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Cited by 79Pain Mechanisms and TreatmentsIon Channels and ReceptorsMigraine and Headache Studies

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Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury through vasopressin-1A receptors of the rat trigeminal ganglia

Kubo, Asako, Shinoda, Masamichi, Katagiri, Ayano, Takeda, Mamoru, Suzuki, Tatsuro, Asaka, Junichi, Yeomans, David C., Iwata, Koichi·2017·Pain
DOI 10.1097/j.pain.0000000000000808
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Abstract

Oxytocin (OXT) is a neuropeptide hormone synthesized and secreted by hypothalamic neurons and has been reported to play a significant role in pain modulation. However, the mechanisms underlying OXT's antinociceptive effect on neuropathic pain are not fully understood. In this study, we examined the peripheral effect of OXT on mechanical hypersensitivity induced by partial ligation of the infraorbital nerve (PNL) in rats. Mechanical hypersensitivity in the whisker pad skin after PNL was attenuated by the direct administration of OXT into the trigeminal ganglion (TG). The proportion of vasopressin-1A receptor (V1A-R)-immunoreactive, but not OXT-receptor–immunoreactive, neurons significantly increased among TG neurons innervating the whisker pad skin after PNL. In a patch-clamp recording from TG neurons isolated from PNL rats, the resting membrane potential of OXT-treated neurons was significantly decreased, and the current thresholds of OXT-treated neurons for spike generation (rheobases) were significantly greater than those of vehicle-treated neurons. In addition, OXT increased voltage-gated K + channel currents in PNL animals. Furthermore, intra-TG administration of a selective V1A-R antagonist reversed the OXT-induced alleviation of mechanical hypersensitivity, and coapplication of the antagonist opposed OXT's effects on the resting membrane potential, rheobase, and K + current. These findings suggest that OXT is effective at suppressing TG neuronal hyperexcitability after nerve injury, likely by modulation of voltage-gated K + channels through V1A-R. This signaling mechanism represents a potential therapeutic target for the treatment of orofacial neuropathic pain.

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Metadata

Authors
Kubo, A., Shinoda, M., Katagiri, A., Takeda, M., Suzuki, T., Asaka, J., Yeomans, D. C., & Iwata, K.
Affiliations
  • Nihon University (JP)
  • Azabu University (JP)
  • Stanford Medicine (US)
Corresponding author
Kubo, Asako
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-01-07
Volume
158
Issue
4
Pages
649-659
ISSN
  • 0304-3959 (ISSN-L)
  • 1872-6623
DOI
10.1097/j.pain.0000000000000808
OpenAlex
W2567737288
Cited by
79
References
51
Citations by year
2026: 2 · 2025: 2 · 2024: 10 · 2023: 6 · 2022: 7 · 2021: 9 · 2020: 11 · 2019: 13 · 2018: 13 · 2017: 6
FWCI
8.73
Type
journal article
Language
en
Open access
closed
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (17K11654)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Health Sciences › Medicine › Clinical Neurology › Migraine and Headache Studies
Keywords
oxytocin, vasopressin 1a receptor, trigeminal ganglion, infraorbital nerve injury, orofacial neuropathic pain, mechanical hypersensitivity, voltage-gated potassium channels, neuronal hyperexcitability, antinociception, pain modulation
MeSH terms
Animals, Cells, Cultured, Disease Models, Animal, Facial Pain, Hormone Antagonists, Hyperalgesia, Indoles, Male, Membrane Potentials, Neurons, Oxytocin, Pyrrolidines, Trigeminal Ganglion, Vibrissae, Rats, Sprague-Dawley, Pain Threshold, Receptors, Vasopressin, Receptors, Oxytocin, Rats

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