Sex-related differences in human pain and rat afferent discharge evoked byinjection of glutamate into the masseter muscle

Animal studies have suggested that tissue injury-related increased levels o f glutamate may be involved in peripheral nociceptive mechanisms in deep cr aniofacial tissues. Indeed, injection of glutamate (0.1-1 M, 10 mul) into t he temporomandibular region evokes reflex jaw muscle responses through acti vation of peripheral excitatory amino acid receptors. It has recently been found that this glutamate-evoked reflex muscle activity is significantly gr eater in female than male rats. However, it is not known whether peripheral administration of glutamate, in the same concentrations that evoke jaw mus cle activity in rats, causes pain in humans or activates deep craniofacial nociceptive afferents. Therefore we examined whether injection of glutamate into the masseter muscle induces pain in male and female volunteers and, s ince masseter afferent recordings were not feasible in humans, whether glut amate excites putative nociceptive afferents supplying the masseter muscle of male and female rats. Injection of glutamate (0.5 M or 1.0 M, 0.2 ml) in to the masseter muscle of both men and women caused significantly higher le vels of peak pain, duration of pain, and overall pain than injection of iso tonic saline (0.2 ml). In addition, glutamate-evoked peak and overall muscl e pain in women was significantly greater than in men. In rats of both sexe s, glutamate (10 mul, 0.5 M) evoked activity in a subpopulation of masseter muscle afferents (n = 36) that projected to the subnucleus caudalis, an im portant relay of noxious input from the craniofacial region. The largest re sponses to glutamate were recorded in muscle afferents with the slowest con duction velocities (2.5-5 m/s). Further, glutamate-evoked masseter muscle a fferent activity was significantly greater in female than in male rats. The se results indicate that glutamate injection into the masseter muscle evoke s pain responses that are greater in women than men and that one possible m echanism for this difference may be a greater sensitivity to glutamate of m asseter muscle afferents in females. These sex-related differences in acute experimental masseter muscle pain are particularly interesting given the h igher prevalence of many chronic muscle pain conditions in women.