Sex-Related Differences in Human Pain and Rat Afferent Discharge Evoked by Injection of Glutamate Into the Masseter Muscle

1 Faculty of Dentistry, The University of Toronto, Toronto, Ontario M5G 1G6, Canada; 2 Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, DK-9220 Aalborg; and 3 Department of Prosthetic Dentistry and Stomatognathic Physiology, Orofacial Pain Clinic, Royal Dental College, Aarhus University, DK-8000 Aarhus, Denmark Cairns, Brian E., James W. Hu, Lars Arendt-Nielsen, Barry J. Sessle, and Peter Svensson. Sex-Related Differences in Human Pain and Rat Afferent Discharge Evoked by Injection of Glutamate Into the Masseter Muscle. J. Neurophysiol. 86: 782-791, 2001. Animal studies have suggested that tissue injury-related increased levels of glutamate may be involved in peripheral nociceptive mechanisms in deep craniofacial tissues. Indeed, injection of glutamate (0.1-1 M, 10 µl) into the temporomandibular region evokes reflex jaw muscle responses through activation of peripheral excitatory amino acid receptors. It has recently been found that this glutamate-evoked reflex muscle activity is significantly greater in female than male rats. However, it is not known whether peripheral administration of glutamate, in the same concentrations that evoke jaw muscle 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, since masseter afferent recordings were not feasible in humans, whether glutamate 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) into the masseter muscle of both men and women caused significantly higher levels of peak pain, duration of pain, and overall pain than injection of isotonic saline (0.2 ml). In addition, glutamate-evoked peak and overall muscle pain in women was significantly greater than in men. In rats of both sexes, glutamate (10 µl, 0.5 M) evoked activity in a subpopulation of masseter muscle afferents ( n = 36) that projected to the subnucleus caudalis, an important relay of noxious input from the craniofacial region. The largest responses to glutamate were recorded in muscle afferents with the slowest conduction velocities (2.5-5 m/s). Further, glutamate-evoked masseter muscle afferent activity was significantly greater in female than in male rats. These results indicate that glutamate injection into the masseter muscle evokes p