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Original Article

Exp Neurobiol 2014; 23(4): 372-380

Published online December 31, 2014

© The Korean Society for Brain and Neural Sciences

Involvement of Endoplasmic Reticulum Stress Response in Orofacial Inflammatory Pain

Eun Sun Yang1, Jin Young Bae1, Tae Heon Kim1, Yun Sook Kim1, Kyoungho Suk2 and Yong Chul Bae1*

1Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, 2Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 700-422, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-53-660-6860, FAX: 82-53-426-7731

Received: September 17, 2014; Revised: October 22, 2014; Accepted: October 22, 2014


Endoplasmic reticulum (ER) stress is involved in many neurological diseases and inflammatory responses. Inflammatory mediators induce neuronal damage and trigger the neuropathic or inflammatory pain. But there is very little data on the role of the ER stress response in pain mechanisms. In this study, we explored whether the ER stress response is involved in orofacial inflammatory pain by using a complete Freund's adjuvant (CFA)-injected rat model. The thermal pain hypersensitivity increased significantly after CFA injection. We found that the protein and mRNA levels of ER stress response genes, GRP78/Bip and p-eIF2α, increased significantly in trigeminal ganglion (TG) of CFA-injected rats compared to control animals. In immunofluorescence analysis, a significant increase of GRP78 and p-eIF2α immunopositive neurons was observed in CFA-injected TG compared to control TG. When we administered an ER stress modulator, salubrinal, CFA-induced thermal pain hypersensitivity was temporally reduced. Thus, our study suggests that ER stress responses in TG neurons contribute to CFA-induced inflammatory pain, and may comprise an important molecular mechanism underlying the orofacial inflammatory pain pathway.

Keywords: ER stress, trigeminal ganglion, inflammatory pain, orofacial pain