Trigeminal pain mechanisms: Influence of estrus cycle stage on response properties of rat masseter muscle afferent fibres

Abstract

Masticatory muscle pressure pain thresholds (PPTs) vary through the menstrual cycle in both healthy women and those suffering from a temporomandibular disorder (J Orofac Pain 16:105-117, 2002; J Oral Rehabil 29:1042-1051, 2002). It is not clear whether cyclic changes in the response properties of masticatory muscle nociceptors contribute to this phenomenon. To date, estrus cycle-related differences in the response properties of small diameter afferent fibres that innervate the masticatory muscles of female rats have not been identified. However, the excitability of only a small number of putative nociceptive and non-nociceptive fibres have been examined in each stage of the cycle, which may have confounded the identification of estrus cycle-related changes in nociceptor sensitivity in past studies. To re-examine this issue, all masseter muscle afferent fibre data recorded extracellularly from the trigeminal ganglion of anesthetized female rats over a 6 year period was pooled and re-analyzed. Estrus cycle stage was determined by microscopic examination of a vaginal lavage. Mechanical threshold was measured with a Von Frey hair and response to chemical stimulation was assessed by intramuscular injection of glutamate (500 mM, 10 μl). Data was analyzed by non-parametric (Kruskal Wallis) ANOVA, followed by post-hoc analysis with Dunn's method. Analysis of a mix population of masseter afferent fibres (conduction velocity 1.4 - 21 m/sec, n=112) revealed no significant estrus cycle-related difference in mechanical threshold. However, if only putative nociceptors (conduction velocity < 10 m/sec, n= 78) were analyzed, the mechanical threshold of fibres recorded during proestrus was significantly lower than during diestrus. No significant estrus cycle-related differences in the glutamate evoked activity of a mix population of afferent fibres (n=73) or putative nociceptors (n=44) were identified. This finding suggests that changes in mechanical sensitivity of nociceptors could partly underlie the observed variability in masticatory muscle PPTs through the menstrual cycle.