Repeated Muscle Injury as a Presumptive Trigger for Chronic Masticatory Muscle Pain

skeletal muscles sustain a significant loss of maximal contractile force after injury, but terminally damaged fibers can eventually be replaced by the growth of newmuscle (regeneration), with full restoration of contractile force over time. After a second injury, limb muscles exhibit a smaller reduction in maximal force and reduced inflammation compared with that after the initial injury (i.e., repeated bout effect). In contrast, masticatory muscles exhibit diminished regeneration and persistent fibrosis, after a single injury; following a second injury, plasma extravasation is greater than after a single injury and maximal force is decreased more than after the initial injury. Thus, masticatory muscles do not exhibit a repeated bout effect and are instead increasingly damaged by repeated injury. We propose that the impaired ability of masticatory muscles to regenerate contributes to chronic muscle pain by leading to an accumulation of tissue damage, fibrosis, and a persistent elevation and prolonged membrane translocation of nociceptive channels such as P2X(3) as well as enhanced expression of neuropeptides including CGRP within primary afferent neurons. These transformations prime primary afferent neurons for enhanced responsiveness upon subsequent injury thus triggering and/or exacerbating chronic muscle pain.