Sex differences in pain: Spinal cord injury in female and male mice elicits behaviors related to neuropathic pain

Abstract

Spinal cord injury (SCI) in humans frequently causes intractable chronic pain. Females are susceptible to worsened pain compared to males, and females may show higher pain prevalence after SCI in humans. Despite this difference in clinical prevalence of SCI pain, few preclinical studies have systematically studied in rodents sex differences in SCI-elicited pain symptoms. Here, we leverage data from a large cohort of mice to test whether contusion SCI consistently causes pain symptoms in mice, and to establish whether female (vs. male) mice display heightened hypersensitivity after SCI. Mechanical and heat sensory thresholds were assessed using the von Frey test and Hargreaves test, respectively. In an initial experiment, female mice receiving moderate 60 kDyn SCI or moderate-to-severe 75 kDyn SCI both exhibited mechanical and heat pain symptoms compared to sham controls. 75 kDyn SCI caused excess motor deficits that confounded defining pain sensitivity at acute times, so the moderate SCI force was used for subsequent experiments. Next, adult female and male C57BL6/J mice received sham surgery or T9 contusion SCI. Comparing female to male mice after SCI, we reveal that mice of both sexes displayed mechanical and heat hypersensitivity compared to sham controls, from acute-to-chronic post-injury times. Females had amplified SCI-elicited hypersensitivity compared to males. Our data suggest that thoracic contusion SCI elicits consistent and persistent pain symptoms, which are more intense in female vs. male mice. These results have important implications for uncovering sex-specific mechanisms and therapeutic targets to ameliorate neuropathic pain after SCI.