Preemptive Morphine Analgesia Attenuates the Long-Term Consequences of Neonatal Inflammation in Male and Female Rats

Despite mounting evidence on the importance of pain management in preterm infants, clinical use of analgesics in this population is limited. Our previous studies have shown that neonatal inflammation results in long-term alterations in adult somatosensory thresholds, characterized by decreased baseline nociceptive sensitivity, and enhanced hyperalgesia after a subsequent inflammatory insult. The present studies were conducted to determine whether preemptive morphine attenuates these negative consequences. At P0, pups received an injection of morphine sulfate before an intraplantar injection of 1% carrageenan. Control pups received either saline (SAL) followed by intraplantar carrageenan, morphine Sulfate followed by intraplantar SAL, or SAL followed by intraplantar SAL. Preemptive morphine significantly attenuated neonatal injury-induced hypoalgesia in adolescence and adulthood. Similarly, morphine pretreated animals displayed significantly less hyperalgesia and recovered faster from a subsequent inflammatory insult compared with controls. Neonatal morphine had no significant effect on morphine analgesia in adulthood. Interestingly, neonatally injured animals that did not receive morphine displayed a significant rightward shift in the morphine dose-response cuve in the absence of peripheral inflammation. Together, these results demonstrate that preemptive morphine significantly attenuates the long-term behavioral impact of neonatal inflammatory injury. (Pediatr Res 64: 625-630, 2008)