Neonatal Injury Results in Sex-Dependent Nociceptive Hypersensitivity and Social Behavioral Deficits During Adolescence, Without Altering Morphine Response.

Unlabelled: Neonatal injury is associated with persistent changes in sensory function and altered nociceptive thresholds that give rise to aberrant pain sensitivity in later life. Although these changes are well documented in adult rodents, little is known about the consequences of neonatal injury during adolescence. Because adolescence is a critical developmental period during which persistent pain conditions can arise, we examined the effect of neonatal injury on nociception, social behavior, and response to morphine in adolescent Sprague Dawley rats. Male and female rats exposed to plantar incision injury at postnatal day 3 displayed mechanical hypersensitivity that resolved by 24 hours after incision. When these animals reached adolescence (postnatal day 28-40), neonatally-injured male rats showed ipsilaterally restricted mechanical, heat, and cold hypersensitivity, as well as social behavioral deficits. In contrast, these effects were not seen in female rats. Neonatal injury did not alter acute morphine antinociception or the development of analgesic tolerance in either sex. Morphine-induced conditioned place preference, behavioral sensitization, and physical withdrawal were also not affected by neonatal incision. Thus, early-life injury results in sex-dependent pain-related hypersensitivity and social behavior deficits during adolescence, without altering the response to opioids.

Perspective: Neonatal surgery has greater effects on adolescent male than female rats, resulting in pain-related hypersensitivity and social behavioral deficits. Neonatal surgery does not alter the antinociceptive effects of morphine or abuse liability.