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

Abstract

Our recent work has demonstrated that the 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. However, whether neonatal VNC treatment alters baseline pain sensitivity throughout adulthood remains unknown. It is also unclear if pediatric VNC exposure can ‘prime’ developing nociceptive pathways, and thereby exacerbate chronic pain, following subsequent trauma later in life. Therefore, the present study investigated the degree to which neonatal VNC administration influences mechanical and thermal pain hypersensitivity in the absence or presence of tissue injury sustained during adulthood. Rats received five total doses of 60 mg/kg VNC (or vehicle) on postnatal days (P) 11, 13, 17, 19 and 21, which is known to evoke mechanical pain and skin denervation by P26 (Schappacher et al., 2017). Immunohistochemical analysis of the skin suggested that a resolution of the peripheral neuropathy occurs by 13–15 weeks of age, as there were no differences in the density of intraepidermal nerve fibers or activated Langerhans cells between the VNC and vehicle‐treated groups at this time point. Baseline mechanical pain sensitivity, as measured with von Frey hairs, was also similar between the experimental groups during adulthood, confirming recovery to neonatal VNC treatment. To explore the potential long‐term effects of early life VNC on the behavioral response to subsequent insults, a surgical incision of the hindpaw was administered to adult rats exposed to either VNC or vehicle during the neonatal period. We observed no significant overall effect of early life VNC on the magnitude of post‐operative pain following adult incision. In addition, in order to model 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 subsequently administered VNC during adulthood (five injections at 100 mg/kg). There was no significant effect of prior VNC exposure on the level of mechanical pain hypersensitivity produced by adult VNC treatment. Collectively, these findings suggest that neonatal VNC does not increase the susceptibility to develop chronic pain as adults.Support or Funding InformationSupported by National Institutes of Health (NS080889 to MLB).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.