Pub Date : 2013-07-26DOI: 10.2174/1876386320130624001
Xianze Meng, L. Lao, Xueyong Shen, B. Berman, K. Ren, P. Wei, Rui‐xin Zhang
Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund's adjuvant (CFA, 0.08 ml, 40 µg Mycobacterium tuberculosis) into the hind paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 µl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or -IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located in astrocytes and IL-17RA and NR1 are in neurons, the data suggest that EA alleviates pain by modulating glia-neuronal interactions that involve IL-17A, IL-17RA, and NR1 phosphorylation.
{"title":"Electroacupuncture inhibits spinal interleukin-17A to alleviate inflammatory pain in a rat model","authors":"Xianze Meng, L. Lao, Xueyong Shen, B. Berman, K. Ren, P. Wei, Rui‐xin Zhang","doi":"10.2174/1876386320130624001","DOIUrl":"https://doi.org/10.2174/1876386320130624001","url":null,"abstract":"Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund's adjuvant (CFA, 0.08 ml, 40 µg Mycobacterium tuberculosis) into the hind paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 µl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or -IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located in astrocytes and IL-17RA and NR1 are in neurons, the data suggest that EA alleviates pain by modulating glia-neuronal interactions that involve IL-17A, IL-17RA, and NR1 phosphorylation.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"183-189"},"PeriodicalIF":0.0,"publicationDate":"2013-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68125337","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}
Pub Date : 2013-07-12DOI: 10.2174/1876386301306010176
R. Kremer, M. Granot, D. Yarnitsky, Y. Crispel, S. Fadel, L. Best, R. Nir
Background and Objectives: Despite the established association between greater pain catastrophizing and enhanced postoperative pain, it is still unclear: (i) what is the relative contribution of each of the pain catastrophizing scale (PCS) dimensions in the prediction of acute and chronic postoperative pain; and (ii) whether PCS scores mediate the association between acute and chronic postoperative pain intensity. Methods: The current prospective, observational study was conducted at Rambam Health Care Campus, Haifa, Israel. PCS was obtained in 48 pain-free patients a day before an elective thoracotomy in response to tonic heat pain. Acute postthoracotomy pain (APTP) was assessed during rest, including general pain (Rest general ), and incision-related pain (Rest incision ), and in response to provoked physical activity, including hand elevation (Provoked hand ) and cough (Provoked- cough ). Chronic postthoracotomy pain (CPTP) was assessed after 4.5±2.3 months. Results: Of the PCS subscales, only rumination: (i) was correlated with Rest general scores (r=0.337, P=0.027); and (ii) predicted chronic postthoracotomy pain in a regression analysis (P=0.001). General PCS and its subscales mediated the correlation between Rest general and chronic postthoracotomy pain intensity (Ps<0.006). Conclusions: Findings may elucidate the unique role of the rumination subscale in reflecting an individual's postoperative acute and chronic pain responsiveness. The transition from acute to chronic postoperative pain seems to be facilitated by enhanced pain catastrophizing.
