Pub Date : 2012-02-01DOI: 10.2174/1876386301205010001
T. Toelle, Roxana Varvara, M. Nimour, B. Emir, M. Brasser
Background: Neuropathic pain is associated with many conditions. Pregabalin has demonstrated efficacy in randomized, controlled trials (RCTs) in peripheral and central neuropathic pain. Observational studies complement findings from RCTs by enabling an agent to be studied in real-world patients and circumstances. Methods: Patients with neuropathic pain were treated with pregabalin 150-600 mg/day in this 6 week observational study. Analyses of subsets of patients with painful diabetic peripheral neuropathy (DPN; n=4633), back pain with a neuropathic component (n=3800), and cancer-related neuropathic pain (n=345) were undertaken. Results: The mean pregabalin doses ranged from 219 to 250 mg/day across the disease groups. Mean baseline pain scores (6.4 to 7.0 across the three disease states) indicated patients had moderate to severe pain. Pregabalin was associated with a rapid and significant reduction in pain from week 1 to endpoint in all groups. Over 80% in each of the groups had a � 30% pain reduction in their pain at 6 weeks, and over two-thirds had a � 50% reduction. Pain-related sleep interference decreased rapidly and significantly. Most patients (87%) were either very satisfied or satisfied with the action of pregabalin. General well-being improved significantly over the 6 weeks. Pregabalin was generally well tolerated; the most common adverse event overall was dizziness (1.4%). Few patients (� 6.1%/group) discontinued due to adverse events. Conclusions: In neuropathic pain patients in day-to-day practice, pregabalin was associated with notable reductions in pain and sleep interference. The benefits of pregabalin were reflected in the high level of patient satisfaction and improvement in general well-being.
{"title":"Pregabalin in Neuropathic Pain Related to DPN, Cancer and Back Pain:Analysis of a 6-Week Observational Study","authors":"T. Toelle, Roxana Varvara, M. Nimour, B. Emir, M. Brasser","doi":"10.2174/1876386301205010001","DOIUrl":"https://doi.org/10.2174/1876386301205010001","url":null,"abstract":"Background: Neuropathic pain is associated with many conditions. Pregabalin has demonstrated efficacy in randomized, controlled trials (RCTs) in peripheral and central neuropathic pain. Observational studies complement findings from RCTs by enabling an agent to be studied in real-world patients and circumstances. Methods: Patients with neuropathic pain were treated with pregabalin 150-600 mg/day in this 6 week observational study. Analyses of subsets of patients with painful diabetic peripheral neuropathy (DPN; n=4633), back pain with a neuropathic component (n=3800), and cancer-related neuropathic pain (n=345) were undertaken. Results: The mean pregabalin doses ranged from 219 to 250 mg/day across the disease groups. Mean baseline pain scores (6.4 to 7.0 across the three disease states) indicated patients had moderate to severe pain. Pregabalin was associated with a rapid and significant reduction in pain from week 1 to endpoint in all groups. Over 80% in each of the groups had a � 30% pain reduction in their pain at 6 weeks, and over two-thirds had a � 50% reduction. Pain-related sleep interference decreased rapidly and significantly. Most patients (87%) were either very satisfied or satisfied with the action of pregabalin. General well-being improved significantly over the 6 weeks. Pregabalin was generally well tolerated; the most common adverse event overall was dizziness (1.4%). Few patients (� 6.1%/group) discontinued due to adverse events. Conclusions: In neuropathic pain patients in day-to-day practice, pregabalin was associated with notable reductions in pain and sleep interference. The benefits of pregabalin were reflected in the high level of patient satisfaction and improvement in general well-being.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"5 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2012-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124574","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 : 2012-01-01DOI: 10.2174/1876386301205010024
Octavia Plesh, Stuart A Gansky, Donald A Curtis
This is a longitudinal study of a large US biracial community cohort of 732 young women - 50% African-American and 50% Caucasian - specifically investigating incidence, remission, and progression of, as well as factors associated with common chronic pains (back, head, face, chest and abdomen). The results show back, head and abdominal pains were the most common, severe and persistent pains. Facial pain, although less common and severe, was the only pain presenting significant racial differences with Caucasians having higher prevalence, incidence and persistence; incidence per 1000 person-years was 58 for Caucasians and 18 for African-Americans while remission per 1000 person-years was 107 for Caucasians and 247 for African-Americans (p<0.05). Risk factors associated with incidence (I) differed from those associated with persistence(P), perhaps due to the young age and shorter pain duration in this population. Face pain incidence, but not persistence for example, was associated with student status, fatigue, perceived stress and general health. Depression does not seem to be associated with any of these pains. However, increased number of existing pain sites was related to subsequent increase chance of developing new pain (I) or maintaining the existing pain (P).
