Open Pain Journal最新文献

{"title":"TRP Receptors in Arthritis, Gaining Knowledge for Translation from Experimental Models","authors":"E. Fernandes, S. Awal, R. Karadaghi, S. Brain","doi":"10.2174/1876386301306010050","DOIUrl":"https://doi.org/10.2174/1876386301306010050","url":null,"abstract":"Arthritis is a condition characterised by mainly pain, reduced joint movement and signs of inflammation, such as swelling. The disorder has many different types, of which osteoarthritis (a degenerative joint disease) and rheumatoid arthritis (a chronic autoimmune disease) are the two most common forms. There are >6 million sufferers in the UK and both conditions have a huge potential to impair capabilities and contribute to social and economic burdens. Whilst there are a wide range of arthritic therapies available, many patients under treatment complain of poor pain relief. Thus there is a need for novel therapeutic approaches, and the transient receptor potential (TRP) family of receptor channels has been investigated. One particular area of recent research has been the ligand-gated transient receptor potential vanilloid 1 (TRPV1) channel. Findings from numerous pre-clinical models and scientific studies have shown that TRPV1 desensitisa- tion, or the use of TRPV1 antagonists alleviates pain and some inflammatory aspects. New findings have started to unveil the potential of other TRP channels in mediating arthritic pain and inflammation. With the understanding that the cur- rently available treatments for arthritis are limited, researchers have looked into the exciting prospect that TRP receptor antagonists may be developed into effective, specific drugs, which would potentially protect against the complications of arthritis. These antagonists are still under development, although only data from studies from pre-clinical models are cur- rently available. This review acts to summarize knowledge of the potential influence of TRP receptors in arthritis to date.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"50-61"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPV1 Antagonists as Analgesic Agents","authors":"M. Trevisani, R. Gatti","doi":"10.2174/1876386301306010108","DOIUrl":"https://doi.org/10.2174/1876386301306010108","url":null,"abstract":"The last decade (2001 - 2010), declared as the Decade of Pain Control and Research by the United States Con- gress, brought significantly advances in our understanding of pain biology. Unfortunately, this has not translated into ad- ditional effective treatments of chronic pain conditions. Chronic pain is a debilitating and complex clinical state usually associated with diabetic neuropathy, postherpetic neuralgia, low back pathology, fibromyalgia, and neurological disorders. Standard pain drugs, even narcotic opioid analgesic agents, often provide unsatisfactory pain relief while causing impor- tant side-effect such as sedation, tolerance, dependence, respiratory depression and constipation. Furthermore, the effec- tive management of chronic pain needs a multidisciplinary management approach and still represents one of the most ur- gent unmet medical need. Recently, preclinical research has uncovered new molecular mechanisms underlying the genera- tion and transduction of pain, many of which represent new targets for innovative pharmacological interventions. This re- view focuses on Transient Receptor Potential (TRP) Vanilloid Type 1 (TRPV1) channel as a target for treating chronic pain. TRPV1 is a multifunctional ion channel involved in thermosensation (heat) and taste perception. Importantly, TRPV1 also functions as a molecular integrator for a broad variety of seemingly unrelated noxious stimuli. Indeed, TRPV1 is thought to be a major transducer of the thermal hyperalgesia that follows inflammation and/or tissue injury. De- sensitization to topical TRPV1 agonists (e.g. capsaicin creams and patches) has been in clinical use for decades to treat chronic painful conditions like diabetic neuropathy. Most recently, a number of potent, small molecule TRPV1 antago- nists have been advanced into clinical trials for pain relief. Perhaps not unexpectedly given the prominent role of TRPV1 in thermosensation, some of these antagonists showed worrisome adverse effects (hyperthermia and impaired noxious heat sensation) in humans, leading to their withdrawal from clinical trials. However, recent reports of TRPV1 antagonists that do not affect core body temperature in preclinical species suggest a potential opportunity to reduce at least this impor- tant side effect.