Lower Pain Sensitivity in Ovariectomized Mice Using HIV Gp120 and Chemotherapy‐induced Chronic Pain Models

Abstract

Pain is an uncomfortable sensation linked with a vast majority of health complications. It is a result of complex interactions involving the peripheral and central nervous system, which vary between different types of pain. It is important to improve the analgesic effects of drugs for different types of pain while maintaining patient well‐being. For this reason, our laboratory focused on understanding the behavioral antinociceptive effects of cisplatin (a chemotherapeutic drug) and HIV gp120 on both male and female mice. We also tested the analgesic effects of CP55, 940 (a cannabinoid CB1/CB2 receptor agonist) in an HIV‐gp120 mouse model after neuropathic effects were documented. Cannabinoid receptor agonists have been shown to be effective in pain animal models by inhibiting acute nociceptive responses and reversing the behavioral hypersensitivity. Because of this, we hypothesize that neuropathic pain on this HIV‐gp120 mouse model will also be reversed. All of this was experimented in ovariectomized mice in order to improve our understanding of pro‐ or anti‐ nociceptive processes and the potential role of sex hormones. We tested the effect of cisplatin (0.5 mg/kg intraperitoneal injection once a week for 4 weeks) or HIV‐gp120 (200 ng) treatment on mechanical (von Frey) and cold (acetone) allodynia in control (male and female) and ovariectomized mice. We also conducted daily vaginal lavages in the female mice. Our results suggest that both, cisplatin and HIV‐gp120 mouse models, induce mechanical and cold pain sensitivity in both male and female. Only HIV‐gp120 female mice show an increase in mechanical and cold pain sensitivity relative to male. Both, ovariectomized mice treated with cisplatin and ovariectomized HIV‐gp120 mice show a decrease in mechanical and cold pain sensitivity relative to control female mice. As for treatment with Cp55, 940 analgesic effects were clearly present at 10mg/kg for all mice. However, 1mg/kg had no analgesic effects. We also observed disturbance in the estrous cycle of the HIV‐gp120 mice group. As a conclusion, we confirm that hormonal changes are influencing pain sensitivity and therefore demonstrate the importance of sex‐hormones in pain transmission. Further studies are needed to better understand the mechanisms of action of these findings.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.