Characterization of nociceptive responses to bee venom-induced inflammation in neonatal rats

To assess developmental characteristics of nociceptive responses induced by bee venom (BV) injection in neonatal rats, we exposed pups to intra-plantar injection of various BV concentrations given at different time points between postnatal day 1 and day 28 (P1-P28). Persistent spontaneous nociception (PSN) as well as thermal and mechanical nociceptive response was compared before and after a BV injection. There were distinct age-related changes in the baseline paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) when examined on P1, P4, P7, P14, P21, and P28. The lowest and highest baseline PWTL was shown on P1 and P7, respectively, and PWTL was unchanged from P7 to P28. In contrast, the baseline PWMT remained low before P21 but increased dramatically afterward. Neonatal rats receiving intra-plantar BV injection showed a time-dependent change in nociceptive responses, including (1) a dose-related increase in PSN from P1 to P28; (2) a non-specific decrease (indistinguishable between saline and BV injection) in PWTL and PWMT up to P14 and P21, respectively; and (3) a specific decrease (in response to BV injection only) in PWTL and PWMT after P14 and P21, respectively. These findings indicate that characteristic changes in the baseline and BV-induced nociceptive response are both time-dependent and modality-specific in neonatal rats. The data reveal a critical postnatal period during which nociceptive stimulation could have a significant influence on nociceptive behavior in adult rats and suggest that preclinical models of neonatal nociception should be evaluated according to different postnatal time points.