Contribution of G Protein-Coupled Receptor 55 to Periaqueductal Gray-Mediated Antinociception in the Inflammatory Pain

The brain mechanism of inflammatory pain is an understudied area of research, particularly concerning the descending pain modulatory system. The G protein-coupled receptor 55 (GPR55) is a lysophosphatidylinositol-sensitive receptor that has also been involved in cannabinoid signaling. It is widely expressed throughout the central nervous system, including the periaqueductal gray (PAG), a brainstem area and key element of the descending pain modulatory system. In this study, we used behavioral, stereotaxic injections, pharmacological tools, and two inflammatory pain models (formalin and carrageenan) to determine if GPR55 in the PAG plays a role in the pain associated with inflammation in rats. It was found that the blockade of GPR55 action in PAG can drive the descending pain modulatory system to mitigate inflammatory pain. These data show that GPR55 plays a role in the descending pain modulatory system in inflammatory pain.