• Masatoshi Ando, Yoshinori Hayashi, Suzuro Hitomi, Ikuko Shibuta, Akihiko Furukawa, Tatsuki Oto, Takanobu Inada, Tomoyuki Matsui, Chikashi Fukaya, Noboru Noma, Masakazu Okubo, Yoshiyuki Yonehara, Tadayoshi Kaneko, Koichi Iwata, and Masamichi Shinoda.
• Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, Tokyo 101-8310, Japan.
• Int J Mol Sci. 2020 Dec 1; 21 (23).

AbstractWe evaluated the mechanisms underlying the oxytocin (OXT)-induced analgesic effect on orofacial neuropathic pain following infraorbital nerve injury (IONI). IONI was established through tight ligation of one-third of the infraorbital nerve thickness. Subsequently, the head withdrawal threshold for mechanical stimulation (MHWT) of the whisker pad skin was measured using a von Frey filament. Trigeminal ganglion (TG) neurons innervating the whisker pad skin were identified using a retrograde labeling technique. OXT receptor-immunoreactive (IR), transient receptor potential vanilloid 1 (TRPV1)-IR, and TRPV4-IR TG neurons innervating the whisker pad skin were examined on post-IONI day 5. The MHWT remarkably decreased from post-IONI day 1 onward. OXT application to the nerve-injured site attenuated the decrease in MHWT from day 5 onward. TRPV1 or TRPV4 antagonism significantly suppressed the decrement of MHWT following IONI. OXT receptors were expressed in the uninjured and Fluoro-Gold (FG)-labeled TG neurons. Furthermore, there was an increase in the number of FG-labeled TRPV1-IR and TRPV4-IR TG neurons, which was inhibited by administering OXT. This inhibition was suppressed by co-administration with an OXT receptor antagonist. These findings suggest that OXT application inhibits the increase in TRPV1-IR and TRPV4-IR TG neurons innervating the whisker pad skin, which attenuates post-IONI orofacial mechanical allodynia.

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