Sex differences in serotonin enhancement of capsaicin-evoked calcitonin gene-related peptide release from human dental pulp

Date

2012-10

Authors

Lloyd, Dayna R.
Sun, Xiaoling X.
Locke, Erin E.
Salas, Margaux M.
Hargreaves, Kenneth M.

Journal Title

Journal ISSN

Volume Title

Publisher

Lippincott

Abstract

Serotonin (5HT) enhances transient receptor potential V1 channel (TRPV1)–evoked calcitonin gene-related peptide (CGRP) release from female, but not male, human dental pulp. This enhancement occurs greatest during the luteal phase of the menstrual cycle.

Serotonin (5HT) is a pronociceptive mediator in the periphery, and evidence implicates involvement in trigeminal pain processing. However, the mechanism(s) by which 5HT modulates trigeminal nociceptors remains unclear. Trigeminal pain can be evoked by the transient receptor potential V1 channel (TRPV1), which is expressed by nociceptive trigeminal neurons and induces release of proinflammatory calcitonin gene-related peptide (CGRP). In our preclinical models, 5HT evoked thermal hyperalgesia and enhanced calcium influx and CGRP release from the TRPV1 population of trigeminal nociceptors. Whether this occurs in humans is unknown. As dental pulp is densely innervated by trigeminal nociceptors, routine tooth extractions offer a unique opportunity to examine whether 5HT enhances CGRP release from human nociceptors. Pulpal tissue was collected from 140 extracted molar teeth from men and women, and basal release samples were collected before treatment with saline or 5HT 100 μmol/L. CGRP release was then stimulated with the TRPV1 agonist capsaicin 1 μmol/L and quantitated by enzyme immunoassay. Additional samples were collected for Western blots to examine 5HT receptor expression. We report that 5HT induced a significant increase in capsaicin-evoked CGRP release, and that this enhancement was observed only in female dental pulp, with no effect of 5HT on male dental pulp. The greatest amount of CGRP release occurred in dental pulp from women in the luteal phase of the menstrual cycle. These results indicate that 5HT enhances capsaicin-evoked CGRP release from human trigeminal nociceptors in a sexually dimorphic manner providing a mechanistic basis for prevalence of trigeminal pain disorders in women.

Description

Article originally published in Pain, 153(10), 2061–2067. English. Published online October 2012. https://doi.org/10.1016/j.pain.2012.06.018

Keywords

CGRP, 5HT, Craniofacial, Orofacial, Teeth, Pain

Citation

This is the abstract for an article that is available at: https://doi.org/10.1016/j.pain.2012.06.018. Recommended citation: Loyd, D. R., Sun, X. X., Locke, E. E., Salas, M. M., & Hargreaves, K. M. (2012). Sex differences in serotonin enhancement of capsaicin-evoked calcitonin gene-related peptide release from human dental p ulp. Pain, 153(10), 2061–2067. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.

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