Dextromethorphan attenuated the higher vulnerability to inflammatory thermal hyperalgesia caused by prenatal morphine exposure in rat offspring

Fifty μl of carrageenan (20 mg/ml) was injected subcutaneously into the plantar surface of the right hind paw in p18 rats to induce hyperalgesia. Mean paw withdrawal latency was measured in the plantar test to index the severity of hyperalgesia. Using Western blotting and RT-PCR, the quantitative analyses of NMDA receptor NR1 and NR2B subunits were performed in spinal cords from different groups of animals.In the carrageenan-induced hyperalgesia model, rat offspring passively exposed to morphine developed a severe hyperalgesia on postnatal day 18 (p18), which also had a more rapid time course than those in the controls. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Western blot and RT-PCR analysis showed that the levels of protein and mRNA of NMDA receptor NR1 and NR2B subunits were significantly higher in the lumbar spinal cords of rats (p14) exposed to prenatal morphine; the co-administration of DM could reverse the effect of morphine on NR1 and attenuate the effect on NR2B.Thus, DM may have a great potential in the prevention of higher vulnerability to inflammatory thermal hyperalgesia in the offspring of morphine-addicted mothers.Growth retardation, delayed motor development and behavior abnormalities have been proposed in offspring of heroin-addicted mothers [1]. Infants passively exposed to morphine through their addicted mothers easily developed morphine withdrawal syndrome after birth, and even needed intensive care [2-4]. In our previous studies, we observed that many adverse effects caused by prenatal exposure of morphine could be prevented by the co-administration of dextromethorphan (DM) in morphine-dependent rat dams [5,6]. However, the possible impacts of prenatal exposure of morphine on the vulnerability to hyperalgesia have never been examined. In humans, the liability to inflammatory hyperalgesia is often affected by acquired physical conditions and social factors in offspring from