Prenatal exposure to methamphetamine alters the mechanical withdrawal threshold and tonic hyperalgesia in the offspring

Maternal methamphetamine (MA) abuse during pregnancy has been proved to induce various impacts on the development of infant and child. In this study, we examined whether prenatal exposure to MA would affect the development of nociceptive system by measuring the responses to noxious stimulation in the developing rat. Adult female Sprague-Dawley rats received bi-daily subcutaneous injection of methamphetamine (5 mg/kg) or isovolumetric normal saline since the day of mating till the day of delivery. Birth profiles of the offspring including birth length, weight, and body temperature were recorded during the first postnatal month. Mechanical withdrawal thresholds were measured by von Frey filaments on postnatal day (PND) 30 and 60, and hyperalgesic behaviors following plantar formalin injection (2%, 50. μl) were evaluated on PND 60. The birth body weight and length of rats born to MA-injected dam rats (MA group) were significantly lower than those of the control rats during the first postnatal month; however, their body temperature was significantly higher than those of the control rats during the first 3 days after birth. The MA group rats had significantly lower tactile withdrawal values in von Frey test and higher pain scores in the late phase of pain in the formalin test than those of the control rats. There is a gender difference of nociceptive hypersensitivity manifested as that the female MA group rats had significantly lower withdrawal thresholds and higher pain scores in response to formalin injection than the male MA group rats. These results suggest that prenatal MA exposure could predispose an alteration in the development of nociceptive neuronal network, which leads to a long-lasting status of hypersensitivity to pain stimulations in the offspring.