{"title":"The Role of Pain Catastrophizing in the Prediction of Acute and Chronic Postoperative Pain","authors":"R. Kremer, M. Granot, D. Yarnitsky, Y. Crispel, S. Fadel, L. Best, R. Nir","doi":"10.2174/1876386301306010176","DOIUrl":"https://doi.org/10.2174/1876386301306010176","url":null,"abstract":"Background and Objectives: Despite the established association between greater pain catastrophizing and enhanced postoperative pain, it is still unclear: (i) what is the relative contribution of each of the pain catastrophizing scale (PCS) dimensions in the prediction of acute and chronic postoperative pain; and (ii) whether PCS scores mediate the association between acute and chronic postoperative pain intensity. Methods: The current prospective, observational study was conducted at Rambam Health Care Campus, Haifa, Israel. PCS was obtained in 48 pain-free patients a day before an elective thoracotomy in response to tonic heat pain. Acute postthoracotomy pain (APTP) was assessed during rest, including general pain (Rest general ), and incision-related pain (Rest incision ), and in response to provoked physical activity, including hand elevation (Provoked hand ) and cough (Provoked- cough ). Chronic postthoracotomy pain (CPTP) was assessed after 4.5±2.3 months. Results: Of the PCS subscales, only rumination: (i) was correlated with Rest general scores (r=0.337, P=0.027); and (ii) predicted chronic postthoracotomy pain in a regression analysis (P=0.001). General PCS and its subscales mediated the correlation between Rest general and chronic postthoracotomy pain intensity (Ps<0.006). Conclusions: Findings may elucidate the unique role of the rumination subscale in reflecting an individual's postoperative acute and chronic pain responsiveness. The transition from acute to chronic postoperative pain seems to be facilitated by enhanced pain catastrophizing.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"176-182"},"PeriodicalIF":0.0,"publicationDate":"2013-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68125575","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}
Pub Date : 2013-05-30DOI: 10.2174/1876386301306010165
S. Held, R. Rolke, R. Treede, K. Schmieder, Z. Karimi, S. Sudhaus, M. Hasenbring
Most pain and disability variance in patients with low back pain still remains unexplained. The aim of this study was to enhance the degree of explained variance by including measures of pain and tactile sensitivity as well as pain-related endurance and fear-avoidance responses. Thirty-six post lumbar disc surgery patients completed psychomet- ric questionnaires (Avoidance-Endurance Questionnaire, Fear-Avoidance Beliefs Questionnaire, Beck Depression Inven- tory) and underwent quantitative sensory testing (QST) with measures of pain (pressure (PPT) and mechanical pain threshold) and tactile sensitivity (MDT). Bivariate correlations and hierarchical multiple regression analysis were com- puted. In addition to the contribution of fear-avoidance responses, pressure pain sensitivity and endurance behavior sig- nificantly contributed to explanations of pain variance, whereas disability was primarily predicted by fear-avoidance. While all psychological variables and MDT were positively related to pain or disability, PPT was negatively related to pain. The regression model accounted for 69 % of the variance in back pain intensity and 68 % of the variance in disabil- ity. Tactile hypaesthesia was related to increased clinical pain. Pain-related endurance responses and pressure pain hyper- algesia were significant additional predictors for pain, but not for disability. These findings are compatible with general- ized disinhibition via descending pathways and a general inhibition of tactile acuity by ongoing pain.
{"title":"Pain-Related Endurance, Fear-Avoidance and Somatosensory Sensitivity as Correlates of Clinical Status after Lumbar Disc Surgery","authors":"S. Held, R. Rolke, R. Treede, K. Schmieder, Z. Karimi, S. Sudhaus, M. Hasenbring","doi":"10.2174/1876386301306010165","DOIUrl":"https://doi.org/10.2174/1876386301306010165","url":null,"abstract":"Most pain and disability variance in patients with low back pain still remains unexplained. The aim of this study was to enhance the degree of explained variance by including measures of pain and tactile sensitivity as well as pain-related endurance and fear-avoidance responses. Thirty-six post lumbar disc surgery patients completed psychomet- ric questionnaires (Avoidance-Endurance Questionnaire, Fear-Avoidance Beliefs Questionnaire, Beck Depression Inven- tory) and underwent quantitative sensory testing (QST) with measures of pain (pressure (PPT) and mechanical pain threshold) and tactile sensitivity (MDT). Bivariate correlations and hierarchical multiple regression analysis were com- puted. In addition to the contribution of fear-avoidance responses, pressure pain sensitivity and endurance behavior sig- nificantly contributed to explanations of pain variance, whereas disability was primarily predicted by fear-avoidance. While all psychological variables and MDT were positively related to pain or disability, PPT was negatively related to pain. The regression model accounted for 69 % of the variance in back pain intensity and 68 % of the variance in disabil- ity. Tactile hypaesthesia was related to increased clinical pain. Pain-related endurance responses and pressure pain hyper- algesia were significant additional predictors for pain, but not for disability. These findings are compatible with general- ized disinhibition via descending pathways and a general inhibition of tactile acuity by ongoing pain.