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"108-118"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in TRP Channels Expression in Painful Conditions","authors":"M. Bishnoi, L. Premkumar","doi":"10.2174/1876386301306010010","DOIUrl":"https://doi.org/10.2174/1876386301306010010","url":null,"abstract":"Over the last fifteen years after the successful cloning of the first nociceptive Transient Receptor Potential (TRP) channel, TRP Vanilloid 1, other members of the TRP channel family have been cloned, characterized and implicated in different modalities of pain. Tremendous progress has been made with regard to the specific role of these TRP channels in nociception using electrophysiological and molecular methods, along with behavioral models combined with gene disruption techniques. This review summarizes the evidence supporting the role of TRP channels (TRP Vanilloid 1, TRP Vanilloid 2, TRP Vanilloid 3, TRP Vanilloid 4, TRP Ankyrin 1, TRP Melastatin 2, TRP Melastatin 3, TRP Melastatin 8, TRP Mucolipin 3 and TRP Canonical 1, 6) involved in nociception. The review also highlights the current status and future avenues for developing TRP channel modulators as analgesic agents.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"10-22"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of TRPA1 in Pain Pathophysiology and Implications for the Development of a New Class of Analgesic Drugs","authors":"O. Radresa, H. Dahllof, E. Nyman, A. Nolting, J. Albert, P. Raboisson","doi":"10.2174/1876386301306010137","DOIUrl":"https://doi.org/10.2174/1876386301306010137","url":null,"abstract":"The Transient Receptor Potential A1 (TRPA1) ion channel has evolved in animals to respond to signals from a variety of sensory stimuli. Many structural determinants of its multimodal activation have been identified to date. TRPA1 activities include responses to exogenous chemical irritants, responses to endogenous inflammatory mediators, zinc, volt- age, temperature or stretch and subtle yet critical modulation by calcium ions. TRPA1 has emerged as an important target for several types of pain and inflammatory conditions because of its limited expression profile and its demonstrated roles in mediating different types of pain and sensitization of peripheral sensory afferents. Despite observed species differences in channel pharmacology, recent genetic evidence in human brings some hope that preclinical efficacy in disease models will translate to patient condition. During the past decade, various groups have investigated the development of a new class of analgesic drugs or anti-tussive agents aimed at blocking TRPA1 activity in primary sensory afferents. Several companies are advancing toward clinical proof of concept studies. This review aims to summarize key advances in the understanding of TRPA1 with regard to its roles and implications for patient conditions.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"137-153"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRP Channels in Visceral Pain","authors":"L. Blackshaw, S. Brierley, A. Harrington, P. Hughes","doi":"10.2174/1876386301306010023","DOIUrl":"https://doi.org/10.2174/1876386301306010023","url":null,"abstract":"Visceral pain is both different and similar to somatic pain - different in being poorly localized and usually referred elsewhere to the body wall, but similar in many of the molecular mechanisms it employs (like TRP channels) and the specialization of afferent endings to detect painful stimuli. TRPV1 is sensitive to low pH. pH is lowest in gastric juice, which may cause severe pain when exposed to the oesophageal mucosa, and probably works via TRPV1. TRPV1 is found in afferent fibres throughout the viscera, and the TRPV1 agonist capsaicin can recapitulate symptoms experienced in disease. TRPV1 is also involved in normal mechanosensory function in the gut. Roles for TRPV4 and TRPA1 have also been described in visceral afferents, and TRPV4 is highly enriched in them, where it plays a major role in both mechanonociception and chemonociception. It may provide a visceral-specific nociceptor target for drug development. TRPA1 is also involved in mechano-and chemosensory function, but not as selectively as TRPV4. TRPA1 is colocalized with TRPV1 in visceral afferents, where they influence each other's function. Another modulator of TRPV1 is the cool/mint receptor TRPM8, which, when activated can abrogate responses mediated via TRPV1, suggesting that TRPM8 agonists may provide analgesia via this pathway. In all, the viscera are rich in TRP channel targets on nociceptive neurones which we hope will provide opportunities for therapeutic analgesia.