Involvement of Endoplasmic Reticulum Stress Response in Orofacial Inflammatory Pain

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.

Distribution of Peripherin Immunoreactive Axons in Rat Molar Pulp / 체질인류학회지

Dental pulp is innervated mostly by unmyelinated axons and small myelinated axons. These axons are implicated pain transmission and contain various neurotransmitters and receptors. However, little information, so far, is available on the distribution pattern and characterization of axons involved in the dental pain. In this study, to enhance understanding of dental pain processing, we observed distribution of axons expressing peripherin, an unmyelinated and small myelinated axonal marker, the in rat maxillary molar pulp. Peripherin-immunopositive (+) axons are mostly distributed in the peripheral pulp, and a few peripherin+ axons ascend into the odontoblast layer. Peripherin+ axons expressing NF200 are more frequently observed in the odontoblast layer (86.3+/-3.0%) than in the pulpal core region (79.3+/-2.8%) and nerve plexus region (78.6+/-1.9%). In contrast, peripherin+ axons expressing CGRP are less frequently observed in the odontoblast layer (17.7+/-5.0%) than in the pulpal core (37.7+/-10.1%) and nerve plexus regions (40.0+/-5.7%). These findings indicate that small myelinated axons are implicated in the transmission of dental pain arising from the odontoblast layer while peptidergic unmyelinated axons are implicated in the transmission of dental pain arising from central core and nerve plexus regions of the dental pulp.