260,699 research outputs found
R-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids
No full textBackground: 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 PPAR gamma 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
Attention focus, trait anxiety, and pain perception in patients undergoing colposcopy
No full textFew studies have compared the relative efficacy of attention-focus strategies in reducing clinical pain. Colposcopy, a medical diagnostic examination performed to identify premalignant cervical cell changes, elicits both anxiety and pain in patients, while allowing little or no behavioural control over the event. Employing a multi-group experimental design, the present study sought to investigate how different types of attention-focus strategies impacted upon pain perception, state anxiety, and affect, in a sample of 123 colposcopy patients. Patients were randomly assigned to one of three groups: sensory focusing, active distraction, and undirected control. Psychometric measures of pre-colposcopy pain expectancy and dispositional trait anxiety were also taken, in order to assess whether these factors further contributed to outcomes. Overall, when controlling for pain expectancy and trait anxiety, self-reported pain intensity, sensory pain, and affective pain did not differ across groups. Further, there were no significant between-groups differences in colposcopy-related state anxiety or affect. However, pre-colposcopy psychometric measures were found to be predictive of a range of outcomes. Pre-colposcopy pain expectancy, but not trait anxiety, was found to be positively related to colposcopy-related pain. It was further demonstrated that heightened state anxiety following colposcopy was due to experienced pain and pain unpleasantness, rather than to aspects of the pre-colposcopy prediction of pain. The results have implications for management of acute clinical pain
'I think positivity breeds positivity': a qualitative exploration of the role of family members in supporting those with chronic musculoskeletal pain to stay at work
No full textBackground: It is proposed that family members are important sources of support in helping those with chronic musculoskeletal pain to remain at work, but the phenomenon remains largely unexplored. The aim of this study was to examine the extent and nature of support provided by family members in this respect.
Methods: Qualitative data were collected from workers and their ‘significant others’ spouses/partners/close family members) in two un-related studies focused on working with pain; one conducted in the United Kingdom (n = 10 dyads) and one in the Netherlands (n = 21 dyads). Thematic analysis techniques were applied to both sets of data independently, and findings were then assimilated to establish common themes.
Results: Findings were broadly similar in both studies. Workers acknowledged significant other support in helping them to manage their pain and remain at work, and their descriptions of the type of support provided and required were echoed by their significant others. Three common themes were identified - ‘connectivity’, ‘activity’ and ‘positivity’. Worker and significant other responses were largely congruent, but significant others provided more in-depth information on the nature of their support, their concerns and the impact on their relationship.
Conclusions: This research presents novel insights about the specific contribution made by significant others in helping their relatives with chronic musculoskeletal pain to stay at work. These findings add to the under-represented ‘social’ dimension of the biopsychosocial model currently applied to our understanding and treatment of pain, and point to harnessing support from significant others as a potentially effective management strategy
The effects of graded motor imagery and its components on chronic pain: A systematic review and meta-analysis
No full textThis is the post-print version of the final paper published in The Journal of Pain. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 The American Pain Society.Graded motor imagery (GMI) is becoming increasingly used in the treatment of chronic pain conditions. The objective of this systematic review was to synthesize all evidence concerning the effects of GMI and its constituent components on chronic pain. Systematic searches were conducted in 10 electronic databases. All randomized controlled trials (RCTs) of GMI, left/right judgment training, motor imagery, and mirror therapy used as a treatment for chronic pain were included. Methodological quality was assessed using the Cochrane risk of bias tool. Six RCTs met our inclusion criteria, and the methodological quality was generally low. No effect was seen for left/right judgment training, and conflicting results were found for motor imagery used as stand-alone techniques, but positive effects were observed for both mirror therapy and GMI. A meta-analysis of GMI versus usual physiotherapy care favored GMI in reducing pain (2 studies, n = 63; effect size, 1.06 [95% confidence interval, .41, 1.71]; heterogeneity, I2 = 15%). Our results suggest that GMI and mirror therapy alone may be effective, although this conclusion is based on limited evidence. Further rigorous studies are needed to investigate the effects of GMI and its components on a wider chronic pain population.NHMR
Accelerated aging in adults with knee osteoarthritis pain: consideration for frequency, intensity, time, and total pain sites
No full textabstract: Introduction: Individuals with osteoarthritis (OA) show increased morbidity and mortality. Telomere length, a measure of cellular aging, predicts increased morbidity and mortality. Telomeres shorten with persisting biological and psychosocial stress. Living with chronic OA pain is stressful. Previous research exploring telomere length in people with OA has produced inconsistent results. Considering pain severity may clarify the relationship between OA and telomeres.
