Effects of morphine, pentobarbital and amphetamine on formalin-induced behaviours in infant rats: sedation versus specific suppression of pain.

The behavioural response of infant rats to intraplantar injection of formalin consists of specific directed behaviours (limb flexion, shaking and licking the injected paw) and non-specific behaviours that are also induced by non-nociceptive stimulation (squirming, hind limb kicks and whole body jerks), with specific indicators becoming more frequent as pups mature. The present study examined the effects of systemic morphine, pentobarbital and D-amphetamine on formalin-induced behaviours and behavioural state in rat pups from 1 to 20 days of age. Morphine (1 mg/kg) almost completely suppressed both specific and non-specific indicators of pain, and produced mild sedation relative to handled control pups. Pentobarbital (10 mg/kg) produced a similar degree of sedation and suppression of non-specific measures as morphine, but only had weak effects on specific measures in pups less than 1 week old, and no effects thereafter. Suppression of both specific and non-specific pain measures after amphetamine (2 mg/kg) emerged during the 2nd week of life and was not associated with sedation. Thus, morphine produced behavioural analgesia in infant rats in a model of injury-induced inflammatory pain from the 1st postnatal day, when their neurological maturity is similar to a 25-week human fetus, and 1 week before antinociception is observed in thermal and pressure tests. The effects of morphine were qualitatively different from a sedative dose of pentobarbital. The data support the contention that opioids have specific analgesic effects in premature human neonates and underline the need for pain measures that discriminate between sedation and analgesia.