Contribution of proprioceptors in the mesencephalic trigeminal nucleus and their surrounding astrocytes to acidic saline-induced chronic jaw muscle pain in rodents

Introduction Chronic jaw muscle pain is a common clinical condition whose etiology remains ill-defined. Using acidic saline injections into the masseter muscle to mimic it, we examined the hypothesis that hyperexcitability of jaw closing muscles spindle afferents (MSA) that have previously been observed in this model result from neuron glia interactions in the trigeminal mesencephalic nucleus (NVmes) lead to activation of nociceptive pathways. Methods This was assessed using whole-cell patch-clamp recordings from NVmes neurons combined to pharmacological and astrocytic optogenetic stimulations and immunohistochemistry against cFos in the ventrolateral pole of the subnucleus interpolaris/caudalis transition region (vl-Vi/Vc), and GFAP in vl-Vi/Vc and NVmes regions in rats and mice Results Acidic saline injection into the masseter muscle led to increases in: (1) cFos expression in vl-Vi/Vc at 9 days after the injection, (2) reactivity of astrocytes in NVmes, and (3) Excitability of NVmes neurons that manifested spontaneously or in response to astrocytic stimulation. This increased activity is thought to result from the release of the astrocytic Ca 2+ -binding protein S100β, since it was not observed in S100β knock-out mice, which also did not show increased expression of cFos in vl-Vi/Vc, despite showing increased reactivity of NVmes astrocytes. Discussion These findings suggest that acidic saline injection into the masseter muscles induced long-term activation of astrocytes in the NVmes and promoted ectopic firing of NVmes neurons via astrocyte-released S100β, and subsequent activation of nociceptive pathways.