Exp Neurobiol.  2014 Dec;23(4):372-380. 10.5607/en.2014.23.4.372.

Involvement of Endoplasmic Reticulum Stress Response in Orofacial Inflammatory Pain

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

Abstract

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-eIF2alpha, increased significantly in trigeminal ganglion (TG) of CFA-injected rats compared to control animals. In immunofluorescence analysis, a significant increase of GRP78 and p-eIF2alpha 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.

Keyword

ER stress; trigeminal ganglion; inflammatory pain; orofacial pain

MeSH Terms

Animals
Endoplasmic Reticulum
Endoplasmic Reticulum Stress*
Facial Pain
Fluorescent Antibody Technique
Freund's Adjuvant
Hypersensitivity
Models, Animal
Neurons
Rats
RNA, Messenger
Trigeminal Ganglion
Freund's Adjuvant
RNA, Messenger
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