consent were included in this study. Patients in the music group listened to their preferred music (classical, jazz, English or Dutch Popular) during the sigmoidoscopy. The control group received care as usual. The outcome measures were pain intensity during sigmoidoscopy (measured with a 100-mm-long visual analogue scale) and the proportion of patients with at least moderate pain during sigmoidoscopy (pain intensity score of 50 mm or higher). The music groups consisted of 153 patients, the control group of 154 patients. The mean pain intensity + or - standard deviation was 36 + or - 27 mm in the music group and 40 + or - 29 in the control group (P=0.27) during sigmoidoscopy. The proportion of patients with at least moderate pain during sigmoidoscopy was 29 and 37% in the respective groups (P=0.12). Listening to music by patients did not reduce pain intensity during sigmoidoscopy. As a consequence, music during sigmoidoscopy is not recommended for this purpose.

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

    Science.gov (United States)

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

    2017-08-29

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

  3. Cancer Pain Management Education Rectifies Patients' Misconceptions of Cancer Pain, Reduces Pain, and Improves Quality of Life.

    Science.gov (United States)

    Koh, Su-Jin; Keam, Bhumsuk; Hyun, Min Kyung; Ju Seo, Jeong; Uk Park, Keon; Oh, Sung Yong; Ahn, Jinseok; Lee, Ja Youn; Kim, JinShil

    2018-03-26

    More than half of the patients have reported improper management of breakthrough cancer pain. Empirical evidence is lacking concerning the effectiveness of cancer pain education on breakthrough pain control. This study aimed to examine the effects of individual pain education on pain control, use of short-acting analgesics for breakthrough pain, quality of life outcomes, and rectification of patients' misconceptions regarding cancer pain. A quasi-experimental design was used. In total, 176 (102 inpatients and 74 outpatients) and 163 (93 inpatients and 70 outpatients) cancer patients completed questionnaires on pain intensity, quality of life, use of short-acting medication for breakthrough pain, and misconceptions about cancer pain and opioid use before and immediately and/or seven days after individual pain education. The mean age of the participants was 60.9 years (±11.2), and 56.3% were male. The most common cancers were lung cancer (17.0%), colon cancer (15.9%), and breast cancer (12.5%). The subjects' reasons for attrition were conditional deterioration, death, or voluntary withdrawal (N = 13, 7.4%). Following the education, there was a significant reduction in overall pain intensity over 24 hours (P < 0.001). The outpatients showed more use of short-acting analgesics for breakthrough pain. Sleep quality change was most significantly associated with intervention; other quality of life aspects (e.g., general feelings and life enjoyment) also improved. Pain education also significantly reduced misconceptions regarding cancer pain management. The present educational intervention was effective in encouraging short-acting analgesic use for breakthrough pain, improving quality of life outcomes, and rectifying patients' misconceptions about analgesic use.

  4. Acupuncture Reduces Breast Cancer Joint Pain | Division of Cancer Prevention

    Science.gov (United States)

    In the largest, most rigorous study of its kind, acupuncture was found to significantly reduce the debilitating joint pain experienced by tens of thousands of women each year while being treated for early stage breast cancer with aromatase inhibitors (AIs). |

  5. Drug Reduces Cancer Treatment-Related Joint Pain

    Science.gov (United States)

    A Cancer Currents blog post about a clinical trial demonstrating that duloxetine (Cymbalta®) may reduce joint pain caused by aromatase inhibitors in women being treated for early-stage breast cancer.

  6. Music reduces pain and increases functional mobility in fibromyalgia

    DEFF Research Database (Denmark)

    Garza-Villarreal, Eduardo A.; Wilson, Andrew D; Vase, Lene

    2014-01-01

    task (not during), therefore the effect cannot be explained merely by motor entrainment to a fast rhythm. Cognitive and emotional mechanisms seem to be central to music-induced analgesia. Our findings encourage the use of music as a treatment adjuvant to reduce chronic pain in FM and increase......The pain in Fibromyalgia (FM) is difficult to treat and functional mobility seems to be an important comorbidity in these patients that could evolve into a disability. In this study we wanted to investigate the analgesic effects of music in FM pain. Twenty-two FM patients were passively exposed...... to (1) self-chosen, relaxing, pleasant music, and to (2) a control auditory condition (pink noise). They rated pain and performed the “timed-up & go task (TUG)” to measure functional mobility after each auditory condition. Listening to relaxing, pleasant, self-chosen music reduced pain and increased...

  7. 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

  8. 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

  9. 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.

  10. 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

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

    Science.gov (United States)

    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.

  12. 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

  13. 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...

  14. Using cold air for reducing needle-injection pain.

    Science.gov (United States)

    Al-Qarqaz, Firas; Al-Aboosi, Mustafa; Al-shiyab, Diala; Al Dabbagh, Ziad

    2012-07-01

    Pain is associated with skin injections. Reducing injection-associated pain is important especially when multiple injections are needed in difficult areas, such as the palms. We present a new safe application for cold air used in laser therapy. The main objectives of this study are to see whether cold air can reduce needle-injection pain and to evaluate the safety of this new application. Patients undergoing skin injection (n=40) were included. Assessment of pain level using visual analog scale (VAS) was done using cold air and again without cold air in the same patient. Comparison of pain scores was performed. Thirty-three patients had lower VAS scores using cold air. Five patients had worse VAS scores, and two patients did not have any change in their pain score. In the group of patients where injections were made to the palms (n=5), there was even more reduction in VAS scores. There were no significant immediate or delayed side effects. Cold air seems to be useful in reducing needle-injection pain in the majority of patients, especially in the palms. This procedure is safe, apart from immediate tolerable discomfort when used around the nose. © 2012 The International Society of Dermatology.

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

    DEFF Research Database (Denmark)

    Elmholdt, Else-Marie; Skewes, Joshua Charles; Dietz, Martin

    2017-01-01

    Previous studies suggest that religious prayer can alter the experience of pain via expectation mechanisms. While brain processes related to other types of top-down modulation of pain have been studied extensively, no research has been conducted on the potential effects of active religious coping....... Here, we aimed at investigating the neural mechanisms during pain modulation by prayer and their dependency on the opioidergic system. Twenty-eight devout Protestants performed religious prayer and a secular contrast prayer during painful electrical stimulation in two fMRI sessions. Naloxone or saline...... was administered prior to scanning. Results show that pain intensity was reduced by 11% and pain unpleasantness by 26% during religious prayer compared to secular prayer. Expectancy predicted large amounts (70–89%) of the variance in pain intensity. Neuroimaging results revealed reduced neural activity during...

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

    Science.gov (United States)

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

    2017-01-01

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

  17. Are Pain-Related Fears Mediators for Reducing Disability and Pain in Patients with Complex Regional Pain Syndrome Type 1? An Explorative Analysis on Pain Exposure Physical Therapy

    Science.gov (United States)

    Barnhoorn, Karlijn J.; Staal, J. Bart; van Dongen, Robert T. M.; Frölke, Jan Paul M.; Klomp, Frank P.; van de Meent, Henk; Samwel, Han; Nijhuis-van der Sanden, Maria W. G.

    2015-01-01

    Objective To investigate whether pain-related fears are mediators for reducing disability and pain in patients with Complex Regional Pain Syndrome type 1 when treating with Pain Exposure Physical Therapy. Design An explorative secondary analysis of a randomised controlled trial. Participants Fifty-six patients with Complex Regional Pain Syndrome type 1. Interventions The experimental group received Pain Exposure Physical Therapy in a maximum of five treatment sessions; the control group received conventional treatment following the Dutch multidisciplinary guideline. Outcome measures Levels of disability, pain, and pain-related fears (fear-avoidance beliefs, pain catastrophizing, and kinesiophobia) were measured at baseline and after 3, 6, and 9 months follow-up. Results The experimental group had a significantly larger decrease in disability of 7.77 points (95% CI 1.09 to 14.45) and in pain of 1.83 points (95% CI 0.44 to 3.23) over nine months than the control group. The potential mediators pain-related fears decreased significantly in both groups, but there were no significant differences between groups, which indicated that there was no mediation. Conclusion The reduction of pain-related fears was comparable in both groups. We found no indication that pain-related fears mediate the larger reduction of disability and pain in patients with Complex Regional Pain Syndrome type 1 treated with Pain Exposure Physical Therapy compared to conventional treatment. Trial registration International Clinical Trials Registry NCT00817128 PMID:25919011

  18. 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...

  19. 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.

  20. Pilates workouts can reduce pain in pregnant women.

    Science.gov (United States)

    Oktaviani, Ika

    2018-05-01

    This study aims to evaluate the effects of Pilates exercises for a decreasing pain in pregnant women. A total of 40 pregnant women were divided into two groups, a control group (followed a standard pregnancy exercise regimen) and a Pilates group (completed a Pilates exercise regimen). A pain assessment was carried out after exercise, using a visual analog scale. The Pilates group workout program lasted 70-80 min per day, once a week, for 8 weeks. The reduction in the level of pain was found to be significantly greater in the group of pregnant women who completed the Pilates workout (p Pilates is an effective, healthy, and feasible method of reducing pain in pregnancy, and is therefore a beneficial alternative workout for the suppression of pain in the third trimester of pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. Orofacial neuropathic pain reduces spontaneous burrowing behavior in rats.

    Science.gov (United States)

    Deseure, K; Hans, G

    2018-07-01

    It was recently reported that spontaneous burrowing behavior is decreased after tibial nerve transection, spinal nerve transection and partial sciatic nerve ligation. It was proposed that spontaneous burrowing could be used as a measure of the impact of neuropathic pain after peripheral nerve injury. It has remained unclear whether the reduction in burrowing behavior is caused directly by pain or hypersensitivity in the affected limbs, making it more difficult to perform burrowing, or by a pain induced decrease in the general wellbeing, thus reducing the motivation to burrow. We studied burrowing behavior after infraorbital nerve injury, a model of orofacial neuropathic pain that does not affect the limbs. Burrowing behavior was significantly reduced after infraorbital nerve injury. Isolated face grooming and responsiveness to mechanical von Frey stimulation of the infraorbital nerve territory were significantly increased after infraorbital nerve injury, indicative, respectively, of spontaneous pain and mechanical allodynia. It is concluded that spontaneous burrowing may provide a measure of the global impact of pain on the animal's wellbeing after peripheral nerve injury and incorporation of this behavioral assay in preclinical drug testing may improve the predictive validity of currently used pain models. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

    Science.gov (United States)

    Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

    2016-06-01

    Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. 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...

  7. Music reduces pain and increases functional mobility in fibromyalgia

    Science.gov (United States)

    Garza-Villarreal, Eduardo A.; Wilson, Andrew D.; Vase, Lene; Brattico, Elvira; Barrios, Fernando A.; Jensen, Troels S.; Romero-Romo, Juan I.; Vuust, Peter

    2014-01-01

    The pain in Fibromyalgia (FM) is difficult to treat and functional mobility seems to be an important comorbidity in these patients that could evolve into a disability. In this study we wanted to investigate the analgesic effects of music in FM pain. Twenty-two FM patients were passively exposed to (1) self-chosen, relaxing, pleasant music, and to (2) a control auditory condition (pink noise). They rated pain and performed the “timed-up & go task (TUG)” to measure functional mobility after each auditory condition. Listening to relaxing, pleasant, self-chosen music reduced pain and increased functional mobility significantly in our FM patients. The music-induced analgesia was significantly correlated with the TUG scores; thereby suggesting that the reduction in pain unpleasantness increased functional mobility. Notably, this mobility improvement was obtained with music played prior to the motor task (not during), therefore the effect cannot be explained merely by motor entrainment to a fast rhythm. Cognitive and emotional mechanisms seem to be central to music-induced analgesia. Our findings encourage the use of music as a treatment adjuvant to reduce chronic pain in FM and increase functional mobility thereby reducing the risk of disability. PMID:24575066

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

    Directory of Open Access Journals (Sweden)

    Lin Chih-Shin

    2009-07-01

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

  9. 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.

  10. 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.

  11. The Effectiveness of Aromatherapy in Reducing Pain: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Shaheen E. Lakhan

    2016-01-01

    Full Text Available Background. Aromatherapy refers to the medicinal or therapeutic use of essential oils absorbed through the skin or olfactory system. Recent literature has examined the effectiveness of aromatherapy in treating pain. Methods. 12 studies examining the use of aromatherapy for pain management were identified through an electronic database search. A meta-analysis was performed to determine the effects of aromatherapy on pain. Results. There is a significant positive effect of aromatherapy (compared to placebo or treatments as usual controls in reducing pain reported on a visual analog scale (SMD = −1.18, 95% CI: −1.33, −1.03; p<0.0001. Secondary analyses found that aromatherapy is more consistent for treating nociceptive (SMD = −1.57, 95% CI: −1.76, −1.39, p<0.0001 and acute pain (SMD = −1.58, 95% CI: −1.75, −1.40, p<0.0001 than inflammatory (SMD = −0.53, 95% CI: −0.77, −0.29, p<0.0001 and chronic pain (SMD = −0.22, 95% CI: −0.49, 0.05, p=0.001, respectively. Based on the available research, aromatherapy is most effective in treating postoperative pain (SMD = −1.79, 95% CI: −2.08, −1.51, p<0.0001 and obstetrical and gynecological pain (SMD = −1.14, 95% CI: −2.10, −0.19, p<0.0001. Conclusion. The findings of this study indicate that aromatherapy can successfully treat pain when combined with conventional treatments.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Tayler D Sheahan

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

  14. 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.

  15. Audiovisual distraction reduces pain perception during shockwave lithotripsy.

    Science.gov (United States)

    Marsdin, Emma; Noble, Jeremy G; Reynard, John M; Turney, Benjamin W

    2012-05-01

    Lithotripsy is an established method to fragment kidney stones that can be performed without general anesthesia in the outpatient setting. Discomfort and/or noise, however, may deter some patients. It has been demonstrated that audiovisual distraction (AV) can reduce sedoanalgesic requirements and improve patient satisfaction in nonurologic settings, but to our knowledge, this has not been investigated with lithotripsy. This randomized controlled trial was designed to test the hypothesis that AV distraction can reduce perceived pain during lithotripsy. All patients in the study received identical analgesia before a complete session of lithotripsy on a fixed-site Storz Modulith SLX F2 lithotripter. Patients were randomized to two groups: One group (n=61) received AV distraction via a wall-mounted 32″ (82 cm) television with wireless headphones; the other group (n=57) received no AV distraction. The mean intensity of treatment was comparable in both groups. Patients used a visual analogue scale (0-10) to record independent pain and distress scores and a nonverbal pain score was documented by the radiographer during the procedure (0-4). In the group that received AV distraction, all measures of pain perception were statistically lower. The patient-reported pain score was reduced from a mean of 6.1 to 2.4 (P<0.0001), and the distress score was reduced from a mean of 4.4 to 1.0 (P=0.0001). The mean nonverbal score recorded by the radiographer was reduced from 1.5 to 0.5 (<0.0001). AV distraction significantly lowered patients' reported pain and distress scores. This correlated with the nonverbal scores reported by the radiographer. We conclude that AV distraction is a simple method of improving acceptance of lithotripsy and optimizing treatment.

  16. 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.

  17. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Arjun eMuralidharan

    2016-05-01

    Full Text Available Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤450g of gravel on any two days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund’s complete adjuvant (FCA or saline, or underwent unilateral chronic constriction injury (CCI of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA- and CCI-rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Chao Wang

    2015-01-01

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

  20. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

    Science.gov (United States)

    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor. Copyright © 2016. Published by Elsevier Ireland Ltd.

  1. 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.

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

    Science.gov (United States)

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

    2012-09-01

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

  3. Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet.

    Directory of Open Access Journals (Sweden)

    David N Ruskin

    2009-12-01

    Full Text Available The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain and inflammation directly, we fed juvenile and adult rats a control diet (standard rodent chow or ketogenic diet (79% fat ad libitum for 3-4 weeks. We then quantified hindpaw thermal nociception as a pain measure and complete Freund's adjuvant-induced local hindpaw swelling and plasma extravasation (fluid movement from the vasculature as inflammation measures. Independent of age, maintenance on a ketogenic diet reduced the peripheral inflammatory response significantly as measured by paw swelling and plasma extravasation. The ketogenic diet also induced significant thermal hypoalgesia independent of age, shown by increased hindpaw withdrawal latency in the hotplate nociception test. Anti-inflammatory and hypoalgesic diet effects were generally more robust in juveniles. The ketogenic diet elevated plasma ketones similarly in both age groups, but caused slowed body growth only in juveniles. These data suggest that applying a ketogenic diet or exploiting cellular mechanisms associated with ketone-based metabolism offers new therapeutic opportunities for controlling pain and peripheral inflammation, and that such a metabolic strategy may offer significant benefits for children and adults.

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

    Directory of Open Access Journals (Sweden)

    Cui Guang-bin

    2012-02-01

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

  5. 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.

  6. Effectiveness of Biomodulator in treating chronic pain and reducing medications pain and reducing medications

    Science.gov (United States)

    2017-01-12

    care Nursing Competencies and Practice: Patient outcomes Quality and safety Translate research into practice/evidence-based practice...Preparing tomorrow’s leaders Care of the caregiver Other: Army Nurse Corps High Priority Research Topic: Evaluation of CAM for Pain and Well-Being... care + PEMF participants that cannot be fully explained; and it is in contrast to small, clinically insignificant decreases in reported depression

  7. 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

  8. 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

    Full Text Available Abstract Background N-ethyl-N-nitrosourea mutagenesis was used to induce a point mutation in C57BL/6 J mice. Pain-related phenotype screening was performed in 915 G3 mice. We report the detection of a heritable recessive mutant in meiotic recombinant N1F1 mice that caused an abnormal pain sensitivity phenotype with spontaneous skin inflammation in the paws and ears. Methods We investigated abnormal sensory processing, neuronal peptides, and behavioral responses after the induction of autoinflammatory disease. Single-nucleotide polymorphism (SNP markers and polymerase chain reaction product sequencing were used to identify the mutation site. Results All affected mice developed paw inflammation at 4–8 weeks. Histological examinations revealed hyperplasia of the epidermis in the inflamed paws and increased macrophage expression in the spleen and paw tissues. Mechanical and thermal nociceptive response thresholds were reduced in the affected mice. Locomotor activity was decreased in affected mice with inflamed hindpaws, and this reduction was attributable to the avoidance of contact of the affected paw with the floor. Motor strength and daily activity in the home cage in the affected mice did not show any significant changes. Although Fos immunoreactivity was normal in the dorsal horn of affected mice, calcitonin gene-related peptide immunoreactivity significantly increased in the deep layer of the dorsal horn. The number of microglia increased in the spinal cord, hippocampus, and cerebral cortex in affected mice, and the proliferation of microglia was maintained for a couple of months. Two hundred eighty-five SNP markers were used to reveal the affected gene locus, which was found on the distal part of chromosome 18. A point mutation was detected at A to G in exon 8 of the pstpip2 gene, resulting in a conserved tyrosine residue at amino acid 180 replaced by cysteine (Y180 C. Conclusions The data provide definitive evidence that a mutation

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Educational outreach to reduce immunization pain in office settings.

    Science.gov (United States)

    Schechter, Neil L; Bernstein, Bruce A; Zempsky, William T; Bright, Nancy S; Willard, Alice K

    2010-12-01

    The goal was to examine the impact of a teaching module on immunization pain reduction practices in pediatric offices 1 and 6 months after the intervention. Fourteen practices were selected randomly to receive a 1-hour teaching session on immunization pain reduction techniques, and 13 completed the study. Before the intervention, telephone interviews were conducted with parents concerning their children's recent immunization experiences. At 1 and 6 months after the intervention, parents of children who had recent immunizations were interviewed by using the same questionnaires. Clinicians also were surveyed at baseline and at 6 months. A total of 839 telephone interviews and 92 clinician surveys were included. Significant changes from baseline were identified at 1 and 6 months after the intervention. At 1 month, parents were more likely to report receiving information (P = .04), using strategies to reduce pain (P hour teaching session had measurable effects on the use of pain-reducing strategies at 1 and 6 months after the intervention. This research supports the hypothesis that small-group teaching sessions at the site of care can be associated with changes in practice behaviors.

  12. 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.

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. 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.

  16. Citral reduces nociceptive and inflammatory response in rodents

    OpenAIRE

    Quintans-Júnior, Lucindo J.; Guimarães, Adriana G.; Santana, Marilia T. de; Araújo, Bruno E.S.; Moreira, Flávia V.; Bonjardim, Leonardo R.; Araújo, Adriano A. S.; Siqueira, Jullyana S.; Antoniolli, Ângelo R.; Botelho, Marco A.; Almeida, Jackson R. G. S.; Santos, Márcio R. V.

    2011-01-01

    Citral (CIT), which contains the chiral enantiomers, neral (cis) and geranial (trans), is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT...

  17. 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.

  18. Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia

    Directory of Open Access Journals (Sweden)

    Luke Parkitny

    2017-04-01

    Full Text Available Fibromyalgia (FM is a complex, multi-symptom condition that predominantly affects women. The majority of those affected are unlikely to gain significant symptomatic control from the few treatments that are approved for FM. In this 10-week, single-blind, crossover trial we tested the immune effects of eight weeks of oral administration of low-dose naltrexone (LDN. We enrolled eight women with an average age of 46 years, symptom severity of 62 out of 100, and symptom duration of 14 years. We found that LDN was associated with reduced plasma concentrations of interleukin (IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN-α, transforming growth factor (TGF-α, TGF-β, tumor necrosis factor (TNF-α, and granulocyte-colony stimulating factor (G-CSF. We also found a 15% reduction of FM-associated pain and an 18% reduction in overall symptoms. The findings of this pilot trial suggest that LDN treatment in fibromyalgia is associated with a reduction of several key pro-inflammatory cytokines and symptoms. The potential role of LDN as an atypical anti-inflammatory medication should be explored further.

  19. Combined inhibition of monoacylglycerol lipase and cyclooxygenases synergistically reduces neuropathic pain in mice

    Science.gov (United States)

    Crowe, Molly S; Leishman, Emma; Banks, Matthew L; Gujjar, Ramesh; Mahadevan, Anu; Bradshaw, Heather B; Kinsey, Steven G

    2015-01-01

    Background and Purpose Neuropathic pain is commonly treated with GABA analogues, steroids or non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs inhibit one or more COX isozymes but chronic COX inhibition paradoxically increases gastrointestinal inflammation and risk of unwanted cardiovascular events. The cannabinoids also have analgesic and anti-inflammatory properties and reduce neuropathic pain in animal models. The present study investigated the analgesic effects of inhibiting both monoacylglycerol lipase (MAGL) and COX enzymes, using low doses of both inhibitors. Experimental Approach Mice subjected to chronic constriction injury (CCI) were tested for mechanical and cold allodynia after administration of the MAGL inhibitor, JZL184, or the non-selective COX inhibitor diclofenac. Then, both drugs were co-administered at fixed dose proportions of 1:3, 1:1 and 3:1, based on their ED50 values. PGs, endocannabinoids and related lipids were quantified in lumbar spinal cord. Key Results Combining low doses of JZL184 and diclofenac synergistically attenuated mechanical allodynia and additively reduced cold allodynia. The cannabinoid CB1 receptor antagonist, rimonabant, but not the CB2 receptor antagonist, SR144528, blocked the analgesic effects of the JZL184 and diclofenac combination on mechanical allodynia, implying that CB1 receptors were primarily responsible for the anti-allodynia. Diclofenac alone and with JZL184 significantly reduced PGE2 and PGF2α in lumbar spinal cord tissue, whereas JZL184 alone caused significant increases in the endocannabinoid metabolite, N-arachidonoyl glycine. Conclusions and Implications Combining COX and MAGL inhibition is a promising therapeutic approach for reducing neuropathic pain with minimal side effects. PMID:25393148

  20. Can Indian classical instrumental music reduce pain felt during venepuncture?

    Science.gov (United States)

    Balan, Rajiv; Bavdekar, S B; Jadhav, Sandhya

    2009-05-01

    Local anesthetic agent is not usually used to reduce pain experienced by children undergoing venepuncture. This study was undertaken to determine comparative efficacy of local anesthetic cream, Indian classical instrumental music and placebo, in reducing pain due to venepuncture in children. Children aged 5-12 yr requiring venepuncture were enrolled in a prospective randomized clinical trial conducted at a tertiary care center. They were randomly assigned to 3 groups: local anesthetic (LA), music or placebo (control) group. Eutactic mixture of local anesthetic agents (EMLA) and Indian classical instrumental music (raaga-Todi) were used in the first 2 groups, respectively. Pain was assessed independently by parent, patient, investigator and an independent observer at the time of insertion of the cannula (0 min) and at 1- and 5 min after the insertion using a Visual Analog Scale (VAS). Kruskal- Wallis and Mann-Whitney U tests were used to assess the difference amongst the VAS scores. Fifty subjects were enrolled in each group. Significantly higher VAS scores were noted in control (placebo) group by all the categories of observers (parent, patient, investigator, independent observer) at all time points. The VAS scores obtained in LA group were lowest at all time points. However, the difference between VAS scores in LA group were significantly lower than those in music group only at some time-points and with some categories of observers (parent: 1 min; investigator: 0-, 1-, 5 min and independent observer: 5 min). Pain experienced during venepuncture can be significantly reduced by using EMLA or Indian classical instrumental music. The difference between VAS scores with LA and music is not always significant. Hence, the choice between EMLA and music could be dictated by logistical factors.

  1. 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.

  2. 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.

  3. Comparison of lbuprofen with Acupuncture in Reducing Knee Osteoarthritis Pain

    Directory of Open Access Journals (Sweden)

    MR Emad

    2008-01-01

    Full Text Available ABSTRACT: Introduction & Objective: Osteoarthritis is the most common joint disease of humans. Acupuncture is one of the treatments for osteoarthritis. This study aimed to compare lbuprofen with acupuncture in the pain reduction in knee osteoarthritis. Materials & Methods: This is a clinical trial which was performed in Shiraz Medical School Clinics in 2007. Forty six patients with chronic pain due to the knee osteoarthritis were recruited using strict inclusion and exclusion criteria. All the patients were randomly divided into two groups (A and B who received lbuprofen (1200 mg/day or acupuncture (2 sessions per week for 2 weeks, respectively. Evaluating measuring tools were pain intensity (based on VAS, ROM (based on degree and morning stiffness of the knee joint. Collected data were analyzed by Chi-Square test, using SPSS software. Results: Pain intensity at baseline, after the course of treatment and 3 weeks after the treatment in group A was 7.29 ± 0.61, 4.20±0.93 and 5.20± 1.32 cm, respectively while these figures for group B were 7.35±0.82, 3.43±0.96 and 4.93±1.32 cm, respectively (p<0.005. Also knee ROM degree in group A was 21.54±7.46, 13.08±5.60 and 15.38±3.2 and for group B was 20.36±7.19, 12.40±5.78 and 10.36±5.30, respectively (p=0.003. Knee morning stiffness improved more in group B. Conclusion: Result of this study showed that both modalities significantly reduced the pain in patients with knee osteoarthritis and improved ROM while morning stiffness improved more in group B.

  4. 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.

  5. 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.

  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. 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. 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...

  9. Cell saver for on-pump coronary operations reduces systemic inflammatory markers: a randomized trial

    DEFF Research Database (Denmark)

    Damgaard, Sune; Nielsen, Claus Henrik; Andersen, Lars Willy

    2010-01-01

    This study investigated whether intraoperative use of a cell saver reduces the systemic inflammatory response after coronary operations using cardiopulmonary bypass (CPB).......This study investigated whether intraoperative use of a cell saver reduces the systemic inflammatory response after coronary operations using cardiopulmonary bypass (CPB)....

  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. 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.

  12. 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

  13. 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...

  14. 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

  15. Pre-emptive tramadol could reduce pain after ureteroscopic lithotripsy.

    Science.gov (United States)

    Mimić, Ana; Denčić, Nataša; Jovičić, Jelena; Mirković, Jelena; Durutović, Otaš; Milenković-Petronić, Dragica; Lađević, Nebojša

    2014-09-01

    Optimal analgesia in ambulatory urology patients still remains a challenge. The aim of this study was to examine if the pre-emptive use of intravenous tramadol can reduce pain after ureteroscopic lithotripsy in patients diagnosed with unilateral ureteral stones. This prospective pilot cohort study included 74 patients diagnosed with unilateral ureteral stones who underwent ureteroscopic lithotripsy under general anesthesia in the Urology Clinic at the Clinical Center of Serbia from March to June 2012. All patients were randomly allocated to two groups: one group (38 patients) received intravenous infusion of tramadol 100 mg in 500 mL 0.9%NaCl one hour before the procedure, while the other group (36 patients) received 500 mL 0.9%NaCl at the same time. Visual analogue scale (VAS) scores were recorded once prior to surgery and two times after the surgery (1 h and 6 h, respectively). The patients were prescribed additional postoperative analgesia (diclofenac 75 mg i.m.) when required. Pre-emptive effects of tramadol were assessed measuring pain scores, VAS1 and VAS2, intraoperative fentanyl consumption, and postoperative analgesic requirement. The average VAS1 score in the tramadol group was significantly lower than that in the non-tramadol group. The difference in average VAS2 score values between the two groups was not statistically significant; however, there were more patients who experienced severe pain in the non-tramadol group (ppain. The patients who received pre-emptive tramadol were less likely to experience severe post-operative pain.

  16. 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

  17. 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

  18. Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides.

    Science.gov (United States)

    Pannell, Maria; Labuz, Dominika; Celik, Melih Ö; Keye, Jacqueline; Batra, Arvind; Siegmund, Britta; Machelska, Halina

    2016-10-07

    During the inflammation which occurs following nerve damage, macrophages are recruited to the site of injury. Phenotypic diversity is a hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti-inflammatory M2 populations. Our aim in this study was to investigate the ability of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine their relative contribution to the modulation of neuropathic pain. Mouse bone marrow-derived cells were cultured as unstimulated M0 macrophages or were stimulated into an M1 phenotype using lipopolysaccharide and interferon-γ or into an M2 phenotype using interleukin-4. The macrophage phenotypes were verified using flow cytometry for surface marker analysis and cytokine bead array for cytokine profile assessment. Opioid peptide levels were measured by radioimmunoassay and enzyme immunoassay. As a model of neuropathic pain, a chronic constriction injury (CCI) of the sciatic nerve was employed. Polarized M0, M1, and M2 macrophages (5 × 10 5 cells) were injected perineurally twice, on days 14 and 15 following CCI or sham surgery. Mechanical and heat sensitivity were measured using the von Frey and Hargreaves tests, respectively. To track the injected macrophages, we also transferred fluorescently stained polarized cells and analyzed the surface marker profile of endogenous and injected cells in the nerves ex vivo. Compared to M0 and M1 cells, M2 macrophages contained and released higher amounts of opioid peptides, including Met-enkephalin, dynorphin A (1-17), and β-endorphin. M2 cells transferred perineurally at the nerve injury site reduced mechanical, but not heat hypersensitivity following the second injection. The analgesic effect was reversed by the perineurally applied opioid receptor antagonist naloxone methiodide. M2 cells did not affect sensitivity following sham surgery. Neither M0 nor M1 cells altered mechanical and heat sensitivity in CCI or sham-operated animals. Tracing the

  19. D-Aspartate Modulates Nociceptive-Specific Neuron Activity and Pain Threshold in Inflammatory and Neuropathic Pain Condition in Mice

    Directory of Open Access Journals (Sweden)

    Serena Boccella

    2015-01-01

    Full Text Available D-Aspartate (D-Asp is a free D-amino acid found in the mammalian brain with a temporal-dependent concentration based on the postnatal expression of its metabolizing enzyme D-aspartate oxidase (DDO. D-Asp acts as an agonist on NMDA receptors (NMDARs. Accordingly, high levels of D-Asp in knockout mice for Ddo gene (Ddo−/− or in mice treated with D-Asp increase NMDAR-dependent processes. We have here evaluated in Ddo−/− mice the effect of high levels of free D-Asp on the long-term plastic changes along the nociceptive pathway occurring in chronic and acute pain condition. We found that Ddo−/− mice show an increased evoked activity of the nociceptive specific (NS neurons of the dorsal horn of the spinal cord (L4–L6 and a significant decrease of mechanical and thermal thresholds, as compared to control mice. Moreover, Ddo gene deletion exacerbated the nocifensive responses in the formalin test and slightly reduced pain thresholds in neuropathic mice up to 7 days after chronic constriction injury. These findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.

  20. 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 =

  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)

    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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

  7. 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.

  8. R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids

    Science.gov (United States)

    Marian, Claudiu; Häussler, Annett; Wijnvoord, Nina; Ziebell, Simone; Metzner, Julia; Koch, Marco; Myrczek, Thekla; Bechmann, Ingo; Kuner, Rohini; Costigan, Michael; Dehghani, Faramarz; Geisslinger, Gerd; Tegeder, Irmgard

    2010-01-01

    Background R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. Methodology/Principal Findings We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH) and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARγ and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. Conclusion Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain. PMID:20498712

  9. R-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids.

    Directory of Open Access Journals (Sweden)

    Philipp Bishay

    Full Text Available BACKGROUND: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB, which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARgamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. CONCLUSION: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain.

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

    Directory of Open Access Journals (Sweden)

    Fang Xu

    2018-05-01

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

  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. Lidocaine patches reduce pain in trauma patients with rib fractures.

