title: Oxytocin alleviates orofacial mechanical hypersensitivity associated with infraorbital nerve injury through vasopressin-1A receptors of the rat trigeminal ganglia.
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.
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Kubo
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.|Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.|Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Katagiri
authors.affiliation: Laboratory of Food and Physiological Sciences, Department of Life and Food Sciences, School of Life and Environmental Sciences, Azabu University, Kanagawa, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Division of Applied Oral Science, Nihon University Graduate School of Dentistry, Tokyo, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Asaka
authors.affiliation: Faculty of Anesthesia, Stanford University, School of Medicine, Stanford, CA, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Yeomans
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.|Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005157:Facial Pain / Q000150:complications* / Q000188:drug therapy; D006727:Hormone Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D010121:Oxytocin / Q000627:therapeutic use*; D017288:Pain Threshold / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000473:pathology; D014738:Vibrissae / Q000294:innervation
chemical_list: D006727:Hormone Antagonists; D007211:Indoles; D011759:Pyrrolidines; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D010121:Oxytocin; C082134:relcovaptan