Background: Paclitaxel-induced neuropathic pain is a frequent and debilitating side effect of cancer therapy. Sex differences have been described in taxane treatment toxicities, including pain development. The endocannabinoid system (ECS) plays a crucial role in regulating pain neurotransmission.

Objective: The aim of this study was to evaluate whether paclitaxel administration induced sex-related changes in the expression of different components of the ECS, as well as in the development of allodynia, locomotor alterations and weight loss.  

Methods: Adult male and female animals receiving paclitaxel (PAX, 4mg/kg, 4 administrations on alternate days) or saline (CTL) were weighed periodically. Mechanical and cold allodynia were assessed using Von Frey and Choi Tests, while locomotor activity was analyzed with an Open Field Test. By using real time RT-PCR, the expression levels of cannabinoid receptors (CB1, CB2) and enzymes involved in the synthesis (DAGLa, DAGLb, NAPE-PLD) and degradation (MGL, FAAH) of endocannabinoids were evaluated in lumbar dorsal root ganglia (DRGs) 15 days after initiating PAX administration.

Results: Paclitaxel treated male animals developed mechanical and cold allodynia and exhibited a significant attenuation in their growth curves but did not show changes in locomotor activity. Female rats receiving the neurotoxic antineoplastic agent developed cold allodynia but no attenuation in weight gain or motor activity.  When evaluating the expression of different components of the ECS, a significant downregulation of DAGLa was detected in male DRGs, while an upregulation of DAGLb was observed in female ganglia. No changes were detected in the mRNA levels corresponding to other endocannabinoid system enzymes or receptors, in either male or femlae animals.

Conclusions: Our results reveal the existence of some sex-related differences in the development of paclitaxel-induced allodynia and in the expression of the main enzyme involved in 2-arachydonoylglycerol synthesis.