This study demonstrates that reliable sex differences in nociceptive and antinociceptive mechanisms are present in even very young subjects. Sex differences were observed in mice tested either on the day of birth or 1 week later on basal tail-flick latency and morphine analgesic magnitude. Female mice had longer tail-withdrawal latencies; male mice demonstrated stronger analgesic responses to morphine. In addition, basal pain behavior and analgesic responsiveness differed between day-old and week-old animals on the hot plate, with day-old mice showing enhanced pain behavior and reduced morphine antinociception compared to week-old subjects. These findings further support the competence of pain processing circuitry in even very young subjects and highlight the early development of nociceptive and antinociceptive mechanisms.
Perspective: This study highlights the competence of nociceptive circuitry and the analgesic efficacy of morphine as early as the day of birth in mice, reinforcing the importance of evaluating and treating pain in even the youngest subjects. Sex differences were present, suggesting infant sex as one of several potential factors that predict the experience of procedural or pathological pain and analgesic requirement.