Background & Aims

Trigeminal nerve injury is known to cause severe persistent pain in the orofacial regions. Various molecules are released in the trigeminal ganglion (TG), which enhance TG neuronal activity, resulting in orofacial mechanical allodynia. However, the detailed mechanism underlying mechanical allodynia in the orofacial region remains unclear. Recently, it has been reported that Interferon-? (IFN-?) signaling in the trigeminal spinal subnucleus caudalis is involved in facial mechanical allodynia caused by infraorbital nerve injury (IONI), whereas that in TG is unknown. In the present study, we investigated the role of IFN-? signaling in the TG in facial mechanical allodynia after IONI.

Methods

The ION was partially ligated in male SD rats under deep anesthesia to develop a rat model of IONI (IONI group). Rats receiving oral mucosal incision and ION exposure were in the sham group. The mechanical head-withdrawal threshold to the whisker pad skin (MHWT) was measured in IONI and sham rats for 14 days after the operation. IFN-? receptor (IFNGR?) antagonist or vehicle was continuously administered into the TG of IONI rats, and MHWT was measured until day 14 after IONI. In addition, IFN-? was continuously administered into the TG of naive rats, and MHWT was measured until day 14 post-injury. TGs were removed on day 7 after IONI, and the amount of IFN-? protein was measured. IFN-?, IFNGR?, and CD-8 (cytotoxic T-cell marker) expression was precisely analyzed in the TG immunohistochemically.

Results

MHWT was significantly lower in IONI rats compared to sham rats until day 14, and continuous IFN-? administration into TG caused a significant reduction of MHWT in naive rats. The MHWT was significantly recovered in IONI rats after the administration of IFNGR? antagonist into TG. On day 7, the IFN-? protein in the TG was considerably larger in IONI rats compared with sham rats. IFN-?-immunoreactivity was observed in CD8-immunoreactive cells and neurons in TG and IFNGR? in satellite cells, and the number of those positive cells was significantly more significant in ION rats than in sham rats.

Conclusions

These findings suggest that IFN-? signaling in T cells and neurons in the TG activates satellite cells expressing IFNGR?, and activated satellite cells may cause the hyperactivation of TG neurons, resulting in the facial mechanical allodynia associated with IONI.

References

1.Benoliel R, Teich S, Eliav E. Painful traumatic trigeminal neuropathy. Oral Maxillofac Surg Clin North Am 2016
2.Pestka S, Krause CD, Walter MR. Interferons, interferon-like cytokines, and their receptors. Immunol Rev 2004
3.Tanga FY, Nutile-McMenemy N, DeLeo JA. The CNS role of toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci U S A 2005
4.Peter-paul A, Anna E, Tamana K. T-cells in human trigeminal ganglia express canonical tissue-resident memory T-cell markers. J . Neuroinflammation 2022
5.Sayaka A, Akiko O, Momoyo K. Involvement of interferon gamma signaling in spinal trigeminal caudal subnucleus astrocyte in orofacial neuropathic pain in rats with infraorbital nerve injury. Mol pain 2023

Presenting Author

Momoyo Kobayashi

Poster Authors

MOMOYO KOBAYASHI

D.D.S

Department of oral medicine,NUSD

Lead Author

E-mail

Akiko Okada,D.D.S,Ph.D.

Department of oral medicine,NUSD,JAPAN

Lead Author

E-mail

Koichi Iwata

Nihon University

Lead Author

E-mail

NOBORU NOMA

Department of oral medicine,NUSD,JAPAN

Lead Author

E-mail

Masamichi Shinoda,D.D.S,Ph.D.

Department of physiology,NUSD,JAPAN

Lead Author

E-mail

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral