Evaluation of sex-related differences in oxaliplatin-induced changes in the expression of endocannabinoid receptors and enzymes in lumbar ganglia.

M.V NOYA-RIOBÓ; C.A MIGUEL; T GIOVANNETTI; M POODTS; PABLO R. BRUMOVSKY; M.J. VILLAR; M.F CORONEL

Congreso; Annual Meting 2022 PNS; 2022

Introduction: Oxaliplatin-induced neuropathic pain is a frequent and debilitating side effect ofcancer therapy. The endocannabinoid system (ECS), integrated by endogenous ligands,enzymes and receptors, plays a crucial role in regulating pain neurotransmission. Sexdifferences have been observed in clinical and experimental pain, including pain induced bysome chemotherapeutic agents. The aim of this study was to evaluate whether oxaliplatinadministration induced changes in the expression of different components of the ECS, and ifthose changes, as well as the development of allodynia, differed between male and female rats.Methods: Von Frey and Choi Tests were used to evaluate the development of mechanical andcold allodynia in animals receiving oxaliplatin. By using real time RT-PCR, the expression levelsof cannabinoid canonical (CB1, CB2) and non-canonical receptors (GPR55, 5HT1A), and the mainenzymes involved in the synthesis (DAGL, DAGL, NAPE-PLD) and degradation (MGL, FAAH) ofendocannabinoids were evaluated in lumbar dorsal root ganglia from male and female rats.Results: Oxaliplatin administration induced the development of mechanical and coldhypersensitivity and allodynia. No significant sex-related differences were observed in thesepain-related behaviors. The antineoplastic agent also induced robust changes in the expressionof the different components of the ECS in lumbar ganglia. A marked upregulation of CB1, CB2and 5HT1A was detected in both sexes. While DAGL mRNA levels remained unchanged,DAGL was downregulated in male and upregulated in female rats. Finally, MGL and NAPE-PLDshowed increased levels only in male animals, while FAAH resulted upregulated in both sexes.Conclusions: Our results reveal previously undescribed sex-related changes in cannabinoidreceptors and enzymes that may contribute to the physiopathology of oxaliplatin-inducedneuropathic pain in male and female rats.