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.
Highlights
Human immunodeficiency virus-1 (HIV)-associated neuropathic pain is a debilitating condition affecting 55%–67% of the 36.9 million people living with HIV worldwide
HIV-associated neuropathic pain can occur at any time during the entire process of the disease; it remains a common and debilitating condition frequently reported in the clinics, despite the availability of combination antiretroviral therapy [1]
Gp120 has been found in the brains of patients with HIV encephalitis who suffer from dementia [2]
Summary
Human immunodeficiency virus-1 (HIV)-associated neuropathic pain is a debilitating condition affecting 55%–67% of the 36.9 million people living with HIV worldwide (available online: http: //www.who.int/hiv/data/en/). HIV-associated neuropathic pain can occur at any time during the entire process of the disease; it remains a common and debilitating condition frequently reported in the clinics, despite the availability of combination antiretroviral therapy (cART) [1]. A new spectrum of problems is emerging as a result of the action of HIV-viral proteins. In the spinal cord dorsal horn, gp120 has been found at greater concentrations among pain-positive versus pain-negative HIV patients [3]. The involvement of this viral protein in the pathogenesis of HIV-related neuropathic pain has been demonstrated in animal models [3,4,5]
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