Sex-dependent endocannabinoid adaptations in supraspinal pain modulatory circuits after peripheral nerve injury
Peripheral nerve injury produces persistent pain-related behaviours that differ between sexes, but whether chronic neuropathic pain is accompanied by sex-dependent alterations in endocannabinoid signalling across pain-modulatory circuits remains unclear. We quantified endocannabinoids and related N-acylethanolamines and expression of cannabinoid receptors and metabolic enzymes across supraspinal…
Sex-dependent adaptations in endocannabinoid systems occur in pain-modulating circuits following peripheral nerve injury, leading to divergent alterations in males and females. After spared nerve injury, male rats exhibited increased levels of 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA) in the prefrontal cortex, alongside reduced pain sensitivity.
Concurrently, females showed heightened monoacylglycerol lipase expression in the periaqueductal grey. These sex-specific changes in endocannabinoid components were noted within limbic regions, while no significant alterations were observed in the spinal cord or plasma. The study reveals distinct patterns of supraspinal cannabinoid plasticity following chronic nerve injury, suggesting disparate responses in males and females.
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