A myelin basic protein fragment induces sexually dimorphic transcriptome signatures of neuropathic pain in mice
Andrei V. Chernov, Swathi K. Hullugundi, Kelly A. Eddinger, Jennifer Dolkas, Albert G. Remacle, Mila Angert, Brian P. James, Tony L. Yaksh, Alex Y. Strongin, Veronica I. Shubayev
Abstract
-dependent nociceptive signaling induction in females that was suppressed in males (tier 2). IP3R inactivation by intrathecal xestospongin C attenuated the female-specific hypersensitivity induced by MBP(84-104). According to sustained sensitization in tiers 1 and 2, T cell-related signaling spreads to the DRG and spinal cord in females, but remains localized to the sciatic nerve in males (tier 3). These results are consistent with our previous finding that MBP(84-104)-induced pain is T cell-dependent. In summary, an autoantigenic peptide endogenously released in nerve injury triggers multisite, sex-specific transcriptome changes, leading to neuropathic pain only in female mice. MBP(84-104) acts through sustained co-activation of metabolic, estrogen receptor-mediated nociceptive, and autoimmune signaling programs.