{"title":"Chronic Pain in a Biracial Cohort of Young Women.","authors":"Octavia Plesh, Stuart A Gansky, Donald A Curtis","doi":"10.2174/1876386301205010024","DOIUrl":"10.2174/1876386301205010024","url":null,"abstract":"<p><p>This is a longitudinal study of a large US biracial community cohort of 732 young women - 50% African-American and 50% Caucasian - specifically investigating incidence, remission, and progression of, as well as factors associated with common chronic pains (back, head, face, chest and abdomen). The results show back, head and abdominal pains were the most common, severe and persistent pains. Facial pain, although less common and severe, was the only pain presenting significant racial differences with Caucasians having higher prevalence, incidence and persistence; incidence per 1000 person-years was 58 for Caucasians and 18 for African-Americans while remission per 1000 person-years was 107 for Caucasians and 247 for African-Americans (p<0.05). Risk factors associated with incidence (I) differed from those associated with persistence(P), perhaps due to the young age and shorter pain duration in this population. Face pain incidence, but not persistence for example, was associated with student status, fatigue, perceived stress and general health. Depression does not seem to be associated with any of these pains. However, increased number of existing pain sites was related to subsequent increase chance of developing new pain (I) or maintaining the existing pain (P).</p>","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"5 ","pages":"24-31"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906924/pdf/nihms498273.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32084467","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}
Pub Date : 2011-11-25DOI: 10.2174/1876386301104010008
M. Ortiz, G. Castañeda-Hernández, J. Izquierdo-Vega, H. Ponce-Monter
It has been shown that the association of non-steroidal anti-inflammatory drugs (NSAIDs) with analgesic agents can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between lumiracoxib and lidocaine at the local peripheral level in the rat using the 1% formalin test and isobolographic analysis. Lumiracoxib, lidocaine or fixed-dose ratio (1:1) lumiracoxib-lidocaine combinations were administered locally in the formalin-injured paw and the antinociceptive effect was evaluated. All treatments produced a dose-dependent antinociceptive effect. ED40 values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED40 for the lumiracoxib- lidocaine combination was 599.3 ± 58.8 � g/paw, being significantly higher than the actually observed experimental ED40 value, 393.6 ± 39.7 � g/paw. This result correspond to a synergistic interaction between lumiracoxib and lidocaine at the local peripheral level, potency being about one and half times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the lumiracoxib-lidocaine combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of procedural or inflammatory pain.
{"title":"Peripheral Synergistic Interaction Between Lidocaine and Lumiracoxib on the 1% Formalin Test in Rats","authors":"M. Ortiz, G. Castañeda-Hernández, J. Izquierdo-Vega, H. Ponce-Monter","doi":"10.2174/1876386301104010008","DOIUrl":"https://doi.org/10.2174/1876386301104010008","url":null,"abstract":"It has been shown that the association of non-steroidal anti-inflammatory drugs (NSAIDs) with analgesic agents can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between lumiracoxib and lidocaine at the local peripheral level in the rat using the 1% formalin test and isobolographic analysis. Lumiracoxib, lidocaine or fixed-dose ratio (1:1) lumiracoxib-lidocaine combinations were administered locally in the formalin-injured paw and the antinociceptive effect was evaluated. All treatments produced a dose-dependent antinociceptive effect. ED40 values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED40 for the lumiracoxib- lidocaine combination was 599.3 ± 58.8 � g/paw, being significantly higher than the actually observed experimental ED40 value, 393.6 ± 39.7 � g/paw. This result correspond to a synergistic interaction between lumiracoxib and lidocaine at the local peripheral level, potency being about one and half times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the lumiracoxib-lidocaine combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of procedural or inflammatory pain.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"4 1","pages":"8-14"},"PeriodicalIF":0.0,"publicationDate":"2011-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124567","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 : 2011-10-18DOI: 10.2174/1876386301104010004
W. Jost
