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Malin Ernberg - One of the best experts on this subject based on the ideXlab platform.
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expression of 5 ht3 receptors and ttx resistant sodium channels nav1 8 on muscle nerve fibers in pain free humans and patients with chronic myofascial temporomandibular disorders
Journal of Headache and Pain, 2014Co-Authors: Nikolaos Christidis, Isabell Kang, Brian E Cairns, Ujendra Kumar, Xudong Dong, Annika Rosen, Sigvard Kopp, Malin ErnbergAbstract:Previous studies have shown that 5-HT3-Antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P < .001). This study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.
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expression of 5 ht3 receptors and ttx resistant sodium channels nav1 8 on muscle nerve fibers in pain free humans and patients with chronic myofascial temporomandibular disorders
Journal of Headache and Pain, 2014Co-Authors: Nikolaos Christidis, Isabell Kang, Brian E Cairns, Ujendra Kumar, Xudong Dong, Annika Rosen, Sigvard Kopp, Malin ErnbergAbstract:Background: Previous studies have shown that 5-HT3-Antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. Methods: Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. Results: A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P<.001). In the patients, significantly more fibers per section were found with an average of 3.8±3 fibers per section in the masseter muscle compared to 2.7±0.2 in the healthy controls (P=.024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P<.001). Conclusions: This study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.
Xudong Dong - One of the best experts on this subject based on the ideXlab platform.
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expression of 5 ht3 receptors and ttx resistant sodium channels nav1 8 on muscle nerve fibers in pain free humans and patients with chronic myofascial temporomandibular disorders
Journal of Headache and Pain, 2014Co-Authors: Nikolaos Christidis, Isabell Kang, Brian E Cairns, Ujendra Kumar, Xudong Dong, Annika Rosen, Sigvard Kopp, Malin ErnbergAbstract:Previous studies have shown that 5-HT3-Antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P < .001). This study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.
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expression of 5 ht3 receptors and ttx resistant sodium channels nav1 8 on muscle nerve fibers in pain free humans and patients with chronic myofascial temporomandibular disorders
Journal of Headache and Pain, 2014Co-Authors: Nikolaos Christidis, Isabell Kang, Brian E Cairns, Ujendra Kumar, Xudong Dong, Annika Rosen, Sigvard Kopp, Malin ErnbergAbstract:Background: Previous studies have shown that 5-HT3-Antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. Methods: Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. Results: A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P<.001). In the patients, significantly more fibers per section were found with an average of 3.8±3 fibers per section in the masseter muscle compared to 2.7±0.2 in the healthy controls (P=.024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P<.001). Conclusions: This study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.
Brian E Cairns - One of the best experts on this subject based on the ideXlab platform.
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expression of 5 ht3 receptors and ttx resistant sodium channels nav1 8 on muscle nerve fibers in pain free humans and patients with chronic myofascial temporomandibular disorders
Journal of Headache and Pain, 2014Co-Authors: Nikolaos Christidis, Isabell Kang, Brian E Cairns, Ujendra Kumar, Xudong Dong, Annika Rosen, Sigvard Kopp, Malin ErnbergAbstract:Previous studies have shown that 5-HT3-Antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P < .001). This study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.
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expression of 5 ht3 receptors and ttx resistant sodium channels nav1 8 on muscle nerve fibers in pain free humans and patients with chronic myofascial temporomandibular disorders
Journal of Headache and Pain, 2014Co-Authors: Nikolaos Christidis, Isabell Kang, Brian E Cairns, Ujendra Kumar, Xudong Dong, Annika Rosen, Sigvard Kopp, Malin ErnbergAbstract:Background: Previous studies have shown that 5-HT3-Antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT3-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (NaV) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT3A-receptors alone and in combination with NaV1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls. Methods: Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT3A-receptors and NaV1.8 sodium-channels. Results: A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT3A-receptors. The expression of NaV1.8 by 5-HT3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P<.001). In the patients, significantly more fibers per section were found with an average of 3.8±3 fibers per section in the masseter muscle compared to 2.7±0.2 in the healthy controls (P=.024). Further, the frequency of nerve fibers that co-expressed NaV1.8 and 5-HT3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P<.001). Conclusions: This study showed that the 5-HT3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT3-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.
Ahmad Reza Dehpour - One of the best experts on this subject based on the ideXlab platform.
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involvement of nitric oxide cyclic guanosine monophosphate pathway in the antidepressant like effect of tropisetron and ondansetron in mice forced swimming test and tail suspension test
European Journal of Pharmacology, 2016Co-Authors: Arya Hajmirzaian, Nastaran Kordjazy, Shayan Amiri, Hossien Aminikhoei, Sattar Ostadhadi, Ahmad Reza DehpourAbstract:Antidepressant-like effects of 5-hydroxytryptamine subtype 3 (5-HT3) Antagonists including tropisetron and ondansetron have been previously demonstrated in the literature. It was reported that stimulation of 5-HT3 receptors activate the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, which is involved in regulation of behavioral and emotional functions. In our study, treating animals with tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01 and 0.1µg/kg) significantly decreased the immobility time in forced swimming test (FST) and tail-suspension test (TST). Co-administration of subeffective doses of tropisetron (1mg/kg) and ondansetron (0.001µg/kg) with subeffective dose of l-NAME (10mg/kg, nonselective NO synthase (NOS) inhibitor) and 7-nitroindazole (25mg/kg, neural NOS inhibitor) exerted antidepressant-like effect in FST and TST, while aminoguanidine (50mg/kg, inducible NOS inhibitor) did not enhance the antidepressant-like effect of 5-HT3 Antagonists. Besides, l-arginine (750mg/kg, NO precursor) and sildenafil (5mg/kg, phosphodiesterase inhibitor) suppressed the anti-immobility effect of 5-HT3 Antagonists. None of the treatments altered the locomotor behavior of mice in open-field test. Also, hippocampal (but not cortical) nitrite level was significantly lower in tropisetron and ondansetron-treated mice compared with saline-injected mice. Also, co-administration of 7-nitroindazole with tropisetron or ondansetron caused a significant decrease in hippocampal nitrite levels. In conclusion, we suggest that antidepressant-like effect of tropisetron and ondansetron are partially mediated by modulation of NO-cGMP pathway.
