The role of peripheral NMDA receptors in nerve growth factor-induced muscle pain


Intramuscular injections of nerve growth factor (NGF) into human masseter muscle induce a local mechanical sensitization that mimics the symptoms of myofascial pain in patients with temporomandibular disorders. I hypothesize that NGF induces the myofascial mechanical sensitization in part by increasing the expression of N-methyl-D-aspartate (NMDA) receptors in primary afferent neurons. In behavioral experiments, injection of NGF into rat masseter muscle induced a prolonged local mechanical sensitization that was greater in female rats than in male rats. This NGF-induced sensitization was partly attenuated by a local injection of the NMDA receptor antagonist APV at 3 days post NGF injection in the male rats but not in the female rats. Immunohistochemical studies found that this NGF-induced mechanical sensitization was accompanied by the increased expression of NMDA receptor subtype 2B (NR2B) in trigeminal ganglion neurons innervating the masseter muscle in both sexes, as well as an increase in the average soma size of NR2B-expressing neurons. An increase in the expression of neuropeptides (CGRP/SP) was also observed in the female rats but not in the male rats. In in vivo extracellular recordings of masseter trigeminal ganglion neurons, NGF increased NMDA-induced mechanical sensitization in the male rats but not in the female rats. However, in the female rats, this effect was greater in slow Aδ fibers (2-7 m/s) than fast Aδ fibers (>7-12 m/s). My results suggest that NGF-induced mechanical sensitization is mediated, in part, through an effect on peripheral NMDA receptors in a sexually dimorphic manner.Medicine, Faculty ofGraduat

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