Sex Differences in a Rodent Model of HIV-1-Associated Neuropathic Pain

Abstract

Worldwide, women account for approximately 51% of human immunodeficiency virus-1 (HIV) seropositive individuals. The prevalence of neuropathic pain among individuals with HIV and a lack of preclinical data characterizing sex differences prompted us to address this knowledge gap. C57BL/6 male and female mice received multiple intrathecal injections of HIV-glycoprotein 120 (gp120), followed by determination of mechanical allodynia and thermal hypersensitivity for four weeks. The influence of ovarian hormones in the gp120 pain model was evaluated by comparison of ovariectomized (OVX) mice versus sham control. We found that gp120-induced neuropathic pain-like behaviors are sex-dependent. Female mice showed both increased mechanical allodynia and increased cold sensitivity relative to their male counterparts. The OVX mice showed reduced pain sensitivity compared to sham, suggesting a role of the ovarian hormones in sex differences in pain sensitivity to gp120. Gp120-induced neuropathic pain caused a shift in estrous cycle toward the estrus phase. However, there is a lack of clear correlation between the estrous cycle and the development of neuropathic pain-like behaviors during the four week recording period. This data provided the first evidence for sex differences in a rodent model of HIV-related neuropathic pain, along with a potential role of ovarian hormones.