Oxytocin-Dependent Regulation of TRPs Expression in Trigeminal Ganglion Neurons Attenuates Orofacial Neuropathic Pain Following Infraorbital Nerve Injury in Rats

• Main Authors: 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, Masamichi Shinoda
• Format: Article
• Language: English
• Published: MDPI AG 2020-12-01
• Series: International Journal of Molecular Sciences
• Subjects: oxytocin; TRPV1; TRPV4; infraorbital nerve injury; orofacial mechanical allodynia
• Online Access: https://www.mdpi.com/1422-0067/21/23/9173

We 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.