Nucleoside reverse transcriptase inhibitors (NRTIs), drugs used to treat HIV infection, can cause neuropathic pain (NP) and neuroinflammation. An NRTI, 2'-3'-dideoxycytidine (ddC), was reported to induce mechanical allodynia and increase proinflammatory cytokines in the brains of female mice. In some models of NP, microglia activation is important for NP pathophysiology in male mice, while T cells are important in female mice. Age-matched female and male mice (BALB/c strain) treated intraperitoneally once daily with ddC for 5 days developed mechanical allodynia. Treatment with ddC increased Cd11b, H2-Aa, Cd3e, Mapk1, Il1b, Tnf, and Il10 mRNA levels in the spinal cords of female, but not male, mice, whereas there was no alteration found in Gfap and Mapk14 transcripts in both sexes on day 7 after ddC administration. The protein expression of CD11b and phospho-p38 MAPK was significantly increased in the spinal cords of ddC-treated female, but not male, mice, whereas Iba1 protein was elevated in ddC-treated male mice. There was no change in GFAP, CD3e, and phospho-p44/42 MAPK protein levels in both sexes. Thus, changes in neuroimmune cells and molecules in the spinal cords during ddC-induced neuroinflammation were sex-dependent, with female mice being more prone to neuroimmune changes than male mice.
Keywords: T cells; antiretroviral drug; cytokines; ddC; gene expression; mechanical allodynia; microglia; neuroinflammation; neuropathic pain; protein expression; sex differences.