    Science.gov (United States)

    Zink, Karen A; Mayberry, John C; Peck, Ellen G; Schreiber, Martin A

    2011-04-01

    Rib fracture pain is notoriously difficult to manage. The lidocaine patch is effective in other pain scenarios with an excellent safety profile. This study assesses the efficacy of lidocaine patches for treating rib fracture pain. A prospectively gathered cohort of patients with rib fracture was retrospectively analyzed for use of lidocaine patches. Patients treated with lidocaine patches were matched to control subjects treated without patches. Subjective pain reports and narcotic use before and after patch placement, or equivalent time points for control subjects, were gathered from the chart. All patients underwent long-term follow-up, including a McGill Pain Questionnaire (MPQ). Twenty-nine patients with lidocaine patches (LP) and 29 matched control subjects (C) were analyzed. During the 24 hours before patch placement, pain scores and narcotic use were similar (LP 5.3, C 4.6, P = 0.19 and LP 51, C 32 mg morphine, P = 0.17). In the 24 hours after patch placement, LP patients had a greater decrease in pain scores (LP 1.2, C 0.0, P = 0.01) with no change in narcotic use (LP -8.4, C 0.5-mg change in morphine, P = 0.25). At 60 days, LP patients had a lower MPQ pain score (LP 7.7, C 12.2, P rib fracture pain. Lidocaine patches resulted in a sustained reduction in pain, outlasting the duration of therapy.

  16. Expectations contribute to reduced pain levels during prayer in highly religious participants.

    Science.gov (United States)

    Jegindø, Else-Marie Elmholdt; Vase, Lene; Skewes, Joshua Charles; Terkelsen, Astrid Juhl; Hansen, John; Geertz, Armin W; Roepstorff, Andreas; Jensen, Troels Staehelin

    2013-08-01

    Although the use of prayer as a religious coping strategy is widespread and often claimed to have positive effects on physical disorders including pain, it has never been tested in a controlled experimental setting whether prayer has a pain relieving effect. Religious beliefs and practices are complex phenomena and the use of prayer may be mediated by general psychological factors known to be related to the pain experience, such as expectations, desire for pain relief, and anxiety. Twenty religious and twenty non-religious healthy volunteers were exposed to painful electrical stimulation during internal prayer to God, a secular contrast condition, and a pain-only control condition. Subjects rated expected pain intensity levels, desire for pain relief, and anxiety before each trial and pain intensity and pain unpleasantness immediately after on mechanical visual analogue scales. Autonomic and cardiovascular measures provided continuous non-invasive objective means for assessing the potential analgesic effects of prayer. Prayer reduced pain intensity by 34 % and pain unpleasantness by 38 % for religious participants, but not for non-religious participants. For religious participants, expectancy and desire predicted 56-64 % of the variance in pain intensity scores, but for non-religious participants, only expectancy was significantly predictive of pain intensity (65-73 %). Conversely, prayer-induced reduction in pain intensity and pain unpleasantness were not followed by autonomic and cardiovascular changes.

  17. Isometric Exercise for the Cervical Extensors Can Help Restore Physiological Lordosis and Reduce Neck Pain: A Randomized Controlled Trial.

    Science.gov (United States)

    Alpayci, Mahmut; İlter, Server

    2017-09-01

    The aim of this study was to investigate whether isometric neck extension exercise restores physiological cervical lordosis and reduces pain. Sixty-five patients with loss of cervical lordosis were randomly assigned to exercise (27 women, 7 men; mean age, 32.82 ± 8.83 yrs) and control (26 women, 5 men; mean age, 33.48 ± 9.67 yrs) groups. Both groups received nonsteroidal anti-inflammatory drugs for 10 days. The exercise group received additional therapy as a home exercise program, which consisted of isometric neck extension for 3 mos. Neck pain severity and cervical lordosis were measured at baseline and at 3 mos after baseline. Compared with baseline levels, cervical lordosis angle was significantly improved in the exercise group (P cervical lordosis angle returned to physiological conditions (85.2% vs. 22.5%; P pain intensity was significantly reduced in both groups compared with baseline levels (for all, P pain was about twice in the exercise group compared with the control group (P cervical lordosis and pain.

  18. Reduced acute nociception and chronic pain in Shank2 ?/? mice

    OpenAIRE

    Ko, Hyoung-Gon; Oh, Seog-Bae; Zhuo, Min; Kaang, Bong-Kiun

    2016-01-01

    Autism spectrum disorder is a debilitating mental illness and social issue. Autism spectrum disorder patients suffer from social isolation, cognitive deficits, compulsive behavior, and sensory deficits, including hyposensitivity to pain. However, recent studies argued that autism spectrum disorder patients show physiological pain response and, in some cases, even extremely intense pain response to harmless stimulation. Recently, Shank gene family was reported as one of the genetic risk factor...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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

  1. Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

    NARCIS (Netherlands)

    Bos, P.A.; Montoya, E.R.; Hermans, E.; Keysers, C.; Honk, J. van

    2015-01-01

    Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have

  2. Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

    NARCIS (Netherlands)

    Bos, Peter A; Montoya, Estrella R; Hermans, Erno J; Keysers, C.; van Honk, Jack

    Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have

  3. 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.

  4. Listening to music does not reduce pain during sigmoidoscopy

    NARCIS (Netherlands)

    Meeuse, Jan J.; Koornstra, Jan Jacob; Reyners, An K. L.

    Objective Up to 40% of the sigmoidoscopies are considered painful by patients. Nonpharmacological intervention would be attractive, as sedation and analgesia carry the risk of side-effects and increase procedure-related costs. Music might have the potential of pain reduction, but its effect during

  5. 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.

  6. Swimming Training Reduces Neuroma Pain by Regulating Neurotrophins.

    Science.gov (United States)

    Tian, Jinge; Yu, Tingting; Xu, Yongming; Pu, Shaofeng; Lv, Yingying; Zhang, Xin; DU, Dongping

    2018-01-01

    Neuroma formation after peripheral nerve transection leads to severe neuropathic pain in amputees. Previous studies suggested that physical exercise could bring beneficial effect on alleviating neuropathic pain. However, the effect of exercise on neuroma pain still remained unclear. In addition, long-term exercise can affect the expression of neurotrophins (NT), such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), which play key roles in nociceptor sensitization and nerve sprouting after nerve injury. Here, we investigated whether long-term swimming exercise could relieve neuroma pain by modulating NT expression. We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. After TNT surgery, rats performed swimming exercise for 5 wk. Neuroma pain and tactile sensitivities were detected using von Frey filaments. Immunofluorescence was applied to analyze neuroma formation. NGF and BDNF expressions in peripheral neuroma, dorsal root ganglion, and the spinal cord were measured using enzyme-linked immunosorbent assay and Western blotting. TNT led to neuroma formation, induced neuroma pain, and mechanical allodynia in hind paw. Five-week swimming exercise inhibited neuroma formation and relieved mechanical allodynia in the hind paw and neuroma pain in the lateral ankle. The analgesic effect lasted for at least 1 wk, even when the exercise ceased. TNT elevated the expressions of BDNF and NGF in peripheral neuroma, dorsal root ganglion, and the spinal cord to different extents. Swimming also decreased the elevation of NT expression. Swimming exercise not only inhibits neuroma formation induced by nerve transection but also relieves pain behavior. These effects might be associated with the modulation of NT.

  7. 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

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

    Science.gov (United States)

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

    2013-01-01

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

  9. 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.

  10. Taping reduces pain and disability in patients with knee osteoarthritis.

    NARCIS (Netherlands)

    Ende, E. van den

    2004-01-01

    Question: Is taping of the knee effective in improving pain and disability in patients with osteoarthritis of the knee? Design Randomised controlled trial. Setting University and private practices in Melbourne, Australia. Patients: Volunteers who responded to advertisements in local newspapers.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Cortisol reduces recall of explicit contextual pain memory in healthy young men.

    Science.gov (United States)

    Schwegler, Kyrill; Ettlin, Dominik; Buser, Iris; Klaghofer, Richard; Goetzmann, Lutz; Buddeberg, Claus; Alon, Eli; Brügger, Mike; de Quervain, Dominique J-F

    2010-09-01

    Remembering painful incidents has important adaptive value but may also contribute to clinical symptoms of posttraumatic stress disorder and chronic pain states. Because glucocorticoids are known to impair memory retrieval processes, we investigated whether cortisol affects recall of previously experienced pain in healthy young men. In a double-blind, placebo-controlled crossover study, 20 male participants were presented pictures, half of them combined with a heat-pain stimulus. The next day, the same pictures were shown in the absence of pain. Cortisol (20 mg) administered 1h before retention testing reduced recall of explicit contextual pain memory, whereas it did not affect pain threshold or pain tolerance. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. Use of Temporary Implantable Biomaterials to Reduce Leg Pain and Back Pain in Patients with Sciatica and Lumbar Disc Herniation

    Directory of Open Access Journals (Sweden)

    Gere S. diZerega

    2010-05-01

    Full Text Available The principle etiology of leg pain (sciatica from lumbar disc herniation is mechanical compression of the nerve root. Sciatica is reduced by decompression of the herniated disc, i.e., removing mechanical compression of the nerve root. Decompression surgery typically reduces sciatica more than lumbar back pain (LBP. Decompression surgery reduces mechanical compression of the nerve root. However, decompression surgery does not directly reduce sensitization of the sensory nerves in the epidural space and disc. In addition, sensory nerves in the annulus fibrosus and epidural space are not protected from topical interaction with pain mediators induced by decompression surgery. The secondary etiology of sciatica from lumbar disc herniation is sensitization of the nerve root. Sensitization of the nerve root results from a mechanical compression, b exposure to cellular pain mediators, and/or c exposure to biochemical pain mediators. Although decompression surgery reduces nerve root compression, sensory nerve sensitization often persists. These observations are consistent with continued exposure of tissue in the epidural space, including the nerve root, to increased cellular and biochemical pain mediators following surgery. A potential contributor to lumbar back pain (LBP is stimulation of sensory nerves in the annulus fibrosus by a cellular pain mediators and/or b biochemical pain mediators that accompany annular tears or disruption. Sensory fibers located in the outer one-third of the annulus fibrosus increase in number and depth as a result of disc herniation. The nucleus pulposus is comprised of material that can produce an autoimmune stimulation of the sensory nerves located in the annulus and epidural space leading to LBP. The sensory nerves of the annulus fibrosus and epidural space may be sensitized by topical exposure to cellular and biochemical pain mediators induced by lumbar surgery. Annulotomy or annular rupture allows the nucleus pulposus

  16. Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases—Promises, Perspectives, and Pitfalls

    Directory of Open Access Journals (Sweden)

    Anouk Kaulmann

    2016-01-01

    Full Text Available Inflammatory bowel diseases (IBDs are characterized by autoimmune and inflammation-related complications of the large intestine (ulcerative colitis and additional parts of the digestive tract (Crohn’s disease. Complications include pain, diarrhoea, chronic inflammation, and cancer. IBD prevalence has increased during the past decades, especially in Westernized countries, being as high as 1%. As prognosis is poor and medication often ineffective or causing side effects, additional preventive/adjuvant strategies are sought. A possible approach is via diets rich in protective constituents. Polyphenols, the most abundant phytochemicals, have been associated with anti-inflammatory, antioxidant, immunomodulatory, and apoptotic properties. Locally reducing oxidative stress, they can further act on cellular targets, altering gene expression related to inflammation, including NF-κB, Nrf-2, Jak/STAT, and MAPKs, suppressing downstream cytokine formation (e.g., IL-8, IL-1β, and TNF-α, and boosting the bodies’ own antioxidant status (HO-1, SOD, and GPx. Moreover, they may promote, as prebiotics, healthy microbiota (e.g., Bifidobacteria, Akkermansia, short-chain fatty acid formation, and reduced gut permeability/improved tight junction stability. However, potential adverse effects such as acting as prooxidants, or perturbations of efflux transporters and phase I/II metabolizing enzymes, with increased uptake of undesired xenobiotics, should also be considered. In this review, we summarize current knowledge around preventive and arbitrary actions of polyphenols targeting IBD.

  17. Interpersonal issues between pain physician and patient: strategies to reduce conflict.

    Science.gov (United States)

    Diesfeld, Kate

    2008-11-01

    This article analyzes scholarship on the interpersonal challenges that pain physicians face, with an emphasis on strategies to reduce conflicts within therapeutic relationships. Scholarship on the dilemmas pain physicians face suggests that 1) there are unique and perhaps unrecognized features of pain medicine that generate stress; 2) interpersonal conflict may contribute to stress; and 3) clinicians' biases may interfere with the doctor-patient relationship and with the best practice of pain medicine. Application of a framework based on clinicians' beliefs and Papadimos' reflections on justice and temperance may reduce such conflicts. The challenges of pain medicine may be complicated by the clinician's undisclosed attitudes regarding their roles and their perceptions of pain sufferers. A strategy for physicians to examine their beliefs within a supportive environment may aid physicians caring for people with chronic pain. Papadimos' reflections upon the virtues of justice and tolerance guide this analysis.

  18. Chenopodium ambrosioides L. Reduces Synovial Inflammation and Pain in Experimental Osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Gustavo P Calado

    Full Text Available The chronicity of osteoarthritis (OA, characterized by pain and inflammation in the joints, is linked to a glutamate receptor, N-methyl-D-aspartate (NMDA. The use of plant species such as Chenopodium ambrosioides L. (Amaranthaceae as NMDA antagonists offers a promising perspective. This work aims to analyze the antinociceptive and anti-inflammatory responses of the crude hydroalcoholic extract (HCE of C. ambrosioides leaves in an experimental OA model. Wistar rats were separated into six groups (n = 24: clean (C, negative control (CTL-, positive control (CTL+, HCE0.5, HCE5 and HCE50. The first group received no intervention. The other groups received an intra-articular injection of sodium monoiodoacetate (MIA (8 mg/kg on day 0. After six hours, they were orally treated with saline, Maxicam plus (meloxicam + chondroitin sulfate and HCE at doses of 0.5 mg/kg, 5 mg/kg and 50 mg/kg, respectively. After three, seven and ten days, clinical evaluations were performed (knee diameter, mechanical allodynia, mechanical hyperalgesia and motor activity. On the tenth day, after euthanasia, synovial fluid and draining lymph node were collected for cellular quantification, and cartilage was collected for histopathological analysis. Finally, molecular docking was performed to evaluate the compatibility of ascaridole, a monoterpene found in HCE, with the NMDA receptor. After the third day, HCE reduced knee edema. HCE5 showed less cellular infiltrate in the cartilage and synovium and lower intensities of allodynia from the third day and of hyperalgesia from the seventh day up to the last treatment day. The HCE5 and HCE50 groups improved in forced walking. In relation to molecular docking, ascaridole showed NMDA receptor binding affinity. C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain. This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.

  19. From painkiller to empathy killer: acetaminophen (paracetamol) reduces empathy for pain.

    Science.gov (United States)

    Mischkowski, Dominik; Crocker, Jennifer; Way, Baldwin M

    2016-09-01

    Simulation theories of empathy hypothesize that empathizing with others' pain shares some common psychological computations with the processing of one's own pain. Support for this perspective has largely relied on functional neuroimaging evidence of an overlap between activations during the experience of physical pain and empathy for other people's pain. Here, we extend the functional overlap perspective to the neurochemical level and test whether a common physical painkiller, acetaminophen (paracetamol), can reduce empathy for another's pain. In two double-blind placebo-controlled experiments, participants rated perceived pain, personal distress and empathic concern in response to reading scenarios about another's physical or social pain, witnessing ostracism in the lab, or visualizing another study participant receiving painful noise blasts. As hypothesized, acetaminophen reduced empathy in response to others' pain. Acetaminophen also reduced the unpleasantness of noise blasts delivered to the participant, which mediated acetaminophen's effects on empathy. Together, these findings suggest that the physical painkiller acetaminophen reduces empathy for pain and provide a new perspective on the neurochemical bases of empathy. Because empathy regulates prosocial and antisocial behavior, these drug-induced reductions in empathy raise concerns about the broader social side effects of acetaminophen, which is taken by almost a quarter of adults in the United States each week. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  20. Modest Amounts of Voluntary Exercise Reduce Pain- and Stress-Related Outcomes in a Rat Model of Persistent Hind Limb Inflammation.

    Science.gov (United States)

    Pitcher, Mark H; Tarum, Farid; Rauf, Imran Z; Low, Lucie A; Bushnell, Catherine

    2017-06-01

    Aerobic exercise improves outcomes in a variety of chronic health conditions, yet the support for exercise-induced effects on chronic pain in humans is mixed. Although many rodent studies have examined the effects of exercise on persistent hypersensitivity, the most used forced exercise paradigms that are known to be highly stressful. Because stress can also produce analgesic effects, we studied how voluntary exercise, known to reduce stress in healthy subjects, alters hypersensitivity, stress, and swelling in a rat model of persistent hind paw inflammation. Our data indicate that voluntary exercise rapidly and effectively reduces hypersensitivity as well as stress-related outcomes without altering swelling. Moreover, the level of exercise is unrelated to the analgesic and stress-reducing effects, suggesting that even modest amounts of exercise may impart significant benefit in persistent inflammatory pain states. Modest levels of voluntary exercise reduce pain- and stress-related outcomes in a rat model of persistent inflammatory pain, independently of the amount of exercise. As such, consistent, self-regulated activity levels may be more relevant to health improvement in persistent pain states than standardized exercise goals. Published by Elsevier Inc.

  1. 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.

  2. A modification of a previous model fo r inflammatory tooth pain: Effects of different capsaicin and formalin concentrations and ibuprofen

    Directory of Open Access Journals (Sweden)

    Maryam Raoof DDS, MS

    2012-09-01

    Full Text Available BACKGROUND AND AIM:This study aimed to solve the problems faced with the previous model of inflammatory tooth painin rats.METHODS:After cutting 2 mm of the distal extremities, the polyethylene crownswere placed on the mandibularincisors. In contrast to the original model, we used flow composite instead of wire in order to maximize the retention ofcrowns. Different concentrations of capsaicin (10, 25 and 100 mg/ml and formalin were administrated into the cavitiesunder the crowns. The algesic agent-induced behaviors were evaluated.RESULTS:The modified model had no liquid leakage. Furthermore, composite allowed the crowns to remain for alonger period of time. Capsaicin 25, 100 mg/ml and formalin applications induced significantly more painfulstimulation compared with control groups (P < 0.001. These responses were significantly reduced by theadministration of ibuprofen, 20 minutes prior to the capsaicin 100 mg/ml injection.CONCLUSIONS:This model seems to be adequate for long-term pain related experiments in which fluid leakageelimination is important.

  3. Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels.

    Science.gov (United States)

    Srebro, Dragana P; Vučković, Sonja M; Dožić, Ivan S; Dožić, Branko S; Savić Vujović, Katarina R; Milovanović, Aleksandar P; Karadžić, Branislav V; Prostran, Milica Š

    2018-02-01

    In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum. Magnesium sulfate administered subcutaneously (0.005-45mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity. Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  4. Effect of Patient Education on Reducing Medication in Spinal Cord Injury Patients With Neuropathic Pain.

    Science.gov (United States)

    Shin, Ji Cheol; Kim, Na Young; Chang, Shin Hye; Lee, Jae Joong; Park, Han Kyul

    2017-08-01

    To determine whether providing education about the disease pathophysiology and drug mechanisms and side effects, would be effective for reducing the use of pain medication while appropriately managing neurogenic pain in spinal cord injury (SCI) patients. In this prospective study, 109 patients with an SCI and neuropathic pain, participated in an educational pain management program. This comprehensive program was specifically created, for patients with an SCI and neuropathic pain. It consisted of 6 sessions, including educational training, over a 6-week period. Of 109 patients, 79 (72.5%) initially took more than two types of pain medication, and this decreased to 36 (33.0%) after the educational pain management program was completed. The mean pain scale score and the number of pain medications decreased, compared to the baseline values. Compared to the non-response group, the response group had a shorter duration of pain onset (p=0.004), and a higher initial number of different medications (ppain management program, can be a valuable complement to the treatment of spinal cord injured patients with neuropathic pain. Early intervention is important, to prevent patients from developing chronic SCI-related pain.

  5. The efficacy of local anesthetics in reducing post operative pain after appendectomy

    Directory of Open Access Journals (Sweden)

    Masood Baghaee vaji

    2004-09-01

    Full Text Available Reducing post operative pain is a common issue in surgeries. This study was to evaluate the efficacy of wound infiltration with local anesthetics in reducing postoperative pain after appendectomy. This is a double-blind, placebo-controlled, randomized clinical trial on 40 patients with non-complicated acute appendicitis. Cases received a combination of lidocaine hydrochloride and bupivacaine hydrochloride after appendectomy and before closing the wound. Controls received the same volume of saline solution. Injections were done both under the fascia of external oblique muscle and intradermal. Pain assessment was done by two pain measuring scales, VAS and NRS, in 4, 8, 12 and 24 hours after the operation. Cases and controls were the same in age, sex, and history of opium addiction. Pain peaked in the 8th hour after operation in both groups and reduced afterwards. Pain assessments showed the same pattern using the NRS and VAS measuring scales. T-test showed the pain to be significantly less in cases comparing with the controls in all time points. No significant difference was seen in the time of receiving the first analgesic after the operation but the frequency of analgesic consumption was significantly lower in controls. This study showed local anesthetic infiltration to be effective in reducing the postoperative pain in patients undergoing appendectomy which is in contrast with the previous studies. This may be due to a different infiltration technique or pain assessment in the first 24 hours after the operation.

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

    Science.gov (United States)

    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.

  7. Tramadol versus Celecoxib for reducing pain associated with outpatient hysteroscopy: a randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Hassan, A; Wahba, A; Haggag, H

    2016-01-01

    Which is better, Tramadol or Celecoxib, in reducing pain associated with outpatient hysteroscopy? Both Tramadol and Celecoxib are effective in reducing pain associated with outpatient hysteroscopy but Celecoxib may be better tolerated. Pain is the most common cause of failure of outpatient hysteroscopy. A systematic review and meta-analysis showed that local anaesthetics were effective in reducing pain associated with hysteroscopy but there was insufficient evidence to support the use of oral analgesics, opioids and non-steroidal anti-inflammatory drugs, to reduce hysteroscopy-associated pain and further studies were recommended. This was a randomized double-blind placebo-controlled trial with balanced randomization (allocation ratio 1:1:1) conducted in a university hospital from May 2014 to November 2014. Two hundred and ten women who had diagnostic outpatient hysteroscopy were randomly divided into three equal groups: Group 1 received oral Tramadol 100 mg, group 2 received Celecoxib 200 mg and group 3 received an oral placebo. All the drugs were given 1 h before the procedure. A patient's perception of pain was assessed during the procedure, immediately afterwards and 30 min after the procedure with the use of a visual analogue scale (VAS). There was a significant difference in the pain scores among the groups during the procedure, immediately afterwards and 30 min after the procedure (Ppain scores when compared with the placebo during the procedure (mean difference = 1.54, 95% confidence interval (CI) (0.86, 2.22), P pain scores than the placebo during the procedure (mean difference = 1.28, 95% CI (0.62, 1.94), P pain scores between Tramadol and Celecoxib at any time. Time until no pain differed significantly among the groups (P = 0.01); it was shorter with both Tramadol and Celecoxib groups when compared with placebo (P = 0.002 and 0.046, respectively). The procedure failed to be completed in one patient in the placebo group but no failure to complete the

  8. 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

  9. Root Canal Therapy Reduces Multiple Dimensions of Pain: A National Dental PBRN Study

    Science.gov (United States)

    Law, Alan S.; Nixdorf, Donald R.; Rabinowitz, Ira; Reams, Gregory J.; Smith, James A.; Torres, Anibal V.; Harris, D. Robert

    2014-01-01

    Background Initial orthograde root canal therapy (RCT) is used to treat dentoalveolar pathosis. The affect RCT has on pain intensity has been frequently reported, but the affect on other dimensions of pain has not. Also, the lack of large prospective studies involving diverse groups of patients and practitioners that are not involved in data collection suggest that there are multiple opportunities for bias to be introduced when this data is systematically aggregated. Method This prospective observational study assessed pain intensity, duration, and its interference with daily activities among RCT patients. Sixty-two practitioners (46 general dentists, 16 endodontists) in the National Dental Practice-Based Research Network enrolled patients requiring RCT. Patient reported data were collected before, immediately following, and one week after treatment using the Graded Chronic Pain Scale. Results Enrollment of 708 patients was completed over 6 months with 655 patients (93%) providing one-week follow-up data. Prior to treatment, patients reported a mean (±standard deviation) worst pain intensity of 5.3±3.8 (0-10 scale), 50% had “severe” pain (≥7), and mean days in pain and days pain interfered with activities were 3.6±2.7 and 0.5±1.2, respectively. Following treatment, patients reported a mean worst pain intensity of 3.0±3.2, 19% had “severe” pain, and mean days in pain and days with pain interference were 2.1±2.4 and 0.4±1.1, respectively. All changes were statistically significant (ppain, significantly reducing pain intensity, duration, and related interference. Further research is needed to reduce the proportion of patients reporting “severe” post-operative pain. PMID:25190605

  10. 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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. "Do unto others"? Distinct psychopathy facets predict reduced perception and tolerance of pain.

    Science.gov (United States)

    Brislin, Sarah J; Buchman-Schmitt, Jennifer M; Joiner, Thomas E; Patrick, Christopher J

    2016-07-01

    Recent research has sought to understand how individuals high in psychopathic traits perceive pain in others (Decety, Skelly, & Kiehl, 2013; Marsh et al., 2013). Perception of pain in others is presumed to act as a prosocial signal, and underreactivity to others' pain may contribute to engagement in exploitative-aggressive behaviors among individuals high in psychopathic traits (Jackson, Meltzoff, & Decety, 2005). The current study tested for associations between facets of psychopathy as defined by the triarchic model (Patrick, Fowles, & Krueger, 2009) and decreased sensitivity to pain in 105 undergraduates tested in a laboratory pain assessment. A pressure algometer was used to index pain tolerance, and participants also rated their perceptions of and reactivity to the algometer-induced pain during the assessment and again 3 days later. A unique positive relationship was found between pain tolerance and the meanness facet of psychopathy, which also predicted reduced fear of painful algometer stimulation. Other psychopathy facets (boldness, disinhibition) showed negative relations with fear of pain stimulation during testing and at follow-up. Findings from this study extend the nomological network surrounding callousness (meanness) and suggest that increased pain tolerance may be a mechanism contributing to insensitivity to expressions of discomfort in others. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  15. ‘Do Unto Others’?: Distinct Psychopathy Facets Predict Reduced Perception and Tolerance of Pain

    Science.gov (United States)

    Brislin, Sarah J.; Buchman-Schmitt, Jennifer M.; Joiner, Thomas E.; Patrick, Christopher J.

    2016-01-01

    Recent research has sought to understand how individuals high in psychopathic traits perceive pain in others (Decety, Skelly, & Kiehl, 2013; Marsh et al., 2013). Perception of pain in others is presumed to act as a prosocial signal, and underreactivity to others’ pain may contribute to engagement in exploitative-aggressive behaviors among individuals high in psychopathic traits (Jackson, Meltzoff, & Decety; 2005). The current study tested for associations between facets of psychopathy as defined by the triarchic model (Patrick, Fowles, & Krueger, 2009) and decreased sensitivity to pain in 105 undergraduates tested in a laboratory pain assessment. A pressure algometer was used to index pain tolerance, and participants also rated their perceptions of and reactivity to the algometer-induced pain during the assessment and again three days later. A unique positive relationship was found between pain tolerance and the meanness facet of psychopathy, which also predicted reduced fear of painful algometer stimulation. Other psychopathy facets (boldness, disinhibition) showed negative relations with fear of pain stimulation during testing and at follow-up. Findings from this study extend the nomological network surrounding callousness (meanness) and suggest that increased pain tolerance may be a mechanism contributing to insensitivity to expressions of discomfort in others. PMID:26950545

  16. Organizing workplace health literacy to reduce musculoskeletal pain and consequences

    DEFF Research Database (Denmark)

    Larsen, Anne Konring; Holtermann, Andreas; Mortensen, Ole Steen

    2015-01-01

    of the workplace as an arena for improving health literacy has developed emphasizing the organizational responsibility in facilitating and supporting that employees obtain basic knowledge and information needed to understand and take action on individual and occupational health concerns. The literature about...... workplace health literacy is very limited but points at the importance of educating employees to be able to access, appraise and apply health information and of organizing the infrastructure and communication in the organization. This study suggests a concrete operationalization of health literacy...... and effect of workplace health initiatives might be due to the fact that pain and the consequences of pain are affected by various individual, interpersonal and organizational factors in a complex interaction. Recent health literacy models pursue an integrated approach to understanding health behavior...

  17. 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.

  18. Ar Rahman-Based Dysmenorrhea Gymnastic to Reduce Pain

    OpenAIRE

    Sumaryani, Sri; Puspita Sari, Praditiana Indah

    2015-01-01

    Introduction: More than 50% dysmenorrhea are caused by excessive amounts of prostaglandin hormone during menstruation.  The combination of dysmenorrhea gymnastics and Qur'an Surah Ar-Rahman relaxation techniques is a new innovation in non-pharmacological therapy to overcome dysmenorrhoea. The purpose of this study was to determine the level of pain differences on respondents who were given dysmenorrhea gymnastics treatment, Al Quran Surah Ar-Rahman recitation, and dysmenorrhea gymnastics comb...

  19. Reducing neonatal pain during routine heel lance procedures.

    Science.gov (United States)

    Morrow, Carla; Hidinger, Andrea; Wilkinson-Faulk, Debbie

    2010-01-01

    To measure the difference in pain scores for newborns who were held and swaddled while undergoing routine heel lance procedures compared to newborns who were lying on their backs and not swaddled during heel lance. Additionally, we sought to compare the total amount of time it took to collect the specimens in each group. A total of 42 neonates recruited from a large tertiary hospital were enrolled in a randomized controlled trial. Infants in the experimental group (n = 22) were swaddled and held in an upright position during routine heel lance procedures while neonates in the control group (n = 20) remained in a standard care position. Pain was measured with the Neonatal Inventory Pain Scale (NIPS) at two points in time for each group (just before the heel lance procedure and at the completion of the heel lance). Total collection time was measured using a stopwatch accurate to 1/100th of a second. Specimen quality was measured based on the number of rejected specimens for each group. Descriptive statistics and t tests were used to analyze the data. The mean NIPS score for neonates who were swaddled and held during the procedure (experimental group) was significantly lower (M = 1.3, SD = .9) than the score for infants in the standard position (control group) (M = 2.7, SD = 1.3), t (40) = -4.48, p lance procedures offers nurses a nonpharmacologic method of neonatal pain reduction for heel sticks. This technique can be easily implemented on any unit independent of facility protocols. Furthermore, the technique is not associated with any cost or policy development, making it more likely that nurses can use it in practice.

  20. 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.

  1. Clinical use of virtual reality distraction system to reduce anxiety and pain in dental procedures.

    Science.gov (United States)

    Wiederhold, Mark D; Gao, Kenneth; Wiederhold, Brenda K

    2014-06-01

    Virtual reality (VR) has been used by clinicians to manage pain in clinical populations. This study examines the use of VR as a form of distraction for dental patients using both subjective and objective measures to determine how a VR system affects patients' reported anxiety level, pain level, and physiological factors. As predicted, results of self-evaluation questionnaires showed that patients experienced less anxiety and pain after undergoing VR treatment. Physiological data reported similar trends in decreased anxiety. Overall, the favorable subjective and objective responses suggest that VR distraction systems can reduce discomfort and pain for patients with mild to moderate fear and anxiety.

  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. Transcutaneous electrical nerve stimulation reduces acute low back pain during emergency transport.

    Science.gov (United States)

    Bertalanffy, Alexander; Kober, Alexander; Bertalanffy, Petra; Gustorff, Burkhard; Gore, Odette; Adel, Sharam; Hoerauf, Klaus

    2005-07-01

    Patients with acute low back pain may require emergency transport because of pain and immobilization. Transcutaneous electrical nerve stimulation (TENS) is a nonpharmaceutical therapy for patients with low back pain. To evaluate the efficacy of paramedic-administered TENS in patients with acute low back pain during emergency transport. This was a prospective, randomized study involving 74 patients transported to hospital. The patients were randomly assigned to two groups: group 1 (n = 36) was treated with true TENS, while group 2 (n = 36) was treated with sham TENS. The authors recorded pain and anxiety as the main outcome variables using a visual analog scale (VAS). The authors recorded a significant (p pain reduction (mean +/- standard deviation) during transport in group 1 (79.2 +/- 6.5 mm VAS to 48.9 +/- 8.2 mm VAS), whereas pain scores remained unchanged in group 2 (75.9 +/- 16.4 mm VAS and 77.1 +/- 11.2 mm VAS). Similarly, the scores for anxiety were significantly reduced (p TENS was found to be effective and rapid in reducing pain during emergency transport of patients with acute low back pain and should be considered due to its ease of use and lack of side effects in the study population.

