Sexual dimorphism in cognitive disorders in a murine model of neuropathic pain

Background A sex-difference in susceptibility to chronic pain is well-known. Although recent studies have begun to reveal the sex-dependent mechanisms of nerve injury-induced pain sensitization, sex differences in the affective and cognitive brain dysfunctions associated with chronic pain have not been investigated. Therefore, we tested whether chronic pain leads to affective and cognitive disorders in a mouse neuropathic pain model and whether those disorders are sexually dimorphic. Methods Chronic neuropathic pain was induced in male and female mice by L5 spinal nerve transection (SNT) injury. Pain sensitivity was measured with the von Frey test. Affective behaviors such as depression and anxiety were assessed by the forced swim, tail suspension, and open field tests. Cognitive brain function was assessed with the Morris water maze and the novel object location and novel object recognition tests. Results Mechanical allodynia was induced and maintained for up to 8 weeks after SNT in both male and female mice. Depressive- and anxiety-like behaviors were observed 8 weeks post-SNT injury regardless of sex. Chronic pain-induced cognitive deficits measured with the Morris water maze and novel object location test were seen only in male mice, not in female mice. Conclusions Chronic neuropathic pain is accompanied by anxiety- and depressive-like behaviors in a mouse model regardless of sex, and male mice are more vulnerable than female mice to chronic pain-associated cognitive deficits.This work was supported by the Samsung Science & Technology Foundation (SSTF-BA1502-13), and WS was supported with a postdoctoral fellowship from the National Research Foundation funded by the Korean Government (NRF-2016935834)