Early life vincristine exposure does not prime the developing pain circuitry for subsequent injury

By Lauren Styczynski, Medical Sciences Advisor: Mark Baccei Presentation ID: PM_B19 Abstract: Our group has found early life administration of vincristine (VNC), commonly used to treat pediatric leukemias, evokes peripheral neuropathy and mechanical pain hypersensitivity in rats that persists into adolescence. Whether neonatal VNC treatment alters baseline pain sensitivity throughout adulthood remains unknown. It is unclear if pediatric VNC exposure can 'prime' developing nociceptive pathways, and thereby exacerbate chronic pain, following subsequent trauma later in life. The present study investigated the degree to which neonatal VNC administration influences mechanical and thermal pain hypersensitivity in the presence of tissue injury sustained during adulthood. Immunohistochemistry suggested a resolution of the peripheral neuropathy occurs by 13-15 weeks of age; there were no differences in density of intraepidermal nerve fibers or activated Langerhans cells between groups. Baseline mechanical pain sensitivity was similar between experimental groups during adulthood, confirming recovery. To explore potential long-term effects of neonatal VNC on behavioral response to subsequent insults, a surgical incision of the hindpaw was administered to adult rats exposed to either VNC or vehicle neonatally. We observed no significant overall effect of early life VNC on the magnitude of post-operative pain. Modelling the clinical scenario where cancer relapse necessitates a second round of chemotherapy, separate groups of rats that had been treated with VNC (or vehicle) as neonates were administered VNC during adulthood. There was no significant effect of prior VNC exposure on the level of mechanical pain hypersensitivity produced by adult VNC treatment. These findings suggest neonatal VNC does not increase the susceptibility to develop chronic pain as adults.