Oxytocin receptor: Expression in the trigeminal nociceptive system and potential role in the treatment of headache disorders

Cephalalgia. 2016 Sep;36(10):943-50. doi: 10.1177/0333102415618615. Epub 2015 Nov 20.

Abstract

Aims: Our studies investigated the location of oxytocin receptors in the peripheral trigeminal sensory system and determined their role in trigeminal pain.

Methods: Oxytocin receptor expression and co-localization with calcitonin gene-related peptide was investigated in rat trigeminal ganglion using immunohistochemistry. Enzyme-linked immunosorbent assay was used to determine the effects of facial electrocutaneous stimulation and adjuvant-induced inflammation of the temporomandibular joint on oxytocin receptor expression in the trigeminal ganglion. Finally, the effects of oxytocin on capsaicin-induced calcitonin gene-related peptide release from dural nociceptors were investigated using isolated rat dura mater.

Results: Oxytocin receptor immunoreactivity was present in rat trigeminal neurons. The vast majority of oxytocin receptor immunoreactive neurons co-expressed calcitonin gene-related peptide. Both electrocutaneous stimulation and adjuvant-induced inflammation led to a rapid upregulation of oxytocin receptor protein expression in trigeminal ganglion neurons. Oxytocin significantly and dose-dependently decreased capsaicin-induced calcitonin gene-related peptide release from dural nociceptors.

Conclusion: Oxytocin receptor expression in calcitonin gene-related peptide containing trigeminal ganglion neurons, and the blockade of calcitonin gene-related peptide release from trigeminal dural afferents suggests that activation of these receptors may provide therapeutic benefit in patients with migraine and other primary headache disorders.

Keywords: CGRP; Oxytocin; headache; inflammation; pain; trigeminal.

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / analysis
  • Calcitonin Gene-Related Peptide / biosynthesis
  • Calcitonin Gene-Related Peptide / genetics
  • Gene Expression Regulation
  • Headache Disorders / genetics
  • Headache Disorders / metabolism*
  • Male
  • Nociceptors / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Oxytocin / analysis
  • Receptors, Oxytocin / biosynthesis*
  • Receptors, Oxytocin / genetics
  • Treatment Outcome
  • Trigeminal Ganglion / chemistry
  • Trigeminal Ganglion / metabolism*

Substances

  • Receptors, Oxytocin
  • Calcitonin Gene-Related Peptide