Research papers Glutamate-evoked pain and mechanical allodynia in the human masseter muscle Peter Svensson a,b,c, * , Brian E. Cairns d , Kelun Wang b , James W. Hu e , Thomas Graven-Nielsen b , Lars Arendt-Nielsen b , Barry J. Sessle e a Department of Clinical Oral Physiology, Dental School, Aarhus University, DK-8000 Aarhus C, Denmark b Orofacial Pain Laboratory, Center for Sensory–Motor Interaction, Aalborg University, DK-9220 Aalborg, Denmark c Department of Maxillofacial Surgery, Aalborg Hospital, DK-9000 Aalborg, Denmark d Department of Anesthesia, Harvard Medical School/Children’s Hospital, Boston, MA 02115, USA e Faculty of Dentistry, The University of Toronto, Toronto, Ontario, Canada M5G 1G6 Received 13 August 2001; received in revised form 19 February 2002; accepted 14 March 2002 Abstract The present study examined the effect of peripheral administration of the excitatory amino acid (EAA) glutamate on the intensity of perceived pain and pressure pain thresholds (PPTs) in healthy young women ðn ¼ 17Þ and men ðn ¼ 18Þ. Two injections separated by 25 min of 0.2 ml, 1.0 M glutamate into the masseter muscle produced significantly higher scores of pain on 0–10 cm visual analogue scales (VAS) in women than in men (analysis of variance, ANOVA: P , 0:001). There was no significant difference between the VAS scores for the first and the second injections in either men or women. The PPTs determined in the masseter muscle were significantly reduced following the first injection and further significantly reduced after the second injection (ANOVA: P , 0:001). Furthermore, the PPTs were reduced to a similar extent in both women and men (maximum 44–56%), suggesting that gender did not influence the process of sensitization. There were no significant difference in VAS scores or PPTs between women taking oral contraceptives ðn ¼ 9Þ and those who did not ðn ¼ 8Þ (ANOVAs: P ¼ 0:709, P ¼ 0:153). It is concluded that the VAS scores produced by intramuscular administration of 1.0 M glutamate may reflect a gender-dependent activation of nociceptive pathways which, in part, may be mediated through peripheral EAA receptors. The reduction of PPTs in the masseter muscle following administration of glutamate in a concentration of 1.0 M may reflect allodynia to mechanical stimuli. This process of sensitization was not gender-dependent. The present results suggest that injection of 1.0 M glutamate into the masseter muscle may provide a useful experimental method to test sensitization and efficacy of peripheral EAA receptor antagonists in human subjects. q 2002 Published by Elsevier Science B.V. on behalf of International Association for the Study of Pain. Keywords: Trigeminal pain; Masseter muscle; Gender; Temporomandibular disorders 1. Introduction The etiology and pathophysiology of persistent myofas- cial pain in the craniofacial region is still unknown but recent studies have provided substantial insight into some of the possible underlying neurobiological and psychophy- siological mechanisms (Stohler, 1999; Sessle, 2000). One consistent and important finding is the predominance of women of reproductive age with painful temporomandibu- lar disorders (TMD) (Drangsholt and LeResche, 1999). The use of exogenous hormones containing estrogen has, indeed, been linked to a higher risk for having a painful TMD problem (LeResche et al., 1997). Experimental pain studies have so far provided equivocal results with respect to gender effects (for review see Dao and LeResche, 2000; Fillingim and Ness, 2000), but in particular longer-lasting stimuli which may involve temporal summation mechanisms appear to evoke significantly greater responses in women than in men (Fillingim et al., 1998). Further studies are, however, still needed to answer the question of whether there are gender differences in perceived pain intensity of longer-lasting painful stimuli applied to the deep craniofa- cial tissues. Various algesic chemicals injected into deep tissues can be used to elicit pain in human volunteers (for a review see Svensson and Graven-Nielsen, 2001). Hypertonic saline (Stohler et al., 1992), capsaicin (Arima et al., 2000; Witting et al., 2000), serotonin (5-HT) and bradykinin (Babenko et al., 1999, 2000; Kopp, 2001) and acidic solutions (Steen et al., 2000, 2001) elicit mild to moderately intense levels of Pain 101 (2003) 221–227 0304-3959/02/$20.00 q 2002 Published by Elsevier Science B.V. on behalf of International Association for the Study of Pain. doi:10.1016/S0304-3959(02)00079-9 www.elsevier.com/locate/pain * Corresponding author. Tel.: 145-8942-4191; fax: 145-8619-5665. E-mail address: psvensson@odont.au.dk (P. Svensson).