Expression of 5-HT^sub 3^ receptors and TTX resistant sodium channels (Na^sub V^1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders: [Doc 1007]

Abstract

Previous studies have shown that 5-HT^sub 3^-antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT^sub 3^-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (Na^sub 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^sub 3A^-receptors alone and in combination with Na^sub V^1.8 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-HT^sub 3A^-receptors and Na^sub V^1.8 sodium-channels.

A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT^sub 3A^-receptors. The expression of Na^sub V^1.8 by 5-HT^sub 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^sub V^1.8 and 5-HT^sub 3A^ receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P<.001).

This study showed that the 5-HT^sub 3A^-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT^sub 3A^-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT^sub 3^-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.[PUBLICATION ABSTRACT]