Sensory and Sympathetic Nerve Localization in Mouse Temporomandibular Joint and Knee Joint Neuro-Musculoskeletal Tissues.

Objective: Sympathetic-sensory coupling is increasingly implicated in joint homeostasis and disease. Towards the long-term goal of deciphering its role in temporomandibular disorders (TMDs), we characterised the spatial relationships of sympathetic and sensory nerves and their receptors in the mouse temporomandibular joint (TMJ) and trigeminal ganglion (TG), using the knee joint for comparison.

Materials and methods: RNAscope was used for localisation of sympathetic nerve markers tyrosine hydroxylase (Th) and adrenergic receptor alpha 2a (Adrα2a); and brain-derived neurotrophic factor (Bdnf) and its receptor neurotrophic receptor tyrosine kinase 2 (Ntrk2) that stimulate sympathetic nerve growth. Sensory marker calcitonin gene-related peptide (CGRP) was detected through immunofluorescence.

Results: Th, Adrα2a, Bdnf and Ntrk2 were expressed in the TMJ and knee joint tissues, including condylar and disc cartilages, muscles and bone marrow. CGRP+ sensory neurons were abundant in the TG and, to a lesser extent, in TMJ and knee tissues, where they were often located near Th- or Adrα2a-expressing sympathetic cells. Some CGRP+ neurons in the TG also co-expressed Adrα2a.

Conclusion: Our findings reveal the presence of sympathetic and sensory nerves within the TMJ, knee joint and TG, with these nerves often located near each other. Along with the presence of Adrα2a on CGRP+ sensory fibres, this suggests sympathetic-sensory coupling and potential crosstalk in physiologic and pathologic responses. Expression of Bdnf and Ntrk2 in the TMJ and knee implicates this neurotrophin signalling in modulating sympathetic activity via neural sprouting. Further studies will clarify the functional contributions of this neurological architecture to tissue homeostasis, disease and pain.