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; P.R. BRUMOVSKY; M.J. VILLAR; M.F. CORONEL

Miami

Congreso; Annual meeting of the Peripheral Nerve Society; 2022

Peripheral Nerve Society

Introduction: Oxaliplatin-induced neuropathic pain is a frequent and debilitating side effect of cancer therapy. The endocannabinoid system (ECS), integrated by endogenous ligands, enzymes and receptors, plays a crucial role in regulating pain neurotransmission. Sex differences have been observed in clinical and experimental pain, including pain induced by some chemotherapeutic agents. The aim of this study was to evaluate whether oxaliplatin administration induced changes in the expression of different components of the ECS, and if those 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 and cold allodynia in animals receiving oxaliplatin. By using real time RT-PCR, the expression levels of cannabinoid canonical (CB1, CB2) and non-canonical receptors (GPR55, 5HT1A), and the main enzymes involved in the synthesis (DAGL, DAGL, NAPE-PLD) and degradation (MGL, FAAH) of endocannabinoids were evaluated in lumbar dorsal root ganglia from male and female rats. Results: Oxaliplatin administration induced the development of mechanical and cold hypersensitivity and allodynia. No significant sex-related differences were observed in these pain-related behaviors. The antineoplastic agent also induced robust changes in the expression of the different components of the ECS in lumbar ganglia. A marked upregulation of CB1, CB2 and 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-PLD showed increased levels only in male animals, while FAAH resulted upregulated in both sexes.Conclusions: Our results reveal previously undescribed sex-related changes in cannabinoid receptors and enzymes that may contribute to the physiopathology of oxaliplatin-induced neuropathic pain in male and female rats.