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"23-30"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INTRODUCTION - Targeting TRP Channels for Pain Relief: TRPV1 and Beyond","authors":"M. Chung","doi":"10.2174/1876386301306010008","DOIUrl":"https://doi.org/10.2174/1876386301306010008","url":null,"abstract":"Management of chronic and pathological pain without incurring systemic side effects is a major medical challenge. Currently available drugs, such as non-steroidal antiinflammatory drugs or opioid agonists, are efficacious through peripheral and central mechanisms. However, various complications and development of tolerance are serious problems. Other classes of drugs, such as antidepressants and anti-convulsants, are often used for multiple pain syndromes. However, the efficacy of these drugs is commonly unsatisfactory, and their mechanism of action is not clear. For establishing novel, selective anti-hyperalgesic therapeutic approaches, targeted inhibition of pain-specific pathways or molecules would be ideal, and these approaches suggest straightforward strategies. A new era of exploring such “straightforward” approaches was opened with regard to peripheral nociceptors by the identification of the vanilloid receptor-1 (VR-1), which was designated transient receptor potential channel vanilloid subtype 1 (TRPV1). TRPV1 is a receptor for capsaicin, proton, and noxious heat. Capsaicin has long been known to be a natural compound capable of evoking an intense burning sensation and pain in human and experimental animals. It has been hypothesized that specific manipulation of TRPV1 may selectively relieve pain under injury or inflammatory conditions. Interfering with TRPV1 has been a central focus of these efforts during the 15 years following the cloning of TRPV1. Numerous pharmacological compounds have been developed targeting TRPV1. The characteristics and roles of TRPV1 have been rigorously studied using multiple approaches ranging from biophysical characterization to clinical trials in human subjects. Meanwhile, other members of the TRP channel family in addition to TRPV1 have been suggested to be also involved in nociception under pathophysiological conditions. These studies have identified targets in addition to TRPV1 as potential candidates for selective anti-hyperalgesic treatment free from complications.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Qualitative Hyperalgesia Profile: A New Metric to Assess Chronic Post-Thoracotomy Pain.","authors":"Jeffrey Chi-Fei Wang,&nbsp;Ching-Hsia Hung,&nbsp;Peter Gerner,&nbsp;Ru-Rong Ji,&nbsp;Gary R Strichartz","doi":"10.2174/1876386301306010190","DOIUrl":"https://doi.org/10.2174/1876386301306010190","url":null,"abstract":"<p><p>Thoracotomy often results in chronic pain, characterized by resting pain and elevated mechano-sensitivity. This paper defines complex behavioral responses to tactile stimulation in rats after thoracotomy, shown to be reversibly relieved by systemic morphine, in order to develop a novel qualitative \"pain\" score. A deep incision and 1 hour of rib retraction in male Sprague-Dawley rats resulted in reduced threshold and a change in the locus of greatest tactile (von Frey filament) sensitivity, from the lower back to a more rostral location around the wound site, and extending bilaterally. The fraction of rats showing nocifensive responses to mild stimulation (10 gm) increased after thoracotomy (from a pre-operative value of 0/10 to 8/10 at 10 days post-op), and the average threshold decreased correspondingly, from 15 gm to ∼4 gm. The nature of the nocifensive responses to tactile stimulation, composed pre-operatively only of no response (Grade 0) or brief contractions of the local subcutaneous muscles (Grade I), changed markedly after thoracotomy, with the appearance of new behaviors including a brisk lateral \"escape\" movement and/or a 180° rotation of the trunk (both included as Grade II), and whole body shuddering, and scratching and squealing (Grade III). Systemic morphine (2.5 mg/kg, i.p.) transiently raised the threshold for response and reduced the frequency of Grade II and III responses, supporting the interpretation that these represent pain. The findings support the development of a Qualitative Hyperalgesic Profile to assess the complex behavior that indicates a central integration of hyperalgesia.