Effect of sympathetic and parasympathetic mediators on the release of calcitonin gene-related peptide and prostaglandin E2 from rat dura mater, in vitro

Although not without controversy, an influence of the autonomic nervous system in headache is a matter for current debate. A possible contact site of autonomic and sensory nerves is the dura mater, where they form a dense network accompanying blood vessels. We investigated interactions between autonomic and nociceptive fibres by measuring release of calcitonin gene-related peptide (CGRP) and prostaglandin E-2 (PGE(2)) from the dura mater, in vitro. The parasympathomimetic agent carbachol did not change basal release of CGRP or PGE(2), whereas it diminished release induced by a mixture of inflammatory mediators. Norepinephrine did not change induced release of CGRP or PGE(2), nor basal release of CGRP. However, basal release of PGE(2) was enhanced by norepinephrine, and this enhancement was reduced by serotonin through 5-HT1D receptors. We conclude that sympathetic transmitters may control nociceptor sensitivity via increased basal PGE(2) levels, a possible mechanism to facilitate headache generation. Parasympathetic transmitters may reduce enhanced nociceptor activity.