Objectives: We hypothesized that individuals with high OA chronic pain severity would have shorter telomeres than those with no or low chronic pain severity.
Methods: One hundred thirty-six adults, ages 45 to 85 years old, with and without symptomatic knee OA were included in the analysis. Peripheral blood leukocyte telomere length was measured, and demographic, clinical, and functional data were collected. Participants were categorized into 5 pain severity groups based on an additive index of frequency, intensity, time or duration, and total number of pain sites (FITT). Covariates included age, sex, race or ethnicity, study site, and knee pain status.
Results: The no or low chronic pain severity group had significantly longer telomeres compared with the high pain severity group, P50.025. A significant chronic pain severity dose response emerged for telomere length, P50.034. The FITT chronic pain severity index was highly correlated with the clinical and functional OA pain measures. However, individual clinical and functional measures were not associated with telomere length.
Conclusion: Results demonstrate accelerated cellular aging with high knee OA chronic pain severity and provide evidence for the potential utility of the FITT chronic pain severity index in capturing the biological burden of chronic pain.The final version of this article, as published in PAIN Reports, can be viewed online at: https://insights.ovid.com/crossref?an=01938936-201706000-0000
Visually induced analgesia: seeing the body reduces pain
No full textGiven previous reports of strong interactions between vision and somatic senses, we investigated whether vision of the body modulates pain perception. Participants looked into a mirror aligned with their body midline at either the reflection of their own left hand (creating the illusion that they were looking directly at their own right hand) or the reflection of a neutral object. We induced pain using an infrared laser and recorded nociceptive laser-evoked potentials (LEPs). We also collected subjective ratings of pain intensity and unpleasantness. Vision of the body produced clear analgesic effects on both subjective ratings of pain and the N2/P2 complex of LEPs. Similar results were found during direct vision of the hand, without the mirror. Furthermore, these effects were specific to vision of one’s own hand and were absent when viewing another person’s hand. These results demonstrate a novel analgesic effect of non-informative vision of the body
Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats
No full textTreating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the beta-catenin-dependent pathway in the spinal cord and the beta-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats. Sciatic nerve injury causes a rapid-onset and long-lasting expression of Wnt3a, Wnt5b, and Ryk receptors in primary sensory neurons, and dorsal horn neurons and astrocytes. Spinal blocking of the Wnt/Ryk receptor signaling inhibits the induction and persistence of neuropathic pain without affecting normal pain sensitivity and locomotor activity. Blocking activation of the Ryk receptor with anti-Ryk antibody, in vivo or in vitro, greatly suppresses nerve injury-induced increased intracellular Ca 21 and hyperexcitability of the sensory neurons, and also the enhanced plasticity of synapses between afferent C-fibers and the dorsal horn neurons, and activation of the NR2B receptor and the subsequent Ca 21 -dependent signals CaMKII, Src, ERK, PKCg, and CREB in sensory neurons and the spinal cord. These findings indicate a critical mechanism underlying the pathogenesis of neuropathic pain and suggest that targeting the Wnt/Ryk signaling may be an effective approach for treating neuropathic pain.National Natural Science Foundation of China [NSFC81320108012, NSFC81271241, NSFC81371242]; Peking University Health Science Center [BMU20120310]; Chinese Ministry of Education [DEC20130001110013]; Parker Research Foundation (United States) [PRF-BSR11120708]SCI(E)[email protected]
EphrinB-EphB receptor signaling contributes to bone cancer pain via Toll-like receptor and proinflammatory cytokines in rat spinal cord