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"165-175"},"PeriodicalIF":0.0,"publicationDate":"2013-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68125483","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}
Pub Date : 2013-03-08DOI: 10.2174/1876386301306010037
G. Oxford, J. Hurley
TRP channels are members of a large family of non-selective cation channels. The family which numbers over 30 is classified into 6 groups based on amino acid sequence homology. TRP channels are distributed in many peripheral tissues as well as central and peripheral nervous system. These channels are important in sensing a wide range of chemical and physical stimuli. Several TRP channels, including TRPV1 and TRPA1 are important in pain transduction pathways. This review will focus on the function of TRP channels in the trigeminovascular system and other anatomical regions which are relevant to migraine. We will discuss the possible role of TRP channels in migraine, including the potential role of TRPV1 in the hypersensitivity and allodynia frequently observed in migraine patients. We will review the status of TRP channel drugs in migraine therapeutics. We will also discuss the possible roles of TRP channels in triggering migraine attacks, a process which is not well-understood. Kewords: Migraine, trigeminal, TRP receptor, pain, neurogenic, inflammation.
{"title":"The Role of TRP Channels in Migraine","authors":"G. Oxford, J. Hurley","doi":"10.2174/1876386301306010037","DOIUrl":"https://doi.org/10.2174/1876386301306010037","url":null,"abstract":"TRP channels are members of a large family of non-selective cation channels. The family which numbers over 30 is classified into 6 groups based on amino acid sequence homology. TRP channels are distributed in many peripheral tissues as well as central and peripheral nervous system. These channels are important in sensing a wide range of chemical and physical stimuli. Several TRP channels, including TRPV1 and TRPA1 are important in pain transduction pathways. This review will focus on the function of TRP channels in the trigeminovascular system and other anatomical regions which are relevant to migraine. We will discuss the possible role of TRP channels in migraine, including the potential role of TRPV1 in the hypersensitivity and allodynia frequently observed in migraine patients. We will review the status of TRP channel drugs in migraine therapeutics. We will also discuss the possible roles of TRP channels in triggering migraine attacks, a process which is not well-understood. Kewords: Migraine, trigeminal, TRP receptor, pain, neurogenic, inflammation.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"37-49"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124528","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}
Pub Date : 2013-03-08DOI: 10.2174/1876386301306010031
G. Chung, S. Oh
Despite the high incidence of dental pain, the mechanism underlying its generation is mostly unknown. Functional expression of temperature-sensitive transient receptor potential (thermo-TRP) channels, such as TRPV1, TRPV2, TRPM8, and TRPA1 in dental primary afferent neurons and TRPV1, TRPV2, TRPV3, TRPV4, and TRPM3 in odontoblasts, has been demonstrated and suggested as responsible for dental pain elicited by hot and cold food. However, dental pain induced by light touch or sweet substance cannot be explained by the role of thermo-TRP channels. Most of current therapeutics of dentin hypersensitivity is based on hydrodynamic theory, which argues that light stimuli such as air puff and temperature changes cause fluid movement within dentinal tubule, which is then transduced as pain. To test this theory, various TRP channels as candidates of cellular mechanotransducers were studied for expression in dental primary afferents and odontoblasts. The expression of TRPV1, TRPV2, TRPA1, TRPV4, and TRPM3 in trigeminal neurons and TRPV1, TRPV2, TRPV3, TRPV4 and TRPM3 in odontoblasts has been revealed. However, their roles as cellular mechanotransducers are controversial and contribution to generation of dental pain is still elusive. This review discusses recent advances in understanding of molecular mechanism underlying development of dental pain.