Botulinum toxin is a therapeutic option in chronic migraine. No dose-finding studies have been conducted so far. Some authors maintain that one injection into the corrugator muscle will do. Objective: We studied the effect of Botulinum toxin (BTX) injections in patients with strictly unilateral migraine. Methods: We treated 22 patients (ITT) in a crossover design for 4 months with 2 x 5 units Onabotulinum toxin (in the cor- rugator and occipitalis muscle ipsilaterally). Aside from patient data, we also gathered information on undesired drug ef- fects, besides IQOLA SF36, SF-MPQ SADP, OLBPDQ, VAS (pain intensity and daily living skills), PPI, frequency of at- tacks and application of medication. The statistical evaluation was guided by SPSS (V.13). Results: Assessed were 19 patients (PP) aged 45.2 ± 11.1 years, thereof 17 women. In both injection intervals there were no clinically relevant and/or statistically significant differences as to the target parameters (for example: VAS pain inten- sity p=0.702), with a notably evident placebo effect (VAS in placebo prior to the injection was 61.4, after 6 weeks 45.1; good or excellent improvement (TOQ) was quoted by 36.8% after 6 weeks in the placebo group). BTX merely proved su- perior in two aspects: Regarding the pain quality "throbbing" (SF-MPQ SADP), 11 patients initially indicated a pro- nounced intensity; after BTX only 4 of them did. As to the severity of the pain felt, (PPI) 42.2 of the subjects described "limiting" or "horrible" pain prior to the injection versus 26.3% six weeks after the injection and 21.1% 4 months later. The placebo group started out with 31.6%, that figure remaining the same (31.6%) 6 weeks later, rising to 42.2% after 4 months. 84.2% of the BTX-group and 63.2% in the placebo group requested a reinjection when the study was completed. Conclusion: The injection of low-dosed Botulinumtoxin A did not show any relevant or significant effects in patients with unilateral migraine without aura. One injection into the corrugator muscle alone must be considered as ineffective. The place-value of the two injection sites remains in the open.
{"title":"Low-dosed Botulinum Toxin A in the Prophylactic Management of Unilateral Migraine: A Randomized Double-blind Placebo-Controlled Crossover Study","authors":"W. Jost","doi":"10.2174/1876386301104010004","DOIUrl":"https://doi.org/10.2174/1876386301104010004","url":null,"abstract":"Botulinum toxin is a therapeutic option in chronic migraine. No dose-finding studies have been conducted so far. Some authors maintain that one injection into the corrugator muscle will do. Objective: We studied the effect of Botulinum toxin (BTX) injections in patients with strictly unilateral migraine. Methods: We treated 22 patients (ITT) in a crossover design for 4 months with 2 x 5 units Onabotulinum toxin (in the cor- rugator and occipitalis muscle ipsilaterally). Aside from patient data, we also gathered information on undesired drug ef- fects, besides IQOLA SF36, SF-MPQ SADP, OLBPDQ, VAS (pain intensity and daily living skills), PPI, frequency of at- tacks and application of medication. The statistical evaluation was guided by SPSS (V.13). Results: Assessed were 19 patients (PP) aged 45.2 ± 11.1 years, thereof 17 women. In both injection intervals there were no clinically relevant and/or statistically significant differences as to the target parameters (for example: VAS pain inten- sity p=0.702), with a notably evident placebo effect (VAS in placebo prior to the injection was 61.4, after 6 weeks 45.1; good or excellent improvement (TOQ) was quoted by 36.8% after 6 weeks in the placebo group). BTX merely proved su- perior in two aspects: Regarding the pain quality \"throbbing\" (SF-MPQ SADP), 11 patients initially indicated a pro- nounced intensity; after BTX only 4 of them did. As to the severity of the pain felt, (PPI) 42.2 of the subjects described \"limiting\" or \"horrible\" pain prior to the injection versus 26.3% six weeks after the injection and 21.1% 4 months later. The placebo group started out with 31.6%, that figure remaining the same (31.6%) 6 weeks later, rising to 42.2% after 4 months. 84.2% of the BTX-group and 63.2% in the placebo group requested a reinjection when the study was completed. Conclusion: The injection of low-dosed Botulinumtoxin A did not show any relevant or significant effects in patients with unilateral migraine without aura. One injection into the corrugator muscle alone must be considered as ineffective. The place-value of the two injection sites remains in the open.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"4 1","pages":"4-7"},"PeriodicalIF":0.0,"publicationDate":"2011-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124558","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 : 2011-08-17DOI: 10.2174/1876386301104010001
S. Omoigui, F. Hashmat, Zeudi Bernardo
Ketamine can be used in the treatment of opioid withdrawal symptoms. Here are two case discussions of treatment of withdrawal symptoms in opioid dependent patients undergoing detoxification. Our case reports endorse the hypothesis that N-methyl D-aspartate (NMDA) antagonists may selectively inhibit the expression of opiate withdrawal. The use of intravenous ketamine can be considered as a bridge to successful initiation of buprenorphine to wean the patient off from high opioid doses while providing adequate analgesia during the transition period.
