Journal of Pain & Relief
Open Access

Abstract

Transition from acute to chronic pain depends on long lasting sensitization of nociceptive neurons located along peripheral and central pain transmission pathway. Neuroplasticity of nociceptive dorsal root ganglion (DRG) neurons (nociceptors) induced by pro-inflammatory mediators contributes to nociceptor sensitization. Prostaglandin E2 (PGE2), a well-known pro-inflammatory mediator enriched in inflamed tissues, not only directly sensitizes DRG neurons, but also potentiates the sensitizing effects of other pain mediators such as capsaicin and its receptor transient receptor potential vanilloid-1 (TRPV1). It has been known that PGE2 potentiates TRPV1 activity at the functional level. It remains much less known whether facilitating TRPV1 synthesis and cell surface trafficking in DRG neurons contributes to PGE2 potentiation of TRPV1 activity. We will provide evidence which supports this hypothesis. We found that PGE2 increased TRPV1 externalization in cultured rat DRG neurons. EP1 and EP4 receptors as well as CaMKII, PLC, PKC/PKC�µ, cAMP/PKA and ERK/MAPK.are involved in mediating PGE2-induced TRPV1 externalization. Preexposure to PGE2 2d earlier potentiated pain peptide CGRP release evoked by subsequent capsaicin stimulation. This event was blocked by the inhibitors of protein synthesis and export, suggesting that PGE2-induced TRPV1 synthesis and export is coupled to enhanced TRPV1 activity. Intraplantar injection of PGE2 7d earlier not only prolonged tactile allodynia evoked by subsequent capsaicin challenge, but also induced a prolonged and delayed increase in TRPV1 levels in L4-6 DRG, sciatic nerves and plantar skin. We conclude that facilitating TRPV1 synthesis and cell surface trafficking is a possible novel mechanism underlying PGE2 potentiation of TRPV1 activity.

Biography

Email: weiya.ma@douglas.mcgill.ca