Neuropathic pain arises in males and females through distinct neuroimmune signaling. Yet the behavioral (or clinical) features of neuropathic pain are not sexually dimorphic. Mapplebeck et al. demonstrate that KCC2—though regulated in multiple, sex-specific ways—is uniquely responsible for the synaptic disinhibition causing neuropathic pain in both sexes.
Mapplebeck, J. C. S., Lorenzo, L. E., Lee, K. Y., Gauthier, C., Muley, M. M., De Koninck, Y., … Salter, M. W. (2019). Chloride Dysregulation through Downregulation of KCC2 Mediates Neuropathic Pain in Both Sexes. Cell Reports, 28(3), 590-596.e4. https://doi.org/10.1016/j.celrep.2019.06.059