  4. The Effectiveness of Aromatherapy in Reducing Pain: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Sheafer, Heather; Tepper, Deborah

    2016-01-01

    Background. Aromatherapy refers to the medicinal or therapeutic use of essential oils absorbed through the skin or olfactory system. Recent literature has examined the effectiveness of aromatherapy in treating pain. Methods. 12 studies examining the use of aromatherapy for pain management were identified through an electronic database search. A meta-analysis was performed to determine the effects of aromatherapy on pain. Results. There is a significant positive effect of aromatherapy (compared to placebo or treatments as usual controls) in reducing pain reported on a visual analog scale (SMD = −1.18, 95% CI: −1.33, −1.03; p aromatherapy is more consistent for treating nociceptive (SMD = −1.57, 95% CI: −1.76, −1.39, p aromatherapy is most effective in treating postoperative pain (SMD = −1.79, 95% CI: −2.08, −1.51, p aromatherapy can successfully treat pain when combined with conventional treatments. PMID:28070420

  5. Knee arthritis pain is reduced and range of motion is increased following moderate pressure massage therapy.

    Science.gov (United States)

    Field, Tiffany; Diego, Miguel; Gonzalez, Gladys; Funk, C G

    2015-11-01

    The literature on massage therapy effects on knee pain suggests that pain was reduced based on self-report, but little is known about range of motion (ROM) effects. Medical School staff and faculty who had knee arthritis pain were randomly assigned to a moderate pressure massage therapy or a waitlist control group (24 per group). Self-reports included the WOMAC (pain, stiffness and function) and the Pittsburgh Sleep Quality Index. ROM and ROM-related pain were assessed before and after the last sessions. The massage group showed an immediate post-massage increase in ROM and a decrease in ROM-associated pain. On the last versus the first day of the study, the massage group showed greater increases in ROM and decreases in ROM-related pain as well as less self-reported pain and sleep disturbances than the waitlist control group. These data highlight the effectiveness of moderate pressure massage therapy for increasing ROM and lessening ROM-related pain and long-term pain and sleep disturbances. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Efficacy of tramadol and butorphanol pretreatment in reducing pain on propofol injection: A placebo-controlled randomized study

    Directory of Open Access Journals (Sweden)

    Arvinderpal Singh

    2016-01-01

    Conclusion: Pretreatment with both butorphanol and tramadol significantly reduced pain on propofol injection; however, they exhibited comparable efficacy among each other. Thus, either of these two drugs can be considered for pretreatment to reduce propofol injection pain.

  7. AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema.

    Science.gov (United States)

    Cheng, Xiao-Yu; Li, Yang-Yang; Huang, Cheng; Li, Jun; Yao, Hong-Wei

    2017-04-04

    Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM). Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence. Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells. Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice. This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement. Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs. In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

  8. Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.

    Science.gov (United States)

    Vendrig, J C; Coffeng, L E; Fink-Gremmels, J

    2012-12-01

    Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs isolated from the same mares, mRNA expression of tumour necrosis factor-alpha, interleukin-6 and interleukin-10 was measured as well as the protein levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). Equine colostral carbohydrates significantly reduced LPS-induced TNF-alpha protein at both times measured and significantly reduced LPS-induced TNF-alpha, IL-6 and IL-10 mRNA expression by PBMCs. Moreover, cell viability significantly increased in the presence of high concentrations of colostral carbohydrates. Carbohydrates derived from equine colostrum reduce LPS-induced inflammatory responses of equine PBMCs. Colostrum and milk-derived carbohydrates are promising candidates for new concepts in preventive and regenerative medicine.

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

    OpenAIRE

    Mustafa Sally; Looper Karl; Zelkowitz Phyllis; Purden Margaret; Baron Murray

    2012-01-01

    Abstract Background 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). Methods Patients (n = 104) of 7.61 months mean duration of inflammatory arthritis completed self-report questionnaires on sociodemographics, disease character...

  10. Xanthophyll supplementation reduced inflammatory mediators and apoptosis in hens and chicks.

    Science.gov (United States)

    Gao, Y-Y; Jin, L; Ji, J; Sun, B-L; Xu, L-H; Wang, Q-X; Wang, C-K; Bi, Y-Z

    2016-05-01

    This study investigated effects of xanthophylls (containing 40% lutein and 60% zeaxanthin) on gene expression of inflammatory mediators ( [] and []) and apoptosis ( [] and ) of breeding hens and chicks. In Exp. 1, 432 hens were divided into 3 groups and fed diets supplemented with 0 (as the control group), 20, or 40 mg/kg xanthophylls. The liver, duodenum, jejunum, and ileum were sampled after 35 d. Results showed that 40 mg/kg of xanthophyll addition decreased in the liver, in the liver and duodenum, and in the liver and jejunum while increasing level in the liver and jejunum. Experiment 2 was a 2 × 2 factorial design. Male chicks hatched from hens fed 0 or 40 mg/kg xanthophyll diets were fed diets containing either 0 or 40 mg/kg xanthophylls. The liver, duodenum, jejunum, and ileum were sampled at 0, 7, 14, and 21 d after hatching. Results showed that in ovo xanthophylls reduced inflammatory mediators and apoptosis in the liver, duodenum, and jejunum of chicks mainly within 1 wk after hatching, whereas dietary xanthophylls only decreased expression in the liver from 2 wk onward. These results underlined important anti-inflammatory and antiapoptotic effects of maternal but not progeny dietary xanthophylls. In conclusion, xanthophylls can suppress inflammatory mediators and apoptosis in different tissues of hens and chicks.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Biaryl amide compounds reduce the inflammatory response in macrophages by regulating Dectin-1.

    Science.gov (United States)

    Hyung, Kyeong Eun; Lee, Mi Ji; Lee, Yun-Jung; Lee, Do Ik; Min, Hye Young; Park, So-Young; Min, Kyung Hoon; Hwang, Kwang Woo

    2016-03-01

    Macrophages are archetypal innate immune cells that play crucial roles in the recognition and phagocytosis of invading pathogens, which they identify using pattern recognition receptors (PRRs). Dectin-1 is essential for antifungal immune responses, recognizing the fungal cellular component β-glucan, and its role as a PRR has been of increasing interest. Previously, we discovered and characterized a novel biaryl amide compound, MPS 03, capable of inhibiting macrophage phagocytosis of zymosan. Therefore, in this study we aimed to identify other biaryl amide compounds with greater effectiveness than MPS 03, and elucidate their cellular mechanisms. Several MPS 03 derivatives were screened, four of which reduced zymosan phagocytosis in a similar manner to MPS 03. To establish whether such phagocytosis inhibition influenced the production of inflammatory mediators, pro-inflammatory cytokine and nitric oxide (NO) levels were measured. The production of TNF-α, IL-6, IL-12, and NO was significantly reduced in a dose-dependent manner. Moreover, the inflammation-associated MAPK signaling pathway was also affected by biaryl amide compounds. To investigate the underlying cellular mechanism, PRR expression was measured. MPS 03 and its derivatives were found to inhibit zymosan phagocytosis by decreasing Dectin-1 expression. Furthermore, when macrophages were stimulated by zymosan after pretreatment with biaryl amide compounds, downstream transcription factors such as NFAT, AP-1, and NF-κB were downregulated. In conclusion, biaryl amide compounds reduce zymosan-induced inflammatory responses by downregulating Dectin-1 expression. Therefore, such compounds could be used to inhibit Dectin-1 in immunological experiments and possibly regulate excessive inflammatory responses. Copyright © 2016. Published by Elsevier B.V.

  14. Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses.

    Directory of Open Access Journals (Sweden)

    Qi Ying Lean

    Full Text Available Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS. Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8, colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis.

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

    DEFF Research Database (Denmark)

    Geenen, Rinie; Overman, Cécile L.; Christensen, Robin

    2018-01-01

    options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly...... positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta...

  16. Efficacy of aromatherapy for reducing pain during labor: a randomized controlled trial.

    Science.gov (United States)

    Tanvisut, Rajavadi; Traisrisilp, Kuntharee; Tongsong, Theera

    2018-05-01

    Many strategies for labor pain management have been studied, including aromatherapy, which is a noninvasive, alternative medicine used as an adjunct for labor pain control. Nevertheless, the results were contradictory. Therefore, we conducted this study to determine the effectiveness of aromatherapy for reducing pain during labor. A randomized controlled trial was carried out on Thai laboring primigravidae who were a low-risk singleton pregnancy undergoing vaginal delivery. All participants, both study and control group, received standard obstetric care. Aromatherapy was only provided to the study group during the first stage of labor. The women rated their pain intensity by rating scales at different stages of labor. The primary outcome was pain scores and the secondary outcomes were necessity of painkiller usage, labor time, aromatherapy-associated complications, route of delivery, and Apgar scores. A total of 104 women were recruited, 52 in each group. Baseline characteristics and baseline pain scores were comparable. The median pain score of latent and early active phase was lower in the aromatherapy group, 5 vs 6 and 7 vs 8, respectively. The mean differences of pain scores between latent and early active phase and the baseline were significantly lower in the aromatherapy group, 1.88 vs 2.6 (p = 0.010) and 3.82 vs 4.39 (p = 0.031), respectively. Late active phase pain scores and other perinatal outcomes were not significantly different. Aromatherapy is helpful in reducing pain in latent and early active phase, and can probably be used as an adjunctive method for labor pain control without serious side effects.

  17. Borneol, a Bicyclic Monoterpene Alcohol, Reduces Nociceptive Behavior and Inflammatory Response in Mice

    Directory of Open Access Journals (Sweden)

    Jackson Roberto Guedes da Silva Almeida

    2013-01-01

    Full Text Available Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P<0.01 reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.. When the hot plate test was conducted, borneol (in higher dose produced an inhibition (P<0.05 of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination.

  18. 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.

  19. The association between inflammatory back pain characteristics and MRI findings in the spine and sacroiliac joints

    DEFF Research Database (Denmark)

    Arnbak, Bodil; Jurik, Anne G; Jensen, Tue S

    2018-01-01

    OBJECTIVE: To investigate the association between MRI findings at the sacroiliac joints (SIJs) and vertebral endplates and pain characteristics assumed to be indicative of axial inflammation. METHODS: Patients aged 18-40 years with persistent low back pain referred to an outpatient spine clinic...

  20. Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

    Directory of Open Access Journals (Sweden)

    BA Walter

    2016-07-01

    Full Text Available The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4 ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

  1. 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.

  2. 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

  3. A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery

    DEFF Research Database (Denmark)

    Mathiesen, Ole; Dahl, Benny; Thomsen, Berit A

    2013-01-01

    and postoperative nausea and vomiting (PONV) treatment protocol would improve pain treatment in this population. METHODS: A new regimen with acetaminophen, NSAIDs, gabapentin, S-ketamine, dexamethasone, ondansetron and epidural local anesthetic infusion or patient controlled analgesia with morphine, was introduced......PURPOSE: Major spine surgery with multilevel instrumentation is followed by large amount of opioid consumption, significant pain and difficult mobilization in a population of predominantly chronic pain patients. This case-control study investigated if a standardized comprehensive pain...... and dizziness on POD 1-6. CONCLUSIONS: In this study of patients scheduled for multilevel spine surgery, it was demonstrated that compared to a historic group of patients receiving usual care, a comprehensive and standardized multimodal pain and PONV protocol significantly reduced opioid consumption, improved...

  4. 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.

  5. Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems.

    Science.gov (United States)

    Younger, Jarred; Aron, Arthur; Parke, Sara; Chatterjee, Neil; Mackey, Sean

    2010-10-13

    The early stages of a new romantic relationship are characterized by intense feelings of euphoria, well-being, and preoccupation with the romantic partner. Neuroimaging research has linked those feelings to activation of reward systems in the human brain. The results of those studies may be relevant to pain management in humans, as basic animal research has shown that pharmacologic activation of reward systems can substantially reduce pain. Indeed, viewing pictures of a romantic partner was recently demonstrated to reduce experimental thermal pain. We hypothesized that pain relief evoked by viewing pictures of a romantic partner would be associated with neural activations in reward-processing centers. In this functional magnetic resonance imaging (fMRI) study, we examined fifteen individuals in the first nine months of a new, romantic relationship. Participants completed three tasks under periods of moderate and high thermal pain: 1) viewing pictures of their romantic partner, 2) viewing pictures of an equally attractive and familiar acquaintance, and 3) a word-association distraction task previously demonstrated to reduce pain. The partner and distraction tasks both significantly reduced self-reported pain, although only the partner task was associated with activation of reward systems. Greater analgesia while viewing pictures of a romantic partner was associated with increased activity in several reward-processing regions, including the caudate head, nucleus accumbens, lateral orbitofrontal cortex, amygdala, and dorsolateral prefrontal cortex--regions not associated with distraction-induced analgesia. The results suggest that the activation of neural reward systems via non-pharmacologic means can reduce the experience of pain.

  6. 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.

  7. Comparative Survey of Holding Positions for Reducing Vaccination Pain in Young Infants

    Directory of Open Access Journals (Sweden)

    Hui-Chu Yin

    2017-01-01

    Full Text Available Background. Infant holding position may reduce vaccination pain. However, the optimal position for young infants remains controversial. Objectives. To compare the effectiveness of holding infants in the supine position and the effectiveness of holding infants in upright position for relieving acute pain from vaccine injection. Methods. This prospective cohort study enrolled 6–12-week-old healthy infants. We examined infant pain responses by evaluating the following three categories: (1 crying, (2 irritability, and (3 facial expression. Results. In total, 282 infants were enrolled, with 103 and 179 held in the supine and upright positions, respectively. At 30 s after vaccination, the infants in the supine position showed a larger decrease in crying (p<0.001, irritability (p=0.002, and pained facial expression (p=0.001 than did those in the upright position. However, there was no significant difference in pain response between two groups at 180 s after intervention. Conclusion. In 2-month-old infants, the supine position may reduce acute pain more effectively than does the upright position. Our findings provide a clinical strategy for relieving vaccination pain in young infants.

  8. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    Science.gov (United States)

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  9. Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

    Science.gov (United States)

    Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

    2016-08-10

    There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

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

    Directory of Open Access Journals (Sweden)

    Deise Prehs Montrucchio

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

  11. A Comparison of the 2/3/5 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Sarah Nickolls

    2011-01-01

    Full Text Available GABAA receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia. However, this approach is prone to a range of side effects including sedation, cognitive impairment, and abuse as a consequence of the widespread influence of GABA. The ability to make subtype selective low-efficacy benzodiazepine compounds, which potentiate the action of GABA at specific α subunits, has the potential to reduce this side effect profile. In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models. We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated.

  12. Comparison of granisetron and lidocaine on reducing injection pain of etomidate: a controlled randomized study

    Directory of Open Access Journals (Sweden)

    Alireza Saliminia

    Full Text Available Abstract Background and objectives Reducing pain on injection of anesthetic drugs is of importance to every anesthesiologist. In this study we pursued to define if pretreatment by granisetron reduces the pain on injection of etomidate similar to lidocaine. Methods Thirty patients aged between 18 and 50 years of American Society of Anesthesiologists physical status class I or II, whom were candidates for elective laparoscopic cholecystectomy surgery were enrolled in this study. Two 20 gauge cannulas were inserted into the veins on the dorsum of both hands and 100 mL of normal saline was administered during a 10 min period from each cannula. Using an elastic band as a tourniquet, venous drainage of both hands was occluded. 2 mL of granisetron was administered into one hand and 2 mL of lidocaine 2% at the same time into the other hand. One minute later the elastic band was opened and 2 mL of etomidate was administered to each hand with equal rates. The patients were asked to give a score from 0 to 10 (0 = no pain, 10 = severe pain to each the pain sensed in each hand. Results Two patients were deeply sedated after injection of etomidate and unable to answer any questions. The mean numerical rating score for injection pain of intravenously administered etomidate after intravenous granisetron was 2.3 ± 1.7, which was lower when compared with pain sensed due to intravenously administered etomidate after administration of lidocaine 2% (4.6 ± 1.8, p < 0.05. Conclusion The result of this study demonstrated that, granisetron reduces pain on injection of etomidate more efficiently than lidocaine.

  13. 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

  14. 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

  15. Reduced inflammatory and muscle damage biomarkers following oral supplementation with bioavailable curcumin.

    Science.gov (United States)

    McFarlin, Brian K; Venable, Adam S; Henning, Andrea L; Sampson, Jill N Best; Pennel, Kathryn; Vingren, Jakob L; Hill, David W

    2016-06-01

    Exercise-Induced Muscle Damage (EIMD) and delayed onset muscle soreness (DOMS) impact subsequent training sessions and activities of daily living (ADL) even in active individuals. In sedentary or diseased individuals, EIMD and DOMS may be even more pronounced and present even in the absence of structured exercise. The purpose of this study was to determine the effects of oral curcumin supplementation (Longvida® 400 mg/days) on muscle & ADL soreness, creatine kinase (CK), and inflammatory cytokines (TNF-α, IL-6, IL-8, IL-10) following EMID (eccentric-only dual-leg press exercise). Subjects (N = 28) were randomly assigned to either curcumin (400 mg/day) or placebo (rice flour) and supplemented 2 days before to 4 days after EMID. Blood samples were collected prior to (PRE), and 1, 2, 3, and 4 days after EIMD to measure CK and inflammatory cytokines. Data were analyzed by ANOVA with P < 0.05. Curcumin supplementation resulted in significantly smaller increases in CK (- 48%), TNF-α (- 25%), and IL-8 (- 21%) following EIMD compared to placebo. We observed no significant differences in IL-6, IL-10, or quadriceps muscle soreness between conditions for this sample size. Collectively, the findings demonstrated that consumption of curcumin reduced biological inflammation, but not quadriceps muscle soreness, during recovery after EIMD. The observed improvements in biological inflammation may translate to faster recovery and improved functional capacity during subsequent exercise sessions. These findings support the use of oral curcumin supplementation to reduce the symptoms of EIMD. The next logical step is to evaluate further the efficacy of an inflammatory clinical disease model.

  16. Training reduces catabolic and inflammatory response to a single practice in female volleyball players.

    Science.gov (United States)

    Eliakim, Alon; Portal, Shawn; Zadik, Zvi; Meckel, Yoav; Nemet, Dan

    2013-11-01

    We examined the effect of training on hormonal and inflammatory response to a single volleyball practice in elite adolescent players. Thirteen female, national team level, Israeli volleyball players (age 16.0 ± 1.4 years, Tanner stage 4-5) participated in the study. Blood samples were collected before and immediately after a typical 60 minutes of volleyball practice, before and after 7 weeks of training during the initial phase of the season. Training involved tactic and technical drills (20% of time), power and speed drills (25% of time), interval sessions (25% of time), endurance-type training (15% of time), and resistance training (15% of time). To achieve greater training responses, the study was performed during the early phase (first 7 weeks) of the volleyball season. Hormonal measurements included the anabolic hormones growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3, the catabolic hormone cortisol, the proinflammatory marker interleukin-6 (IL-6), and the anti-inflammatory marker IL-1 receptor antagonist. Training led to a significant improvement of vertical jump, anaerobic properties (peak and mean power by the Wingate Anaerobic Test), and predicted VO2max (by the 20-m shuttle run). Volleyball practice, both before and after the training intervention, was associated with a significant increase of serum lactate, GH, and IL-6. Training resulted in a significantly reduced cortisol response ([INCREMENT]cortisol: 4.2 ± 13.7 vs. -4.4 ± 12.3 ng · ml, before and after training, respectively; p volleyball practice. The results suggest that along with the improvement of power and anaerobic and aerobic characteristics, training reduces the catabolic and inflammatory response to exercise.

  17. Hypoalgesia after exercise and the cold pressor test is reduced in chronic musculuskeletal pain patients with high pain sensitivity

    DEFF Research Database (Denmark)

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

    2016-01-01

    OBJECTIVES: In chronic pain patients, impaired conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH) have been reported. No studies have compared CPM and EIH in chronic musculoskeletal pain patients with high pain sensitivity (HPS) and low pain sensitivity (LPS). MATERIALS.......005). Pain tolerance increased after the cold pressor test and exercise in both groups (PCPM and EIH were partly impaired in chronic pain patients with high versus less pain sensitivity, suggesting that the CPM and EIH responses depend on the degree of pain sensitivity. This has clinical...

  18. CUTANEUS STIMULATION: SLOW-STROKE BACK MASSAGE REDUCES THE INTENSITY OF OSTEOARTRITIS PAIN OF ELDERLY

    Directory of Open Access Journals (Sweden)

    Mira Triharini

    2017-04-01

    Full Text Available Introduction: Osteoarthritis disease is the result of both mechanical and biological process which lead come to unstable degradation and synthesis of condrozyte cartilage and extracellular matrix. The risk factor of this instability is aging process. The aging process stimulates osteophytes formation and degradation of cartilage, and emerged pain as primary clinical symptom. One of the non pharmacological ways to cope this pain is by applying cutaneus stimulation through slow-stroke back massage method. The objective of this study was to analyze the effect of applying cutaneus stimulation with slow-stroke back massage method to osteoarthritis’s pain intensity. Method: Pre experimental design with one group pre test-post test approach was used in this study. The subject of this study were elderly above 50 years old living in Panti Werdha Hargo Dedali Surabaya, 15 participants were involved using purpose sampling technique. This study started on January 29th until February 6th, 2010. Data were collected by interview and observation and analyzed by WIlcoxcon Signed Rank Test α = 0.05, p value <α. Result: The Result showed that the message intervention was significantly affect the elder’s level of osteoarthritis pain in Panti Werdha Hargo Dedali Surabaya (p = 0.003. Discussion: It can be concluded that gives stimulation cutaneus: slow-stroke back massage reduce osteoathritis pain intensity. Slow-stroke back massage increase level of endorphin, so that pain reduction and individual pain perception will decrease.

  19. Reducing Postoperative Pain from Tonsillectomy Using Monopolar Electrocautery by Cooling the Oropharynx

    Directory of Open Access Journals (Sweden)

    Vieira, Lucas

    2014-01-01

    Full Text Available Objective Evaluate intraoperative cooling of the oropharynx to reduce postoperative pain in tonsillectomy using monopolar electrocautery. Methods Sixty-six patients, age 1 to 12 years, were selected for the study, 33 in the control group and 33 in the experimental group. After randomization, patients underwent subcapsular dissection and hemostasis with monopolar electrocautery. Patients in the experimental group had the oropharynx cooled after tonsil dissection and hemostasis for 10 minutes. The procedure was done through the oral cavity by irrigation with 500 mL of 0.9% saline, in temperatures between 5°C and 10°C, for 5 minutes. The evaluation of postoperative pain was made with the pain visual analog scale (VAS for 10 days. As complementary data on the evaluation of pain, we recorded daily use of ketoprofen for pain relief. Results Pain after tonsillectomy assessed by VAS was significantly lower in the experimental group at days 0, 5, and 6 (p < 0.05. There were no differences in the use of ketoprofen between the groups. Conclusion Cooling of the oropharynx after tonsillectomy promotes clinically significant reduction in postoperative pain, without additional complications.

  20. Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms

    Science.gov (United States)

    Wang, Ying; Lei, Jianxun; Gupta, Mihir; Peng, Fei; Lam, Sarah; Jha, Ritu; Raduenz, Ellis; Beitz, Al J.; Gupta, Kalpna

    2016-01-01

    Integrative approaches such as electroacupuncture, devoid of drug effects are gaining prominence for treating pain. Understanding the mechanisms of electroacupuncture induced analgesia would benefit chronic pain conditions such as sickle cell disease (SCD), for which patients may require opioid analgesics throughout life. Mouse models are instructive in developing a mechanistic understanding of pain, but the anesthesia/restraint required to administer electroacupuncture may alter the underlying mechanisms. To overcome these limitations, we developed a method to perform electroacupuncture in conscious, freely moving, unrestrained mice. Using this technique we demonstrate a significant analgesic effect in transgenic mouse models of SCD and cancer as well as complete Freund’s adjuvant-induced pain. We demonstrate a comprehensive antinociceptive effect on mechanical, cold and deep tissue hyperalagesia in both genders. Interestingly, individual mice showed a variable response to electroacupuncture, categorized into high-, moderate-, and non-responders. Mechanistically, electroacupuncture significantly ameliorated inflammatory and nociceptive mediators both peripherally and centrally in sickle mice correlative to the antinociceptive response. Application of sub-optimal doses of morphine in electroacupuncture-treated moderate-responders produced equivalent antinociception as obtained in high-responders. Electroacupuncture in conscious freely moving mice offers an effective approach to develop a mechanism-based understanding of analgesia devoid of the influence of anesthetics or restraints. PMID:27687125

  1. Preoperative dexamethasone reduces acute but not sustained pain after lumbar disk surgery

    DEFF Research Database (Denmark)

    Nielsen, Rikke V; Siegel, Hanna; Fomsgaard, Jonna S

    2015-01-01

    on acute and sustained pain after lumbar disk surgery. In this blinded study, 160 patients undergoing lumbar disk surgery were randomly assigned to 16 mg IV dexamethasone or placebo. All patients received perioperative paracetamol and ibuprofen, and postoperative IV patient-controlled analgesia...... months postoperatively. Acute pain during mobilization (weighted average area under the curve, 2-24 hours) was significantly reduced in the dexamethasone group: 33 (22) mm vs placebo 43 (18) mm, (95% confidence interval [CI] 3-16) P = 0.005. Vomiting 0 to 24 hours postoperatively was reduced....../paralysis of the legs in the dexamethasone and placebo groups, respectively, 3 months postoperatively (P = 0.20). In conclusion, preoperative dexamethasone significantly reduced pain during mobilization and vomiting, after lumbar disk surgery. No significant effects were observed 3 months postoperatively....

  2. Lactobacilli require physical contact to reduce staphylococcal TSST-1 secretion and vaginal epithelial inflammatory response.

    Science.gov (United States)

    Younes, Jessica A; Reid, Gregor; van der Mei, Henny C; Busscher, Henk J

    2016-06-01

    ITALIC! Staphylococcus aureusbiofilms can be found on vaginal epithelia, secreting toxins and causing inflammation. The co-vaginal species ITALIC! Lactobacilluscan alter staphylococcal-induced epithelial secretion of inflammatory cytokines and quench staphylococcal toxic shock syndrome toxin-1 secretion. It is hypothesized that these effects of lactobacilli require direct physical contact between lactobacilli, staphylococci and the epithelium. Indeed, lactobacilli only reduced ITALIC! S. aureus-induced inflammatory cytokine expression when allowed physical contact with vaginal epithelial cells. Furthermore, a reduction in toxic shock syndrome toxin-1 secretion only occurred when a probiotic ITALIC! Lactobacillusstrain was allowed contact, but not when being physically separated from ITALIC! S. aureus Bacterial-probe atomic force microscopy demonstrated that lactobacilli and staphylococci strongly adhere to epithelial cells, while lactobacilli adhere stronger to staphylococci than staphylococci to each other, giving lactobacilli opportunity to penetrate and reside in staphylococcal biofilms, as visualized using confocal laser scanning microscopy with fluorescence ITALIC! in situhybridization probes. These results identify that physical contact and biochemical signaling by lactobacilli are intrinsically linked mechanisms that reduce virulence of ITALIC! S. aureusbiofilm. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. 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.

  4. Exercise, especially combined stretching and strengthening exercise, reduces myofascial pain: a systematic review

    Directory of Open Access Journals (Sweden)

    Juliano Bergamaschine Mata Diz

    2017-01-01

    Full Text Available Question: Among people with myofascial pain, does exercise reduce the intensity of the pain and disability? Design: Systematic review of randomised and quasi-randomised controlled trials. Participants: People with myofascial pain of any duration. Intervention: Exercise versus minimal or no intervention and exercise versus other intervention. Outcome measures: Pain intensity and disability. Results: Eight studies involving 255 participants were included. Pooled estimates from six studies showed statistically significant effects of exercise when compared with minimal or no intervention (support and encouragement or no treatment on pain intensity at short-term follow-up. The weighted mean difference in pain intensity due to exercise was –1.2 points (95% CI –2.3 to –0.1 on a 0 to 10 scale. Pooled estimates from two studies showed a non-significant effect of exercise when compared with other interventions (electrotherapy or dry needling on pain intensity at short-term follow-up. The weighted mean difference in pain intensity due to exercise instead of other therapies was 0.4 points (95% CI –0.3 to 1.1 on a 0 to 10 scale. Individual studies reported no significant effects of exercise on disability compared with minimal intervention (–0.4, 95% CI –1.3 to 0.5 and other interventions (0.0, 95% CI –0.8 to 0.8 at short-term follow-up. Sensitivity analysis suggested that combining stretching and strengthening achieves greater short-term effects on pain intensity compared with minimal or no intervention (–2.3, 95% CI –4.1 to –0.5. Conclusion: Evidence from a limited number of trials indicates that exercise has positive small-to-moderate effects on pain intensity at short-term follow-up in people with myofascial pain. A combination of stretching and strengthening exercises seems to achieve greater effects. These estimates may change with future high-quality studies. [Mata Diz JB, de Souza JRLM, Leopoldino AAO, Oliveira VC (2016 Exercise

  5. Evaluation of a program to reduce back pain in nursing personnel

    Directory of Open Access Journals (Sweden)

    Neusa Maria C Alexandre

    2001-08-01

    Full Text Available OBJECTIVE: To evaluate the effectiveness of a program designed to reduce back pain in nursing aides. METHODS: Female nursing aides from a university hospital who had suffered episodes of back pain for at least six months were included in the study. Participants were randomly divided into a control group and an intervention group. The intervention program involved a set of exercises and an educational component stressing the ergonomic aspect, administered twice a week during working hours for four months. All subjects answered a structured questionnaire and the intensity of pain was assessed before and after the program using a visual analogue scale (VAS. Student's t-test or the Wilcoxon Rank Sum Test for independent samples, and Chi-square test or the Exact Fisher test for categorical analysis, were used. The McNemar test and the Wilcoxon matched pairs test were used to compare the periods before and after the program. RESULTS: There was a statistically significant decrease in the frequency of cervical pain in the last two months and in the last seven days in the intervention group. There was also a reduction in cervical pain intensity in the two periods (2 months, 7 days and lumbar pain intensity in the last 7 days. CONCLUSIONS: The results suggest that a program of regular exercise with an emphasis on ergonomics can reduce musculoskeletal symptoms in nursing personnel.

  6. Evaluation of a program to reduce back pain in nursing personnel

    Directory of Open Access Journals (Sweden)

    Alexandre Neusa Maria C

    2001-01-01

    Full Text Available OBJECTIVE: To evaluate the effectiveness of a program designed to reduce back pain in nursing aides. METHODS: Female nursing aides from a university hospital who had suffered episodes of back pain for at least six months were included in the study. Participants were randomly divided into a control group and an intervention group. The intervention program involved a set of exercises and an educational component stressing the ergonomic aspect, administered twice a week during working hours for four months. All subjects answered a structured questionnaire and the intensity of pain was assessed before and after the program using a visual analogue scale (VAS. Student's t-test or the Wilcoxon Rank Sum Test for independent samples, and Chi-square test or the Exact Fisher test for categorical analysis, were used. The McNemar test and the Wilcoxon matched pairs test were used to compare the periods before and after the program. RESULTS: There was a statistically significant decrease in the frequency of cervical pain in the last two months and in the last seven days in the intervention group. There was also a reduction in cervical pain intensity in the two periods (2 months, 7 days and lumbar pain intensity in the last 7 days. CONCLUSIONS: The results suggest that a program of regular exercise with an emphasis on ergonomics can reduce musculoskeletal symptoms in nursing personnel.

  7. 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.

  8. 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

  9. Acoustic noise in functional magnetic resonance imaging reduces pain unpleasantness ratings.

    Science.gov (United States)

    Boyle, Y; Bentley, D E; Watson, A; Jones, A K P

    2006-07-01

    Functional magnetic resonance imaging (fMRI) is increasingly used in cognitive studies. Unfortunately, the scanner produces acoustic noise during the image acquisition process. Interference from acoustic noise is known to affect auditory, visual and motor processing, raising the possibility that acoustic interference may also modulate processing of other sensory modalities such as pain. With the increasing use of fMRI in the investigation of the mechanisms of pain perception, particularly in relation to attention, this issue has become highly relevant. Pain is a complex experience, composed of sensory-discriminative, affective-motivational and cognitive-evaluative components. The aim of this experiment was to assess the effect of MRI scanner noise, compared to white noise, on the affective (unpleasantness) and the sensory-discriminative (localisation) components of pain. Painful radiant heat from a CO(2) laser was delivered to the skin of the right forearm in 24 healthy volunteers. The volunteers attended to either pain location or pain unpleasantness during three conditions: i) no noise, ii) exposure to MRI scanner noise (85 dB) or iii) exposure to white noise (85 dB). Both MRI scanner noise and white noise significantly reduced unpleasantness ratings (from 5.1 +/- 1.6 in the control condition to 4.7 +/- 1.5 (P = 0.002) and 4.6 +/- 1.6 (P white noise respectively), whereas the ability to localise pain was not significantly affected (from 85.4 +/- 9.2% correct in the control condition to 83.1 +/- 10.3% (P = 0.06) and 83.9 +/- 9.5% (P = 0.27) with MRI scanner and white noise respectively). This phenomenon should be taken into account in the design of fMRI studies into human pain perception.

  10. Inflammatory arthritis mimicking Complex Regional Pain Syndrome (CRPS) in a child: A case report.

    Science.gov (United States)

    Egilmez, Zeliha; Turgut, Selin Turan; Icagasioglu, Afitap; Bicakci, Irem

    2016-01-01

    Joint complaints in childhood are seen frequently and differential diagnosis can be difficult. Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood. It involves peripheral joint arthritis, chronic synovitis, and extra-articular manifestations. Accurate diagnosis can take a long time and sometimes multiple diagnoses are used while following the patient until a final diagnosis can be reached. Arthritis may be triggered by trauma and confused with other diseases like complex regional pain syndrome (CRPS), in which trauma plays a role in the etiology. In the present case, ankle pain in an 8-year-old girl was misdiagnosed as CRPS.