{"title":"TRP Channels in Dental Pain","authors":"G. Chung, S. Oh","doi":"10.2174/1876386301306010031","DOIUrl":"https://doi.org/10.2174/1876386301306010031","url":null,"abstract":"Despite the high incidence of dental pain, the mechanism underlying its generation is mostly unknown. Functional expression of temperature-sensitive transient receptor potential (thermo-TRP) channels, such as TRPV1, TRPV2, TRPM8, and TRPA1 in dental primary afferent neurons and TRPV1, TRPV2, TRPV3, TRPV4, and TRPM3 in odontoblasts, has been demonstrated and suggested as responsible for dental pain elicited by hot and cold food. However, dental pain induced by light touch or sweet substance cannot be explained by the role of thermo-TRP channels. Most of current therapeutics of dentin hypersensitivity is based on hydrodynamic theory, which argues that light stimuli such as air puff and temperature changes cause fluid movement within dentinal tubule, which is then transduced as pain. To test this theory, various TRP channels as candidates of cellular mechanotransducers were studied for expression in dental primary afferents and odontoblasts. The expression of TRPV1, TRPV2, TRPA1, TRPV4, and TRPM3 in trigeminal neurons and TRPV1, TRPV2, TRPV3, TRPV4 and TRPM3 in odontoblasts has been revealed. However, their roles as cellular mechanotransducers are controversial and contribution to generation of dental pain is still elusive. This review discusses recent advances in understanding of molecular mechanism underlying development of dental pain.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"31-36"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124518","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}
Pub Date : 2013-03-08DOI: 10.2174/1876386301306010154
Carlos Fernández-Peña, F. Viana
Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by cold temperature and cooling agents. TRPM8 is expressed in peripheral cold thermoreceptors and plays a fundamental role in sensing mild, cool temperatures. In addition, cumulative evidence obtained in humans and different animals models, combined with pharmacological and gene silencing techniques, suggest that TRPM8 may also play a role in cold discomfort and the pathophysiology of cold pain. This article reviews the available evidence in a critical fashion. In addition, the article reviews the possible role of TRPM8 in basal tearing, cold urticaria and airway irritation. Collectively, these results suggest that pharmacological modulators of TRPM8 could have potential indications in a variety of conditions, including dry eye disease, airway irritation, teeth hypersensitivity, migraine and neuropathic pain. However, additional studies, especially in humans, are needed to verify these preliminary observations. The paucity of potent, specific pharmacological TRPM8 antagonists available is a current limitation for further progress in this field.
{"title":"Targeting TRPM8 for Pain Relief","authors":"Carlos Fernández-Peña, F. Viana","doi":"10.2174/1876386301306010154","DOIUrl":"https://doi.org/10.2174/1876386301306010154","url":null,"abstract":"Transient receptor potential melastatin 8 (TRPM8) is a non-selective cation channel activated by cold temperature and cooling agents. TRPM8 is expressed in peripheral cold thermoreceptors and plays a fundamental role in sensing mild, cool temperatures. In addition, cumulative evidence obtained in humans and different animals models, combined with pharmacological and gene silencing techniques, suggest that TRPM8 may also play a role in cold discomfort and the pathophysiology of cold pain. This article reviews the available evidence in a critical fashion. In addition, the article reviews the possible role of TRPM8 in basal tearing, cold urticaria and airway irritation. Collectively, these results suggest that pharmacological modulators of TRPM8 could have potential indications in a variety of conditions, including dry eye disease, airway irritation, teeth hypersensitivity, migraine and neuropathic pain. However, additional studies, especially in humans, are needed to verify these preliminary observations. The paucity of potent, specific pharmacological TRPM8 antagonists available is a current limitation for further progress in this field.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"154-164"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68125468","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}
Pub Date : 2013-03-08DOI: 10.2174/1876386301306010007
A. Szallasi
With over 600 reviews, Transient Receptor Potential (TRP) channels arguably represent today’s most extensively reviewed pharmacological targets. The literature on TRP channels is vast and still growing: it has exploded from a mere 21 papers in 1995 to over 2,000 in the past two years. In the past fifteen years, the field had shown spectacular progress. From the cloning of the vanilloid (capsaicin) recep a novel class of analgesic agents.