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involvement of n methyl d aspartate receptors in the antidepressant like effect of 5 hydroxytryptamine 3 Antagonists in mouse forced swimming test and tail suspension test
Pharmacology Biochemistry and Behavior, 2016Co-Authors: Nastaran Kordjazy, Arya Hajmirzaian, Shayan Amiri, Hossien Aminikhoei, Sattar Ostadhadi, Ahmad Reza DehpourAbstract:Recent evidence indicates that 5-hydroxytryptamine 3 (5-HT3) Antagonists such as ondansetron and tropisetron exert positive behavioral effects in animal models of depression. Due to the ionotropic nature of 5-HT3 and N-methyl-d-aspartate (NMDA) receptors, plus their contribution to the pathophysiology of depression, we investigated the possible role of NMDA receptors in the antidepressant-like effect of 5-HT3 receptor Antagonists in male mice. In order to evaluate the animals' behavior in response to different treatments, we performed open-field test (OFT), forced swimming test (FST), and tail-suspension test (TST), which are considered as valid tasks for measuring locomotor activity and depressive-like behaviors in mice. Our data revealed that intraperitoneal (i.p.) administration of tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01, and 0.1μg/kg) significantly decreased the immobility time in FST and TST. Also, co-administration of subeffective doses of tropisetron (1mg/kg, i.p.) or ondansetron (0.001μg/kg, i.p.) with subeffective doses of NMDA receptor Antagonists, ketamine (1mg/kg, i.p.), MK-801 (0.05mg/kg, i.p.) and magnesium sulfate (10mg/kg, i.p.) resulted in a reduced immobility time both in FST and TST. The subeffective dose of NMDA (NMDA receptor agonist, 75mg/kg, i.p.) abolished the effects of 5-HT3 Antagonists in FST and TST, further supporting the presumed interaction between 5-HT3 and NMDA receptors. These treatments did not affect the locomotor behavior of animals in OFT. Finally, the results of our study suggest that the positive effects of 5-HT3 Antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation.
Paul J Hesketh - One of the best experts on this subject based on the ideXlab platform.
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chemotherapy induced nausea and vomiting
The New England Journal of Medicine, 2008Co-Authors: Paul J HeskethAbstract:Despite considerable progress in the management of chemotherapy-associated nausea and vomiting, these symptoms remain among the most feared by patients beginning cytotoxic chemotherapy. 5-HT3 Antagonists have decreased the frequency of postchemotherapy vomiting. However, emesis remains a problem for a significant minority of patients. In addition, nausea continues to be a formidable challenge despite the better control of vomiting with current treatment options [1]. The relative likelihood of significant emesis in a given individual is dependent upon both patient- and treatment-related factors. Patient factors with predictive value for decreased emesis include heavy alcohol consumption and male sex [2]. A number of other factors including younger age [3], poor performance status [3], severe emesis during pregnancy [4], and susceptibility to motion sickness [5] have all been noted to be predictive of increased emesis with chemotherapy. Treatment-related factors include the intrinsic emetogenicity of the cytotoxic agent(s), the dose and schedule, treatment setting, as well as additive effects of combinations [6].
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treatment of chemotherapy induced emesis in the 1990s impact of the 5 ht3 receptor Antagonists
Supportive Care in Cancer, 1994Co-Authors: Paul J HeskethAbstract:Considerable progress has been made in the development of means to limit nausea and vomiting arising from cancer chemotherapy. A number of key conceptual advances in the last decade have been critically important. These include recognition of the value of combination antiemetic therapy, identification of important patient- and treatment-related factors predictive of emesis, and appreciation of the importance of serotonin (5-HT) in the pathophysiology of emesis and the value of selective Antagonists of the type-3 serotonin receptor. Comparative trials of the 5-HT3 receptor Antagonists and classic antiemetic agents have helped define optimal antiemetic approaches in a number of settings. A combination of a 5-HT3 antagonist and dexamethasone is the treatment of choice for patients receiving single- and multiple-day cisplatin. The 5-HT3 Antagonists are also effective agents with noncisplatin chemotherapy. Clear-cut superiority to classic antiemetics such as dexamethasone has not been consistently demonstrated, however. Results with the 5-HT3 Antagonists in cisplatin-induced delayed emesis have been disappointing to date. The results of ongoing prospective trials should define their role more clearly. At present a combination of metoclopramide and dexamethasone is the treatment of choice in this setting. Results of trials comparing 5-HT3 Antagonists are beginning to emerge. Available information suggests no clinically relevant differences in antiemetic efficacy between these agents. Many questions regarding the optimal use of the 5-HT3 Antagonists and their integration into clinical practice remain unanswered and are the appropriate focus for additional study.