{"title":"Use of Ketamine in Ameliorating Opioid Withdrawal Symptoms During an Induction Phase of Buprenorphine","authors":"S. Omoigui, F. Hashmat, Zeudi Bernardo","doi":"10.2174/1876386301104010001","DOIUrl":"https://doi.org/10.2174/1876386301104010001","url":null,"abstract":"Ketamine can be used in the treatment of opioid withdrawal symptoms. Here are two case discussions of treatment of withdrawal symptoms in opioid dependent patients undergoing detoxification. Our case reports endorse the hypothesis that N-methyl D-aspartate (NMDA) antagonists may selectively inhibit the expression of opiate withdrawal. The use of intravenous ketamine can be considered as a bridge to successful initiation of buprenorphine to wean the patient off from high opioid doses while providing adequate analgesia during the transition period.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"4 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2011-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124493","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 : 2010-11-11DOI: 10.2174/1876386301003010134
C. Mohn, O. Vassend, B. S. Krogstad, S. Knardahl
Background: Personality traits and general health complaints may influence the course of and treatment of chronic pain. However, only few studies compare more than one or two personality characteristics in chronic pain patients and healthy controls. This study compares the comprehensive non-pathological personality structure of female patients with temporomandibular disorders (TMD) and pain-free controls. Moreover, this study controls for the influence of Neu- roticism, self-presentation bias, and acute pain sensitivity on the subjective report of general health complaints. Methods: Twenty-five TMD patients were compared to 25 matched controls on personality traits (NEO Personality Inven- tory-Revised; NEO-PI-R), self-presentation bias (Social Desirability Scale; SDS), psychological distress (Symptom Checklist 90-Revised; SCL-90-R), and general somatic complaints. Experimental pain sensitivity was assessed by electro- cutaneous and pressure pain stimulation. Results: Compared to the controls, Extraversion and Openness were lower in the TMD group, and the TMD patients ex- hibited higher levels of psychological and musculoskeletal complaints also when Neuroticism, self-presentation bias, and acute pain sensitivity were held constant. Conclusions: Low levels of Extraversion and Openness may dispose TMD patients to isolation and negative thought pat- terns. The elevated levels of psychological distress and general musculoskeletal pain in the TMD group add to previous reports of TMD as a complex condition also involving structures and processes outside of the orofacial region.