{"title":"Preface by the Editor","authors":"A. Szallasi","doi":"10.2174/1876386301306010007","DOIUrl":"https://doi.org/10.2174/1876386301306010007","url":null,"abstract":"With over 600 reviews, Transient Receptor Potential (TRP) channels arguably represent today’s most extensively reviewed pharmacological targets. The literature on TRP channels is vast and still growing: it has exploded from a mere 21 papers in 1995 to over 2,000 in the past two years. In the past fifteen years, the field had shown spectacular progress. From the cloning of the vanilloid (capsaicin) recep a novel class of analgesic agents.","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":"68124135","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}
Pub Date : 2013-03-08DOI: 10.2174/1876386301306010081
K. Bley
Changes in cutaneous innervation are a hallmark of neuropathic pain syndromes. Although in few cases the density of cutaneous innervation increases in painful areas, for the most part the density of nociceptive sensory nerve endings decreases and the degree of deinnervation seems to correlate with the severity of pain. In combination with tests for nociceptor function, immunostaining for protein gene product 9.5 (PGP 9.5) is commonly used as diagnostic tool to indicate these pathophysiological changes in cutaneous innervation. However, sole reliance on PGP 9.5 may underestimate the presence of regenerating sensory nerve terminals or fail to capture changes in the expression of proteins such as ion channels or receptors. Topical capsaicin consistently reduces intra-epidermal nerve fiber density assayed via PGP 9.5, and also increases thresholds for activation of some thermoreceptors. The mechanism of action involves a highly localized insult to cutaneous nociceptors mediated by activation of TRPV1 and calcium overload, and perhaps even a direct toxicity to mitochondria. It is possible that topical capsaicin and lidocaine share an ability to reduce cutaneous innervation by inducing localized toxicity in mitochondria-rich nociceptive terminals. Overall, the high local concentrations of drugs and even excipients delivered by topical analgesics into the skin may be able to activate secondary pharmacodynamic processes. Optimizing topical formulations of capsaicin or other analgesics to maximize pain relief with the fewest adverse effects is not a simple matter of varying drug concentration, and it is highly questionable whether 'bioequivalence' could ever be based simply upon equivalent cutaneous drug delivery.
{"title":"Effects of Topical Capsaicin on Cutaneous Innervation: Implications for Pain Management","authors":"K. Bley","doi":"10.2174/1876386301306010081","DOIUrl":"https://doi.org/10.2174/1876386301306010081","url":null,"abstract":"Changes in cutaneous innervation are a hallmark of neuropathic pain syndromes. Although in few cases the density of cutaneous innervation increases in painful areas, for the most part the density of nociceptive sensory nerve endings decreases and the degree of deinnervation seems to correlate with the severity of pain. In combination with tests for nociceptor function, immunostaining for protein gene product 9.5 (PGP 9.5) is commonly used as diagnostic tool to indicate these pathophysiological changes in cutaneous innervation. However, sole reliance on PGP 9.5 may underestimate the presence of regenerating sensory nerve terminals or fail to capture changes in the expression of proteins such as ion channels or receptors. Topical capsaicin consistently reduces intra-epidermal nerve fiber density assayed via PGP 9.5, and also increases thresholds for activation of some thermoreceptors. The mechanism of action involves a highly localized insult to cutaneous nociceptors mediated by activation of TRPV1 and calcium overload, and perhaps even a direct toxicity to mitochondria. It is possible that topical capsaicin and lidocaine share an ability to reduce cutaneous innervation by inducing localized toxicity in mitochondria-rich nociceptive terminals. Overall, the high local concentrations of drugs and even excipients delivered by topical analgesics into the skin may be able to activate secondary pharmacodynamic processes. Optimizing topical formulations of capsaicin or other analgesics to maximize pain relief with the fewest adverse effects is not a simple matter of varying drug concentration, and it is highly questionable whether 'bioequivalence' could ever be based simply upon equivalent cutaneous drug delivery.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"81-94"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124234","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}
