Chronic constriction of the sciatic nerve does not induce mood-related comorbidities in female mice.

Neuropathic pain affects around 7-8% of the population and is associated with a high level of lifetime anxio-depressive comorbidities. Despite the higher incidence of the pathology in women, preclinical studies using rodents almost exclusively focused on males so far. Sciatic nerve cuffing is a well-characterized model of neuropathy in which anxio-depressive comorbidities develop over time in male mice. In order to examine potential sex-differences in this model, we compared the alterations in the mechanical sensitivity using von Frey testing and used three ethologically relevant tests to explore their well-being (nest building), social behaviour (dyadic social interaction), and depression-like state (splash test) seven weeks after surgery. We also examined sex-related differences in neuroinflammation by quantifying changes in cytokine expression in the brainstem, a region critically involved in descending pain modulation. Both male and female mice developed mechanical hypersensitivity following cuff surgery. However, no alteration in nest building ability, social dyadic interaction or grooming activity was observed in female mice seven weeks after surgery. Our data therefore suggest sex differences in the development of comorbidities associated with mechanical hypersensitivity. In addition, we evidenced in the brainstem sex-related differences in the expression of cytokines relevant to human neuropathy. Altogether, these results emphasize the need for additional comparisons between males and females to better grasp the role of neuroinflammation in pain sensitization and associated comorbidities.