Sex-related exacerbation of injury-induced mechanical hypersensitivity in GAD67 haplodeficient mice - CNRS - Centre national de la recherche scientifique
Journal Articles Pain Year : 2023

Sex-related exacerbation of injury-induced mechanical hypersensitivity in GAD67 haplodeficient mice

Aude Charron
  • Function : Author
Lucie Pepino
  • Function : Author
Pascale Malapert
  • Function : Author
Vincent Debrauwer
  • Function : Author
Chiara Salio
  • Function : Author

Abstract

Abstract Decreased GABA levels in injury-induced loss of spinal inhibition are still under intense interest and debate. Here, we show that GAD67 haplodeficient mice exhibited a prolonged injury-induced mechanical hypersensitivity in postoperative, inflammatory, and neuropathic pain models. In line with this, we found that loss of 1 copy of the GAD67-encoding gene Gad1 causes a significant decrease in GABA contents in spinal GABAergic neuronal profiles. Consequently, GAD67 haplodeficient males and females were unresponsive to the analgesic effect of diazepam. Remarkably, all these phenotypes were more pronounced in GAD67 haplodeficient females. These mice had significantly much lower amount of spinal GABA content, exhibited an exacerbated pain phenotype during the second phase of the formalin test, developed a longer lasting mechanical hypersensitivity in the chronic constriction injury of the sciatic nerve model, and were unresponsive to the pain relief effect of the GABA-transaminase inhibitor phenylethylidenehydrazine. Our study provides strong evidence for a role of GABA levels in the modulation of injury-induced mechanical pain and suggests a potential role of the GABAergic system in the prevalence of some painful diseases among females.

Dates and versions

hal-04246585 , version 1 (17-10-2023)

Identifiers

Cite

Aude Charron, Lucie Pepino, Pascale Malapert, Vincent Debrauwer, Francis Castets, et al.. Sex-related exacerbation of injury-induced mechanical hypersensitivity in GAD67 haplodeficient mice. Pain, 2023, ⟨10.1097/j.pain.0000000000003012⟩. ⟨hal-04246585⟩
12 View
0 Download

Altmetric

Share

More