How sensory neurons encode axonal injury signals has been a longstand-ing area of neurological research. Insights into the cellular and transcrip-tional changes in the injured neurons have driven many new therapeutic strategies to improve repair. In contrast, less focus has been centered on the systemic or transneuronal changes that may arise from these injuries and how they may impact or factor into the alterations in gene expres-sion, physiology and neuropathology, such as mirror image pain, arising in regions either directly contralateral or those remote to the injury site. Research in this area is clinically relevant. In patients with chronic uni-lateral pain due to multiple pathologies, many of which involve nerve trauma, there is a very high incidence of bilateral sensory abnormalities reported with 33–50% of patients with mechanical abnormalities report-ing contralateral sensory abnormalities (Konopka et al., 2012). This has implications when evaluating sensory abnormalities or pain states in pa-tients, as the contralateral side is often used as the non-affected control. Further, the bilateral nature of these sensory abnormalities, albeit usually less severe on the contralateral side, support that a systemic or central nervous system component is involved in this aspect of the pathology. It highlights the need to better understand the mechanisms underlying these bilateral responses as this will likely impact therapeutic treatments for these patients.