Sensory innervation of masseter, temporal and lateral pterygoid muscles in common marmosets

Abstract

Myogenous temporomandibular disorders (TMD-M) are the most prevalent group of painful orofacial conditions, and the second most frequent among musculoskeletal pain conditions. TMD-M is associated with an increased responsiveness of nerves innervating the masseter (MM), temporal (TM), medial pterygoid closing (MPM) and lateral pterygoid gliding muscles (LPM). Treatment of this disorder remains difficult and is further complicated by each muscle having diverse and functionally distinct nerve innervation. This study examined expression of sensory markers in MM, TM and LPM of adult male common marmosets, a type of non-human primate. Using immunohistochemistry, we found that masticatory muscles were predominantly innervated with A-fibers (NFH+). All C-fibers (pgp9.5+/NFH-) observed in masticatory muscles were peptidergic (CGRP+) and lacked antibody labeling for mrgprD, trpV1 and the silent nociceptive marker, CHRNA3. The proportion of C- to A-fibers was highest in LPM, while MM had a minimal percentage (6-8%) of C-fibers. Interestingly, C-fibers in masticatory muscle may have myelin sheath, since many NFH- nerves were labeled with GFAP+. A-fiber types were also dissimilar among these muscles. Thus, there are substantially more peptidergic A-fibers (CGRP+/NFH+) in TM and LPM compared to MM. Almost all A-fibers in MM expressed trkC, with some of them having trkB and parvalbumin (PV). In contrast, a lesser number of TM and LPM nerves expressed trkC, lacked trkB and had fewer PV+ fibers in LPM. Along with sensory fibers, the masticatory muscles contain sympathetic fibers (tyrosine hydroxylase; TH+), which are located around blood vessels. This TH expression was absent in trigeminal neurons. Overall, the masticatory muscles of male marmosets have distinct expression patterns when compared to each muscle of the jaw and cutaneous fibers innervated by DRG neurons.

Three‐dimensional topography of rat trigeminal ganglion neurons using a combination of retrograde labeling and tissue‐clearing techniques

“…Previous studies have reported that a single trigeminal ganglion cell innervates multiple regions. For example, single cells are known to project to both the nasal epithelium and olfactory bulb (Schaefer et al., 2002), to multiple masticatory muscles and temporomandibular joint (Hovhannisyan et al., 2023), and to both the tongue and pulp of a mandibular molar (Ohara et al., 2013). In the last experiment of the current study, double fluorescent labeling was performed by injecting AAV PHP.S‐CAG‐tdTomato in combination with fast blue, but no double‐labeled ganglion cells were observed.…”

“…The greater distribution of small thermosensitive ganglion neurons in the skin/mucosa, rather than in deep tissues, may be important for protection against burns from hot and cold temperatures in the external environment. Recently, it has been reported that not only differences in cell body size but also the expression patterns of chemical markers are characteristics in ganglion cells innervating different regions (Ambalavanar et al., 2003; Buchholtz et al., 2020; Hovhannisyan et al., 2023; Ibrahim et al., 2023; Leijon et al., 2019; Lindquist et al., 2021; Reid et al., 2011; Wu et al., 2018; Yang et al., 2022). In the future, the integration of data on chemical markers expressed by ganglion cells, axonal projection targets, and cell body localization within the trigeminal ganglion should provide a complete picture of trigeminal ganglion function.…”

“…These are referred to as myogenic toothaches (Fukuda, 2016; Travell & Simons, 1983). Previous studies have shown that single ganglion cells can simultaneously project their axons to the multiple masticatory muscles and temporomandibular joints (Hovhannisyan et al., 2023), as well as to the pulp of molars and tongue (Ohara et al., 2013). This multiregional control by single neurons may be involved in ectopic pain.…”