  11. 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.

  12. 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

  13. Risk factors associated with reduced work productivity among people with chronic knee pain.

    Science.gov (United States)

    Agaliotis, M; Fransen, M; Bridgett, L; Nairn, L; Votrubec, M; Jan, S; Heard, R; Mackey, M

    2013-09-01

    To determine the burden and risk factors associated with reduced work productivity among people with chronic knee pain. A longitudinal study, nested within a randomised controlled trial (RCT) evaluating the long-term effects of dietary supplements, was conducted among people with chronic knee pain in paid employment (n = 360). Participants recorded days off work (absenteeism) and reduced productivity while at work (presenteeism) for seven days every two months over a 12-month period in a study specific diary. Examined risk factors included knee pain severity, occupational group, radiographic disease severity, physical activity, body mass index (BMI), health-related quality of life (SF-12) and co-morbidity. Over the 12-month follow up period, 50 (14%) participants reported one or more days off work due to knee problems, while 283 (79%) reported reduced productivity while at work (presenteeism absenteeism was having an SF-12 Mental Component Summary (MCS) score labour (OR: 2.23 [1.09-4.59]) or manual labour (OR: 6.40 [1.44-28.35]) or a high maximum knee pain (4-6 out of 10) (OR: 2.29 [1.17-4.46]). This longitudinal study found that among this cohort of people with chronic knee pain, the burden of reduced work productivity is mainly attributable to presenteeism rather absenteeism. This study demonstrated that effective strategies to increase work productivity should focus on reducing knee pain or physical disability especially among workers in manual or semi-manual labour. © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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

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

    Science.gov (United States)

    2017-10-01

    genotyping repositories to look for associations between genetic variants and pain phenotypes Major Task 1: Preliminary analyses conducted to confirm...extract the data from the various repositories , to merge the data and curate the dataset for analysis; and to conduct the genetic association analysis

  17. 17-AAG kills intracellular Leishmania amazonensis while reducing inflammatory responses in infected macrophages.

    Science.gov (United States)

    Petersen, Antonio Luis de Oliveira Almeida; Guedes, Carlos Eduardo Sampaio; Versoza, Carolina Leite; Lima, José Geraldo Bomfim; de Freitas, Luiz Antônio Rodrigues; Borges, Valéria Matos; Veras, Patrícia Sampaio Tavares

    2012-01-01

    Leishmaniasis is a neglected endemic disease with a broad spectrum of clinical manifestations. Pentavalent antimonials have been the treatment of choice for the past 70 years and, due to the emergence of resistant cases, the efficacy of these drugs has come under scrutiny. Second-line drugs are less efficacious, cause a range of side effects and can be costly. The formulation of new generations of drugs, especially in developing countries, has become mandatory. We investigated the anti-leishmanial effect of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an HSP90 inhibitor, in vitro. This inhibitor is currently in clinical trials for cancer treatment; however, its effects against intracellular Leishmania remain untested. Macrophages infected with L. amazonensis were treated with 17-AAG (25-500 nM) and parasite load was quantified using optical microscopy. Parasite load declined in 17-AAG-treated macrophages in a dose- and time-dependent manner. Intracellular parasite death became irreversible after 4 h of treatment with 17-AAG, and occurred independent of nitric oxide (NO) and superoxide (O(2) (-)) production. Additionally, intracellular parasite viability was severely reduced after 48 h of treatment. Interestingly, treatment with 17-AAG reduced pro-inflammatory mediator production, including TNF-α, IL-6 and MCP-1, yet IL-12 remained unaffected. Electron microscopy revealed morphological alterations, such as double-membrane vacuoles and myelin figures at 24 and 48 h after 17-AAG treatment. The HSP90 inhibitor, 17-AAG, possesses high potency under low dosage and reduces both pro-inflammatory and oxidative molecule production. Therefore, further studies are warranted to investigate this inhibitor's potential in the development of new generations of anti-leishmanials.

  18. Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats.

    Science.gov (United States)

    Turan, Inci; Ozacmak, Hale Sayan; Ozacmak, V Haktan; Barut, Figen; Araslı, Mehmet

    2017-11-15

    Oxidative stress and inflammatory response are major factors causing several tissue injuries in intestinal ischemia and reperfusion (I/R). Agmatine has been reported to attenuate I/R injury of various organs. The present study aims to analyze the possible protective effects of agmatine on intestinal I/R injury in rats. Four groups were designed: sham control, agmatine-treated control, I/R control, and agmatine-treated I/R groups. IR injury of small intestine was induced by the occlusion of the superior mesenteric artery for half an hour to be followed by a 3-hour-long reperfusion. Agmatine (10mg/kg) was administered intraperitoneally before reperfusion period. After 180min of reperfusion period, the contractile responses to both carbachol and potassium chloride (KCl) were subsequently examined in an isolated-organ bath. Malondialdehyde (MDA), reduced glutathione (GSH), and the activity of myeloperoxidase (MPO) were measured in intestinal tissue. Plasma cytokine levels were determined. The expression of the intestinal inducible nitric oxide synthase (iNOS) was also assessed by immunohistochemistry. The treatment with agmatine appeared to be significantly effective in reducing the MDA content and MPO activity besides restoring the content of GSH. The treatment also attenuated the histological injury. The increases in the I/R induced expressions of iNOS, IFN-γ, and IL-1α were brought back to the sham control levels by the treatment as well. Our findings indicate that the agmatine pretreatment may ameliorate reperfusion induced injury in small intestine mainly due to reducing inflammatory response and oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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

  20. Tocopherol Supplementation Reduces NO Production and Pulmonary Inflammatory Response to Bleomycin

    Science.gov (United States)

    Shi, Jin Dong; Golden, Thea; Guo, Chang-Jiang; Tu, Shui Ping; Scott, Pamela; Lee, Mao-Jung; Yang, Chung S.; Gow, Andrew J.

    2013-01-01

    Bleomycin causes acute lung injury through production of reactive species and initiation of inflammation. Previous work has shown alteration to the production of reactive oxygen species results in attenuation of injury. Vitamin E, in particular, γ-tocopherol, isoform, has the potential to scavenge reactive oxygen and nitrogen species. This study examines the utility of dietary supplementation with tocopherols in reducing bleomycin-mediated acute lung injury. Male C57BL6/J mice were intratracheally instilled with PBS or 2 units/kg bleomycin. Animals were analyzed 3 and 8 days post instillation at the cellular, tissue, and organ levels. Results showed successful delivery of tocopherols to the lung via dietary supplementation. Also, increases in reactive oxygen and nitrogen species due to bleomycin are normalized in those mice fed tocopherol diet. Injury was not prevented but inflammation progression was altered, in particular macrophage activation and function. Inflammatory scores based on histology demonstrate limited progression of inflammation in those mice treated with bleomycin and fed tocopherol diet compared to control diet. Upregulation of enzymes and cytokines involved in pro-inflammation were limited by tocopherol supplementation. Day 3 functional changes in elastance in response to bleomycin are prevented, however, 8 days post injury the effect of the tocopherol diet is lost. The effect of tocopherol supplementation upon the inflammatory process is demonstrated by a shift in the phenotype of macrophage activation. The effect of these changes on resolution and the progression of pulmonary fibrosis has yet to be elucidated. PMID:23669183

  1. Oral Magnesium Treatment Reduces Anemia and Levels of Inflammatory Markers in Experimental Diabetes.

    Science.gov (United States)

    Ige, A O; Adewoye, E O

    2016-07-26

    Magnesium has been reported to improve glucose utilization in diabetes mellitus. However, information on its effects on anemic and inflammatory markers in diabetes mellitus is limited. This study investigated the effect of oral magnesium (Mg) treatment on some markers of anemia and inflammation in 25 male Wistar rats. Rats (200 ± 15 g) were randomly divided into five groups (n = 5). Group 1 was control (received orally 0.2 mL distilled water daily), group 2 (Diabetic Untreated), group 3 (Diabetic Mg treated-100 mg/kg bw), group 4 (Diabetic Mg treated-250 mg/kg bw), group 5 (Diabetic Insulin treated-1 IU/kg bw). Diabetes was induced with a single dose of alloxan (100 mg/kg intraperitoneal (i.p.)). All treatments were done for 14 days. Anemic and inflammatory markers were investigated on blood samples obtained from each animal using standard laboratory methods. Significant increase (p DMg 100 (5.86 ± 0.74 × 10 9 /L) and DMg 250 (5.06 ± 0.78 × 10 9 /L). Hemoglobin concentration, packed cell volume (PCV) and red blood cell (RBC) count was decreased (p DMg 100, and DI rats. Erythrocyte sedimentation rate (ESR) was significantly increased (p DMg 100, DMg 250, and DI groups. Fibrinogen level was increased (p DMg 100 (0.30 ± 0.03 g/dL), DMg 250 (0.22 ± 0.04 g/dL), and DI (0.36 ± 0.02 g/dL) rats were comparable to control (0.26 ± 0.02 g/dL). Total protein, albumin, and globulin levels were decreased in DU rats compared to normal control, DMg 100, DMg 250, and DI rats. In conclusion, anemia and increased hematologic and metabolic inflammatory markers may be associated with untreated diabetes mellitus. Treatment of alloxan-induced diabetic rats with magnesium improved the anemic state and reduced hematologic and metabolic inflammatory markers.

  2. Reduced basal ganglia μ-opioid receptor availability in trigeminal neuropathic pain: A pilot study

    Directory of Open Access Journals (Sweden)

    DosSantos Marcos

    2012-09-01

    Full Text Available Abstract Background Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. Findings In this study, we examined the regional μ-opioid receptor (μOR availability in vivo (non-displaceable binding potential BPND of TNP patients with positron emission tomography (PET using the μOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced μOR BPND in the left nucleus accumbens (NAc, an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the μOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. Conclusions Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous μ-opioid system, rather than only to the peripheral pathology. The decreased availability of μORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.

  3. Music for reducing the anxiety and pain of patients undergoing a biopsy: A meta-analysis.

    Science.gov (United States)

    Song, Mingzhi; Li, Nanyang; Zhang, Xianbin; Shang, Yuru; Yan, Litao; Chu, Jin; Sun, Ran; Xu, Yun

    2018-05-01

    This study aimed to evaluate the efficacy of music therapy for reducing the anxiety and pain of patients who underwent a biopsy. Music can affect human anxiety and pain by triggering a neuroendocrine effect. Clinical study results indicated that music can influence the anxiety and pain caused by invasive procedures. There is no effective solution for anxiety and pain arising from a biopsy. Although researchers in this field have different views, music still holds promise in reducing the anxiety and pain in patients undergoing the biopsy. Systematic review and meta-analysis of randomized controlled trials. Systematic searches were conducted in PubMed, Embase, Medline and Cochrane databases for studies reported in the English language. The review period covered 2000 - December 2016. The outcome measure of interest was anxiety and pain. This review followed Cochrane methods. Studies were selected according to the PICOS framework. The methodological quality of studies was assessed with the Cochrane risk of bias tool. A systematic review of effectiveness was conducted by using GRADE approach. Nine randomized controlled trials with a total of 326 participants in the music intervention group and 323 controls met the inclusion criteria. Music had a tendency towards decreasing systolic blood pressure before the biopsy, State-Trait Anxiety Inventory scores after the biopsy, diastolic blood pressure after the biopsy and heart rate after the biopsy. Similarly, music also tended to be more effective for controlling pain after the biopsy. There was moderate quality evidence for the outcome: State-Trait Anxiety Inventory scores after the biopsy; and low- or very low-quality evidence for other outcomes. Music can be used for patients before and during the biopsy procedure. This approach may be performed by nurses to promote the recovery of patients after the biopsy. © 2017 John Wiley & Sons Ltd.

  4. 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.

  5. EFFECTIVENESS OF MC KENZIE EXERCISES IN REDUCING NECK AND BACK PAIN AMONG MADRASSA STUDENTS

    Directory of Open Access Journals (Sweden)

    Saima Aziz

    2016-02-01

    Full Text Available Background: In this advanced era, neck and back pain has become a common musculoskeletal problem. These symptoms have a high prevalence in the community and now they are affecting even our adolescents leaving a major impact on youth’s functional and educational activities. Nevertheless, the burden of these musculoskeletal pains, which relates not only to its prevalence but also to increase in physiological and psychological stress among them, distressing their creativity. Madrassa students have a daily exposure to neck and back pain due to poor posture. The McKenzie method is a popular treatment for back and neck pain among physical therapists. So, the intention of this study is to test the effectiveness of McKenzie exercises in neck and back pain, because hardly any data is available on McKenzie technique and its outcome in Pakistan. The objective of the study is to determine the effectiveness of McKenzie exercises in reducing neck and back pain among madrassa students. Methods: The students were recruited from Madrassa Darul Akram (Baldia town and Jamia Ashraf-ul-madrassa (Gulshan-e-Iqbal Karachi. One sixty three students aged between 12–18 years of both genders who were fulfilling the inclusion criteria were selected from Madrassa Darul Akram (Baldia town and Jamia Ashraf-ul-madrassa (Gulshane-Iqbal. The participants received McKenzie exercises programs intervention for three consecutive weeks. Outcome Measure: Neck Disability Index (NDI, Modified Oswestry Low Back Pain Disability Index (ODI and Numeric Pain Rating Scale (NPRS Results: The present study showed significant results in all three scales in both genders (p<0.001.Among sections, the Hafiz students revealed greater score in all 3 scales before treatment as compared to ‘Alim/Alima’ and ‘Nazra’ students and after treatment showed significant results in all 3 domains (p<0.001. Conclusion: Findings of this study revealed that madrassa students were more prone to develop neck

  6. Neck arthritis pain is reduced and range of motion is increased by massage therapy.

    Science.gov (United States)

    Field, Tiffany; Diego, Miguel; Gonzalez, Gladys; Funk, C G

    2014-11-01

    The literature on the effects of massage therapy on neck arthritis pain is mixed depending on the dose level, and it is also based on self-report. In the present study an attempt was made to enhance the effects of weekly massage therapy by having the participants massage themselves daily. And in addition to self-reports on pain, range of motion (ROM) and the associated ROM pain were assessed before and after the first massage session and pre-post the last session one month later. Staff and faculty members at a medical school who were eligible for the study if they had neck arthritis pain were randomly assigned to a massage or a waitlist control group (N = 24 per group). The massage group received moderate pressure massages weekly by a massage therapist plus daily self-massages. The waitlist control group received the same schedule massages one month after being control subjects. The massage group showed significant short-term reductions after the first and last day massages in self-reported pain and in ROM-associated pain as well as an increase in ROM. Comparisons between the massage group (N = 23) and the control group (N = 14) on the last versus the first day data suggested significantly different changes including increased ROM and reduced ROM-associated pain for the massage group and reduced ROM and increased ROM-associated pain for the control group. These changes occurred specifically for flexion and right and left lateral flexion motions. These data highlight the importance of designing massage therapy protocols that target the most affected neck muscle groups and then assessing range of motion and related pain before and after the massage therapy. Comparisons with other studies also suggest that moderate pressure may contribute to the massage effects, and the use of daily self-massages between sessions may sustain the effects and serve as a cost-effective therapy for individuals with neck arthritis pain. Copyright © 2014. Published by Elsevier Ltd.

  7. Analgesic and antihyperalgesic effects of melatonin in a human inflammatory pain model

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Gögenur, Ismail; Fenger, Andreas Q

    2015-01-01

    . The design was a randomized, double-blind, placebo-controlled, three-arm crossover study. Each volunteer participated in 3 identical study sessions with intravenous administration of placebo, melatonin 10 mg, or melatonin 100 mg. Sixty minutes after bolus injection of study medication, a BI was induced...... by a computerized contact thermode (47.0°C, 420 seconds, 5.0 × 2.5 cm). Pain ratings during the BI and quantitative sensory testing at baseline and at 1, 2, 4, and 6 hours after the BI were performed. Quantitative sensory testing included assessments of secondary hyperalgesia areas, mechanical and thermal...... thresholds in the BI area, and pressure algometry. Furthermore, markers of inflammation, skin-reflectance spectrophotometry, and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area. Pain during the BI and secondary hyperalgesia areas were defined...

  8. Comparison Efficacy of Topical Piroxicam Gel and Lidocaine with Intravenous Pethidine in Reducing Pain during ESWL

    Directory of Open Access Journals (Sweden)

    F Mohammad Alibeigi

    2011-06-01

    Full Text Available Introduction & Objective: ESWL is a non-invasive method of breaking stones, using acoustic shock waves. Shock waves cause temporary deep visceral pain and discomfort in entry therefore, administration of sedatives is necessary. The purpose of this study was to compare the effect of topical lidocaine and piroxicam gel with intravenous pethidine in reducing pain during ESWL. Materials & Methods: This clinical trial study was performed on 159 patients who referred to Ayatollah Kashani Hospital in Shahrkord for ESWL in 2009. Patients were randomly divided into three-groups. For the first group, intravenous pethidine (0.5 mg/kg alone was administered. The second group received topical piroxicam, and the third group received topical lidocaine in the area of flank for half an hour before ESWL. During the operation, those patients who had unbearable pain, received another 0.5 mg/kg of pethidine. Data was collected using MC Gill questionnaires and analyzed using the SPSS software, using parametric, nonparametric methods and Dunn's Multiple Comparisons tests. Results: The mean of pain scores in the first group (pethidine was 6.2 ± 6.9 while these scores were 3.2 ± 2 .7 and 3.9 ± 3.1 for the second (piroxicam gel and third group (lidocaine gel respectively. The differences in the mean score of pain was significant in the pethidine group compared to the other groups (P <0.05. The average pethidin consumption were 24 ± 16 mg for the first group (pethidine, 10 ± 13 mg for the second group (piroxicam gel, and 5 ± 9 mg for the third group (lidocaine gel. The mean difference was significant in pethidine treated group in comparison with other two groups (P < 0.05. Conclusion: The use of topical piroxicam or lidocaine reduces pain in patients after ESWL It also reduces the need for sedative drugs.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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...

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

    Science.gov (United States)

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

    2015-09-01

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

  15. 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

    , 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......)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical...

  16. Investigating Efficacy of Melatonin and Gabapentin in Reducing Anxiety and Pain of Lumbar Puncture in Children

    Directory of Open Access Journals (Sweden)

    R Fallah

    2013-10-01

    Full Text Available Introduction: The lumbar puncture is one of the most important diagnostic and therapeutic procedures within children which child’s non-cooperativeness and procedural sedation are regarded necessary to conduct it. This study aimed to compare efficacy and safety of melatonin and gabapentin in reducing anxiety and pain of lumbar puncture in children. Methods: In a parallel single-blinded randomized clinical trial, sixty children aged 6 months -7 years, were evaluated in Pediatric Ward of Shahid Sadoughi Hospital, in Yazd (Iran in 2012. The children were distributedrandomly into two groups (30 children in each group. In group one, they received 0.3 mg/kg/dose of melatonin and theother group received 15 mg/kg/dose of gabapentin. Primary endpoints were success rate in reducing anxiety (anxiety score of≥ four and reducing pain when the needle was inserted to skin for lumbarpuncture (pain score of less than four. The clinicalside effects were investigated as well. Results: Twenty two girls (36.7% and 38 boys (63.3% with mean age of 2.79 ± 1.92 years were evaluated. Anxiety reduction (achieving the anxiety score of ≥ four was obtained in 43.3% in melatonin and in 36.7% in gabapentin groups, respectively and both drugs were equally effective in anxiety reduction (p.value = 0.598.Pain reduction ( achieving the pain score of less than four was obtained in 23.3% in melatonin and in 50% in gabapentin groups, respectively and thus, gabapentin wasproved to be more effective in pain reduction (p.value = 0.032.Mild side effects were observed in 10% of melatonin group and in 16.7% of gabapentin group. No statistically significant differences were seen from viewpoint of safety between the two drugs (p.value=0.448. Conclusion: Melatonin and gabapentin were not effective drugs in anxiety reduction for lumbar puncture of children. However, gabapentin is a safe and effective drug in pain reduction in painful diagnostic therapeutic procedures.

  17. Improved Function and Reduced Pain after Swimming and Cycling Training in Patients with Osteoarthritis.

    Science.gov (United States)

    Alkatan, Mohammed; Baker, Jeffrey R; Machin, Daniel R; Park, Wonil; Akkari, Amanda S; Pasha, Evan P; Tanaka, Hirofumi

    2016-03-01

    Arthritis and its associated joint pain act as significant barriers for adults attempting to perform land-based physical activity. Swimming can be an ideal form of exercise for patients with arthritis. Yet there is no information on the efficacy of regular swimming exercise involving patients with arthritis. The effect of a swimming exercise intervention on joint pain, stiffness, and physical function was evaluated in patients with osteoarthritis (OA). Using a randomized study design, 48 sedentary middle-aged and older adults with OA underwent 3 months of either swimming or cycling exercise training. Supervised exercise training was performed for 45 min/day, 3 days/week at 60-70% heart rate reserve for 12 weeks. The Western Ontario and McMaster Universities Arthritis Index was used to measure joint pain, stiffness, and physical limitation. After the exercise interventions, there were significant reductions in joint pain, stiffness, and physical limitation accompanied by increases in quality of life in both groups (all p swimming and cycling training. Regular swimming exercise reduced joint pain and stiffness associated with OA and improved muscle strength and functional capacity in middle-aged and older adults with OA. Additionally, the benefits of swimming exercise were similar to the more frequently prescribed land-based cycling training. clinicaltrials.gov NCT01836380.

  18. Does wound infi ltration of tramadol reduce postoperative pain in laparoscopic or open herniorrhaphy?

    Directory of Open Access Journals (Sweden)

    Remziye Sıvacı

    2012-09-01

    Full Text Available Introduction: The laparoscopic approach may be associated with more postoperative pain initially. The aim of this study was to evaluate the effects of administered tramadol at wound closure on postoperative painand analgesic requirements under spinal anesthesia in laparoscopic inguinal herniorrhaphy (LH or tension free open inguinal herniorrhaphy (TFOH.Methods: Twenty patients were randomly divided into two groups (n= 10 in each as LH or TFOH. Patients received infiltration of 200 mg tramadol with 40 mL of 0.9% saline solution at wound closure procedure. Postoperative pain was assessed with a Visual Analog Scale (VAS at 3, 6, 12, and 24 hours postoperatively. Additional requirements of tramadol for postoperative pain releif were registered.Results: VAS scores at postoperative 12 and 24 hours were signifi cantly higher according to 3rd hour VAS scores in both groups. The VAS scores at 12 hours after operation signifi cantly lower in LH group than inTFOH group (1.5 ± 0.97 vs 5.1 ± 0.99. Additional requirements of tramadol for postoperative pain releif were significantly lower in LH group.Conclusion: We conclude that wound infi ltration of 200 mg tramadol reduce postoperative pain in LH group.

  19. Plasmid Transfer of Plasminogen K1-5 Reduces Subcutaneous Hepatoma Growth by Affecting Inflammatory Factors

    Directory of Open Access Journals (Sweden)

    Lea A. Koch

    2014-01-01

    Full Text Available There is evidence that plasminogen K1-5 (PlgK1-5 directly affects tumour cells and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects of plasmid encoding PlgK1-5 (pK1-5 on Hepa129, Hepa1-6, and HuH7 cell viability, apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3-phosphorylation were investigated. In vivo, tumour growth, proliferation, vessel density, and effects on vascular endothelial growth factor (VEGF and tumour necrosis factor alpha (TNF-alpha expression were examined following treatment with pK1-5. In vivo, pK1-5 halved cell viability; cell death was increased by up to 15% compared to the corresponding controls. Proliferation was not affected. VEGF, TNF-alpha, and STAT3-phosphorylation were affected following treatment with pK1-5. In vivo, ten days after treatment initiation, pK1-5 reduced subcutaneous tumour growth by 32% and mitosis by up to 77% compared to the controls. Vessel density was reduced by 50%. TNF-alpha levels in tumour and liver tissue were increased, whereas VEGF levels in tumours and livers were reduced after pK1-5 treatment. Taken together, plasmid gene transfer of PlgK1-5 inhibits hepatoma (cell growth not only by reducing vessel density but also by inducing apoptosis, inhibiting proliferation, and triggering inflammation.

  20. Doxycycline inhibits experimental cerebral malaria by reducing inflammatory immune reactions and tissue-degrading mediators.

    Directory of Open Access Journals (Sweden)

    Kim E Schmidt

    Full Text Available Malaria ranks among the most important infectious diseases worldwide and affects mostly people living in tropical countries. Mechanisms involved in disease progression are still not fully understood and specific treatments that might interfere with cerebral malaria (CM are limited. Here we show that administration of doxycycline (DOX prevented experimental CM (ECM in Plasmodium berghei ANKA (PbA-infected C57BL/6 wildtype (WT mice in an IL-10-independent manner. DOX-treated mice showed an intact blood-brain barrier (BBB and attenuated brain inflammation. Importantly, if WT mice were infected with a 20-fold increased parasite load, they could be still protected from ECM if they received DOX from day 4-6 post infection, despite similar parasitemia compared to control-infected mice that did not receive DOX and developed ECM. Infiltration of T cells and cytotoxic responses were reduced in brains of DOX-treated mice. Analysis of brain tissue by RNA-array revealed reduced expression of chemokines and tumour necrosis factor (TNF in brains of DOX-treated mice. Furthermore, DOX-administration resulted in brains of the mice in reduced expression of matrix metalloproteinase 2 (MMP2 and granzyme B, which are both factors associated with ECM pathology. Systemic interferon gamma production was reduced and activated peripheral T cells accumulated in the spleen in DOX-treated mice. Our results suggest that DOX targeted inflammatory processes in the central nervous system (CNS and prevented ECM by impaired brain access of effector T cells in addition to its anti-parasitic effect, thereby expanding the understanding of molecular events that underlie DOX-mediated therapeutic interventions.

  1. Doxycycline inhibits experimental cerebral malaria by reducing inflammatory immune reactions and tissue-degrading mediators.

    Science.gov (United States)

    Schmidt, Kim E; Kuepper, Janina M; Schumak, Beatrix; Alferink, Judith; Hofmann, Andrea; Howland, Shanshan W; Rénia, Laurent; Limmer, Andreas; Specht, Sabine; Hoerauf, Achim

    2018-01-01

    Malaria ranks among the most important infectious diseases worldwide and affects mostly people living in tropical countries. Mechanisms involved in disease progression are still not fully understood and specific treatments that might interfere with cerebral malaria (CM) are limited. Here we show that administration of doxycycline (DOX) prevented experimental CM (ECM) in Plasmodium berghei ANKA (PbA)-infected C57BL/6 wildtype (WT) mice in an IL-10-independent manner. DOX-treated mice showed an intact blood-brain barrier (BBB) and attenuated brain inflammation. Importantly, if WT mice were infected with a 20-fold increased parasite load, they could be still protected from ECM if they received DOX from day 4-6 post infection, despite similar parasitemia compared to control-infected mice that did not receive DOX and developed ECM. Infiltration of T cells and cytotoxic responses were reduced in brains of DOX-treated mice. Analysis of brain tissue by RNA-array revealed reduced expression of chemokines and tumour necrosis factor (TNF) in brains of DOX-treated mice. Furthermore, DOX-administration resulted in brains of the mice in reduced expression of matrix metalloproteinase 2 (MMP2) and granzyme B, which are both factors associated with ECM pathology. Systemic interferon gamma production was reduced and activated peripheral T cells accumulated in the spleen in DOX-treated mice. Our results suggest that DOX targeted inflammatory processes in the central nervous system (CNS) and prevented ECM by impaired brain access of effector T cells in addition to its anti-parasitic effect, thereby expanding the understanding of molecular events that underlie DOX-mediated therapeutic interventions.

  2. Treatment with some anti-inflammatory drugs reduces germ tube formation in Candida albicans strains

    Directory of Open Access Journals (Sweden)

    Elena Rusu

    2014-12-01

    Full Text Available Candida albicans is an opportunistic dimorphic fungus that inhabits various host mucosal sites. It can cause both superficial and serious systemic disease. Conversion from the yeast to the hyphal form has been associated with increased virulence and mucosal invasiveness. The aim of this study was to investigate the effect of sodium diclofenac and aspirin on germs tube formation of different Candida albicans strains. Prostaglandins may play an important role in fungal colonization. Nonsteroidal anti-inflammatory drugs are inhibitors of the cyclooxygenase isoenzymes. These drugs specifically block the biosynthesis of mammalian prostaglandins by inhibiting one or both of cyclooxygenase isoenzymes. In tests for germ tube formation sodium diclofenac reduced the filamentation to the 12.5%- 5.1%. In the presence of aspirin the filamentation was reduced up to 85-45% depending on the tested strain. Our results suggest that cyclooxygenase-depending synthesis of fungal prostaglandins is important for morphogenesis and fungal virulence. Inhibitors of cyclooxygenase isoensymes (aspirin and diclofenac are effective in decreasing germ tube formation of Candida albicans.

  3. A hip abduction exercise prior to prolonged standing increased movement while reducing cocontraction and low back pain perception in those initially reporting low back pain.

    Science.gov (United States)

    Viggiani, Daniel; Callaghan, Jack P

    2016-12-01

    Persons who develop low back pain from prolonged standing exhibit increased muscle cocontraction, decreased movement and increased spine extension. However, it is unclear how these factors relate to pain development. The purpose of this study was to use hip abductor fatigue to manipulate muscle activity patterns and determine its effects on standing behaviours and pain development. Forty participants stood for two hours twice, once following a hip abductor fatigue exercise (fatigue), and once without exercise beforehand (control). Trunk and gluteal muscle activity were measured to determine cocontraction. Lumbo-pelvic angles and force plates were used to assess posture and movement strategies. Visual analog scales differentiated pain (PDs) and non-pain developers (NPDs). PDs reported less low back pain during the fatigue session, with females having earlier reductions of similar scale than males. The fatigue session reduced gluteal and trunk cocontraction and increased centre of pressure movement; male and female PDs had opposing spine posture compensations. Muscle fatigue prior to standing reduced cocontraction, increased movement during standing and reduced the low back pain developed by PDs; the timing of pain reductions depended on spine postures adopted during standing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. An Educational Intervention to Reduce Pain and Improve Pain Management for Malawian People Living With HIV/AIDS and Their Family Carers: A Randomized Controlled Trial.

    Science.gov (United States)

    Nkhoma, Kennedy; Seymour, Jane; Arthur, Antony

    2015-07-01

    Advances being made in improving access to HIV drugs in resource-poor countries mean HIV patients are living longer, and, therefore, experiencing pain over a longer period of time. There is a need to provide effective interventions for alleviating and managing pain. To assess whether a pain educational intervention compared with usual care reduces pain severity and improves pain management in patients with HIV/AIDS and their family carers. This was a randomized, parallel group, superiority trial conducted at HIV and palliative care clinics of two public hospitals in Malawi. A total of 182 adults with HIV/AIDS (Stage III or IV) and their family carers participated; carer participants were those individuals most involved in the patient's unpaid care. The educational intervention comprised a 30 minute face-to-face meeting, a leaflet, and a follow-up telephone call at two weeks. The content of the educational intervention covered definition, causes, and characteristics of pain in HIV/AIDS; beliefs and myths about pain and pain medication; assessment of pain; and pharmacological and nonpharmacological management. The primary outcome was average pain severity measured by the Brief Pain Inventory-Pain Severity subscale. Assessments were recorded at baseline before randomization and at eight weeks after randomization. Of the 182 patient/carer dyads randomly allocated, 157 patient/carer dyads completed the trial. Patients in the intervention group experienced a greater decrease in pain severity (mean difference = 21.09 points, 95% confidence interval = 16.56-25.63; P HIV/AIDS and their family carers. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  5. Intra-Articular Corticosteroids in Addition to Exercise for Reducing Pain Sensitivity in Knee Osteoarthritis

    DEFF Research Database (Denmark)

    Soriano-Maldonado, Alberto; Klokker, Louise; Bartholdy, Cecilie

    2016-01-01

    OBJECTIVE: To assess the effects of one intra-articular corticosteroid injection two weeks prior to an exercise-based intervention program for reducing pain sensitivity in patients with knee osteoarthritis (OA). DESIGN: Randomized, masked, parallel, placebo-controlled trial involving 100 particip......OBJECTIVE: To assess the effects of one intra-articular corticosteroid injection two weeks prior to an exercise-based intervention program for reducing pain sensitivity in patients with knee osteoarthritis (OA). DESIGN: Randomized, masked, parallel, placebo-controlled trial involving 100...... the injections all participants undertook a 12-week supervised exercise program. Main outcomes were changes from baseline in pressure-pain sensitivity (pressure-pain threshold [PPT] and temporal summation [TS]) assessed using cuff pressure algometry on the calf. These were exploratory outcomes from a randomized....... The mean group difference in changes from baseline at week 14 was 0.6 kPa (95% CI: -1.7 to 2.8; P = 0.626) for PPT and 384 mm×sec (95% CI: -2980 to 3750; P = 0.821) for TS. CONCLUSIONS: These results suggest that adding intra-articular corticosteroid injection 2 weeks prior to an exercise program does...

