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Open Access 01-12-2014 | Research article

Expression of 5-HT₃ receptors and TTX resistant sodium channels (Na_V1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders

Authors: Nikolaos Christidis, Isabell Kang, Brian E Cairns, Ujendra Kumar, Xudong Dong, Annika Rosén, Sigvard Kopp, Malin Ernberg

Published in: The Journal of Headache and Pain | Issue 1/2014

Abstract

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 (Na_V) 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-HT_3A-receptors alone and in combination with Na_V1.8 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-HT_3A-receptors and Na_V1.8 sodium-channels.

Results

A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT_3A-receptors. The expression of Na_V1.8 by 5-HT_3A 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 Na_V1.8 and 5-HT_3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P < .001).

Conclusions

This study showed that the 5-HT_3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT_3A-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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Title: 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
Authors: Nikolaos Christidis
Isabell Kang
Brian E Cairns
Ujendra Kumar
Xudong Dong
Annika Rosén
Sigvard Kopp
Malin Ernberg
Publication date: 01-12-2014
Publisher: Springer Milan
Published in: The Journal of Headache and Pain / Issue 1/2014
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/1129-2377-15-63

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Expression of 5-HT₃ receptors and TTX resistant sodium channels (Na_V1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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