Sex-dependent endocannabinoid adaptations in supraspinal pain modulatory circuits after peripheral nerve injury
- 1Pharmacology and Therapeutics, University of Galway
Abstract
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 and spinal regions 100 days after spared nerve injury (SNI) in male and female rats. SNI increased 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA) in the prefrontal cortex and 2-AG in the rostral ventromedial medulla in males, with exploratory associations between these measures and reduced pain-related hypersensitivity. In females, SNI increased monoacylglycerol lipase expression in the periaqueductal grey. Additional sex- and hemisphere-dependent differences in ECS components were observed in limbic regions,whereas no significant injury-related changes were detected in spinal cord or plasma. These findings identify regionally distinct ECS alterations during established neuropathic pain and suggest that chronic nerve injury is associated with different patterns of supraspinal ECS plasticity in males and females.
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BibTeX
@misc{boullon2026sexdependent,
title = {{Sex-dependent endocannabinoid adaptations in supraspinal pain modulatory circuits after peripheral nerve injury}},
author = {L. Boullon and D. P. Finn and A. Llorente-Berzal},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.15.759453},
url = {https://www.biorxiv.org/content/10.64898/2026.10.15.759453v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Sex-dependent endocannabinoid adaptations in supraspinal pain modulatory circuits after peripheral nerve injury
AU - L. Boullon
AU - D. P. Finn
AU - A. Llorente-Berzal
PY - 2026
DA - 2026/10/15
PB - bioRxiv
DO - 10.64898/2026.10.15.759453
UR - https://www.biorxiv.org/content/10.64898/2026.10.15.759453v1
AB - 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 and spinal regions 100 days after spared nerve injury (SNI) in male and female rats. SNI increased 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA) in the prefrontal cortex and 2-AG in the rostral ventromedial medulla in males, with exploratory associations between these measures and reduced pain-related hypersensitivity. In females, SNI increased monoacylglycerol lipase expression in the periaqueductal grey. Additional sex- and hemisphere-dependent differences in ECS components were observed in limbic regions,whereas no significant injury-related changes were detected in spinal cord or plasma. These findings identify regionally distinct ECS alterations during established neuropathic pain and suggest that chronic nerve injury is associated with different patterns of supraspinal ECS plasticity in males and females.
ER -