  6. Reduced Pain and Anxiety with Music and Noise-Canceling Headphones During Shockwave Lithotripsy.

    Science.gov (United States)

    Karalar, Mustafa; Keles, Ibrahim; Doğantekin, Engin; Kahveci, Orhan Kemal; Sarici, Hasmet

    2016-06-01

    We assessed the effects of music and noise-canceling headphones (NCHs) on perceived patient pain and anxiety from extracorporeal shockwave lithotripsy (SWL). Patients with renal calculi scheduled for SWL were prospectively enrolled. All 89 patients between the ages of 19 and 80 years were informed about this study and then randomized into three groups: Group 1 (controls), no headphones and music; Group 2, music with NCHs (patients listened to Turkish classical music with NCHs during SWL); and Group 3, music with non-NCHs (patients listened to Turkish classical music with non-NCHs during SWL). Hemodynamic and respiratory parameters were recorded before and just after the SWL session. All patient visual analog scale (VAS) and State-Trait Anxiety Inventory (STAI) scores were recorded just after the SWL procedure. There were significant differences in VAS scores among the groups (5.1, 3.6, and 4.5, respectively, p < 0.001), including between Groups 2 and 3 (p = 0.018). There were also significant differences in STAI-State anxiety scores among the groups (43.1, 33.5, and 38.9, respectively, p = 0.001), including between Groups 2 and 3 (p = 0.04). Music therapy during SWL reduced pain and anxiety. Music therapy with NCHs was more effective for pain and anxiety reduction. To reduce pain and anxiety, nonpharmacologic therapies such as music therapy with NCHs during SWL should be investigated further and used routinely.

  7. Dextromethorphan Reduces Postoperative Pain of Post Partum Tubal Ligation under General Anesthesia

    Directory of Open Access Journals (Sweden)

    N. Manochehrian

    2009-04-01

    Full Text Available Introduction & Objective: Postoperative pain has harmful effects in many systems. Dextromethorphan reduces postoperative pain in post partum tubal ligation under general anesthesia. Materials & Methods: In this research 40 patients with ASA class I and II in double blind randomized clinical trial were studied in two groups. 90 minutes before surgery the patients received 90 mg dextromethorphan or placebo (oral. The patients induced general anesthesia with thiopental (5mg/kg, fentanyl 1.5 g/kg and succinylcholin(1-1.5 mg/kg and maintenance with halothane and N2O 50%. Patients were observed studied for analgesic requirement, nausea, vomiting, urinary retention and respiratory depression in recovery and 2,4,8 and 24 hours after surgery. Results: There was no significant difference in age, education, . . . Pain in recovery, 2 and 4 hours after surgery in dextromethorphan was less than placebo group. The analgesic requirement (pethidine in dextromethophan was less than placebo group.Conclusion: Administration of 90 mg dextromethorphan 90 minutes before the surgery under GA reduces pain in recovery time , 2 and 4 hours after the surgery.

  8. [Pulsatilla decoction inhibits vulvovaginal Candida albicans proliferation and reduces inflammatory cytokine levels in vulvovaginal candidiasis mice].

    Science.gov (United States)

    Xia, Dan; Zhang, Mengxiang; Shi, Gaoxiang; Xu, Zhiqing; Wu, Daqiang; Shao, Jing; Wang, Tianming; Wang, Changzhong

    2016-02-01

    To explore the possible regulatory effect of Pulsatilla decoction on Th17 cells and inflammatory cytokines of vulvovaginal candidiasis (VVC) mice. Seventy-two female Kunming mice were randomly assigned into six groups: a blank control group, a VVC model group, a fluconazole group and three Pulsatilla decoction groups (dose levels: 22.5, 15.0 and 7.5 g/kg, respectively). The VVC mouse models were established by vaginal inoculation with Candida albicans (C. albicans) in female mice in pseudoestrus state caused by estradiol injection. After 7-day treatment on VVC mice, the vaginal C. albicans burden was assessed using dilution spread plate method; the vaginal C. albicans morphology was observed by Gram staining method; the levels of interleukin 6 (IL-6), IL-17, IL-21 and tumor necrosis factor α (TNF-α) in sera were detected by ELISA. The content of the transcription factor retinoid related orphan receptor gamma t (RORγt) in vaginal tissues was detected by immunohistochemistry. The VVC mouse models were successfully developed. After treatment, the vaginal C. albicans burden of the fluconazole group and 22.5 g/kg Pulsatilla decoction group dropped significantly compared with that of the VVC model group. Gram staining showed that the VVC mice had lots of C. albicans hyphae in vaginal discharge, that 7.5 g/kg Pulsatilla decoction group remained the mycelia-phase C. albicans, and that 15.0 g/kg Pulsatilla decoction group had the majority of yeast-phase C. albicans and a few of mycelia-phase, while no hyphae and only very few of yeast-phase C. albicans were observed in 22.5 g/kg Pulsatilla decoction group and fluconazole group. After 7-day treatment, compared with the model group, the levels of IL-6, IL- 17, IL-21 and TNF-α in the sera of the fluconazole group, 15.0 and 22.5 g/kg Pulsatilla decoction groups were reduced significantly and the levels of RORγt in the vaginal tissues of the fluconazole group, 15.0 and 22.5 g/kg Pulsatilla decoction groups also decreased

  9. The Nonsteroidal Anti-inflammatory Drug Diclofenac Reduces Acid-Induced Heartburn Symptoms in Healthy Volunteers.

    Science.gov (United States)

    Kondo, Takashi; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Okada, Hiroki; Watari, Jiro; Miwa, Hiroto

    2015-07-01

    We investigated the effects of diclofenac, a nonsteroidal anti-inflammatory drug that inhibits prostaglandin production, on induction of esophageal sensation by acid perfusion in healthy men. We performed a prospective, double-blind, placebo-controlled, 2-period, cross-over study over 3 visits in 12 healthy men. Diclofenac was given 6 hours and 2 hours before an acid perfusion test. During the test, hydrochloric acid (0.15 mol/L) was perfused into the lower esophagus for 30 minutes; we evaluated upper gastrointestinal symptoms using a validated categoric rating scale. Then, we calculated and assessed the acid perfusion sensitivity score (APSS). Biopsy specimens were collected by endoscopy of the distal esophagus before and after acid perfusion; levels of prostaglandin E2 (PGE2) (pg/mg) were measured in the samples using an enzyme-linked immunosorbent assay. Compared with placebo, diclofenac significantly reduced the APSS for heartburn (82.2 ± 12.2 for placebo and 47.5 ± 8.9 for diclofenac; P heartburn was reduced significantly by diclofenac. Compared with placebo, diclofenac reduced the overproduction of PGE2 by esophageal tissues after acid perfusion (23.3 ± 5.2 for placebo and 11.4 ± 3.5 for diclofenac; P heartburn and esophageal levels of PGE2 (r = 0.53; P heartburn vs PGE2). Diclofenac attenuated acid-induced heartburn by inhibiting PGE2 overproduction in the esophagus. Esophageal PGE2 might be involved in producing heartburn symptoms. Clinical Trials Registry no: UMIN000014595. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. Lycopene rich extract from red guava (Psidium guajava L.) displays anti-inflammatory and antioxidant profile by reducing suggestive hallmarks of acute inflammatory response in mice.

    Science.gov (United States)

    Vasconcelos, Andreanne G; Amorim, Adriany das G N; Dos Santos, Raimunda C; Souza, Jessica Maria T; de Souza, Luan Kelves M; Araújo, Thiago de S L; Nicolau, Lucas Antonio D; de Lima Carvalho, Lucas; de Aquino, Pedro Everson A; da Silva Martins, Conceição; Ropke, Cristina D; Soares, Pedro Marcos G; Kuckelhaus, Selma Aparecida S; Medeiros, Jand-Venes R; Leite, José Roberto de S A

    2017-09-01

    This study investigated the anti-inflammatory activity of the extract (LEG) and purified (LPG) lycopene from guava (Psidium guajava L.), as well as some mechanisms possibly involved in this effect. The anti-inflammatory activity was initially assessed using paw edema induced by Carrageenan, Dextran, Compound 48/80, Histamine and Prostaglandin E2 in Swiss mice. A peritonitis model was used to evaluate neutrophil migration, the activity of myeloperoxidase (MPO) and reduced glutathione (GSH) concentration; while the effect on the expression of iNOS, COX-2 and NF-κB, was assessed by immunohistochemistry analysis. Results showed that oral and intraperitoneal administration of LEG and LPG inhibited inflammation caused by carrageenan. LPG (12.5mg/kg p.o.) significantly inhibited the edema formation induced by different phlogistic agents and immunostaining for iNOS, COX-2 and NF-κB. Leukocytes migration in paw tissue and peritoneal cavity was reduced, as well as MPO concentration, whereas GSH levels increased. Thus, lycopene-rich extract from red guava has beneficial effect on acute inflammation, offering protection against the consequences of oxidative stress by downregulating inflammatory mediators and inhibiting gene expression involved in inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Effectiveness of physical activity in reducing pain in patients with fibromyalgia: a blinded randomized clinical trial.

    Science.gov (United States)

    Kayo, Andrea Harumi; Peccin, Maria Stella; Sanches, Carla Munhoz; Trevisani, Virgínia Fernandes Moça

    2012-08-01

    The purpose of this study was to evaluate and compare the effectiveness of muscle-strengthening exercises (MS) and a walking program (WA) in reducing pain in patients with fibromyalgia. Ninety women, 30-55 years of age, diagnosed with fibromyalgia according to the American College of Rheumatology 1990 criteria, were randomized into 3 groups: WA Group, MS Group, and control group. Pain (visual analog scale) was evaluated as the primary outcome. Physical functioning (Fibromyalgia Impact Questionnaire, FIQ), health-related quality of life (Short-Form 36 Health Survey, SF-36), and use of medication were evaluated as secondary outcomes. Assessments were performed at baseline, 8, 16, and 28 weeks. Intention-to-treat and efficacy analyses were conducted. Sixty-eight patients completed the treatment protocol. All 3 groups showed improvement after the 16-week treatment compared to baseline. At the 28-week follow-up, pain reduction was similar for the WA and MS groups (P = 0.39), but different from the control group (P = 0.01). At the end of the treatment, 80% of subjects in the control group took pain medication, but only 46.7% in the WA and 41.4% in the MS groups. Mean FIQ total scores were lower for the WA and MS groups (P = 0.96) compared with the control group (P < 0.01). Patients in the WA and MS groups reported higher scores (better health status) than controls in almost all SF-36 subscales. MS was as effective as WA in reducing pain regarding all study variables; however, symptoms management during the follow-up period was more efficient in the WA group.

  12. Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.

    Science.gov (United States)

    Winchester, Wendy J; Gore, Katrina; Glatt, Sophie; Petit, Wendy; Gardiner, Jennifer C; Conlon, Kelly; Postlethwaite, Michael; Saintot, Pierre-Philippe; Roberts, Sonia; Gosset, James R; Matsuura, Tomomi; Andrews, Mark D; Glossop, Paul A; Palmer, Michael J; Clear, Nicola; Collins, Susie; Beaumont, Kevin; Reynolds, David S

    2014-11-01

    The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    Science.gov (United States)

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Comparing the use of Memantine with Dextromethorphan and Placebo to Reduce Pain before Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Mehrdad Taheri

    2017-12-01

    Full Text Available Introduction: To compare the use of Memantine with Dextromethorphan and placebo to reduce pain after orthopedic surgery.Materials and Methods: The present study was a double-blind clinical trial including180 patients undergoing elective orthopedic surgery of the lower limbs. Patients were divided randomly into three groups of 60 patients each. The first group (Group M received 30 mg Memantine orally, the second group (Group D received 45 mg of Dextromethorphan and the third group (Group P received only placebo, two and a half hours before the operation. The intensity of pain (VAS score, sedation score, and nausea and vomiting were recorded postoperatively.Results: In this study, 60 patients were enrolled in each group. The total VAS (Visual Analogue Scale score was significantly lower among patients receiving Memantine and the satisfaction was significantly higher compared to the Dextromethorphan and placebo groups (P-value <0.001.Conclusion: The present study results indicate that Memantine has a relatively better outcome compared to Dextromethorphan or placebo in reducing the post surgical pain among patients undergoing orthopedic surgeries. It also reduced the need for post surgical opioid use and improved the patients’ satisfaction.  

  15. 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

  16. Synergism between fentanyl and tramadol in tonic inflammatory pain: the orofacial formalin test.

    Science.gov (United States)

    Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

    2012-06-01

    Opioids have been used for long time to management of pain, the coadministration of two opioids may induce synergism. The present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent cutaneous nociception in the region innervated by the trigeminal nerve. The i.p. administration of tramadol and fentanyl induced a dose-dependent antinociception with an ED(50) of 2.97 ± 0.32 mg/kg for phase I and 1.79 ± 0.30 mg/kg for phase II and 0.062 ± 0.0040 mg/kg in phase I and 0.041 ± 0.0039 mg/kg in phase II, respectively. The coadministration of fentanyl with tramadol induced synergism in both phases of the test with an interaction index of 0.343 and 0.163 for phase I and phase II, respectively. This finding could be explained by the more complex pharmacology of tramadol compared to fentanyl.

  17. A performance improvement prescribing guideline reduces opioid prescriptions for emergency department dental pain patients.

    Science.gov (United States)

    Fox, Timothy R; Li, James; Stevens, Sandra; Tippie, Tracy

    2013-09-01

    In an effort to reduce prescription opioid abuse originating from our institution, we implement and measure the effect of a prescribing guideline on the rate of emergency department (ED) opioid prescriptions written for patients presenting with dental pain, a complaint previously associated with drug-seeking behavior. After implementing a departmental guideline on controlled substance prescriptions, we performed a structured before-and-after chart review of dental pain patients aged 16 and older. Before the guideline, the rate of opioid prescription was 59% (302/515). After implementation, the rate was 42% (65/153). The absolute decrease in rates was 17% (95% confidence interval 7% to 25%). Additionally, in comparing the 12-month period before and after implementation, the dental pain visit rate decreased from 26 to 21 per 1,000 ED visits (95% confidence interval of decrease 2 to 9 visits/1,000). A performance improvement program involving a departmental prescribing guideline was associated with a reduction in the rate of opioid prescriptions and visits for ED patients presenting with dental pain. Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jae Goo Kim

    2014-06-01

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

  19. A study of ′cough trick′ technique in reducing vaccination prick pain in adolescents

    Directory of Open Access Journals (Sweden)

    Vikram S. Kumar

    2014-01-01

    Full Text Available Background: The ′cough trick′ (CT technique is used in reducing intramuscular prick (IMP pain during vaccinations and also for brief painful procedures like subcutaneous injection, intravenous cannulation, and so forth. We present the utility study of this technique in male adolescents. Materials and Methods: A Randomized Crossover Volunteer Study of 50 early adolescent male children (age 11-13 receiving immunizations was performed. Participants were recruited from four outpatient pediatric clinics. The strategy required a single "warm-up" cough of moderate force, followed by a second cough that coincided with needle puncture. The principle outcome was self-reported pain. Results: Paired ′t′ test revealed that the procedure was effective at a statistically and clinically significant level for participants. Children found the procedure acceptable and effective. Conclusions: The results of this study suggest that the CT can be an effective strategy for the reduction of pain for male adolescent children undergoing routine immunizations. However, additional research is needed with a larger sample size with different age groups and also including girl children.

  20. Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2014-01-01

    Full Text Available Background. Ischemia/reperfusion (I/R injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation. ROS/inflammatory cytokines are involved in I/R injury. 2-Methoxyestradiol (2ME2, an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent. We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions. Methods. BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg or vehicle 12 h before and immediately after renal I/R experiments. The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury. The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF α, caspase-3, hypoxia inducible factor- (HIF 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3 in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB, BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting. In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS production and cell viability in antimycin-A-treated renal mesangial (RMC and tubular (NRK52E cells. Results. Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice. Survival in I/R+2ME2-treated mice was higher than in I/R mice. Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue. Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury. In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin

  1. 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...

  2. 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.

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

    Science.gov (United States)

    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

  4. 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

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

    Science.gov (United States)

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

    2015-09-01

    Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of

  6. Reducing inappropriate non-steroidal anti-inflammatory prescription in primary care patients with chronic kidney disease.

    Science.gov (United States)

    Keohane, David M; Dennehy, Thomas; Keohane, Kenneth P; Shanahan, Eamonn

    2017-08-14

    Purpose The purpose of this paper is to reduce inappropriate non-steroidal anti-inflammatory prescribing in primary care patients with chronic kidney disease (CKD). Once diagnosed, CKD management involves delaying progression to end stage renal failure and preventing complications. It is well established that non-steroidal anti-inflammatories have a negative effect on kidney function and consequently, all nephrology consensus groups suggest avoiding this drug class in CKD. Design/methodology/approach The sampling criteria included all practice patients with a known CKD risk factor. This group was refined to include those with an estimated glomerular filtration rate (eGFR)<60 ml/min per 1.73m2 (stage 3 CKD or greater). Phase one analysed how many prescriptions had occurred in this group over the preceding three months. The intervention involved creating an automated alert on at risk patient records if non-steroidal anti-inflammatories were prescribed and discussing the rationale with practice staff. The re-audit phase occurred three months' post intervention. Findings The study revealed 728/7,500 (9.7 per cent) patients at risk from CKD and 158 (2.1 per cent) who were subsequently found to have an eGFR<60 ml/min, indicating=stage 3 CKD. In phase one, 10.2 per cent of at risk patients had received a non-steroidal anti-inflammatory prescription in the preceding three months. Additionally, 6.2 per cent had received non-steroidal anti-inflammatories on repeat prescription. Phase two post intervention revealed a significant 75 per cent reduction in the total non-steroidal anti-inflammatories prescribed and a 90 per cent reduction in repeat non-steroidal anti-inflammatory prescriptions in those with CKD. Originality/value The study significantly reduced non-steroidal anti-inflammatory prescription in those with CKD in primary care settings. It also created a CKD register within the practice and an enduring medication alert system for individuals that risk nephrotoxic

  7. Innovative Technology Using Virtual Reality in the Treatment of Pain: Does It Reduce Pain via Distraction, or Is There More to It?

    Science.gov (United States)

    Gupta, Anita; Scott, Kevin; Dukewich, Matthew

    2018-01-01

    Virtual reality (VR) is an exciting new technology with almost endless possible uses in medicine. One area it has shown promise is pain management. This selective review focused on studies that gave evidence to the distraction or nondistraction mechanisms by which VR leads to the treatment of pain. The review looked at articles from 2000 to July 29, 2016, focusing on studies concerning mechanisms by which virtual reality can augment pain relief. The data was collected through a search of MEDLINE and Web of Science using the key words of "virtual reality" and "pain" or "distraction." Six studies were identified: four small randomized controlled studies and two prospective/pilot studies. The search results provided evidence that distraction is a technique by which VR can have benefits in the treatment of pain. Both adult and pediatric populations were included in these studies. In addition to acute pain, several studies looked at chronic pain states such as headaches or fibromyalgia. These studies also combined VR with other treatment modalities such as biofeedback mechanisms and cognitive behavioral therapy. These results demonstrate that in addition to distraction, there are novel mechanisms for VR treatment in pain, such as producing neurophysiologic changes related to conditioning and exposure therapies. If these new mechanisms can lead to new treatment options for patients with chronic pain, VR may have the ability to help reduce opioid use and misuse among chronic pain patients. More studies are needed to reproduce results from prospective/pilot studies in large randomized control studies. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  8. Xiaozhi decoction reduced posthemorrhoidectomy pain and analgesic medication consumption: a prospective study

    Directory of Open Access Journals (Sweden)

    Shen JB

    2017-01-01

    : XZD could effectively relieve postoperative pain and reduce analgesic medication consumption after hemorrhoidectomy. Keywords: hemorrhoids, hemorrhoidectomy, traditional Chinese medicine, posthemorrhoidectomy pain 

  9. 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.

  10. Abdominal binders may reduce pain and improve physical function after major abdominal surgery - a systematic review

    DEFF Research Database (Denmark)

    Rothman, Josephine Philip; Gunnarsson, Ulf; Bisgaard, Thue

    2014-01-01

    INTRODUCTION: Evidence for the effect of post-operative abdominal binders on post-operative pain, seroma formation, physical function, pulmonary function and increased intra-abdominal pressure among patients after surgery remains largely un-investigated. METHODS: A systematic review was conducted...... formation and physical function. RESULTS: A total of 50 publications were identified; 42 publications were excluded leaving eight publications counting a total of 578 patients for analysis. Generally, the scientific quality of the studies was poor. Use of abdominal binder revealed a non-significant tendency...... to reduce seroma formation after laparoscopic ventral herniotomy and a non-significant reduction in pain. Physical function was improved, whereas evidence supports a beneficial effect on psychological distress after open abdominal surgery. Evidence also supports that intra-abdominal pressure increases...

  11. Rosiglitazone Reduces Plasma Levels of Inflammatory and Hemostatic Biomarkers and Improves Global Endothelial Function in Habitual Heavy Smokers Without Diabetes Mellitus or Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    I-Chih Chen

    2010-02-01

    Conclusion: Rosiglitazone significantly reduces plasma levels of inflammatory and hemostatic biomarkers, and restores global endothelial dysfunction, independently from insulin sensitization, in healthy smokers.

  12. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis.

    Science.gov (United States)

    Dohnert, Marcelo B; Venâncio, Mirelli; Possato, Jonathann C; Zeferino, Rodrigo C; Dohnert, Luciana H; Zugno, Alexandra I; De Souza, Cláudio T; Paula, Marcos M S; Luciano, Thais F

    2012-01-01

    Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP) have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis. Wistar rats were divided in three treatment groups (n = 15): (1) iontophoresis + diclofenac diethylammonium; (2) iontophoresis + GNP; and (3) iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15). Iontophoresis was administered using 0.3 mA direct current on 1.5 cm(2) electrodes. The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha), which confirms the occurrence of an inflammatory stage in injury (P diclofenac and GNP, results were similar to the control (1.732 ± 239) (P diclofenac and GNPs presented decreased levels, compared with the control (3.221 ± 369) (P < 0.05). The results show the efficacy of drug administration using direct current to treat tendinitis in an animal model, and the potential anti-inflammatory, carrier, and enhancing effects of GNPs in iontophoresis.

  13. Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

    Science.gov (United States)

    Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

    2018-02-05

    Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

  14. Equipment-based Pilates reduces work-related chronic low back pain and disability: A pilot study.

    Science.gov (United States)

    Stieglitz, Dana Duval; Vinson, David R; Hampton, Michelle De Coux

    2016-01-01

    This study investigated effectiveness of an equipment-based Pilates protocol for reducing pain and disability in individuals with work-related chronic low back pain (CLBP). Twelve workers with non-specific CLBP participated in a quasi-experimental, one-group, pretest-posttest pilot study of supervised 6-week equipment-based Pilates exercise. Pain severity was assessed using a 100-mm visual analog scale (VAS). Physical function was assessed using the Oswestry disability index (ODI). The Pilates intervention significantly reduced pain (mean decrease in VAS 30.75 ± 20.27, p Pilates exercise reduced pain and disability in workers with CLBP. Further research is needed to investigate Pilates exercise for rehabilitation of work-related injuries in large populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. [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.

  16. Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and Inflammatory Response: A Randomized Controlled Trial.

    Science.gov (United States)

    Zeng, Wei-Nan; Liu, Jun-Li; Wang, Fu-You; Chen, Cheng; Zhou, Qiang; Yang, Liu

    2018-02-21

    The reductions of perioperative blood loss and inflammatory response are important in total knee arthroplasty. Tranexamic acid reduced blood loss and the inflammatory response in several studies. However, the effect of epinephrine administration plus tranexamic acid has not been intensively investigated, to our knowledge. In this study, we evaluated whether the combined administration of low-dose epinephrine plus tranexamic acid reduced perioperative blood loss or inflammatory response further compared with tranexamic acid alone. This randomized placebo-controlled trial consisted of 179 consecutive patients who underwent primary total knee arthroplasty. Patients were randomized into 3 interventions: Group IV received intravenous low-dose epinephrine plus tranexamic acid, Group TP received topical diluted epinephrine plus tranexamic acid, and Group CT received tranexamic acid alone. The primary outcome was perioperative blood loss on postoperative day 1. Secondary outcomes included perioperative blood loss on postoperative day 3, coagulation and fibrinolysis parameters (measured by thromboelastography), inflammatory cytokine levels, transfusion values (rate and volume), thromboembolic complications, length of hospital stay, wound score, range of motion, and Hospital for Special Surgery (HSS) score. The mean calculated total blood loss (and standard deviation) in Group IV was 348.1 ± 158.2 mL on postoperative day 1 and 458.0 ± 183.4 mL on postoperative day 3, which were significantly reduced (p 0.05). The combined administration of low-dose epinephrine and tranexamic acid demonstrated an increased effect in reducing perioperative blood loss and the inflammatory response compared with tranexamic acid alone, with no apparent increased incidence of thromboembolic and other complications. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

  17. Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial.

    Science.gov (United States)

    Bertrand, Helene; Kyriazis, Marylene; Reeves, K Dean; Lyftogt, John; Rabago, David

    2015-11-01

    Capsaicin specifically activates, and then gradually exhausts, the transient receptor potential vanilloid type 1 (TRPV1) receptor, a key receptor in neuropathic pain. Activation of the TRPV-1 receptor is accompanied by burning pain. A natural substance or medication that can reduce the burning pain resulting from capsaicin application may have therapeutic potential in neuropathic pain. To assess the pain-relieving effects of a mannitol-containing cream in a capsaicin-based pain model. Randomized, placebo-controlled, double-blind clinical trial. Outpatient pain clinic. Twenty-five adults with pain-free lips. Capsaicin .075% cream was applied to both halves of each participant's upper lip, inducing pain via stimulation of the transient receptor potential vanilloid 1 (TRPV1, capsaicin) receptor, then removed after 5 minutes or when participants reported a burning pain of 8/10, whichever came first. A cream containing mannitol and the same cream without mannitol (control) were then immediately applied, 1 on each side of the lip, in an allocation-masked manner. Participants self-recorded a numeric rating scale (NRS, 0-10) pain score for each side of the lip per minute for 10 minutes. A t-test was performed to evaluate the pain score change from baseline between each side of the lip at each recording. Area under the curve (AUC) analysis was used to determine the overall difference between groups. Participants reached a capsaicin-induced pain level of 7.8 ± 1.0 points in 3.3 ± 1.6 minutes that was equal on both sides of the lip. Both groups reported progressive diminution of pain over the 10-minute study period. However, participants reported significantly reduced pain scores on the mannitol cream half-lip compared to control at 3 through 10 minutes (P < .05) and in AUC analysis (P < .001). Mannitol cream reduced self-reported pain scores in a capsaicin pain model more rapidly than a control cream, potentially via a TRPV1 receptor effect. Copyright © 2015 American

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Piracetam for reducing the incidence of painful sickle cell disease crises.

    Science.gov (United States)

    Al Hajeri, Amani; Fedorowicz, Zbys

    2016-02-12

    Sickle cell disease is one of the most common genetic disorders. Sickle cell crises in which irregular and dehydrated cells contribute to blocking of blood vessels are characterised by episodes of pain. Treatment is mainly supportive and symptomatic. In vitro studies with piracetam indicate that it has the potential for inhibition and a reversal of the process of sickling of erythrocytes. This is an update of a previously published Cochrane review. To assess the effectiveness of piracetam for reducing the incidence of painful sickle cell disease crises. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Last search of the Group's Haemoglobinopathies Trials Register: 21 September 2015. Randomised controlled trials comparing orally administered piracetam to placebo or standard care in people, of all ages and both sexes, with sickle cell disease. Two authors independently assessed trial quality and extracted data. Trial authors were contacted for additional information. Adverse effects data were collected from the trials. Three trials involving 169 participants were included in the review. A limited amount of data addressing some of the primary and some of the secondary outcomes were provided, but data were incomplete and based on un-validated assumptions used in the evaluation of outcomes. One trial reported a reduction in the number of pain crises and their severity with active intervention than placebo but presented no data to confirm these results. A second trial presented a monthly global pain score based on the number of sickle cell crises and severity of pain but included no separate data for these primary outcomes. Although there was no significant difference between the piracetam and placebo periods for the number of days of

  3. The effects of compensatory workplace exercises to reduce work-related stress and musculoskeletal pain

    Directory of Open Access Journals (Sweden)

    Fabiana Cristina Taubert de Freitas-Swerts

    2014-08-01

    Full Text Available OBJECTIVES: to assess the effect of a compensatory workplace exercise program on workers with the purpose of reducing work-related stress and musculoskeletal pain.METHOD: quasi-experimental research with quantitative analysis of the data, involving 30 administrative workers from a Higher Education Public Institution. For data collection, questionnaires were used to characterize the workers, as well as the Workplace Stress Scale and the Corlett Diagram. The research took place in three stages: first: pre-test with the application of the questionnaires to the subjects; second: Workplace Exercise taking place twice a week, for 15 minutes, during a period of 10 weeks; third: post-test in which the subjects answered the questionnaires again. For data analysis, the descriptive statistics and non-parametric statistics were used through the Wilcoxon Test.RESULTS: work-related stress was present in the assessed workers, but there was no statistically significant reduction in the scores after undergoing Workplace Exercise. However, there was a statistically significant pain reduction in the neck, cervical, upper, middle and lower back, right thigh, left leg, right ankle and feet.CONCLUSION: the Workplace Exercise promoted a significant pain reduction in the spine, but did not result in a significant reduction in the levels of work-related stress.

  4. Reducing risk of spinal haematoma from spinal and epidural pain procedures.

    Science.gov (United States)

    Breivik, Harald; Norum, Hilde; Fenger-Eriksen, Christian; Alahuhta, Seppo; Vigfússon, Gísli; Thomas, Owain; Lagerkranser, Michael

    2018-04-25

    Central neuraxial blocks (CNB: epidural, spinal and their combinations) and other spinal pain procedures can cause serious harm to the spinal cord in patients on antihaemostatic drugs or who have other risk-factors for bleeding in the spinal canal. The purpose of this narrative review is to provide a practise advisory on how to reduce risk of spinal cord injury from spinal haematoma (SH) during CNBs and other spinal pain procedures. Scandinavian guidelines from 2010 are part of the background for this practise advisory. We searched recent guidelines, PubMed (MEDLINE), SCOPUS and EMBASE for new and relevant randomised controlled trials (RCT), case-reports and original articles concerning benefits of neuraxial blocks, risks of SH due to anti-haemostatic drugs, patient-related risk factors, especially renal impairment with delayed excretion of antihaemostatic drugs, and specific risk factors related to the neuraxial pain procedures. Epidural and spinal analgesic techniques, as well as their combination provide superior analgesia and reduce the risk of postoperative and obstetric morbidity and mortality. Spinal pain procedure can be highly effective for cancer patients, less so for chronic non-cancer patients. We did not identify any RCT with SH as outcome. We evaluated risks and recommend precautions for SH when patients are treated with antiplatelet, anticoagulant, or fibrinolytic drugs, when patients' comorbidities may increase risks, and when procedure-specific risk factors are present. Inserting and withdrawing epidural catheters appear to have similar risks for initiating a SH. Invasive neuraxial pain procedures, e.g. spinal cord stimulation, have higher risks of bleeding than traditional neuraxial blocks. We recommend robust monitoring routines and treatment protocol to ensure early diagnosis and effective treatment of SH should this rare but potentially serious complication occur. When neuraxial analgesia is considered for a patient on anti

  5. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain.

    Science.gov (United States)

    Ragavendran, J Vaigunda; Laferrière, André; Xiao, Wen Hua; Bennett, Gary J; Padi, Satyanarayana S V; Zhang, Ji; Coderre, Terence J

    2013-01-01

    Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle, or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α(2)-adrenergic (α(2)A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent antiallodynic effects in rats with chronic postischemia pain, and the antiallodynic dose-response curves of PDE and PA inhibitors were shifted 2.5- to 10-fold leftward when combined with nonanalgesic doses of α(2)A receptor agonists or NO donors. Topical combinations also produced significant antiallodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 hours after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α(2)A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain. This article presents the synergistic antiallodynic effects of combinations of α(2)A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest that effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected

  6. 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.

  7. Does physical exercise reduce excessive daytime sleepiness by improving inflammatory profiles in obstructive sleep apnea patients?

    Science.gov (United States)

    Alves, Eduardo da Silva; Ackel-D'Elia, Carolina; Luz, Gabriela Pontes; Cunha, Thays Crosara Abrahão; Carneiro, Gláucia; Tufik, Sergio; Bittencourt, Lia Rita Azeredo; de Mello, Marco Tulio

    2013-05-01

    Obstructive sleep apnea syndrome (OSAS) is associated with a variety of long-term consequences such as high rates of morbidity and mortality, due to excessive diurnal somnolence as well as cardiovascular and metabolic diseases. Obesity, recurrent episodes of upper airway obstruction, progressive hypoxemia, and sleep fragmentation during sleep cause neural, cardiovascular, and metabolic changes. These changes include activation of peripheral sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, insulin sensitivity, and inflammatory cytokines alterations, which predispose an individual to vascular damage. Previous studies proposed that OSAS modulated the expression and secretion of inflammatory cytokines from fat and other tissues. Independent of obesity, patients with OSAS exhibited elevated levels of C-reactive protein, tumor necrosis factor-α and interleukin-6, which are associated with sleepiness, fatigue, and the development of a variety of metabolic and cardiovascular diseases. OSAS and obesity are strongly associated with each other and share many common pathways that induce chronic inflammation. Previous studies suggested that the protective effect of exercise may be partially attributed to the anti-inflammatory effect of regular exercise, and this effect was observed in obese patients. Although some studies assessed the effects of physical exercise on objective and subjective sleep parameters, the quality of life, and mood in patients with OSAS, no study has evaluated the effects of this treatment on inflammatory profiles. In this review, we cited some studies that directed our opinion to believe that since OSAS causes increased inflammation and has excessive daytime sleepiness as a symptom and being that physical exercise improves inflammatory profiles and possibly OSAS symptoms, it must be that physical exercise improves excessive daytime sleepiness due to its improvement in inflammatory profiles.

