Session: 9

PS9-10 | Changes in the expression of endocannabinoid receptors and enzymes in primary afferent neurons from male and female animals with oxaliplatin-induced peripheral neuropathic pain.

Maria Victoria Noya Riobo

Laboratorio de dolor asociado a cancer, Instituto de medicina Traslacional, CONICET- Universidad Austral

Oxaliplatin-induced peripheral neuropathic pain is a frequent and debilitating side effect of cancer therapy. The endocannabinoid system is one of the main neurotransmitter systems participating in pain control. Here we explored whether the development of oxaliplatin-induced allodynia correlated with changes in the expression of cannabinoid receptors (CB1 and CB2), non-cannonical receptors (GPR55, TRPV1 and 5HT1A), and the main enzymes involved in the synthesis (DAGL⍺, DAGLβ, NAPE-PLD) and degradation (MGL, FAAH ) of endocannabinoids, in primary afferent neurons from both male and female rats. Animals receiving oxaliplatin developed mechanical and cold allodynia. No statistically significant differences were observed between sexes. Oxaliplatin induced significant changes in the expression of the different components of the endocannabinoid system in primary afferent neurons. The mRNA levels of CB1, CB2, TRPV1 and 5HT1A were found to be increased (p<0,05 vs CTL in all cases), while GPR55 was downregulated (p<0,05 vs CTL) in both male and female animals. While no changes were observed in DAGLβ levels (p>0,05 vs CTL in both cases), DAGL⍺ was downregulated in male and upregulated in female rats (p<0,05 vs CTL in both cases). Finally, MGL and NAPE-PLD showed increased levels (p<0,05 vs CTL) only in male animals. Our results suggest that oxaliplatin-induced changes in the expression of cannabinoid receptors and enzymes in peripheral neurons could underlie pain development.