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

Abstract

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.

Keywords: GPR55; cannabinoids; descending pain modulatory system; inflammatory pain; periaqueductal gray.

FIG. 1.

The design of the experiment (A). PAG pretreatment with ML-193 reduced the second phase (C) of formalin-induced pain-like behaviors, but not the first phase (B). Illustration of cannula placement, site of action, and schematic representation of targeted (Bregma −7.32 mm) (D). Intraplantar injection of ML-193 (0.1–1 μg) did not affect formalin induced pain-like behaviors (E, F). SR141716A and SR 144528 failed to affect the analgesic effect of ML-193 (G, H). Data are presented as mean±SEM. **p<0.01, *p<0.05 (ML-193 vs. vehicle). PAG, periaqueductal gray; ns, not significant.

FIG. 2.

The design of the experiment (A). PAG pretreatment with ML-193 reduced the mechanical allodynia (B) and thermal hypersensitivity (C) induced by carrageenan. SR141716A and SR 144528 failed to affect the analgesic effect of ML-193 in carrageenan-induced mechanical allodynia (D) and thermal hypersensitivity (E). Data are presented as mean±SEM. ***p<0.001. ns, not significant.