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

Masatoshi Ando,Tatsuki Oto,Tomoyuki Matsui,Tadayoshi Kaneko,Ikuko Shibuta,Chikashi Fukaya,Noboru Noma,Takanobu Inada,Koichi Iwata,Akihiko Furukawa,Masamichi Shinoda,Masakazu Okubo,Suzuro Hitomi,Yoshinori Hayashi,Yoshiyuki Yonehara

doi:10.3390/ijms21239173

Masatoshi Ando, Tatsuki Oto + Show 13 more

Open Access

https://doi.org/10.3390/ijms21239173

Copy DOI

Abstract

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.

Highlights

Orofacial neuropathic pain is caused by trigeminal nerve injury, which results from tooth extraction, maxillary bone fracture, or dental implant displacement [1,2]
This study aimed to evaluate the involvement of OXT signaling via OXT receptors in changes in the functional characteristics of transient receptor potential vanilloid 1 (TRPV1) and TRPV4 associated with orofacial neuropathic pain following infraorbital nerve (ION) injury (IONI)
There was a significant decrease in the mechanical head withdrawal threshold (MHWT) on day 1 after infraorbital nerve injury (IONI), which persisted until day 11 after IONI

Summary

Introduction

Orofacial neuropathic pain is caused by trigeminal nerve injury, which results from tooth extraction, maxillary bone fracture, or dental implant displacement [1,2]. Oxytocin (OXT) is a well-known hormone that is synthesized by neurosecretory cells in the paraventricular nucleus and supraoptic nucleus of the hypothalamus; it is secreted from the posterior pituitary gland It is involved in the contraction of uterine smooth muscles and muscle fibers of the mammary gland to promote lactation [4]. OXT receptor was identified in the sensory neurons of the trigeminal ganglion (TG), while orofacial inflammation was identified to cause an upregulation of OXT receptor expression in the TG neurons [10]. These findings suggest that OXT signaling in the TG neurons via the OXT receptor may modulate TG neuronal excitability, which is closely related to orofacial pain sensitivity

Objectives

Methods

Results

Conclusion