Gender differences in the neurochemical response of trigeminal ganglion neurons to peripheral inflammation in mice

It is well established that the majority of headache and other trigeminal nerve-associated disorders have higher prevalence in females than in males. However, the pathogenesis of many chronic trigeminal pain conditions, such as trigeminal neuralgia, migraine and temporo-mandibular disorders, is still not known. One of the proposed mechanisms involve calcitonin gene-related peptide (CGRP), which is considered the most important neuropeptide in the trigeminal system. In various animal models of trigeminal nerve-associated disorders concentration of CGRP has been shown to be increased in trigeminal ganglia (TG). Moreover, intraganglionic release of CGRP has been shown to modulate neuronal transmission of pain signals. In most of these models, pathological changes in the trigeminal system are accompanied by inflammation within peripheral endings of TO neurons. The aim of the present study was to investigate the relation between gender and neurochemical changes in trigeminal ganglia evoked by peripheral inflammation, induced by Complete Freund Adjuvant (CFA) administration. Our studies show significant increase in CGRP expression in female mice, comparing to male mice. Furthermore, we demonstrate, that activation of trigeminal nociceptors by peripheral inflammation causes significant increase in expression of IL-1 beta, IL-6, TNF and BDNF in male mice, comparing to female mice. This phenomenon may be involved in clinically observed gender-dependent differences in the frequency of both migraine and other trigeminal nerve-related facial pain disorders.