Sex differences in serotonin enhancement of capsaicin-evoked calcitonin gene-related peptide release from human dental pulp
| Autor: | Xiaoling X. Sun, Margaux M. Salas, Kenneth M. Hargreaves, Erin E. Locke, Dayna R. Loyd |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Serotonin Adolescent Calcitonin Gene-Related Peptide Population TRPV1 Calcitonin gene-related peptide Article chemistry.chemical_compound Young Adult Sex Factors stomatognathic system Internal medicine Medicine Humans education 5-HT receptor Dental Pulp education.field_of_study business.industry Drug Synergism stomatognathic diseases Anesthesiology and Pain Medicine Endocrinology Nociception Neurology chemistry nervous system Capsaicin Calcitonin Anesthesia Nociceptor Female Neurology (clinical) business |
| Zdroj: | Pain. 153(10) |
| ISSN: | 1872-6623 |
| Popis: | 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 100μmol/L. CGRP release was then stimulated with the TRPV1 agonist capsaicin 1μmol/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. |
| Databáze: | OpenAIRE |
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