Pub Date : 2013-03-08DOI: 10.2174/1876386301306010095
M. Iadarola, G. Gonnella
This review examines existing preclinical and clinical studies related to resiniferatoxin (RTX) and its potential uses in pain treatment. Like capsaicin, RTX is a vanilloid receptor (TRPV1) agonist, only more potent. This increased potency confers both quantitative and qualitative advantages in terms of drug action on the TRPV1 containing nerve terminal, which result in an increased efficacy and a long duration of action. RTX can be delivered by a central route of administration through injection into the subarachnoid space around the lumbosacral spinal cord. It can also be administered peripherally into a region of skin or deep tissue where primary afferents nerves terminate, or directly into a nerve trunk or a dorsal root ganglion. The central route is currently being evaluated as a treatment for intractable pain in patients with advanced cancer. Peripheral administration offers the possibility to treat a wide diversity of pain problems because of the ability to bring the treatment to the site of the pain (the peripheral generator). While not all pain disorders are appropriate for RTX, tailoring treatment to an individual patient's needs via a selective and local intervention that chemically targets a specific population of nerve terminals provides a new capability for pain therapy and a simplified and effective approach to personalized pain medicine.
{"title":"Resiniferatoxin for Pain Treatment: An Interventional Approach to Personalized Pain Medicine","authors":"M. Iadarola, G. Gonnella","doi":"10.2174/1876386301306010095","DOIUrl":"https://doi.org/10.2174/1876386301306010095","url":null,"abstract":"This review examines existing preclinical and clinical studies related to resiniferatoxin (RTX) and its potential uses in pain treatment. Like capsaicin, RTX is a vanilloid receptor (TRPV1) agonist, only more potent. This increased potency confers both quantitative and qualitative advantages in terms of drug action on the TRPV1 containing nerve terminal, which result in an increased efficacy and a long duration of action. RTX can be delivered by a central route of administration through injection into the subarachnoid space around the lumbosacral spinal cord. It can also be administered peripherally into a region of skin or deep tissue where primary afferents nerves terminate, or directly into a nerve trunk or a dorsal root ganglion. The central route is currently being evaluated as a treatment for intractable pain in patients with advanced cancer. Peripheral administration offers the possibility to treat a wide diversity of pain problems because of the ability to bring the treatment to the site of the pain (the peripheral generator). While not all pain disorders are appropriate for RTX, tailoring treatment to an individual patient's needs via a selective and local intervention that chemically targets a specific population of nerve terminals provides a new capability for pain therapy and a simplified and effective approach to personalized pain medicine.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"6 1","pages":"95 - 107"},"PeriodicalIF":0.0,"publicationDate":"2013-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124245","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}
Pub Date : 2013-03-08DOI: 10.2174/1876386301306010062
B. Tóth, T. Bíró
Itch (pruritus) is one of the most often seen sensory phenomena in clinical practice. Recent neurophysiological findings proposed the existence of a novel pruriceptive system which includes a multitude of pruritogenic (itch-inducing) peripheral mediators, itch-selective pruriceptors, sensory afferent networks, spinal cord neurons, and certain central nerv- ous system regions. In this review, we first introduce major features of the pruriceptive system. We then focus on defining the roles of transient receptor potential (TRP) ion channels in skin-coupled itch and provide compelling evidence that cer- tain thermosensitive TRP channels (especially TRPV1, TRPV3, TRPV4, and TRPA1) are indeed key players in pruritus pathogenesis. Finally, we propose TRP-centered future experimental directions towards the therapeutic targeting of TRP channels in the clinical management of itch.
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