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

催产素受体:在三叉神经痛系统中的表达及其在治疗头痛症中的潜在作用

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作者:Alexander Tzabazis, Jordan Mechanic, James Miller, Michael Klukinov, Conrado Pascual, Neil Manering, Dean S Carson, Allon Jacobs, Yanli Qiao, Jason Cuellar, William H Frey 2nd, Daniel Jacobs, Martin Angst, David C Yeomans

Aims

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

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.

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.

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