Opioid analgesia and the somatosensory memory of neonatal surgical injury in the adult rat.

Abstract

Nociceptive input during early development can produce somatosensory memory that influences future pain response. Hind-paw incision during the 1st postnatal week in the rat enhances re-incision hyperalgesia in adulthood. We now evaluate its modulation by neonatal analgesia. Neonatal rats [Postnatal Day 3 (P3)] received saline, intrathecal morphine 0.1 mg kg-1 (IT), subcutaneous morphine 1 mg kg^-1 (SC), or sciatic levobupivacaine block (LA) before and after plantar hind-paw incision (three×2 hourly injections). Six weeks later, behavioural thresholds and electromyography (EMG) measures of re-incision hyperalgesia were compared with an age-matched adult-only incision (IN) group. Morphine effects on spontaneous (conditioned place preference) and evoked (EMG sensitivity) pain after adult incision were compared with prior neonatal incision and saline or morphine groups. The acute neonatal effects of incision and analgesia on behavioural hyperalgesia at P3 were also evaluated. Adult re-incision hyperalgesia was not prevented by neonatal peri-incision morphine (saline, IT, and SC groups > IN; P<0.05-0.01). Neonatal sciatic block, but not morphine, prevented the enhanced re-incision reflex sensitivity in adulthood (LA < saline and morphine groups, P<0.01; LA vs IN, not significant). Morphine efficacy in adulthood was altered after morphine alone in the neonatal period, but not when administered with neonatal incision. Morphine prevented the acute incision-induced hyperalgesia in neonatal rats, but only sciatic block had a preventive analgesic effect at 24 h. Long-term effects after neonatal injury highlight the need for preventive strategies. Despite effective analgesia at the time of neonatal incision, morphine as a sole analgesic did not alter the somatosensory memory of early-life surgical injury.