  8. AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis

    Science.gov (United States)

    Bonnet, Cleo S; Williams, Anwen S; Gilbert, Sophie J; Harvey, Ann K; Evans, Bronwen A; Mason, Deborah J

    2015-01-01

    Objectives Synovial fluid glutamate concentrations increase in arthritis. Activation of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6 (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA and KA GluRs are expressed in human arthritis, and that intra-articular NBQX (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced arthritis (AIA). Methods GluR immunohistochemistry was related to synovial inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). A single intra-articular NBQX injection was given at induction, and knee swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging, RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human primary osteoblast (HOB) activity were determined. Results AMPAR2 and KA1 immunolocalised to remodelling bone, cartilage and synovial cells in human OA and RA, and rat AIA. All arthritic tissues showed degradation and synovial inflammation. NBQX reduced GluR abundance, knee swelling (parthritis. PMID:24130267

  9. Alpha-, gamma- and delta-tocopherols reduce inflammatory angiogenesis in human microvascular endothelial cells.

    Science.gov (United States)

    Wells, Shannon R; Jennings, Merilyn H; Rome, Courtney; Hadjivassiliou, Vicky; Papas, Konstantinos A; Alexander, Jonathon S

    2010-07-01

    Vitamin E, a micronutrient (comprising alpha-, beta-, gamma- and delta-tocopherols, alpha-, beta-, gamma- and delta-tocotrienols), has documented antioxidant and non-antioxidant effects, some of which inhibit inflammation and angiogenesis. We compared the abilities of alpha-, gamma- and delta-tocopherols to regulate human blood cytotoxicity (BEC) and lymphatic endothelial cytotoxicity (LEC), proliferation, invasiveness, permeability, capillary formation and suppression of TNF-alpha-induced VCAM-1 as in vitro models of inflammatory angiogenesis. alpha-, gamma- and delta-tocopherols were not toxic to either cell type up to 40 microM. In BEC, confluent cell density was decreased by all concentrations of delta- and gamma-tocopherol (10-40 microM) but not by alpha-tocopherol. LEC showed no change in cell density in response to tocopherols. delta-Tocopherol (40 microM), but not other isomers, decreased BEC invasiveness. In LEC, all doses of gamma-tocopherol, as well as the highest dose of alpha-tocopherol (40 microM), decreased cell invasiveness. delta-Tocopherol had no effect on LEC invasiveness at any molarity. delta-Tocopherol dose dependently increased cell permeability at 48 h in BEC and LEC; alpha- and gamma-tocopherols showed slight effects. Capillary tube formation was decreased by high dose (40 microM) concentrations of alpha-, gamma- and delta-tocopherol, but showed no effects with smaller doses (10-20 microM) in BEC. gamma-Tocopherol (10-20 microM) and alpha-tocopherol (10 microM), but not delta-tocopherol, increased LEC capillary tube formation. Lastly, in BEC, alpha-, gamma- and delta-tocopherol each dose-dependently reduced TNF-alpha-induced expression of VCAM-1. In LEC, there was no significant change to TNF-alpha-induced VCAM-1 expression with any concentration of alpha-, gamma- or delta-tocopherol. These data demonstrate that physiological levels (0-40 microM) of alpha-, gamma- and delta-tocopherols are nontoxic and dietary tocopherols, especially delta

  10. Two to five repeated measurements per patient reduced the required sample size considerably in a randomized clinical trial for patients with inflammatory rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Smedslund Geir

    2013-02-01

    Full Text Available Abstract Background Patient reported outcomes are accepted as important outcome measures in rheumatology. The fluctuating symptoms in patients with rheumatic diseases have serious implications for sample size in clinical trials. We estimated the effects of measuring the outcome 1-5 times on the sample size required in a two-armed trial. Findings In a randomized controlled trial that evaluated the effects of a mindfulness-based group intervention for patients with inflammatory arthritis (n=71, the outcome variables Numerical Rating Scales (NRS (pain, fatigue, disease activity, self-care ability, and emotional wellbeing and General Health Questionnaire (GHQ-20 were measured five times before and after the intervention. For each variable we calculated the necessary sample sizes for obtaining 80% power (α=.05 for one up to five measurements. Two, three, and four measures reduced the required sample sizes by 15%, 21%, and 24%, respectively. With three (and five measures, the required sample size per group was reduced from 56 to 39 (32 for the GHQ-20, from 71 to 60 (55 for pain, 96 to 71 (73 for fatigue, 57 to 51 (48 for disease activity, 59 to 44 (45 for self-care, and 47 to 37 (33 for emotional wellbeing. Conclusions Measuring the outcomes five times rather than once reduced the necessary sample size by an average of 27%. When planning a study, researchers should carefully compare the advantages and disadvantages of increasing sample size versus employing three to five repeated measurements in order to obtain the required statistical power.

  11. Short-term exercise training reduces anti-inflammatory action of interleukin-10 in adults with obesity.

    Science.gov (United States)

    Barry, Julianne C; Simtchouk, Svetlana; Durrer, Cody; Jung, Mary E; Mui, Alice L; Little, Jonathan P

    2018-06-06

    A key pathological component of obesity is chronic low-grade inflammation, which is propagated by infiltration of immune cells into tissues and overproduction of pro-inflammatory cytokines. Cytokines that possess anti-inflammatory properties, such as interleukin (IL)-10 and IL6, may also play an important role. This study was designed to determine the impact of short-term exercise on the anti-inflammatory action of IL10 and IL6. Thirty-three inactive obese adults were randomized to two weeks of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). Fasting blood samples were collected before and after training. Lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production was measured in whole blood cultures in the presence or absence of IL10 or IL6. IL10 and IL6 receptor expression were measured on circulating monocytes, neutrophils, and T cells. HIIT and MICT reduced the ability of IL10 to inhibit LPS-induced TNFα production, with a greater effect with HIIT (Group × Time and IL10 × Time interactions, p's  0.05). HIIT and MICT differentially affected IL6 function (Group × Time and IL6 × Time interactions, p's < 0.05) with evidence of reductions in the anti-inflammatory ability of IL6 with HIIT. Neither HIIT nor MICT altered levels of circulating IL10, IL6, or TNFα. The impact of short-term HIIT and MICT resulted in differential effects on anti-inflammatory cytokine function. The clinical implications remain to be determined but these novel findings indicate that measuring anti-inflammatory cytokine action could reveal important immunomodulatory effects of exercise. Copyright © 2018. Published by Elsevier Ltd.

  12. The association between ACE inhibitors and the complex regional pain syndrome: Suggestions for a neuro-inflammatory pathogenesis of CRPS.

    Science.gov (United States)

    de Mos, M; Huygen, F J P M; Stricker, B H Ch; Dieleman, J P; Sturkenboom, M C J M

    2009-04-01

    Antihypertensive drugs interact with mediators that are also involved in complex regional pain syndrome (CRPS), such a neuropeptides, adrenergic receptors, and vascular tone modulators. Therefore, we aimed to study the association between the use of antihypertensive drugs and CRPS onset. We conducted a population-based case-control study in the Integrated Primary Care Information (IPCI) database in the Netherlands. Cases were identified from electronic records (1996-2005) and included if they were confirmed during an expert visit (using IASP criteria), or if they had been diagnosed by a medical specialist. Up to four controls per cases were selected, matched on gender, age, calendar time, and injury. Exposure to angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, beta-blockers, calcium channel blockers, and diuretics was assessed from the automated prescription records. Data were analyzed using multivariate conditional logistic regression. A total of 186 cases were matched to 697 controls (102 confirmed during an expert visit plus 84 with a specialist diagnosis). Current use of ACE inhibitors was associated with an increased risk of CRPS (OR(adjusted): 2.7, 95% CI: 1.1-6.8). The association was stronger if ACE inhibitors were used for a longer time period (OR(adjusted): 3.0, 95% CI: 1.1-8.1) and in higher dosages (OR(adjusted): 4.3, 95% CI: 1.4-13.7). None of the other antihypertensive drug classes was significantly associated with CRPS. We conclude that ACE inhibitor use is associated with CRPS onset and hypothesize that ACE inhibitors influence the neuro-inflammatory mechanisms that underlie CRPS by their interaction with the catabolism of substance P and bradykinin.

  13. Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization

    NARCIS (Netherlands)

    Simons, Peter J.; van den Pangaart, Petra S.; Aerts, Johannes M. F. G.; Boon, Louis

    2007-01-01

    Adiponectin and, especially, its oligomeric complex composition have been suggested to be critical in determining insulin sensitivity. Pro-inflammatory cytokines play an important role in the development of insulin resistance in obesity and associated diseases. Therefore, we investigated the effect

  14. Lactobacilli require physical contact to reduce staphylococcal TSST-1 secretion and vaginal epithelial inflammatory response

    NARCIS (Netherlands)

    Younes, Jessica A.; Reid, Gregor; van der Mei, Henny C.; Busscher, Henk J.

    Staphylococcus aureus biofilms can be found on vaginal epithelia, secreting toxins and causing inflammation. The co-vaginal species Lactobacillus can alter staphylococcal-induced epithelial secretion of inflammatory cytokines and quench staphylococcal toxic shock syndrome toxin-1 secretion. It is

  15. Royal Jelly Inhibits Pseudomonas aeruginosa Adherence and Reduces Excessive Inflammatory Responses in Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Heni Susilowati

    2017-01-01

    Full Text Available Pseudomonas aeruginosa is a Gram-negative bacterium and causes respiratory infection especially in elderly patients. Royal jelly has been used worldwide as a traditional remedy and as a nutrient; however, the effect against P. aeruginosa is unclear. The aim of this study was to analyze antibacterial, antiadherent, and anti-inflammatory effects of royal jelly against P. aeruginosa. Wild-type strain PAO1 and clinical isolates of P. aeruginosa were used for antibacterial assay and antiadherent assay to abiotic surface and epithelial cells, which are pharynx (Detroit 562 and lung (NCI-H292 epithelial cells. In anti-inflammatory assay, epithelial cells were pretreated with royal jelly before bacterial exposure to investigate its inhibitory effect on interleukin (IL-8 and macrophage inflammatory protein-3α/CCL20 overproduction. Although royal jelly did not have antibacterial activity at concentration of 50% w/v, antiadherent activity was confirmed on the abiotic surface and epithelial cells under concentration of 25%. Pretreatment with royal jelly significantly inhibited overproduction of IL-8 and CCL20 from both cells. These results demonstrated that royal jelly inhibits P. aeruginosa adherence and protects epithelial cells from excessive inflammatory responses against P. aeruginosa infection. Our findings suggested that royal jelly may be a useful supplement as complementary and alternative medicine for preventing respiratory infection caused by P. aeruginosa.

  16. 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.

  17. Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis.

    Science.gov (United States)

    Sagar, Devi Rani; Ashraf, Sadaf; Xu, Luting; Burston, James J; Menhinick, Matthew R; Poulter, Caroline L; Bennett, Andrew J; Walsh, David A; Chapman, Victoria

    2014-08-01

    Increased subchondral bone turnover may contribute to pain in osteoarthritis (OA). To investigate the analgesic potential of a modified version of osteoprotegerin (osteoprotegerin-Fc (OPG-Fc)) in the monosodium iodoacetate (MIA) model of OA pain. Male Sprague Dawley rats (140-260 g) were treated with either OPG-Fc (3 mg/kg, subcutaneously) or vehicle (phosphate-buffered saline) between days 1 and 27 (pre-emptive treatment) or days 21 and 27 (therapeutic treatment) after an intra-articular injection of MIA (1 mg/50 µl) or saline. A separate cohort of rats received the bisphosphonate zoledronate (100 µg/kg, subcutaneously) between days 1 and 25 post-MIA injection. Incapacitance testing and von Frey (1-15 g) hind paw withdrawal thresholds were used to assess pain behaviour. At the end of the study, rats were killed and the knee joints and spinal cord removed for analysis. Immunohistochemical studies using Iba-1 and GFAP quantified levels of activation of spinal microglia and astrocytes, respectively. Joint sections were stained with haematoxylin and eosin or Safranin-O fast green and scored for matrix proteoglycan and overall joint morphology. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts were quantified. N=10 rats/group. Pre-emptive treatment with OPG-Fc significantly attenuated the development of MIA-induced changes in weightbearing, but not allodynia. OPG-Fc decreased osteoclast number, inhibited the formation of osteophytes and improved structural pathology within the joint similarly to the decrease seen after pretreatment with the bisphosphonate, zoledronate. Therapeutic treatment with OPG-Fc decreased pain behaviour, but did not improve pathology in rats with established joint damage. Our data suggest that early targeting of osteoclasts may reduce pain associated with OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Pulsed Dose Radiofrequency Before Ablation of Medial Branch of the Lumbar Dorsal Ramus for Zygapophyseal Joint Pain Reduces Post-procedural Pain.

    Science.gov (United States)

    Arsanious, David; Gage, Emmanuel; Koning, Jonathon; Sarhan, Mazin; Chaiban, Gassan; Almualim, Mohammed; Atallah, Joseph

    2016-01-01

    center. The procedures were exclusively performed using one model of radiofrequency generator, at one setting for the PDRF and RFA. The difference in the number of levels of ablation was not considered in the analysis of the results. Treating patients with pulsed dose radiofrequency prior to continuous thermal radiofrequency ablation can provide patients with less post-procedural pain during the first 24 hours and also reduce analgesic requirements. Furthermore, the addition of PDRF to standard thermal RFA did not prolong the time of standard thermal radiofrequency ablation procedures, as it was performed during the typically allotted time for local anesthetic action. Low back pain, facet joint disease, medial branch block, Radiofrequency ablation, thermal radiofrequency, pulsed dose radiofrequency, PDRF, zygapophyseal joint.

  19. Fluoxetine ameliorates atopic dermatitis-like skin lesions in BALB/c mice through reducing psychological stress and inflammatory response

    Directory of Open Access Journals (Sweden)

    Yanxi Li

    2016-09-01

    Full Text Available Atopic dermatitis (AD is a common chronic inflammatory skin disorder, and patients with AD suffer from severe psychological stress, which markedly increases the prevalence rate of depression and anxiety disorders in later life. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been reported to exert anti-inflammatory and immunosuppressive effects. However, it is unclear whether fluoxetine is effective in the treatment of AD through reducing psychological stress and inflammatory reaction. Here, we reported that a BALB/c mouse model of AD was induced by application of 2,4‑dinitrochlorobenzene (DNCB onto hairless dorsal skin. Chronic fluoxetine treatment (10 mg/kg per day, i.p. significantly attenuated AD-like symptoms, as reflected by a dramatic decrease in scratching bouts, as well as a decrease in anxiety- and depressive-like behaviors. Furthermore, these behavioral changes were accompanied by a significant decrease in epidermal thickness, the number of mast cells in skin tissue, mRNA levels of interleukin-4 (IL-4 and IL-13 in the spleen, as well as serum immunoglobulin E (IgE in the DNCB-treated mice by treatment with fluoxetine. Taken together, these results indicate that fluoxetine may suppress psychological stress and inflammatory response during AD development, and subsequently ameliorate AD symptoms, suggesting that fluoxetine may be a potential therapeutic agent against AD in clinic.

  20. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis

    Directory of Open Access Journals (Sweden)

    Dohnert MB

    2012-03-01

    Full Text Available Marcelo B Dohnert1,2, Mirelli Venâncio1, Jonathann C Possato1, Rodrigo C Zeferino1, Luciana H Dohnert2, Alexandra I Zugno1, Cláudio T De Souza1, Marcos MS Paula1, Thais F Luciano11Postgraduation Program in Health Sciences, Programa de Pós-graduação em Ciências da Saúde PPGCS, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, 2Department of Physiotherapy, Universidade Luterana do Brasil, Torres, Rio Grande do Sul, BrazilIntroduction: Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. Purpose: This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis.Methods: Wistar rats were divided in three treatment groups (n = 15: (1 iontophoresis + diclofenac diethylammonium; (2 iontophoresis + GNP; and (3 iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15. Iontophoresis was administered using 0.3 mA direct current on 1.5 cm² electrodes. Results: The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha, which confirms the occurrence of an inflammatory stage in injury (P < 0.05. A significant decrease was observed in expression of cytokines interleukin 1 beta in the three treatment groups, in comparison with untreated challenged tendons, although, in the group treated with diclofenac and GNP, results were similar to the control (1.732 ± 239 (P < 0

  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. Biosorbable poly-L-lactide rib-connecting pins may reduce acute pain after thoracotomy.

    Science.gov (United States)

    Iwasaki, A; Hamatake, D; Shirakusa, T

    2004-02-01

    Conventional thoracotomy is currently used as a standard procedure, and is often required to treat numerous diseases. Additionally, rib resections are occasionally required to maintain an adequate field of view for surgery. The benefits of using rib pins for chest closure following such procedures have not yet been established. This study sought to evaluate the usefulness of rib pins in reducing acute postoperative pain. Thirty-three consecutive patients with lung cancer underwent lobectomies using the posterolateral approach. The patients were rib-resected and reconstructed with two techniques: 21 patients with absorbable rib pins (ARP group) and 12 patients by ligation with absorbable sutures (LAS group). Intensity of pain was assessed during the 3 days immediately following surgery. The two groups were assessed using the visual analogue scale (VAS) as a pain scale, amounts consumed of patient-controlled analgesics (PCA), and additional chest x-rays. On the first day following surgery, the mean VAS intensity of the ARP group for patient motion was 2.71 +/- 2.14, compared to 5.33 +/- 2.99 in the LAS group. After three days, the mean score for the ARP group was 1.98 +/- 1.89, compared to 4.60 +/- 1.97 in the LAS group. Scores in the ARP group were significantly lower than in the LAS group one day and three days following thoracotomy. The LAS group (55.0 +/- 15.9 times) made more frequent requests than the ARP group (16.1 +/- 10.3 times). The PCA requirement was also significantly lower in the ARP group. Excessive derangement of the rib (grade 2) was found in one case (4.7 %) in the ARP group compared to five cases (41.6 %) in the LAS group. Rib shifts were seen in numerous cases in the LAS group compared to the ARP group as measured by chest x-rays. Use of absorbable rib pins reduced postoperative pain and may improve long-term prospects for the post-thoracotomy course.

  3. Comparison of relaxation with counterpressure massage techniques for reduce pain first stage of labor

    Science.gov (United States)

    Lisa, U. F.; Jalina, M.; Marniati

    2017-09-01

    Based on interviews of so me mother who entered the first stage of labor lack of care from health workers to the effort to reducing the acuteof labor. Health care workers appertain hospital in effective in implement maternity nursing interventions in reducing acute the first stage of labor. The reducing acute have two method are pharmacological and non-pharmacological. In this case, has several techniques there are: relaxation and counterpressure massage techniques that capable to reducing acute first stage of labor. The of non-pharmacological is one of authority which must be implemented by midwives especially breathing relaxation techniquesand massage. The research is Quasi Exsperimen with pretes-posttest design. The statistic test has T test paired and unpairedt test. To indicatea reducing the level of acute before and after given relaxation technique result p-value pain. Therefore, the health of workers, especially for a study to apply relaxation and massage to provide of mother care, mainly to the primigravida who in experienced in process of labor.

  4. Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Zivkovic AR

    2016-11-01

    Full Text Available Aleksandar R Zivkovic, Jochen Bender, Thorsten Brenner, Stefan Hofer,* Karsten Schmidt* Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany *These authors contributed equally to this work Purpose: Early diagnosis of systemic inflammatory response syndrome is fundamentally important for an effective and a goal-directed therapy. Various inflammation biomarkers have been used in clinical and experimental practice. However, a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. Acetylcholine (Ach has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase [BChE] is the major Ach hydrolyzing enzyme in blood. The role of this enzyme during inflammation has not yet been fully understood. This study tests whether a reduction in the BChE activity could indicate the onset of the systemic inflammatory response upon traumatic injury. Patients and methods: This observational study measured BChE activity in patients with traumatic injury admitted to the emergency room by using point-of-care-test system (POCT. In addition, the levels of routine inflammation biomarkers during the initial treatment period were measured. Injury Severity Score was used to assess the trauma severity. Results: Altered BChE activity was correlated with trauma severity, resulting in systemic inflammation. Reduction in the BChE activity was detected significantly earlier compared to those of routinely measured inflammatory biomarkers. Conclusion: This study suggests that the BChE activity reduction might serve as an early indicator of acute systemic inflammation. Furthermore, BChE activity, measured using a POCT system, might play an important role in the early diagnosis of the trauma-induced systemic inflammation. Keywords: trauma, injury, early diagnostics, cholinergic, pseudocholinesterase, SIRS

  5. High Intensity Interval Training Reduces the Levels of Serum Inflammatory Cytokine on Women with Metabolic Syndrome.

    Science.gov (United States)

    Steckling, F M; Farinha, J B; Santos, D L D; Bresciani, G; Mortari, J A; Stefanello, S T; Courtes, A A; Duarte, T; Duarte, M M M F; Moresco, R N; Cardoso, M S; Soares, F A A

    2016-11-01

    Objectives: This study investigate the effects of a high intensity interval training (HIIT) and 2 weeks of detraining in functional and body composition parameters, lipoproteins, glucose metabolismand inflammation markers in postmenopausal women with metabolic syndrome (MS). Design: 17 untrained women with MS underwent a HIIT program for 12 weeks. Methods: The training was performed in treadmills, 3 days per week, with intensity ranging from 70-90% of the maximum heart rate (HR max ) and 2 weeks untrained (inactive). Functional and body composition parameters were evaluated before and after the training, while maximal oxygen uptake, lipoprotein and inflammation markers were analyzed before, after training and also in detraining. Results: The HITT program resulted in changesparameters as glucose, HbA1cand NOx after training. In addition, a reduction in pro-inflammatory interleukins and an increase in IL-10 after the HIIT program were found. However, an increase in plasma levels of lipoprotein was found and body composition parameters remain unaltered.Besides, only 2 weeks of detraining are able to revert the effects on inflammatory parameters afforded by the HIIT program. Conclusions: The HIIT program used here positively affected inflammatory profile and other parameters, as glucose, HbA1cand NOx, on postmenopausal women with MS. Moreover, 2 weeks of detraining can reverse the beneficial effects of HIIT program. Our results point out the necessity to aply acontinuous HITT program, in order maintain the benefits detected, to post menopausal women with MS. © Georg Thieme Verlag KG Stuttgart · New York.

  6. PPARgamma agonist curcumin reduces the amyloid-beta-stimulated inflammatory responses in primary astrocytes.

    Science.gov (United States)

    Wang, Hong-Mei; Zhao, Yan-Xin; Zhang, Shi; Liu, Gui-Dong; Kang, Wen-Yan; Tang, Hui-Dong; Ding, Jian-Qing; Chen, Sheng-Di

    2010-01-01

    Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Accumulating data indicate that astrocytes play an important role in the neuroinflammation related to the pathogenesis of AD. It has been shown that microglia and astrocytes are activated in AD brain and amyloid-beta (Abeta) can increase the expression of cyclooxygenase 2 (COX-2), interleukin-1, and interleukin-6. Suppressing the inflammatory response caused by activated astrocytes may help to inhibit the development of AD. Curcumin is a major constituent of the yellow curry spice turmeric and proved to be a potential anti-inflammatory drug in arthritis and colitis. There is a low age-adjusted prevalence of AD in India, a country where turmeric powder is commonly used as a culinary compound. Curcumin has been shown to suppress activated astroglia in amyloid-beta protein precursor transgenic mice. The real mechanism by which curcumin inhibits activated astroglia is poorly understood. Here we report that the expression of COX-2 and glial fibrillary acidic protein were enhanced and that of peroxisome proliferator-activated receptor gamma (PPARgamma) was decreased in Abeta(25-35)-treated astrocytes. In line with these results, nuclear factor-kappaB translocation was increased in the presence of Abeta. All these can be reversed by the pretreatment of curcumin. Furthermore, GW9662, a PPARgamma antagonist, can abolish the anti-inflammatory effect of curcumin. These results show that curcumin might act as a PPARgamma agonist to inhibit the inflammation in Abeta-treated astrocytes.

  7. Cervical flexor muscle training reduces pain, anxiety, and depression levels in patients with chronic neck pain by a clinically important amount: A prospective cohort study.

    Science.gov (United States)

    Nazari, Goris; Bobos, Pavlos; Billis, Evdokia; MacDermid, Joy C

    2018-03-14

    Neck pain is the fourth leading cause of disability in the United States and exerts an important socio-economic burden around the world. The aims of this study were to determine the effectiveness of deep and superficial flexor muscle training in addition to home-based exercises in reducing chronic neck pain and anxiety/depression levels. This was a prospective cohort study. Patients between 18 and 65 years old with chronic neck pain were eligible to participate if they had disability levels at least 5 out of 50 on the Neck Disability Index. Patients were divided into three groups: Group A received deep neck flexor and home-based exercises; Group B received superficial muscle and home-based exercises; and Group C received home-based exercises only. The Numeric Pain Rating Scale (NPRS), Neck Disability Index, and Hospital Anxiety and Depression Scale were administered at baseline and 7 weeks later. The highest improvements in pain intensity levels were observed in Group A with 4.75 (1.74) NPRS points, and the lowest were in Group C with 1.00 (1.10). The highest reductions in anxiety and depression levels were noted in Group A (2.80) and Group B (1.65), respectively. The highest improvements in pain intensity levels were observed among Groups A versus C with 2.80 (0.52) NPRS. The highest reductions in anxiety and depression levels were noted among Groups A versus C with 1.75 (1.10) points and Groups B versus C with 1.60 (0.90) points, respectively. Deep and superficial flexor muscle training along with home-based exercises is likely to reduce chronic neck pain and anxiety/depression levels by a clinically relevant amount. Future larger scaled randomized controlled trials are warranted to further support these findings. Copyright © 2018 John Wiley & Sons, Ltd.

  8. Reduced thoracolumbar fascia shear strain in human chronic low back pain

    Directory of Open Access Journals (Sweden)

    Konofagou Elisa E

    2011-09-01

    Full Text Available Abstract Background The role played by the thoracolumbar fascia in chronic low back pain (LBP is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP. Methods We tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity. Results Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p Conclusion Thoracolumbar fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.

  9. Comparison of granisetron and lidocaine on reducing injection pain of etomidate: a controlled randomized study

    Directory of Open Access Journals (Sweden)

    Alireza Saliminia

    2017-11-01

    Full Text Available Background and objectives: Reducing pain on injection of anesthetic drugs is of importance to every anesthesiologist. In this study we pursued to define if pretreatment by granisetron reduces the pain on injection of etomidate similar to lidocaine. Methods: Thirty patients aged between 18 and 50 years of American Society of Anesthesiologists physical status class I or II, whom were candidates for elective laparoscopic cholecystectomy surgery were enrolled in this study. Two 20 gauge cannulas were inserted into the veins on the dorsum of both hands and 100 mL of normal saline was administered during a 10 min period from each cannula. Using an elastic band as a tourniquet, venous drainage of both hands was occluded. 2 mL of granisetron was administered into one hand and 2 mL of lidocaine 2% at the same time into the other hand. One minute later the elastic band was opened and 2 mL of etomidate was administered to each hand with equal rates. The patients were asked to give a score from 0 to 10 (0 = no pain, 10 = severe pain to each the pain sensed in each hand. Results: Two patients were deeply sedated after injection of etomidate and unable to answer any questions. The mean numerical rating score for injection pain of intravenously administered etomidate after intravenous granisetron was 2.3 ± 1.7, which was lower when compared with pain sensed due to intravenously administered etomidate after administration of lidocaine 2% (4.6 ± 1.8, p < 0.05. Conclusion: The result of this study demonstrated that, granisetron reduces pain on injection of etomidate more efficiently than lidocaine. Resumo: Justificativa e objetivos: A redução da dor causada pela injeção de anestésicos é importante para todos os anestesiologistas. Neste estudo buscamos definir se o pré-tratamento com granisetrona reduz a dor causada pela injeção de etomidato de forma semelhante à lidocaína. Métodos: Trinta pacientes com idades entre 18 e 50 anos

  10. Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

    Directory of Open Access Journals (Sweden)

    Jennifer M. Monk

    2014-01-01

    Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

  11. 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

  12. Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model.

    Science.gov (United States)

    Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

    2016-02-01

    Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti-inflammatory drug) patch, SFPP (S(+)-flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)-flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant-induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX-1 (IC50  = 8.97 nM) and COX-2 (IC50  = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

  13. Analgesic Effect of the Newly Developed S(+)‐Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant‐Induced Arthritis Model

    Science.gov (United States)

    Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

    2016-01-01

    ABSTRACT Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant‐induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX‐1 (IC50 = 8.97 nM) and COX‐2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20–28, 2016. © 2016 Wiley Periodicals, Inc. PMID:26763139

  14. Pain

    OpenAIRE

    H.W. Snyman

    1980-01-01

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

  15. Pain

    Directory of Open Access Journals (Sweden)

    H.W. Snyman

    1980-09-01

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

  16. TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Griffiths Gareth

    2009-07-01

    Full Text Available Abstract Background Phosphatidylcholine (PC is a major lipid of the gastrointestinal mucus layer. We recently showed that mucus from patients suffering from ulcerative colitis has low levels of PC. Clinical studies reveal that the therapeutic addition of PC to the colonic mucus using slow release preparations is beneficial. The positive role of PC in this disease is still unclear; however, we have recently shown that PC has an intrinsic anti-inflammatory property. It could be demonstrated that the exogenous application of PC inhibits membrane-dependent actin assembly and TNF-α-induced nuclear NF-κB activation. We investigate here in more detail the hypothesis that the exogenous application of PC has anti-inflammatory properties. Methods PC species with different fatty acid side chains were applied to differentiated and non-differentiated Caco-2 cells treated with TNF-α to induce a pro-inflammatory response. We analysed TNF-α-induced NF-κB-activation via the transient expression of a NF-κB-luciferase reporter system. Pro-inflammatory gene transcription was detected with the help of a quantitative real time (RT-PCR analysis. We assessed the binding of TNF-α to its receptor by FACS and analysed lipid rafts by isolating detergent resistant membranes (DRMs. Results The exogenous addition of all PC species tested significantly inhibited TNF-α-induced pro-inflammatory signalling. The expression levels of IL-8, ICAM-1, IP-10, MCP-1, TNF-α and MMP-1 were significantly reduced after PC pre-treatment for at least two hours. The effect was comparable to the inhibition of NF-kB by the NF-kB inhibitor SN 50 and was not due to a reduced binding of TNF-α to its receptor or a decreased surface expression of TNF-α receptors. PC was also effective when applied to the apical side of polarised Caco-2 cultures if cells were stimulated from the basolateral side. PC treatment changed the compartmentation of the TNF-α-receptors 1 and 2 to DRMs. Conclusion PC

  17. 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

  18. Factors associated with a bad functional prognosis in early inflammatory back pain: results from the DESIR cohort.

    Science.gov (United States)

    Lukas, C; Dougados, M; Combe, B

    2016-01-01

    Spondyloarthritis (SpA) is a heterogeneous disease with hardly predictable potential courses. We aimed at determining prognostic factors of bad functional outcome at 2 years in patients with early inflammatory back pain (IBP). Data from patients included in the French multicentre devenir des spondylarthropathies indifférenciées récentes (DESIR) cohort, that is, suffering from IBP starting before 50 years of age and lasting for 3-36 months, were used. A bad functional outcome at 24 months was defined as an increase in bath ankylosing spondylitis functional index (BASFI), or BASFI at 2 years higher than the 75th centile in the cohort. Demographic, clinical, biological and radiological data collected at inclusion were compared in patients with bad functional outcome versus others, by χ(2) test, then by a multivariate logistic regression model with stepwise selection of relevant factors. 513 patients (54.4% females, 72.2% fulfilling ASAS criteria) were assessed. Of those, 130 (25.3%) fulfilled the aforementioned criteria of a bad functional outcome (BASFI increase ≥4 units or ≥36 at 2 years). Multivariate analysis revealed that not fulfilling ASAS criteria, female sex, age >33 years, lower educational level, active smoking status and high disease activity according to bath ankylosing spondylitis disease activity index (BASDAI) at baseline were independently associated with a bad functional outcome at 24 months. Sensitivity analyses restricted to patients fulfilling ASAS criteria for SpA resulted in similar results. We observed, in a large prospective cohort of patients with early IBP, formerly described bad prognostic factors, especially a low educational level, an older age and a high disease activity at onset, and revealed that active smoking status and female sex were also independently associated with a poor outcome. Fulfilment of ASAS criteria, on the other hand, was predictive of a better outcome, most likely due to the more consensual

  19. Effects on musculoskeletal pain from "Take a Stand!" - a cluster-randomized controlled trial reducing sitting time among office workers

    DEFF Research Database (Denmark)

    Danquah, Ida Høgstedt; Kloster, Stine; Holtermann, Andreas

    2017-01-01

    Objectives Prolonged sitting at work has been found to increase risk for musculoskeletal pain. The office-based intervention "Take a Stand!" was effective in reducing sitting time at work. We aimed to study the effect of the intervention on a secondary outcome: musculoskeletal pain. Methods Take...... a Stand! included 19 offices (317 workers) at four workplaces cluster randomized to intervention or control. The multicomponent intervention lasted three months and included management support, environmental changes, and local adaptation. Control participants behaved as usual. Musculoskeletal pain...

