Enhancement of nerve-injury-induced thermal and mechanical hypersensitivity in adult male and female mice following early life stress

Abstract

Aims: Early life stress contributes to the pathogenesis of psychiatric disorders and chronic pain in adult patients. However, information about the effect of early life stress on chronic pain in mice is limited. In the present study, we evaluated the effect of early life stress on baseline pain sensitivity and thermal or mechanical hypersensitivity induced by nerve injury in male and female mice.

Main methods: Early life stress was induced by maternal separation and social isolation (MSSI). Mice were separated from dam and littermates for 6h/day during postnatal days 15-21 and then were housed individually until the end of the study. At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Thermal and mechanical sensitivity were measured by plantar and von Frey tests.

Key findings: At 7 weeks of age, MSSI induced depression-like behaviors in both male and female mice, but induced anxiety-like behaviors only in female mice. MSSI had no effect on thermal and mechanical sensitivity before nerve injury. However, MSSI enhanced nerve-injury-induced thermal and mechanical hypersensitivity in both male and female mice.

Significance: MSSI exacerbated neuropathic pain in adult male and female mice. Overall, this model may be useful for understanding the molecular mechanisms underlying the reciprocal relationship between early life stress and chronic pain.

Keywords: Anxiety; Depression; Early life stress; Gender difference; Maternal separation; Neuropathic pain.