No full textTreating bone cancer pain poses a major clinical challenge, and the mechanisms underlying bone cancer pain remain elusive. EphrinB-EphB receptor signaling may contribute to bone cancer pain through N-methyl-D-aspartate receptor neuronal mechanisms. Here, we report that ephrinB-EphB signaling may also act through a Toll-like receptor 4 (TLR4)-glial cell mechanism in the spinal cord. Bone cancer pain was induced by tibia bone cavity tumor cell implantation (TCI) in rats. TCI increased the expression of TLR4 and the EphB1 receptor, the activation of astrocytes and microglial cells, and increased levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). The increased expression of TLR4 and EphB1 were colocalized with each other in astrocytes and microglial cells. Spinal knockdown of TLR4 suppressed TCI-induced behavioral signs of bone cancer pain. The TCI-induced activation of astrocytes and microglial cells, as well as the increased levels of IL-1 beta and TNF-alpha, were inhibited by intrathecal administration of TLR4-targeting siRNA2 and the EphB receptor antagonist EphB2-Fc, respectively. The administration of EphB2-Fc suppressed the TCI-induced increase of TLR4 expression but siRNA2 failed to affect TCI-induced EphB1 expression. Intrathecal administration of an exogenous EphB1 receptor activator, ephrinB2-Fc, increased the expression of TLR4 and the levels of IL-1 beta and TNF-alpha, activated astrocytes and microglial cells, and induced thermal hypersensitivity. These ephrinB2-Fc-induced alterations were suppressed by spinal knockdown of TLR4. This study suggests that TLR4 may be a potential target for preventing or reversing bone cancer pain and other similar painful processes mediated by ephrinB-EphB receptor signaling. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.AnesthesiologyClinical NeurologyNeurosciencesSCI(E)PubMed9ARTICLE122823-283515
Innovation in Pain Management
No full textThe transcript of a Witness Seminar held by the Wellcome Trust Centre for the History of Medicine at UCL, London, on 12 December 2002.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2004.©The Trustee of the Wellcome Trust, London, 2004.All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Annotated and edited transcript of a Witness Seminar held on 12 December 2002. Introduction by Dr Christina Faull; edited interview with Professor Patrick Wall.Unrelieved pain caused by cancer is experienced by more than 5 million people worldwide, and over the past 50 years has been accepted as unnecessary by both clinicians and politicians. Major innovations in the understanding of pain and our ability to treat it have been made. This Witness Seminar, chaired by Professor David Clark, describes the development of pain clinics, the introduction of the hospice in Britain, and global implementation of innovative technologies for cancer pain relief and advances in research during the latter part of the twentieth century. International health planners argue that the outstanding challenge is to put this knowledge into practice in healthcare settings around the world, often where resources are limited. Reynolds L A, Tansey E M. (eds) (2004) Innovation in pain management, Wellcome Witnesses to Twentieth Century Medicine, vol. 21. London: The Wellcome Trust Centre for the History of Medicine at UCL.The Wellcome Trust Centre for the History of Medicine at University College London is funded by the Wellcome Trust,which is a registered charity, no. 210183
Hallucinating Pain
No full textThe standard interpretation of quantum mechanics and a standard interpretation of the awareness of pain have a common feature: Both postulate the existence of an irresolvable duality. Whereas many physicists claim that all particles exhibit particle and wave properties, many philosophers working on pain argue that our awareness of pain is paradoxical, exhibiting both perceptual and introspective characteristics. In this chapter, we offer a pessimistic take on the putative paradox of pain. Specifically, we attempt to resolve the supposed paradox by undermining the reasons offered for accepting the introspective side of the dualism
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