Sex Differences in Pain Responses at Maturity Following Neonatal Repeated Minor Pain Exposure in Rats

Abstract

There is mounting evidence of long-lasting changes in pain sensitivity in school-age children who were cared for in a neonatal intensive care unit. Such care involves multiple pain exposures, 70% of which are accounted for by heel lance to monitor physiological well-being. The authors sought to model the repeated brief pain resulting from heel lance by administering repeated paw needle stick to neonatal rat pups. Repeated needle stick during the first 8 days of life was sex-specific in altering responses to mechanical and inflammatory stimuli, but not to a thermal stimulus, at maturity. Specifically, neonatal paw needle stick males exhibited significantly greater mechanical sensitivity in response to von Frey hair testing, whereas neonatal paw needle stick females exhibited significantly greater pain behavior scores following hindpaw formalin injection. This is the first study to show such sex-dependent changes in pain responsiveness at maturity in animals having experienced repeated neonatal needle stick pain. These findings support existing evidence that there are long-term sensory sequelae following neonatal pain experiences in rats and further suggest that there are sex-linked differences in the nature of the consequences. If these relationships hold in humans, these findings suggest that even mild painful insults early in life are not without sensory consequences.