{"title":"Personality Traits and Subjective Health Complaints in Female TMD Patients and Healthy Controls","authors":"C. Mohn, O. Vassend, B. S. Krogstad, S. Knardahl","doi":"10.2174/1876386301003010134","DOIUrl":"https://doi.org/10.2174/1876386301003010134","url":null,"abstract":"Background: Personality traits and general health complaints may influence the course of and treatment of chronic pain. However, only few studies compare more than one or two personality characteristics in chronic pain patients and healthy controls. This study compares the comprehensive non-pathological personality structure of female patients with temporomandibular disorders (TMD) and pain-free controls. Moreover, this study controls for the influence of Neu- roticism, self-presentation bias, and acute pain sensitivity on the subjective report of general health complaints. Methods: Twenty-five TMD patients were compared to 25 matched controls on personality traits (NEO Personality Inven- tory-Revised; NEO-PI-R), self-presentation bias (Social Desirability Scale; SDS), psychological distress (Symptom Checklist 90-Revised; SCL-90-R), and general somatic complaints. Experimental pain sensitivity was assessed by electro- cutaneous and pressure pain stimulation. Results: Compared to the controls, Extraversion and Openness were lower in the TMD group, and the TMD patients ex- hibited higher levels of psychological and musculoskeletal complaints also when Neuroticism, self-presentation bias, and acute pain sensitivity were held constant. Conclusions: Low levels of Extraversion and Openness may dispose TMD patients to isolation and negative thought pat- terns. The elevated levels of psychological distress and general musculoskeletal pain in the TMD group add to previous reports of TMD as a complex condition also involving structures and processes outside of the orofacial region.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"3 1","pages":"134-143"},"PeriodicalIF":0.0,"publicationDate":"2010-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124257","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 : 2010-10-11DOI: 10.2174/18763863010030400117
A. Clark, F. Marchand, Marta D’ Auria, M. Davies, J. Grist, M. Malcangio, S. McMahon
Loss of function is usually considered the major consequence of spinal cord injury (SCI). However, chronic pain severely compromises the quality of life of many SCI patients. Recently, microglial cells in enhanced response states have been proposed to contribute to chronic pain following SCI. Here we report that following contusion injury, the microglial cysteine protease cathepsin S (CatS) is critical for the maintenance of SCI-induced neuropathic pain and spinal microglial response. Following SCI, significant mechanical and thermal hypersensitivity developed in both hind-paws. Prolonged intrathecal administration of the CatS inhibitor LHVS (morpholinurea-leucine-homophenylalanine- vinyl sulfone-phenyl), commencing day 26 post-SCI, resulted in significant attenuation of established mechanical and thermal pain behaviours compared to vehicle. This attenuation was evident as early as 24hrs following treatment initiation, and was maintained throughout the 7 day duration of drug administration. In addition, following the 7 day treatment period LHVS significantly attenuated the SCI-induced response of microglial in the lumbar dorsal horn of the spinal cord. We suggest that following SCI, CatS expressed by spinal microglia, is critical for the maintenance of below the level pain induced by contusion injury and suggest that CatS inhibition constitutes a novel therapeutic approach for the treatment of chronic pain associated with SCI.
{"title":"Cathepsin S Inhibition Attenuates Neuropathic Pain and Microglial Response Associated with Spinal Cord Injury","authors":"A. Clark, F. Marchand, Marta D’ Auria, M. Davies, J. Grist, M. Malcangio, S. McMahon","doi":"10.2174/18763863010030400117","DOIUrl":"https://doi.org/10.2174/18763863010030400117","url":null,"abstract":"Loss of function is usually considered the major consequence of spinal cord injury (SCI). However, chronic pain severely compromises the quality of life of many SCI patients. Recently, microglial cells in enhanced response states have been proposed to contribute to chronic pain following SCI. Here we report that following contusion injury, the microglial cysteine protease cathepsin S (CatS) is critical for the maintenance of SCI-induced neuropathic pain and spinal microglial response. Following SCI, significant mechanical and thermal hypersensitivity developed in both hind-paws. Prolonged intrathecal administration of the CatS inhibitor LHVS (morpholinurea-leucine-homophenylalanine- vinyl sulfone-phenyl), commencing day 26 post-SCI, resulted in significant attenuation of established mechanical and thermal pain behaviours compared to vehicle. This attenuation was evident as early as 24hrs following treatment initiation, and was maintained throughout the 7 day duration of drug administration. In addition, following the 7 day treatment period LHVS significantly attenuated the SCI-induced response of microglial in the lumbar dorsal horn of the spinal cord. We suggest that following SCI, CatS expressed by spinal microglia, is critical for the maintenance of below the level pain induced by contusion injury and suggest that CatS inhibition constitutes a novel therapeutic approach for the treatment of chronic pain associated with SCI.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"3 1","pages":"117-122"},"PeriodicalIF":0.0,"publicationDate":"2010-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124483","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 : 2010-09-28DOI: 10.2174/1876386301003010108
M. Camprubí-Robles, A. Ferrer-Montiel, R. Planells-Cases
Nociceptor sensitization is a process triggered by proinflammatory factors that result in a significant increase in neuronal excitability by affecting both the threshold and frequency of action potential firing. The increased sensory neu- ron activity is due to a metabolic change produced by the activation of intracellular signaling cascades that usually alter the expression and functionality of molecular sensors present in the neuronal surface, i.e. ion channels and metabotropic receptors. Cumulative evidence is showing that inflammatory sensitization of nociceptors is significantly contributed by an enhanced expression of ion channels that directly influence neuronal excitability. Furthermore, recent data indicates that mobilization and regulated exocytosis of a ready-to-go vesicular population of channels as a pivotal event underlying acute inflammatory sensitization of sensory neurons; whereas an increment in transcription and/or translation and traffick- ing is involved in chronic neuronal sensitization. Therefore, identification of the molecular components involved in chan- nel trafficking and exocytosis in the inflamed terminal may provide new strategies for attenuating nociceptor sensitization and their consequences, namely hyperalgesia and allodynia.
