Edwards, Taylor; Ram, Akila; McCarty, Ashley; Bobeck, Erin N (Utah State University)
Faculty Advisor: Bobeck, Erin (College of Science, Biology Department)
First-line chemotherapies against solid tumors are highly efficacious in reducing the tumor burden, but have many adverse side-effects including nerve damage, leading to chronic pain. Non-addictive, efficacious pain relievers are an area of active interest, and we propose a novel target to address this pressing issue. GPR171 is a G-Protein Coupled Receptor that was recently deorphanized and was identified to be expressed in the brain in regions that regulate reward, anxiety, and pain. Within the pain circuit, it was shown previously that systemic administration of the GPR171 agonist enhances morphine antinociception in acute pain tests. Preliminary data from our lab has shown that GPR171 activation can also alleviate persistent inflammatory pain. However, the role of this receptor has not been investigated in other chronic pain models. Given these findings in acute and inflammatory pain, we hypothesize that GPR171 can reduce neuropathic pain. To test this hypothesis, we investigate the role of GPR171 in chronic neuropathic pain. We tested the efficacy of a GPR171 agonist in a chemotherapy-induced neuropathy mouse model. Neuropathic pain was induced by injecting paclitaxel (16 mg/kg) followed by assessment of the pain-relieving effects of activating GPR171 receptors. Mechanical pain thresholds were assessed using Von Frey filaments. We observed an increase in mechanical thresholds following GPR171 agonist treatment. Further, using immunofluorescence we observed that there is a decrease in GPR171 receptors in the periaqueductal gray (PAG) of these mice that have neuropathic pain, indicating that the agonist can bind to the available receptors to produce pain relief. Overall, this study proposes that GPR171 may be a novel target for the treatment of neuropathic pain.