</p>","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 ","pages":"190-198"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/7c/nihms533898.PMC3932053.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32151509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting TRPV3 for the Development of Novel Analgesics.","authors":"Susan M Huang,&nbsp;Man-Kyo Chung","doi":"10.2174/1876386301306010119","DOIUrl":"https://doi.org/10.2174/1876386301306010119","url":null,"abstract":"<p><p>Decades of characterization of the transient receptor potential vanilloid subtype 1 (TRPV1) has led to the realization of its central role in thermosensation and pain perception. A large number of pharmaceutical companies have had interest in developing TPRV1 antagonists for the treatment of pain. The subsequent discovery of multiple other members of this TRPV family has not gone unnoticed. TRPV3 exhibits approximately 40% homology to TRPV1, and has common as well as distinct features from TRPV1 in channel physiology, expression and function. Here we review the current understanding of TRPV3 channel biology, activation, sensitization and the consequences of TRPV3 manipulation for thermosensation and nociception, as well as additional considerations regarding the expression of TRPV3 in the skin. We weigh in on the available evidence in the context of potential development of TRPV3 modulating agents as analgesics.</p>","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 Spec Iss 1","pages":"119-126"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182939/pdf/nihms458599.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32721920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Chronic Fatigue Syndrome and Fibromyalgia with D-Ribose- An Open-label, Multicenter Study","authors":"J. Teitelbaum, Janelle Jandrain, Ryan McGrew","doi":"10.2174/1876386301205010032","DOIUrl":"https://doi.org/10.2174/1876386301205010032","url":null,"abstract":"Objectives: Chronic Fatigue Syndrome and Fibromyalgia (CFS/FMS) are debilitating syndromes affecting ~2- 4% of the population. Although they are heterogeneous conditions associated with many triggers, they appear to have the common pathology of being associated with impaired energy metabolism. As D-ribose has been shown to increase cellular energy synthesis, and was shown to significantly improve clinical outcomes in CFS/FMS in an earlier study, we hypothesized that giving D-ribose would improve function in CFS/FMS patients. Design, Location, and Subjects: An open-label, unblinded study in which 53 US clinics enrolled 257 patients who had been given a diagnosis of CFS/FMS by a health practitioner. Interventions: All subjects were given D-ribose (Corvalen), a naturally occurring pentose carbohydrate, 5-g TID for 3 weeks.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"5 1","pages":"32-37"},"PeriodicalIF":0.0,"publicationDate":"2012-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Targets in Pain, Non-Neuronal Cells, and the Role of Palmitoyletha- nolamide","authors":"J. Hesselink","doi":"10.2174/1876386301205010012","DOIUrl":"https://doi.org/10.2174/1876386301205010012","url":null,"abstract":"Persistent pain in neuropathic conditions is often quite refractory to conventional analgesic therapy, with most patients obtaining, at best, only partial relief of symptoms. The tendency still exists to treat these complex pains with one or a combination of two analgesics at the most. Given the complex nature of the underlying pathogenesis, this approach more often than not fails to produce a meaningful improvement. New targets are therefore badly needed. In this regard non-neuronal cells - glia and mast cells in particular - are emerging as new targets for the treatment of neuropathic pain. An extensive preclinical database exists showing that the naturally occurring fatty acid amide palmitoylethanolamide is endowed with anti-inflammatory activity, and clinical trials assessing the efficacy and safety of palmitoylethanolamide in neuropathic pain have been successful in generating proof-of-concept for treatment in man. Here I will review salient pre- clinical and clinical evidence supporting non-neuronal cells as viable targets in the treatment of neuropathic pain. This will be followed by a discussion of recent proof-of-concept clinical trials demonstrating the efficacy and safety of palmi- toylethanolamide in the treatment of various neuropathic pain states.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"5 1","pages":"12-23"},"PeriodicalIF":0.0,"publicationDate":"2012-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}