The Role of Peripheral Glutamate and Glutamate Receptors in Muscle Pain

Abstract

Objectives: To review evidence that associates elevated muscle interstitial glutamate concentration and the activation of peripheral glutamate receptors with the development and maintenance of muscle pain in conditions such as myofascial temporomandibular disorders [TMDs].

Findings: In certain noninflammatory musculoskeletal pain conditions, an association between pain, elevated glutamate concentrations and the expression of peripheral N-methyl-d-aspartate receptors [NRs] has been made. Myofascial TMDs are a noninflammatory muscle pain disorder characterized by pain and localized mechanical sensitivity in the masticatory muscle and a greater prevalence in young women than in men. Artificial elevation of glutamate concentrations in the masticatory muscles of healthy subjects evokes intense, short duration pain that is significantly greater in woman than in men and induces a more prolonged, localized mechanical sensitization that is similar in both sexes. Glutamate-evoked pain and sensitization may be attenuated by coinjection of the NR antagonist ketamine, which suggests that these effects are mediated, in part, through activation of peripheral NRs. In male and female animals, a two- to three-fold elevation of muscle interstitial glutamate concentrations appears sufficient to both excite and sensitize masticatory muscle nociceptors through activation of peripheral NRs. The magnitude of nociceptor discharge in response to peripheral NR activation is greater in females than in males, and this sex-related difference appears to be due, in part, to an estrogen-mediated enhancement of peripheral NR expression.

Conclusions: These findings suggest that modest elevations of interstitial glutamate concentration could alter musculoskeletal pain sensitivity in a sex-related manner through activation of peripheral NR receptors.

KEYWORDS:

• Glutamate
• mechanical threshold
• masseter muscle
• nociceptor
• myalgia