{"title":"Contribution of Ion Channel Trafficking to Nociceptor Sensitization","authors":"M. Camprubí-Robles, A. Ferrer-Montiel, R. Planells-Cases","doi":"10.2174/1876386301003010108","DOIUrl":"https://doi.org/10.2174/1876386301003010108","url":null,"abstract":"Nociceptor sensitization is a process triggered by proinflammatory factors that result in a significant increase in neuronal excitability by affecting both the threshold and frequency of action potential firing. The increased sensory neu- ron activity is due to a metabolic change produced by the activation of intracellular signaling cascades that usually alter the expression and functionality of molecular sensors present in the neuronal surface, i.e. ion channels and metabotropic receptors. Cumulative evidence is showing that inflammatory sensitization of nociceptors is significantly contributed by an enhanced expression of ion channels that directly influence neuronal excitability. Furthermore, recent data indicates that mobilization and regulated exocytosis of a ready-to-go vesicular population of channels as a pivotal event underlying acute inflammatory sensitization of sensory neurons; whereas an increment in transcription and/or translation and traffick- ing is involved in chronic neuronal sensitization. Therefore, identification of the molecular components involved in chan- nel trafficking and exocytosis in the inflamed terminal may provide new strategies for attenuating nociceptor sensitization and their consequences, namely hyperalgesia and allodynia.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"3 1","pages":"108-116"},"PeriodicalIF":0.0,"publicationDate":"2010-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124226","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 : 2010-09-28DOI: 10.2174/1876386301003010068
A. Jara-Oseguera, Andres Nieto-posadas, A. Szallasi, L. Islas, T. Rosenbaum
Transient Receptor Potential (TRP) cation channels participate in various fundamental processes in cell- and organism-physiology in unicellular eukaryotes, invertebrates and vertebrates. Interestingly, many TRP channels function as detectors of sensory stimuli. The TRPV1 (vanilloid 1) channel serves as an integrator of noxious chemical and physical stimuli known to cause irritation and pain, such as elevated temperatures, acids, and irritant chemical compounds, and its activation has been linked to acute nociceptive pain and neurogenic inflammation. The mechanisms by which the channel detects incoming stimuli, how the sensing domains are coupled to channel gating and how these processes are connected to specific structural regions in the channel are not fully understood, but valuable information is available. Many sites in- volved in agonist detection have been characterized and gating models that describe many features of the channel's behav- ior have been put forward. Structural and functional information indicates TRP channels are similar to voltage-activated potassium channels, with a tetrameric organization and six-transmembrane-region subunits, a pore domain with multi-ion binding properties and an intracellular S6 gate that seems to be the point of convergence of the many activation modalities leading to the opening of the ion conduction pathway. Furthermore, TRPV1 expression is altered in various disease states and TRPV1 gene polymorphism was speculated to play a role in pain sensation. The complex activation and regulation of TRPV1 may have important implications for drug development.