  20. Antibiotics are not useful to reduce pain associated with irreversible pulpitis.

    Science.gov (United States)

    Hoskin, Eileen; Veitz-Keenan, Analia

    2016-09-01

    .45 (SD4.42) in the placebo group; mean difference 2.45 (95%CI -1.23 to 6.13; P value = 0.19). The study did not address adverse events.ConclusionsThere is insufficient evidence to accept or refute the benefit of using penicillin to control pain intensity associated with irreversible pulpitis. This study primarily found that antibiotics given preoperatively (before definitive root canal therapy) do not appear to significantly reduce toothache caused by irreversible pulpitis. Between the two groups, those taking the antibiotics and those taking the placebo, there was no statistical difference in the amount of oral analgesics taken to relieve the pain.

  1. Compound 49b Reduces Inflammatory Markers and Apoptosis after Ocular Blast Injury

    Science.gov (United States)

    2018-02-01

    inflammatory and apoptotic markers, but not to control levels. Figure 1. ELISA results for TNF(left) and IL-1(right) in mouse retina without exposure to...anti- apoptotic protein BcL-xL (bottom left). ELISA results for cleaved caspase 3. *Pɘ.05 vs. NT. #Pɘ.05 vs. blast only at the same time point. N=5...E). ELISA results for cleaved caspase 3 (C) in IGFBP-3 knockdown mice without exposure to blast, IGFBP-3 KD mice exposed to blast for 4, 24, and 72

  2. Accurate laser skin perforation technique aimed at promoting bleeding and reducing pain

    Directory of Open Access Journals (Sweden)

    Han-Chao Chang

    2015-11-01

    Full Text Available Laser skin perforation is an effective and promising technique for use in blood collection. In this study, the relation between the perforation profile of skin and laser irradiation at various energies is discussed. Increasing laser energy does not uniformly expand the size and depth of a hole because the shallow depth of field (DOF of the focused light primarily concentrates energy on the skin surface. In practice, the hole gradually transforms from a semielliptical shape to an upside-down avocado shape as the laser energy increases. This phenomenon can increase the amount of bleeding and reduce pain. The findings support the feasibility of developing an accurate laser skin perforation method.

  3. Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages.

    Science.gov (United States)

    Shin, Jung-Hye; Ryu, Ji Hyeon; Kang, Min Jung; Hwang, Cho Rong; Han, Jaehee; Kang, Dawon

    2013-08-01

    Garlic has a variety of biologic activities, including anti-inflammatory properties. Although garlic has several biologic activities, some people dislike eating fresh raw garlic because of its strong taste and smell. Therefore, garlic formulations involving heating procedures have been developed. In this study, we investigated whether short-term heating affects the anti-inflammatory properties of garlic. Fresh and heated raw garlic extracts (FRGE and HRGE) were prepared with incubation at 25 °C and 95 °C, respectively, for 2 h. Treatment with FRGE and HRGE significantly reduced the LPS-induced increase in the pro-inflammatory cytokine concentration (TNF-α, IL-1β, and IL-6) and NO through HO-1 upregulation in RAW 264.7 macrophages. The anti-inflammatory effect was greater in FRGE than in HRGE. The allicin concentration was higher in FRGE than in HRGE. Allicin treatment showed reduced production of pro-inflammatory cytokines and NO and increased HO-1 activity. The results show that the decrease in LPS-induced NO and pro-inflammatory cytokines in RAW 264.7 macrophages through HO-1 induction was greater for FRGE compared with HRGE. Additionally, the results indicate that allicin is responsible for the anti-inflammatory effect of FRGE. Our results suggest a potential therapeutic use of allicin in the treatment of chronic inflammatory disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

    Science.gov (United States)

    Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

    2014-01-01

    Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS, no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and movement, pressure pain thresholds (PPTs), 6 minute walk test (6MWT), range of motion (ROM), five time sit to stand test (FTSTS), and single leg stance (SLS). Conditioned pain modulation (CPM) was completed at end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. PPTs increased at site of TENS (spine) and outside site of TENS (leg) when compared to placebo TENS or no TENS. During Active TENS CPM was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to how TENS is used clinically, on pain, fatigue, function and quality of life in individuals with fibromyalgia. PMID:23900134

  5. Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials

    NARCIS (Netherlands)

    Olesen, S.S.; Juel, J.; Nielsen, A.K.; Frokjaer, J.B.; Wilder-Smith, O.H.G.; Drewes, A.M.

    2014-01-01

    BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e. pain severity and its pattern in time), complications, and quality

  6. Pain management in sickle cell disease: What remedy to reduce the ...

    African Journals Online (AJOL)

    Sickle cell disease is an inherited disorder, the hallmark of which is recurrent acute painful crises requiring opioid therapy. These acute painful episodes when superimposed on chronic pain could last for years especially in association with comorbidities like osteonecrosis, chronic leg ulcers, cholelithiasis or stuttering ...

  7. Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial

    NARCIS (Netherlands)

    Olesen, S.S.; Bouwense, S.A.W.; Wilder-Smith, O.H.G.; Goor, H. van; Drewes, A.M.

    2011-01-01

    BACKGROUND & AIMS: Pain is a disabling symptom for patients with chronic pancreatitis (CP) and difficult to treat. Evidence from basic science and human studies indicates that pain processing by the central nervous system is abnormal and resembles that observed in patients with neuropathic pain

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

    Science.gov (United States)

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

    2012-03-22

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

  9. Knee osteoarthritis pain in the elderly can be reduced by massage therapy, yoga and tai chi: A review.

    Science.gov (United States)

    Field, Tiffany

    2016-02-01

    This is a review of recently published research, both empirical studies and meta-analyses, on the effects of complementary therapies including massage therapy, yoga and tai chi on pain associated with knee osteoarthritis in the elderly. The massage therapy protocols have been effective in not only reducing pain but also in increasing range of motion, specifically when moderate pressure massage was used and when both the quadriceps and hamstrings were massaged. The yoga studies typically measured pain by the WOMAC. Most of those studies showed a clinically significant reduction in pain, especially the research that focused on poses (e.g. the Iyengar studies) as opposed to those that had integrated protocols (poses, breathing and meditation exercises). The tai chi studies also assessed pain by self-report on the WOMAC and showed significant reductions in pain. The tai chi studies were difficult to compare because of their highly variable protocols in terms of the frequency and duration of treatment. Larger, randomized control trials are needed on each of these therapies using more standardized protocols and more objective variables in addition to the self-reported WOMAC pain scale, for example, range-of-motion and observed range-of-motion pain. In addition, treatment comparison studies should be conducted so, for example, if the lower-cost yoga and tai chi were as effective as massage therapy, they might be used in combination with or as supplemental to massage therapy. Nonetheless, these therapies are at least reducing pain in knee osteoarthritis and they do not seem to have side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury.

    Science.gov (United States)

    Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A; Carlton, Susan M; Walters, Edgar T; Yang, Qing

    2017-03-15

    A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration-approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects.

  12. Intraperitoneal injection of Bupivacaine and Lidocaine in reducing postoperative pain in gynecologic laparoscopic surgeries: a comparative study

    Directory of Open Access Journals (Sweden)

    Alleyassin A

    2007-08-01

    Full Text Available Background: As less invasive surgical procedures, such as laparoscopy, become more common, patients can go home soon after the surgery. However, some pain is accompanied by such procedures due to peritoneal stretching, diaphragmatic irritation, or, to a lesser extent, abdominal puncture. It is important to reduce the level of pain to the point that narcotics are not necessary. The administration of opioids for pain after abdominal surgeries is common. The receptors involved seem to be susceptible to blockade with low-dose local anesthesia, although this is subject to some controversy. In this study, we assess and compare the effectiveness of intraperitoneal Bupivacaine and Lidocaine in pain reduction after diagnostic gynecologic laparoscopy in infertility patients. Methods: In this randomized clinical trial, 150 patients admitted to Dr. Shariati Hospital for diagnostic gynecologic laparoscopy were entered into three randomized groups. Group B received Bupivacaine after the diagnostic laparoscopic procedure, group L received Lidocaine and group C, the control group, received a placebo after the surgery, all administered intraperi- toneally. Postsurgerical pain was assessed using the numeric visual analogue scale at 6 and 24 hours after surgery. Results: In group B, the pain scores at 6 and 24 hours after surgery were significantly less than those of group L. Conclusions: Administration of Bupivacaine after diagnostic gynecologic laparoscopic procedures is more effective in pain control than Lidocaine. The effect of this drug is temporary, yet it significantly decreases early postoperative pain, reducing the need for additional postoperative analgesics. Furthermore, the time at which patients can be discharged from the hospital is significantly reduced.

  13. 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.

  14. 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.

  15. Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy

    DEFF Research Database (Denmark)

    Viscusi, Eugene R; Frenkl, Tara L; Hartrick, Craig T

    2012-01-01

    Abstract Objective: To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively. Research design and methods: In this double......-blind, placebo-controlled, randomized clinical trial, we evaluated postoperative pain following total abdominal hysterectomy over 5 days in patients receiving placebo or etoricoxib administered 90 min prior to surgery and continuing postoperatively. Patients were randomly assigned to receive either placebo (n...... in the active treatment groups by ~10 hours vs. placebo. A greater proportion of patients on etoricoxib (10-30% greater than placebo) achieved mild levels of pain with movement, defined as pain pain measurements were not designated...

  16. 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.

  17. 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

  18. Better cognitive control of emotional information is associated with reduced pro-inflammatory cytokine reactivity to emotional stress.

    Science.gov (United States)

    Shields, Grant S; Kuchenbecker, Shari Young; Pressman, Sarah D; Sumida, Ken D; Slavich, George M

    2016-01-01

    Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of the key pro-inflammatory cytokines IL-1β, IL-6, and IL-8 were measured before and after the experimental manipulation, and following the last cytokine sample, we assessed participants' cognitive control of emotional information using an emotional Stroop task. We also assessed participants' cortisol levels before and after the manipulation to verify that documented effects were specific to cytokines and not simply due to increased nonwater salivary output. As hypothesized, the emotional stressor triggered significant increases in IL-1β, IL-6, and IL-8. Moreover, even in fully adjusted models, better cognitive control following the emotional (but not control) video predicted less pronounced cytokine responses to that stressor. In contrast, no effects were observed for cortisol. These data thus indicate that better cognitive control specifically following an emotional stressor is uniquely associated with less pronounced pro-inflammatory cytokine reactivity to such stress. These findings may therefore help explain why superior cognitive control portends better health over the lifespan.

  19. Does suprascapular nerve block reduce shoulder pain following stroke: a double-blind randomised controlled trial with masked outcome assessment

    Directory of Open Access Journals (Sweden)

    Crotty Maria

    2010-09-01

    Full Text Available Abstract Background Shoulder pain is a common complication of a stroke which can impede participation in rehabilitation programs and has been associated with poorer outcomes. The evidence base for current medical and therapeutic management options of hemiplegic shoulder pain is limited. This study will evaluate the use of suprascapular nerve block injection as part of an interdisciplinary approach to the treatment of shoulder pain following stroke. The technique has previously been proven safe and effective in the treatment of shoulder pain associated with rheumatoid arthritis and degenerative shoulder conditions but its usefulness in a stroke population is unclear. Methods/Design A double blind randomised placebo controlled trial will assess the effect of a suprascapular nerve block compared with placebo in a population of 66 stroke patients. The trial will measure effect of injection on the primary outcome of pain, and secondary outcomes of function and quality of life. Measurements will take place at baseline, and 1, 4 and 12 weeks post intervention. Both groups will continue to receive routine physiotherapy and standard ward care. Discussion The results of this study could reduce pain symptoms in persons with mechanical shoulder pain post stroke and provide improvement in upper limb function. Trial Registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR - ACTRN12609000621213.

  20. A comparative study of collagen dressing versus petrolatum gauze dressing in reducing pain at the donor area

    Directory of Open Access Journals (Sweden)

    B A Ramesh

    2017-01-01

    Full Text Available Background: Skin graft is one of the commonly done procedures by plastic surgeons, dermato surgeons and general surgeons. Pain at the donor area is a common complaint by the patient. The skin graft donor site area is usually covered with petrolatum dressing dermatosurgeons. Aim: This study was done to compare collagen dressing with petroleum gauze dressing in control of post-operative pain on skin graft donor area. Materials and Methods: The study was done on forty patients, twenty as study group who received collagen dressing and twenty as control group who received petroleum gauze dressing. The procedure was randomly selected by permutated block size of four. The post-operative pain was assessed with numerical pain rating scale 0 to 10. Nursing staff did the recording of pain scale. The nursing staff was not aware whether patient had collagen or petroleum gauze dressing. Statistics: Statistical analysis used was independent 't'-test (two-sample test and Levene's test. Results: Statistics proved that study group (collagen dressing had lesser pain than control group (petroleum gauze dressing. Conclusion: The collagen sheet dressing on skin graft donor area reduces pain in post-operative period.

  1. Fasciola hepatica infection reduces Mycobacterium bovis burden and mycobacterial uptake and suppresses the pro-inflammatory response.

    Science.gov (United States)

    Garza-Cuartero, L; O'Sullivan, J; Blanco, A; McNair, J; Welsh, M; Flynn, R J; Williams, D; Diggle, P; Cassidy, J; Mulcahy, G

    2016-07-01

    Bovine tuberculosis (BTB), caused by Mycobacterium bovis, has an annual incidence in cattle of 0.5% in the Republic of Ireland and 4.7% in the UK, despite long-standing eradication programmes being in place. Failure to achieve complete eradication is multifactorial, but the limitations of diagnostic tests are significant complicating factors. Previously, we have demonstrated that Fasciola hepatica infection, highly prevalent in these areas, induced reduced sensitivity of the standard diagnostic tests for BTB in animals co-infected with F. hepatica and M. bovis. This was accompanied by a reduced M. bovis-specific Th1 immune response. We hypothesized that these changes in co-infected animals would be accompanied by enhanced growth of M. bovis. However, we show here that mycobacterial burden in cattle is reduced in animals co-infected with F. hepatica. Furthermore, we demonstrate a lower mycobacterial recovery and uptake in blood monocyte-derived macrophages (MDM) from F. hepatica-infected cattle which is associated with suppression of pro-inflammatory cytokines and a switch to alternative activation of macrophages. However, the cell surface expression of TLR2 and CD14 in MDM from F. hepatica-infected cattle is increased. These findings reflecting the bystander effect of helminth-induced downregulation of pro-inflammatory responses provide insights to understand host-pathogen interactions in co-infection. © 2016 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

  2. Effectiveness of Low-Level Laser Therapy in Reducing Orthodontic Pain: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Deana, Naira Figueiredo; Zaror, Carlos; Sandoval, Paulo

    2017-01-01

    Objectives To assess the effectiveness of low-level laser therapy (LLLT) in reducing orthodontic pain after the application of orthodontic force (OF). Methods A systematic search was conducted in the MEDLINE, EMBASE, Scopus, Cochrane Library, Web of Science, and EBSCOhost databases. The study included randomized clinical trials (RCT) which analysed the effectiveness of LLLT in reducing orthodontic pain assessed at 24 and 72 hrs after the application of OF. The risk of bias of the eligible trials was assessed using the Cochrane Collaboration's risk of bias tool. Standard mean difference was calculated and pooled by meta-analysis using random effect models. Results Of 467 identified articles, 20 RCT were finally included. In the risk of bias assessments, 13 studies presented a high risk, 5 an unclear risk, and 2 a low risk. The meta-analysis showed that in patients treated with laser versus placebo there was a difference in favour of LLLT in spontaneous pain 24 and 72 hrs after the installation of light archwires and spontaneous pain and chewing pain 24 and 72 hrs after the installation of elastomeric separators. Conclusions LLLT proved to be effective in promoting a reduction in spontaneous and chewing pain after the application of OF; however, the poor quality of the evidence requires these results to be treated with caution. PMID:29089818

  3. Comparison of intranasal ketamine versus IV morphine in reducing pain in patients with renal colic.

    Science.gov (United States)

    Farnia, Mohammad Reza; Jalali, Alireza; Vahidi, Elnaz; Momeni, Mehdi; Seyedhosseini, Javad; Saeedi, Morteza

    2017-03-01

    Various drugs have been used to relieve abdominal pain in patients with renal colic. Ketamine is a popular choice as an analgesic. To compare the effectiveness of intranasal (IN) ketamine versus intravenous (IV) morphine in reducing pain in patients with renal colic. A randomized double-blind controlled trial was performed in 53 patients with renal colic recruited from the emergency department (ED) in 2015. Finally, 40 patients were enrolled in this study. Patients in the ketamine group received IN ketamine 1 mg/kg and IV placebo while patients in the control group received IV morphine 0.1mg/kg and IN placebo. Our goal was to assess visual analogue scale (VAS) changes between the 2 groups. Patients' VAS scores were reported before and 5, 15, 30min after drug injection. Before drug administration, the mean±SD VAS score was 7.40±1.18 in the morphine group (group A) and 8.35±1.30 in the ketamine group (group B) (P-value=0.021). After adjustment by the appropriate analysis, the mean±SD VAS score in group (A) and (B) at 5min were (6.07±0.47 vs 6.87±0.47; mean difference -0.79, 95% confidence interval (CI) -1.48 to -1.04) (P-value=0.025), at 15 and 30min, the mean±SD VAS score in group (A) and (B) were (5.24±0.49 vs 5.60±0.49; mean difference -0.36, 95% CI -1.08 to 0.34) and (4.02±0.59 vs 4.17±0.59; mean difference -0.15, 95% CI -1.02 to 0.71) (P-value=0.304 and 0.719) respectively. IN ketamine may be effective in decreasing pain in renal colic. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Intradiscal and intra-articular facet infiltrations with plasma rich in growth factors reduce pain in patients with chronic low back pain

    Science.gov (United States)

    Kirchner, Fernando; Anitua, Eduardo

    2016-01-01

    Context: Low back pain (LBP) is a complex and disabling condition, and its treatment becomes a challenge. Aims: The aim of our study was to assess the clinical outcome of plasma rich in growth factors (PRGF-Endoret) infiltrations (one intradiscal, one intra-articular facet, and one transforaminal epidural injection) under fluoroscopic guidance-control in patients with chronic LBP. PRGF-Endoret which has been shown to be an efficient treatment to reduce joint pain. Settings and Design: The study was designed as an observational retrospective pilot study. Eighty-six patients with a history of chronic LBP and degenerative disease of the lumbar spine who met inclusion and exclusion criteria were recruited between December 2010 and January 2012. Subjects and Methods: One intradiscal, one intra-articular facet, and one transforaminal epidural injection of PRGF-Endoret under fluoroscopic guidance-control were carried out in 86 patients with chronic LBP in the operating theater setting. Statistical Analysis Used: Descriptive statistics were performed using absolute and relative frequency distributions for qualitative variables and mean values and standard deviations for quantitative variables. The nonparametric Friedman statistical test was used to determine the possible differences between baseline and different follow-up time points on pain reduction after treatment. Results: Pain assessment was determined using a visual analog scale (VAS) at the first visit before (baseline) and after the procedure at 1, 3, and 6 months. The pain reduction after the PRGF-Endoret injections showed a statistically significant drop from 8.4 ± 1.1 before the treatment to 4 ± 2.6, 1.7 ± 2.3, and 0.8 ± 1.7 at 1, 3, and 6 months after the treatment, respectively, with respect to all the time evaluations (P PRGF in patients with chronic LBP resulted in significant pain reduction assessed by VAS. PMID:27891035

  5. Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

    OpenAIRE

    Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

    2013-01-01

    Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random or...

  6. [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.

  7. The Clinical Effects of Aromatherapy Massage on Reducing Pain for the Cancer Patients: Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Ting-Hao Chen

    2016-01-01

    Full Text Available Purpose. Aromatherapy massage is an alternative treatment in reducing the pain of the cancer patients. This study was to investigate whether aromatherapy massage could improve the pain of the cancer patients. Methods. We searched PubMed and Cochrane Library for relevant randomized controlled trials without language limitations between 1 January 1990 and 31 July 2015 with a priori defined inclusion and exclusion criteria. The search terms included aromatherapy, essential oil, pain, ache, cancer, tumor, and carcinoma. There were 7 studies which met the selection criteria and 3 studies were eventually included among 63 eligible publications. Results. This meta-analysis included three randomized controlled trials with a total of 278 participants (135 participants in the massage with essential oil group and 143 participants in the control (usual care group. Compared with the control group, the massage with essential oil group had nonsignificant effect on reducing the pain (standardized mean difference = 0.01; 95% CI [-0.23,0.24]. Conclusion. Aromatherapy massage does not appear to reduce pain of the cancer patients. Further rigorous studies should be conducted with more objective measures.

  8. Do Medical Marijuana Laws Reduce Addictions and Deaths Related to Pain Killers?

    OpenAIRE

    David Powell; Rosalie Liccardo Pacula; Mireille Jacobson

    2015-01-01

    Many medical marijuana patients report using marijuana to alleviate chronic pain from musculoskeletal problems and other sources. If marijuana is used as a substitute for powerful and addictive pain relievers in medical marijuana states, a potential overlooked positive impact of medical marijuana laws may be a reduction in harms associated with opioid pain relievers, a far more addictive and potentially deadly substance. To assess this issue, we study the impact of medical marijuana laws on p...

  9. ?Do Unto Others??: Distinct Psychopathy Facets Predict Reduced Perception and Tolerance of Pain

    OpenAIRE

    Brislin, Sarah J.; Buchman-Schmitt, Jennifer M.; Joiner, Thomas E.; Patrick, Christopher J.

    2016-01-01

    Recent research has sought to understand how individuals high in psychopathic traits perceive pain in others (Decety, Skelly, & Kiehl, 2013; Marsh et al., 2013). Perception of pain in others is presumed to act as a prosocial signal, and underreactivity to others? pain may contribute to engagement in exploitative-aggressive behaviors among individuals high in psychopathic traits (Jackson, Meltzoff, & Decety; 2005). The current study tested for associations between facets of psychopathy as defi...

  10. Apigenin reduce lipoteichoic acid-induced inflammatory response in rat cardiomyoblast cells.

    Science.gov (United States)

    Gutiérrez-Venegas, Gloria; González-Rosas, Zeltzin

    2017-02-01

    Infective endocarditis is caused by Streptococcus sanguinis present in dental plaque, which can induce inflammatory responses in the endocardium. The present study depicts research on the properties of apigenin in embryonic mouse heart cells (H9c2) treated with lipoteichoic acid (LTA) obtained from S. sanguinis. Interleukin-1β and cyclooxygenase (COX)-2 expression were detected by reverse transcriptase polymerase chain reaction. In addition, western blot assays and immuno-fluorescence staining were used to assess translocation of nuclear factor kappa beta (NF-κB), degradation of IκB, as well as activity of the mitogen activated protein kinases: extracellular signal-regulated kinase (ERK)1/2, p38, and c-Jun N-terminal kinase (JNK). Effect of apigenin on cell viability was equally assessed in other experimental series. Our results showed that apigenin blocked activation of ERK, JNK, and p38 in cardiomyocytes treated with LTA in a dose-dependent fashion. Moreover, apigenin showed no cytotoxic effects; it blocked NF-κB translocation and IκB degradation. Our findings suggested that apigenin possessed potential value in the treatment of infectious endocarditis.

  11. Anti-Inflammatory Agent Indomethacin Reduces Invasion and Alters Metabolism in a Human Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-03-01

    Full Text Available Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the antiinflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDAMB-435 in Dulbecco's Modified Eagles (DME-based or Roswell Park Memorial Institute (RPMI-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenaseindependent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.

  12. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity

    DEFF Research Database (Denmark)

    Frøkjaer, J B; Bergmann, S; Brock, C

    2016-01-01

    algometry, conditioned pain modulation using a cold pressor test and a liquid meal ultrasonographic gastroduodenal motility test were performed. KEY RESULTS: Cardiac vagal tone increased during active treatment with t-VNS and DSB compared to sham (p = 0.009). In comparison to sham, thresholds to bone pain...... increased (p = 0.001), frequency of antral contractions increased (p = 0.004) and gastroduodenal motility index increased (p = 0.016) with active treatment. However, no effect on muscle pain thresholds and conditioned pain modulation was seen. CONCLUSIONS & INFERENCES: This experimental study suggests...

  13. The Effectiviness of Dysmenorrhea Gymnastics as an Alternative Therapy in Reducing Menstrual Pain

    Directory of Open Access Journals (Sweden)

    Mei Lina Fitri Kumalasari

    2017-04-01

    Full Text Available Menstrual pain occurs due to the imbalance of the hormones which will cause the uterine muscles to contract and lead to colic pain. Approximately 50 % of women worldwide  and  90 % of Indonesian women  suffer from menstrual pain. Pharmacological therapy is the most popular treatment used to relieve menstrual pain. Unfortunately, it leads to indisputable side effects on health. Therefore, safety alternative treatments such as dysmenorrhea gymnastics are signifficantly needed to improve bloodstream in the uterus and produce endorphins which can relieve menstrual pain. The aim of the study wasto determine the effectiveness of dysmenorrhea gymnastics to relieve the level of menstrual pain. The method of study is systematic review on 14 studies of the efectiveness of exercise dysmenorrhea gymnastics to relieve menstrual pain. The results obtained are dysmenorrhea gymnastcs can relieve menstrual pain with a mean value of 4.006. Conclusion: dysmenorrhea gymnastics can relieve menstrual pain and better  done in the afternoon.

  14. Pre-emptive penile ring block with sucrose analgesia reduces pain response to neonatal circumcision.

    Science.gov (United States)

    Roman-Rodriguez, Christian F; Toussaint, Thomas; Sherlock, Douglas J; Fogel, Joshua; Hsu, Chaur-Dong

    2014-04-01

    To compare retrospective use of oral sucrose (SUC) vs oral sucrose plus lidocaine ring block (SUC + RB) in the management of pain during neonatal circumcision. A retrospective review of medical records of newborns circumcised using the "Neonatal Infant Pain Scale" was done. With regard to pain, the SUC group had a significantly greater percentage of those with pain than the SUC + RB group at 1 minute (77.7% vs 69.4%; P = .01) and 5 minutes (65.7% vs 55.7%; P = .004). There was no significant pain difference at 30 minutes. In the multivariate logistic regression analyses, those in the SUC group had significantly greater odds for pain at 1 minute than those in the SUC + RB group (odds ratio 1.45, 95% confidence interval 1.04-2.02; P = .03). No significant difference was noted at 5 minutes. Each of the SUC and SUC + RB groups had significant decreases in pain percentages at 5 minutes and 30 minutes (P analgesia. In addition, for post-term neonates, we recommend greater focus on pain levels, including considering higher dosages of pain medications. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2018-04-01

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

  16. 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 ...

  17. Sr-doped nanowire modification of Ca-Si-based coatings for improved osteogenic activities and reduced inflammatory reactions

    Science.gov (United States)

    Li, Kai; Hu, Dandan; Xie, Youtao; Huang, Liping; Zheng, Xuebin

    2018-02-01

    Biomedical coatings for orthopedic implants should facilitate osseointegration and mitigate implant-induced inflammatory reactions. In our study, Ca-Si coatings with Sr-containing nanowire-like structures (NW-Sr-CS) were achieved via hydrothermal treatment. In order to identify the effect of nanowire-like topography and Sr dopant on the biological properties of Ca-Si-based coatings, the original Ca-Si coating, Ca-Si coatings modified with nanoplate (NP-CS) and similar nanowire-like structure (NW-CS) were fabricated as the control. Surface morphology, phase composition, surface area, zeta potential and ion release of these coatings were characterized. The in vitro osteogenic activities and immunomodulatory properties were evaluated with bone marrow stromal cells (BMSCs) and RAW 264.7 cells, a mouse macrophage cell line. Compared with the CS and NP-CS coatings, the NW-CS coating possessed a larger surface area and pore volume, beneficial protein adsorption, up-regulated the expression levels of integrin β1, Vinculin and focal adhesion kinase and promoted cell spreading. Furthermore, the NW-CS coating significantly enhanced the osteogenic differentiation and mineralization as indicated by the up-regulation of ALP activity, mineralized nodule formation and osteoblastogenesis-related gene expression. With the introduction of Sr, the NW-Sr-CS coatings exerted a greater effect on the BMSC proliferation rate, calcium sensitive receptor gene expression as well as PKC and ERK1/2 phosphorylation. In addition, the Sr-doped coatings significantly up-regulated the ratio of OPG/RANKL in the BMSCs. The NW-Sr-CS coatings could modulate the polarization of macrophages towards the wound-healing M2 phenotype, reduce the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and enhance anti-inflammatory cytokines (IL-1ra, IL-10). The Sr-doped nanowire modification may be a valuable approach to enhance osteogenic activities and reduce inflammatory reactions.

  18. Randomised controlled trial of integrated care to reduce disability from chronic low back pain in working and private life.

    Science.gov (United States)

    Lambeek, Ludeke C; van Mechelen, Willem; Knol, Dirk L; Loisel, Patrick; Anema, Johannes R

    2010-03-16

    To evaluate the effectiveness of an integrated care programme, combining a patient directed and a workplace directed intervention, for patients with chronic low back pain. Population based randomised controlled trial. Primary care (10 physiotherapy practices, one occupational health service, one occupational therapy practice) and secondary care (five hospitals). 134 adults aged 18-65 sick listed for at least 12 weeks owing to low back pain. Patients were randomly assigned to usual care (n=68) or integrated care (n=66). Integrated care consisted of a workplace intervention based on participatory ergonomics, involving a supervisor, and a graded activity programme based on cognitive behavioural principles. The primary outcome was the duration of time off work (work disability) due to low back pain until full sustainable return to work. Secondary outcome measures were intensity of pain and functional status. The median duration until sustainable return to work was 88 days in the integrated care group compared with 208 days in the usual care group (P=0.003). Integrated care was effective on return to work (hazard ratio 1.9, 95% confidence interval 1.2 to 2.8, P=0.004). After 12 months, patients in the integrated care group improved significantly more on functional status compared with patients in the usual care group (P=0.01). Improvement of pain between the groups did not differ significantly. The integrated care programme substantially reduced disability due to chronic low back pain in private and working life. Trial registration Current Controlled Trials ISRCTN28478651.

  19. Comparison thoracic epidural and intercostal block to improve ventilation parameters and reduce pain in patients with multiple rib fractures.

    Science.gov (United States)

    Hashemzadeh, Shahryar; Hashemzadeh, Khosrov; Hosseinzadeh, Hamzeh; Aligholipour Maleki, Raheleh; Golzari, Samad E J; Golzari, Samad

    2011-01-01

    Chest wall blunt trauma causes multiple rib fractures and will often be associated with significant pain and may compromise ventilator mechanics. Analgesia has great roll in rib fracture therapies, opioid are useful, but when used as sole agent may require such high dose that they produce respiratory depression, especially in elderly .the best analgesia for a severe chest wall injury is a continuous epidural infusion of local anesthetic. This provides complete analgesia allowing inspiration and coughing without of the risk of respiratory depression. sixty adult patients who with multiple rib fractures were enrolled in this study. They were divided into Group A or thoracic epidural with bupivacaine 0.125 % +1mg/5ml morphine and group B or intercostal block with 0.25% bupivacaine. The patients were assessed through ICU and hospital stay length, ventilation function tests. Pain score among the patients was measured with verbal rating scale, before and after administration of the analgesia. We found a significant improvement in ventilatory function tests during the 1st, 2nd, and 3rd days after epidural analgesia compared with the intercostal block (P pain at rest and pain caused by coughing and deep breathing in group A compared group B... ICU and hospital stay markedly reduced in Group A. thoracic epidural analgesia is superior to intercostals block regarding pain relief of rib fractures. Patients who received epidural analgesia had significantly lower pain scores at all studied times.

  20. Participatory ergonomics to reduce exposure to psychosocial and physical risk factors for low back pain and neck pain: results of a cluster randomised controlled trial.

    Science.gov (United States)

    Driessen, Maurice T; Proper, Karin I; Anema, Johannes R; Knol, Dirk L; Bongers, Paulien M; van der Beek, Allard J

    2011-09-01

    This study investigated the effectiveness of the Stay@Work participatory ergonomics programme to reduce workers' exposure to psychosocial and physical risk factors. 37 departments (n=3047 workers) from four Dutch companies participated in this cluster randomised controlled trial; 19 (n=1472 workers) were randomised to an intervention group (participatory ergonomics) and 18 (n=1575 workers) to a control group (no participatory ergonomics). During a 6 h meeting guided by an ergonomist, working groups devised ergonomic measures to reduce psychosocial and physical workload and implemented them within 3months in their departments. Data on psychosocial and physical risk factors for low back pain and neck pain were collected at baseline and after 6 months. Psychosocial risk factors were measured using the Job Content Questionnaire and physical risk factors using the Dutch Musculoskeletal Questionnaire. Intervention effects were studied using multilevel analysis. Intervention group workers significantly increased on decision latitude (0.29 points; 95% CI 0.07 to 0.52) and decision authority (0.16 points; 95% CI 0.04 to 0.28) compared to control workers. However, exposure to awkward trunk working postures significantly increased in the intervention group (OR 1.86; 95% CI 1.15 to 3.01) compared to the control group. No significant differences between the intervention and control group were found for the remaining risk factors. After 6months, loss to follow-up was 35% in the intervention group and 29% in the control group. Participatory ergonomics was not effective in reducing exposure to psychosocial and physical risk factors for low back pain and neck pain among a large group of workers. ISRCTN27472278.

