The Journal of Pain | 2019
(282) Sex Differences in the Development of Tolerance to Arachidonyl-2-Chloroethalamide (ACEA) in the Mouse Formalin Pain Model
Abstract
Interest in the cannabinoid class of compounds is growing rapidly as an option to treat a variety of conditions, including pain. Arachidonyl-2-chloroethalamide (ACEA), a CB1 specific compound and analog of the endocannabinoid anandamide, has demonstrated efficacy in a variety of animal pain models. Our study evaluated ACEA in the formalin model of pain in male and female C57BL6 mice. Intraplantar injection of 2.5% formalin produces a biphasic pain response modeling both acute and inflammatory pain, measured as time spent attending to the injected paw over the course of one hour. Since development of tolerance to the analgesic effects of cannabinoids is well documented in animal models and an important clinical consideration, we evaluated the analgesic effects of ACEA in both control mice, as well as mice pretreated with ACEA (doses of 0.1, 0.5 and 1 mg/kg) at different time point (ranging from 1 to 8 days) and tested with formalin on the last day of treatment. Our preliminary results reveal sex differences between male and female mice treated with an acute dose of ACEA (0.1, 0.5 and 1 mg/kg I.P.) 30 minutes prior to formalin injection. We also note sex differences in the development of tolerance in male and female mice pretreated with ACEA for different number of days prior to the formalin test. Notably, the development of tolerance to the analgesic effects of ACEA corresponds with an alteration in the estrous cycle in female mice, suggesting that a hormonal component may be involved in this process. Further studies are needed to investigate the mechanisms behind these preclinical interesting findings.