{"title":"Molecular Mechanisms of TRPV1 Channel Activation","authors":"A. Jara-Oseguera, Andres Nieto-posadas, A. Szallasi, L. Islas, T. Rosenbaum","doi":"10.2174/1876386301003010068","DOIUrl":"https://doi.org/10.2174/1876386301003010068","url":null,"abstract":"Transient Receptor Potential (TRP) cation channels participate in various fundamental processes in cell- and organism-physiology in unicellular eukaryotes, invertebrates and vertebrates. Interestingly, many TRP channels function as detectors of sensory stimuli. The TRPV1 (vanilloid 1) channel serves as an integrator of noxious chemical and physical stimuli known to cause irritation and pain, such as elevated temperatures, acids, and irritant chemical compounds, and its activation has been linked to acute nociceptive pain and neurogenic inflammation. The mechanisms by which the channel detects incoming stimuli, how the sensing domains are coupled to channel gating and how these processes are connected to specific structural regions in the channel are not fully understood, but valuable information is available. Many sites in- volved in agonist detection have been characterized and gating models that describe many features of the channel's behav- ior have been put forward. Structural and functional information indicates TRP channels are similar to voltage-activated potassium channels, with a tetrameric organization and six-transmembrane-region subunits, a pore domain with multi-ion binding properties and an intracellular S6 gate that seems to be the point of convergence of the many activation modalities leading to the opening of the ion conduction pathway. Furthermore, TRPV1 expression is altered in various disease states and TRPV1 gene polymorphism was speculated to play a role in pain sensation. The complex activation and regulation of TRPV1 may have important implications for drug development.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"71 1","pages":"68-81"},"PeriodicalIF":0.0,"publicationDate":"2010-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124116","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 : 2010-09-28DOI: 10.2174/1876386301003010082
M. Fischer, S. Mak, P. McNaughton
Nociceptors are peripheral sensory neurones which respond to painful (noxious) stimuli. The terminals of nociceptors, which have a high threshold to stimulation in their native state, undergo a process known as sensitisation, or lowering of threshold, following injury or inflammation. Amongst sensory receptors, sensitisation is a property unique to nociceptors. A shift in the stimulus-response function of nociceptors renders them more sensitive, resulting in both a reduction in the activation threshold, such that previously non-noxious stimuli are perceived as noxious (allodynia) and an increased response to suprathreshold stimuli (hyperalgesia). Sensitisation protects us from harm and is essential for survival, but it can be disabling in conditions of chronic inflammation. This review focuses on three stages in sensitisation: 1) Inflammatory mediators, which are released from damaged resident cells and from others that invade in response to inflammation, and include bradykinin, prostaglandins, serotonin, low pH, ATP, neurotrophins, nitric oxide and cytokines; 2) Intracellular signalling molecules which are important in transmitting the actions of inflammatory mediators and include protein kinase A and C, Src kinase, mitogen-activated protein kinases and the membrane lipid PIP 2 ; and 3) Ion channel targets of intracellular signalling which ultimately cause sensitisation and include the temperature- sensitive transient receptor potential channels, acid-sensitive ion channels, purinoceptor-gated channels, and the voltage- sensitive sodium, potassium, calcium and HCN channels.
{"title":"Sensitisation of Nociceptors – What are Ion Channels Doing?","authors":"M. Fischer, S. Mak, P. McNaughton","doi":"10.2174/1876386301003010082","DOIUrl":"https://doi.org/10.2174/1876386301003010082","url":null,"abstract":"Nociceptors are peripheral sensory neurones which respond to painful (noxious) stimuli. The terminals of nociceptors, which have a high threshold to stimulation in their native state, undergo a process known as sensitisation, or lowering of threshold, following injury or inflammation. Amongst sensory receptors, sensitisation is a property unique to nociceptors. A shift in the stimulus-response function of nociceptors renders them more sensitive, resulting in both a reduction in the activation threshold, such that previously non-noxious stimuli are perceived as noxious (allodynia) and an increased response to suprathreshold stimuli (hyperalgesia). Sensitisation protects us from harm and is essential for survival, but it can be disabling in conditions of chronic inflammation. This review focuses on three stages in sensitisation: 1) Inflammatory mediators, which are released from damaged resident cells and from others that invade in response to inflammation, and include bradykinin, prostaglandins, serotonin, low pH, ATP, neurotrophins, nitric oxide and cytokines; 2) Intracellular signalling molecules which are important in transmitting the actions of inflammatory mediators and include protein kinase A and C, Src kinase, mitogen-activated protein kinases and the membrane lipid PIP 2 ; and 3) Ion channel targets of intracellular signalling which ultimately cause sensitisation and include the temperature- sensitive transient receptor potential channels, acid-sensitive ion channels, purinoceptor-gated channels, and the voltage- sensitive sodium, potassium, calcium and HCN channels.","PeriodicalId":53614,"journal":{"name":"Open Pain Journal","volume":"17 1","pages":"82-96"},"PeriodicalIF":0.0,"publicationDate":"2010-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68124178","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}
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