  1. 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).

  2. 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.

  3. Meditation reduces pain-related neural activity in the anterior cingulate cortex, insula, secondary somatosensory cortex, and thalamus

    Science.gov (United States)

    Nakata, Hiroki; Sakamoto, Kiwako; Kakigi, Ryusuke

    2014-01-01

    Recent studies have shown that meditation inhibits or relieves pain perception. To clarify the underlying mechanisms for this phenomenon, neuroimaging methods, such as functional magnetic resonance imaging, and neurophysiological methods, such as magnetoencephalography and electroencephalography, have been used. However, it has been difficult to interpret the results, because there is some paradoxical evidence. For example, some studies reported increased neural responses to pain stimulation during meditation in the anterior cingulate cortex (ACC) and insula, whereas others showed a decrease in these regions. There have been inconsistent findings to date. Moreover, in general, since the activities of the ACC and insula are correlated with pain perception, the increase in neural activities during meditation would be related to the enhancement of pain perception rather than its reduction. These contradictions might directly contribute to the ‘mystery of meditation.’ In this review, we presented previous findings for brain regions during meditation and the anatomical changes that occurred in the brain with long-term meditation training. We then discussed the findings of previous studies that examined pain-related neural activity during meditation. We also described the brain mechanisms responsible for pain relief during meditation, and possible reasons for paradoxical evidence among previous studies. By thoroughly overviewing previous findings, we hypothesized that meditation reduces pain-related neural activity in the ACC, insula, secondary somatosensory cortex, and thalamus. We suggest that the characteristics of the modulation of this activity may depend on the kind of meditation and/or number of years of experience of meditation, which were associated with paradoxical findings among previous studies that investigated pain-related neural activities during meditation. PMID:25566158

  4. Effects of Massage in Reducing the Pain and Anxiety of the Cardiac Surgery Critically Ill-a Randomized Controlled Trial.

    Science.gov (United States)

    Boitor, Madalina; Martorella, Géraldine; Maheu, Christine; Laizner, Andréa Maria; Gélinas, Céline

    2018-03-30

    To evaluate the effectiveness of hand massage on the pain and anxiety of the cardiac surgery critically ill. A three-arm randomized controlled trial. This study was conducted in a medical-surgical intensive care unit in Canada. Adult patients who underwent elective cardiac surgery, who were able to speak French/English and to self-report symptoms, without a high risk of postoperative complications were eligible. Patients were randomly allocated to standard care plus either two 20-minute hand massages (experimental), two 20-minute hand holdings (active control), or two 20-minute rest periods (passive control/standard care). Pain intensity, pain unpleasantness, anxiety, muscle tension, and vital signs were evaluated before, after, and 30 minutes later for each intervention. From the 83 patients recruited, 60 were randomized (20 massage, 19 hand holding, 21 standard care). After controlling for baseline scores, the massage group reported significantly lower pain intensity, pain unpleasantness, and anxiety for the first data collection set compared with both hand holding and standard care (analysis of covariance, P < 0.02), with an average decrease of two points on a 0-10 scale. No statistically significant differences were noted between hand holding and standard care for any of the symptoms. Similar results were observed for the second data collection set (N = 43). Patients had decreased muscle tension post massage. Vital signs did not differ significantly between groups. Findings suggest that a 20-minute hand massage in addition to routine postoperative pain management can concomitantly reduce pain intensity, pain unpleasantness, and anxiety by two points on average on a 0-10 scale.

  5. Use of remifentanil to reduce propofol injection pain and the required propofol dose in upper digestive tract endoscopy diagnostic tests.

    Science.gov (United States)

    Uliana, Gustavo Nadal; Tambara, Elizabeth Milla; Baretta, Giorgio Alfredo Pedroso

    2015-01-01

    The introduction of propofol (2,6-diisopropylphenol) as a sedative agent has transformed the area of sedation for endoscopic procedures. However, a major drawback of sedation with the use of propofol is its high incidence of injection pain. The most widely used technique in reducing propofol injection pain is through the association of other drugs. The aim of this study was to evaluate the effect of remifentanil-propofol combination on the incidence of propofol injection pain and its influence on the total dose of propofol required for sedation in upper digestive tract endoscopy (UDE) diagnostic tests. One hundred and five patients undergoing upper digestive tract endoscopy were evaluated and randomly divided into 3 groups of 35 patients each. The Control Group received propofol alone; Study-group 1 received remifentanil at a fixed dose of 0.2mg/kg combined with propofol; Study-group 2 received remifentanil at a fixed dose of 0.3mg/kg combined with propofol. The incidence of propofol injection pain and the total dose of propofol required for the test were evaluated. The sample was very similar regarding age, weight, height, sex, and physical status. Statistical analysis was performed according to the nature of the evaluated data. Student's t-test was used to compare the mean of age, weight, height (cm), and dose (mg/kg) variables between groups. The χ(2) test was used to compare sex, physical status, and propofol injection pain between groups. The significance level was αpain and total dose of propofol (mg/kg) used. However, there were no statistical differences between the two study groups for these parameters. We conclude that the use of remifentanil at doses of 0.2mg/kg and 0.3mg/kg was effective for reducing both the propofol injection pain and the total dose of propofol used. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  6. Efficacy of tramadol and butorphanol pretreatment in reducing pain on propofol injection: A placebo-controlled randomized study.

    Science.gov (United States)

    Singh, Arvinderpal; Sharma, Geeta; Gupta, Ruchi; Kumari, Anita; Tikko, Deepika

    2016-01-01

    Pain of propofol injection has been recalled by many patients as the most painful part of the induction of anesthesia. Tramadol and butorphanol are commonly used analgesics for perioperative analgesia in anesthesia practice. However, their potential to relieve propofol injection pain still needs to be explored. A randomized, double-blind, placebo-controlled study was conducted on 90 American Society of Anesthesiologists I and II adult patients undergoing elective surgery under general anesthesia with propofol as an induction agent. Consecutive sampling technique with random assignment was used to allocate three groups of 30 patients each. Group I patients received an injection of normal saline 3 ml intravenously (placebo) while Group II and Group III patients received injection of tramadol 50 mg and butorphanol 1 mg intravenously, respectively. Before induction of anesthesia patients were asked about the intensity of pain on propofol injection by using visual analog scale (VAS) before the loss of consciousness. Descriptive statistics and analysis of variance with Chi-square test were used to analyze the data. The value of P pain in Group I was observed in 80% of the patients, while it was observed in 23.33% and 20% of patients in Group II and III, respectively. Mean VAS scores were 2.27 ± 1.51, 1.14 ± 1.74, and 1.03 ± 1.72 in Group I, II, and Group III patients, respectively. The incidence of pruritus was 10% and 6.7% and erythema in 13.2% and 6.7% in Group II and III, respectively. Pretreatment with both butorphanol and tramadol significantly reduced pain on propofol injection; however, they exhibited comparable efficacy among each other. Thus, either of these two drugs can be considered for pretreatment to reduce propofol injection pain.

  7. Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways.

    Science.gov (United States)

    Singh, Harpal; Kaur, Taranjeet; Manchanda, Shaffi; Kaur, Gurcharan

    2017-08-01

    Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen.

  8. A Novel Pleiotropic Anti-Inflammatory Drug to Reduce ARDS Incidence

    Science.gov (United States)

    2017-07-01

    the gut , which significantly reduced TRB-N0224 adsorption. To solve this problem we have requested a one-year no-cost extension to use an intravenous...use or care of human subjects, vertebrate animals, biohazards, and/or select agents: Nothing to report. Products: Nothing to report Participants

  9. 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.

  10. 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.

  11. Auriculotherapy to reduce anxiety and pain in nursing professionals: a randomized clinical trial.

    Science.gov (United States)

    Kurebayashi, Leonice Fumiko Sato; Turrini, Ruth Natalia Teresa; Souza, Talita Pavarini Borges de; Marques, Carolina Felicio; Rodrigues, Renata Tavares Franco; Charlesworth, Karen

    2017-04-06

    to evaluate the effectiveness of the auricular protocol (APPA) in reducing pain and anxiety and improving the quality of life of the nursing staff of a hospital. randomized clinical trial with an initial sample of 180 professionals divided into 4 groups Control (G1), Seed (G2), Needle (G3) and Tape (G4). The evaluation instruments were the State-Trait Anxiety Inventory, Pain Visual Analog Scale and Quality of Life instrument, applied at the start and after five and 10 sessions (five weeks). Descriptive statistics, analysis of variance (ANOVA) and Cohen's d Index were used in the analysis. there was a statistical difference (p Semilla (G2), Aguja (G3) y Cinta Adhesiva (G4). Los instrumentos de evaluación fueron el Inventario de Ansiedad Rasgo-Estado, la Escala Visual Analógica de Dolor y el instrumento de Calidad de Vida, aplicados en el inicio, y después de cinco y 10 sesiones (cinco semanas). En el análisis se utilizó la estadística descriptiva, la análisis de variancia (ANOVA) y el Índice d de Cohen. hubo diferencia estadística (p < 0,05) para la ansiedad según ANOVA de medidas repetidas, con mejores resultados para el G3 en la última evaluación (índice d de Cohen 1,08/17% de reducción). Hubo reducción de 36% en el G3, 24% en el G2 para el dolor y 13% de aumento en el nivel mental de calidad de vida para el G3, a pesar de que sin diferencias estadísticas. el protocolo APPA redujo los niveles de ansiedad en el equipo de enfermería después de 10 sesiones. Se sugiere realizar más estudios con nuevas poblaciones y en diferentes contextos para que los resultados puedan ser confirmados. RBR-5pc43m.

  12. Does advanced cryotherapy reduce pain and narcotic consumption after knee arthroplasty?

    Science.gov (United States)

    Thienpont, Emmanuel

    2014-11-01

    Cryotherapy has been used to enhance recovery after orthopaedic surgery. Several cooling devices are available but few can guarantee a fixed temperature during a prolonged time and therefore have been criticized. The arrival of new advanced cryotherapy devices made it possible to test the effect of prolonged cooling on rehabilitation after joint replacement. The hypotheses of this randomized controlled trial (RCT) were that advanced cryotherapy devices compared with cold packs result in (1) better postoperative pain control resulting in a lower consumption of narcotics; (2) better early ROM; and (3) less postoperative bleeding and swelling. A priori sample size calculation had determined that to detect a difference of 2 points on the VAS, a sample size of 50 subjects per group at followup would be required, given a study power of 80%. One hundred sixteen patients were included and randomly allocated to receive advanced cryotherapy (n=58) or use of cold packs (n=58). The primary outcomes for the study were to evaluate pain with the VAS and analgesics consumption. Secondary outcomes were postoperative ROM, swelling, and blood loss. One hundred (50 in each group) patients had complete data available for analysis. No statistically significant differences in VAS, need for analgesics, nor in secondary outcomes were observed, except for substantially reduced flexion at 6 weeks in the advanced cryotherapy group (114° versus 120°). Advanced cryotherapy with a continuous temperature for a prolonged period does not deliver expected results of superior early recovery after knee arthroplasty. Greater sample sizes are required to fully determine significant differences between the two techniques for these study parameters. Immobilization of the knee in extension during the prolonged cryotherapy session resulted in lower active flexion at 6 weeks after surgery for the advanced cryotherapy group. Advanced cryotherapy should not be used in fast track knee arthroplasty if the

  13. Creatine supplementation reduces plasma levels of pro-inflammatory cytokines and PGE2 after a half-ironman competition.

    Science.gov (United States)

    Bassit, R A; Curi, R; Costa Rosa, L F B P

    2008-08-01

    The effect of creatine supplementation upon plasma levels of pro-inflammatory cytokines: Interleukin (IL) 1 beta and IL-6, Tumor Necrosis Factor alpha (TNFalpha), and Interferon alpha (INF alpha) and Prostaglandin E(2) (PGE(2)) after a half-ironman competition were investigated. Eleven triathletes, each with at least three years experience of participation in this sport were randomly divided between the control and experimental groups. During 5 days prior to competition, the control group (n = 6) was supplemented with carbohydrate (20 g x d(-1)) whereas the experimental group (n = 5) received creatine (20 g x d(-1)) in a double-blind trial. Blood samples were collected 48 h before and 24 and 48 h after competition and were used for the measurement of cytokines and PGE(2). Forty-eight hours prior to competition there was no difference between groups in the plasma concentrations (pg x ml(-1), mean +/- SEM) of IL-6 (7.08 +/- 0.63), TNFalpha (76.50 +/- 5.60), INF alpha (18.32 +/- 1.20), IL-1 beta (23.42 +/- 5.52), and PGE(2) (39.71 +/- 3.8). Twenty-four and 48 h after competition plasma levels of TNFalpha, INF alpha, IL-1 beta and PGE(2) were significantly increased (P long distance triathlon competition may reduce the inflammatory response induced by this form of strenuous of exercise.

  14. Autologous Fat Grafting Reduces Pain in Irradiated Breast: A Review of Our Experience

    Directory of Open Access Journals (Sweden)

    Fabio Caviggioli

    2016-01-01

    Full Text Available Introduction. Pain syndromes affect women after conservative and radical breast oncological procedures. Radiation therapy influences their development. We report autologous fat grafting therapeutical role in treating chronic pain in irradiated patients. Materials and Methods. From February 2006 to November 2014, we collect a total of 209 patients who meet the definition of “Postmastectomy Pain Syndrome” (PMPS and had undergone mastectomy with axillary dissection (113 patients or quadrantectomy (96 patients. Both procedures were followed by radiotherapy. We performed fat grafting following Coleman’s procedure. Mean amount of adipose tissue injected was 52 cc (±8.9 cc per breast. Seventy-eight in 209 patients were not treated surgically and were considered as control group. Data were gathered through preoperative and postoperative VAS questionnaires; analgesic drug intake was recorded. Results. The follow-up was at 12 months (range 11.7–13.5 months. In 120 treated patients we detected pain decrease (mean ± SD point reduction, 3.19 ± 2.86. Forty-eight in 59 patients stopped their analgesic drug therapy. Controls reported a mean ± SD decrease of pain of 1.14 ± 2.72. Results showed that pain decreased significantly in patients treated (p<0.005, Wilcoxon rank-sum test. Conclusion. Our 8-year experience confirms fat grafting effectiveness in decreasing neuropathic pain.

  15. Music can effectively reduce pain perception in women rather than men.

    Science.gov (United States)

    Ghaffaripour, Sina; Mahmoudi, Hilda; Sahmeddini, Mohammad Ali; Alipour, Abbas; Chohedri, Abdolhamid

    2013-01-01

    Nowadays music is used to decrease pain and increase relaxation in clinical settings. It is hypothesized that music can affect women more easily than men. We assessed the effect of two types of music (Iranian folkloric and preferred music) on pain tolerance and pain rating in cold pressor test. A consecutive sample of 50 healthy Iranian medical students was enrolled. They reported pain tolerance and pain rating in cold pressor test in three different musical conditions served as the outcome measures. The results were analyzed with repeated measurement analysis of variance. Mean tolerance time was significantly higher in preferred music compared to Iranian folkloric music (F (1,48) =25.44, p=0.0001) and no music (F(1,48)=3.51, p=0.0001) conditions. There was a significant interaction when tolerance time in no music condition was compared to preferred music condition, regarding sex; Tolerance time increased more in females (F(1,48)=5.53, p=0.023). The results also indicated that pain ratings, regardless of sex, were different in three musical conditions (F(1.7,81.34)=15.37, p=0.0001). Music distracted attention from pain and Women can be impressed and distracted more easily by music.

  16. Hypnosis can reduce pain in hospitalized older patients: a randomized controlled study.

    Science.gov (United States)

    Ardigo, Sheila; Herrmann, François R; Moret, Véronique; Déramé, Laurence; Giannelli, Sandra; Gold, Gabriel; Pautex, Sophie

    2016-01-15

    Chronic pain is a common and serious health problem in older patients. Treatment often includes non pharmacological approaches despite a relatively modest evidence base in this population. Hypnosis has been used in younger adults with positive results. The main objective of this study was to measure the feasibility and efficacy of hypnosis (including self hypnosis) in the management of chronic pain in older hospitalized patients. A single center randomized controlled trial using a two arm parallel group design (hypnosis versus massage). Inclusion criteria were chronic pain for more than 3 months with impact on daily life activities, intensity of > 4; adapted analgesic treatment; no cognitive impairment. Brief pain inventory was completed. Fifty-three patients were included (mean age: 80.6 ± 8.2--14 men; 26 hypnosis; 27 massage. Pain intensity decreased significantly in both groups after each session. Average pain measured by the brief pain index sustained a greater decrease in the hypnosis group compared to the massage group during the hospitalisation. This was confirmed by the measure of intensity of the pain before each session that decreased only in the hypnosis group over time (P = 0.008). Depression scores improved significantly over the time only in the hypnosis group (P = 0.049). There was no effect in either group 3 months post hospitals discharge. Hypnosis represents a safe and valuable tool in chronic pain management of hospitalized older patients. In hospital interventions did not provide long term post discharge relief. ISRCTN15615614; registered 2/1/2015.

  17. Utilizing Z-track Air Lock Technique to Reduce Pain in Intramuscular Injections

    Directory of Open Access Journals (Sweden)

    Evelyn Hemme Tambunan

    2015-04-01

    Full Text Available Introduction: Injection is one of most painful and common medical interventions that more than 12 billion of it are administered annually throughout the world. Pain remains as one of the unresolved health problems. The objective of this research was to investigate the pain severity utilizing the z-track air lock technique during intra muscular injection procedure. Method:This study was conducted as an unblinded cinical trial, where 90 female subjects aged between 18-25 years old were randomly assigned to three groups of 30. Each group received z-track air lock (Group ZTAL, air lock (AL, and z-track (Group ZT techniques. Neurobion 5000 vitamin used as an injection substance.A Verbal Rating Scale (VRS on 0–3 was used to evaluate the severity of pain during procedure. Data were analized using the SPSS version 19. Groups’ age, Body Mass Index (BMI and pain severity were analyzed through descriptive and One Way ANOVA statistics. Results: Results showed that there were no signifi cant differences of pain severity both within and between groups (p > 0.05. Discussion: Both Z-track and air lock method are less pain compared to traditional method according to previous studies. Noncicepti stimulus inhibited nocicepti stimulus in z-track technique while locking effect inhibit leakeage of substance injection to subcutaneous layer of skin which contain of nerve fi bers. However All techniques are recommended to produce less pain therefore it can be considered as a standard procedure for intra muscular injection. Keywords: intramuscular injection, z-track air lock technique, pain

  18. Neonatal pain and reduced maternal care: Early-life stressors interacting to impact brain and behavioral development.

    Science.gov (United States)

    Mooney-Leber, Sean M; Brummelte, Susanne

    2017-02-07

    Advances in neonatal intensive care units (NICUs) have drastically increased the survival chances of preterm infants. However, preterm infants are still exposed to a wide range of stressors during their stay in the NICU, which include painful procedures and reduced maternal contact. The activation of the hypothalamic-pituitary-adrenal (HPA) axis, in response to these stressors during this critical period of brain development, has been associated with many acute and long-term adverse biobehavioral outcomes. Recent research has shown that Kangaroo care, a non-pharmacological analgesic based on increased skin-to-skin contact between the neonate and the mother, negates the adverse outcomes associated with neonatal pain and reduced maternal care, however the biological mechanism remains widely unknown. This review summarizes findings from both human and rodent literature investigating neonatal pain and reduced maternal care independently, primarily focusing on the role of the HPA axis and biobehavioral outcomes. The physiological and positive outcomes of Kangaroo care will also be discussed in terms of how dampening of the HPA axis response to neonatal pain and increased maternal care may account for positive outcomes associated with Kangaroo care. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Intelligent Physical Exercise Training proves effective in enhancing muscle strength and reducing musculoskeletal pain in a workplace setting

    DEFF Research Database (Denmark)

    Dalager, Tina; Justesen, Just Bendix; Sjøgaard, Gisela

    intensity IPET every week within working hours for one year. The training program was based on baseline health check measures of muscle strength, musculoskeletal pain (self-reported on a 0-9 numeric box scale), cardiorespiratory fitness and health risk indicators, as well as functional capacity including...... compared with REF (~ 20 %). Discussion: High intensity IPET during working hours significantly reduced musculoskeletal pain in neck and shoulders as well as increased muscle strength among office workers. Of note is the large proportion of employees in TG who had pain reductions of ≥1, which is considered...... workers based on health checks and to assess the effect on musculoskeletal health (Sjøgaard G et al. BMC Public Health 2014, 14:652). Methods: Office workers were at each of 6 companies randomized 1:1 to a training group, TG (N=194) or a reference group, REF (N=195). TG received one-hour supervised high...

  20. Modulation of Invading and Resident Inflammatory Cell Activation as a Novel Way to Mitigate Spinal Cord Injury Associated Neuropathic Pain

    Science.gov (United States)

    2016-10-01

    shown by the FDA in the determination of its full range of therapeutic benefits. Tlmeline and Cost Activities Aim 1 Effect of CBD on SCI- NP ...the non-psychoactive cannabinoid cannabidiol (CBD) on spinal cord injury neuropathic pain (SCI- NP ) and associated lnllammation. Changes in thermal and...1 4. Impact ........................................................................... 13 5. Changes/ Problems

  1. Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1

    NARCIS (Netherlands)

    Singhmar, Pooja; Huo, XiaoJiao; Eijkelkamp, Niels; Berciano, Susana Rojo; Baameur, Faiza; Mei, Fang C; Zhu, Yingmin; Cheng, Xiaodong; Hawke, David; Mayor, Federico; Murga, Cristina; Heijnen, Cobi J.; Kavelaars, Annemieke

    2016-01-01

    cAMP signaling plays a key role in regulating pain sensitivity. Here, we uncover a previously unidentified molecular mechanism in which direct phosphorylation of the exchange protein directly activated by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby

  2. The effectiveness of virtual reality on reducing pain and anxiety in burn injury patients: a systematic review.

    Science.gov (United States)

    Morris, Linzette Deidré; Louw, Quinette Abegail; Grimmer-Somers, Karen

    2009-01-01

    To systematically review the current evidence for the effectiveness of Virtual Reality (VR), in conjunction with pharmacologic analgesia on reducing pain and anxiety in burn injury patients undergoing wound dressing changes and physiotherapy management compared with pharmacologic analgesia alone or other forms of distraction. A comprehensive search was conducted between December 2007 and January 2008, and updated in January 2009, before publication. Computerized bibliographic databases were individually searched using specifically developed search strategies to identify eligible studies. Nine studies were deemed eligible for inclusion in this review. Wound dressing changes was the most common procedure during which VR was trialed. Pain was the primary outcome measure in all of the studies included. Anxiety was a secondary outcome measure in 3 of the 9 included studies. VR, in conjunction with pharmacologic analgesics, significantly reduced pain experienced by burn injury patients during wound dressing changes and physiotherapy. There is equivocal evidence for the effect of VR in conjunction with pharmacologic analgesics on reducing anxiety in burn injury patients during wound dressing changes and physiotherapy. This is the first known systematic review to report on the effectiveness of VR, in conjunction with pharmacologic analgesia on reducing pain and anxiety in burn injury patients undergoing wound dressing changes and physiotherapy management compared with pharmacologic analgesia alone or other forms of distraction. Used as an adjunct to the current burn pain management regimens, VR could possibly assist health professionals in making the rehabilitation process for burn patients less excruciating, thereby improving functional outcomes. Further research investigating the effect of VR on anxiety in burn injury patients is warranted.

  3. Protocol for Shoulder function training reducing musculoskeletal pain in shoulder and neck: a randomized controlled trial

    DEFF Research Database (Denmark)

    Andersen, Christoffer H; Andersen, Lars L; Mortensen, Ole S

    2011-01-01

    treated by physical therapists. The exact mechanism of neck pain is rarely revealed by clinical examination and the treatment has varied from passive rest to active treatments. Active treatments have often been divided into either training of the painful area or the surrounding musculature avoiding direct...... training of the painful area. Our study investigates the effect of the latter approach. METHODS/DESIGN: A randomized controlled trial of 10 weeks duration is currently being conducted. Employed office workers with severe neck-shoulder pain are randomized to 3 × 20 min shoulder function training...... with training supervision or to a reference group receiving advice to stay physically active. Shoulder function training primarily focuses on the serratus anterior and lower trapezius muscle with only minimal activation the upper trapezius.An announcement was sent to the administrative section of the university...

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

    Science.gov (United States)

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

    2010-07-01

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

  5. An Extended Exercise-Based Cardiac Rehabilitation Program reduces Key Inflammatory Biomarkers in Atherosclerosis

    DEFF Research Database (Denmark)

    Jørgensen, Malene Munk; Petersen, Annemette Krintel; Mølby Nielsen, Mette

    2018-01-01

    ECR program was more successful in reducing low-grade vascular inflammation, compared to a conventional 8-week ECR program. A total of 110 patients treated for IHD, and referred to ECR, were randomized to a 12-week or 8-week ECR intervention. We measured the concentration of soluble vascular cell...... adhesion molecule 1 (sVCAM-1), interleukin-6 (IL-6), highsensitivity C-reactive protein (hsCRP), before and after participation in either of the two ECRs and at 6-month and one year follow-up. Additionally, we determined the absolute White Blood Cell count (WBC), the absolute monocyte count...... at the end of ECR (IL-6: p=0.002; hsCRP: pprogram. However, this effect was not sustained on a long...

  6. 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

  7. Randomized controlled trial of topical EMLA and breastfeeding for reducing pain during wDPT vaccination.

    Science.gov (United States)

    Gupta, Navratan Kumar; Upadhyay, Amit; Agarwal, Astha; Goswami, Gaurav; Kumar, Jagdish; Sreenivas, V

    2013-11-01

    The primary objective was to evaluate the analgesic effect of a eutectic mixture of local anesthetics (EMLA) during whole cell DPT vaccination. The secondary objective was to evaluate if the analgesic effect of EMLA was synergistic to breastfeeding. A randomized, placebo-controlled trial was done to include infants of up to 3 months of age who came for their first DPT vaccination. The outcome variables were duration of cry, latency of onset of cry, and Modified Facial Coding Score. Thirty babies were enrolled in each of three groups. The groups did not differ significantly in baseline characteristics. Median (interquartile range) of duration of cry was least [34.6 (24.1-72.2) s] in babies receiving EMLA cream with breastfeeding (EB group), followed by 94.2 (46.1-180) s in babies receiving EMLA cream with oral distilled water (EW group), as compared to 180.0 (180-180) s in babies receiving placebo cream with oral distilled water (PCW group) (p cry was significantly greater in EB group [2.4 (1.14) s] and EW group [1.9 (0.62) s] as compared to babies in PCW group [1.5 (0.47) s] (p < 0.05), but the difference between EB and EW groups was not significant. Modified Facial Coding Score was significantly lower in EB group as compared to the other groups (p < 0.05). Topical EMLA is effective in reducing pain and has a synergistic effect in analgesia when combined with breastfeeding during vaccination in infants.

  8. Liposomal Bupivacaine Use in Transversus Abdominis Plane Blocks Reduces Pain and Postoperative Intravenous Opioid Requirement After Colorectal Surgery.

    Science.gov (United States)

    Stokes, Audrey L; Adhikary, Sanjib D; Quintili, Ashley; Puleo, Frances J; Choi, Christine S; Hollenbeak, Christopher S; Messaris, Evangelos

    2017-02-01

    Enhanced recovery protocols frequently use multimodal postoperative analgesia to improve postoperative outcomes in patients undergoing colorectal surgery. The purpose of this study was to evaluate liposomal bupivacaine use in transversus abdominis plane blocks on postoperative pain scores and opioid use after colorectal surgery. This was a retrospective cohort study comparing outcomes between patients receiving nonliposomal anesthetic (n = 104) and liposomal bupivacaine (n = 303) blocks. The study was conducted at a single tertiary care center. Patients included those identified within an institutional database as inpatients undergoing colorectal procedures between 2013 and 2015 who underwent transversus abdominis plane block for perioperative analgesia. The study measured postoperative pain scores and opioid requirements. Patients receiving liposomal bupivacaine had significantly lower pain scores for the first 24 to 36 postoperative hours. Pain scores were similar after 36 hours. The use of intravenous opioids among the liposomal bupivacaine group decreased by more than one third during the hospitalization (99.1 vs 64.5 mg; p = 0.040). The use of ketorolac was also decreased (49.0 vs 18.3 mg; p bupivacaine group but did not achieve statistical significance. The study was limited by its retrospective, single-center design and heterogeneity of block administration. Attenuated pain scores observed with liposomal bupivacaine use were associated with significantly lower intravenous opioid and ketorolac use, suggesting that liposomal bupivacaine-containing transversus abdominis plane blocks are well aligned with the opioid-reducing goals of many enhanced recovery protocols.

  9. Subconjunctival Delivery of p75NTR Antagonists Reduces the Inflammatory, Vascular, and Neurodegenerative Pathologies of Diabetic Retinopathy.

    Science.gov (United States)

    Galan, Alba; Barcelona, Pablo F; Nedev, Hinyu; Sarunic, Marinko V; Jian, Yifan; Saragovi, H Uri

    2017-06-01

    The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections. We compared the pharmacokinetics of a single 40 μg subconjunctival (SCJ) depot to the reported effective 5 μg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death. The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure. Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.

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

    OpenAIRE

    Lionberger, David

    2010-01-01

    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 ac...

  11. Efficacy of port-site and intraperitoneal application of bupivacaine in reducing early post-laparoscopic cholecystectomy pain

    International Nuclear Information System (INIS)

    Ahmad, J.; Khan, Z.A.; Khan, A.

    2015-01-01

    The aim of this study was to assess the analgesic efficacy of Bupivacaine application at port-site and intraperitoneal infiltration in patients with laparoscopic cholecystectomy. Study Design: Randomized Controlled Clinical Trial. Place and Duration: The study was conducted at Rehman Medical Institute (RMI) Peshawar, Pakistan from June 2009 to June 2012. Materials and Methods: Patients who underwent elective laparoscopic cholecystectomy during the study period were included in the study. Eighty patients were randomized into two groups, study group and control group. The study group received 40 ml of 0.25% bupivacaine intraoperatively as intraperitoneal infiltration and local infiltration at the port sites. Pain assessment was done using visual analogue pain score (VAS) of 0-10 at fixed intervals during the first 24 hours post surgery. Results: The mean VAS score in the study group was less as compared to the control group throughout the 24 hours assessment period, however this difference was statistically significant (p<0.001) only during the first three assessments at 1 hour, 4 hours and 8 hours post surgery. The analgesia requirement was also significantly (p<0.001) decreased in the study group. Conclusion: Port site and intraperitoneal application of local anesthetic bupivacaine significantly reduced pain during the first 8 hours post surgery and total analgesia requirement was also significantly reduced. It is a simple and easily applicable technique which increases patient comfort and can be safely used to decrease post operative pain in patients undergoing laparoscopic cholecystectomy. (author)

  12. Nicoboxil/nonivamide cream effectively and safely reduces acute nonspecific low back pain – a randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Blahova Z

    2016-12-01

    Full Text Available Zuzana Blahova,1 Janina Claudia Holm,1 Thomas Weiser,2 Erika Richter,2 Matthias Trampisch,2 Elena Akarachkova3 1Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany; 3I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Background/objective: Low back pain affects many patients and has a high socioeconomic impact. Topical capsaicinoids have been used for decades to treat musculoskeletal pain. This study investigated the effects of the fixed dose combination (FDC of nonivamide (a capsaicinoid and nicoboxil (a nicotinic acid ester cream in the treatment of acute nonspecific low back pain.Materials and methods: This phase III randomized, double-blind, placebo-controlled, multinational, multi-center trial investigated efficacy, safety, and tolerability of topical nicoboxil 1.08%/nonivamide 0.17% (Finalgon® cream in treatment of acute nonspecific low back pain with the endpoints: pain intensity (PI difference between pre-dose baseline and 8 hours after first application and the end of treatment, mobility score, and efficacy score.Results: Patients (n=138, 21–65 years of age, were treated for up to 4 days with FDC or placebo cream. Mean baseline PI was 6.8 on a 0–10 point numerical rating scale. After 8 hours, pain was more reduced with the FDC than with placebo (adjusted means: 2.824 vs. 0.975 points; p<0.0001. On the last treatment day, mean pain reduction by the FDC was stronger than with placebo (adjusted means: 5.132 vs. 2.174 points; p<0.0001. Mobility on Day 1 was in favor of the FDC when compared to placebo (odds ratio [95% confidence interval {CI}]: 7.200 [3.609, 14.363], p<0.0001. At the end of treatment, patients treated with the FDC rated efficacy significantly higher than placebo (odds ratio [95% CI]: 11.370 [5.342, 24.199], p<0.0001. Both treatments were tolerated well. No serious adverse events were reported.Conclusion: Nicoboxil

  13. 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

  14. A CRPS-IgG-transfer-tra