Objective: Premature and ill neonates undergo painful but medically necessary procedures while hospitalized.Although opiate drugs are administered as analgesics,problems associated with their side effects,tolerance,and potential dependence necessitate research into altative pain-relieving medications.Here we test two plant-derived compounds in infant rats: sinomenine,which targets the Mas-related G-protein-coupled receptor member X2 opioid receptor;and salvinorin A,which is a κ opioid receptor agonist.In adult animals both sinomenine and salvinorin A are analgesic,but neither has been tested in infants.Methods: We used the formalin and thermal plantar tests in rats 7 and 21 days of age (PN7 and PN21) for behavioral signs of pain.In addition,brain sections were stained using Fos immunohistochemistry to examine patts of brain activation in the midbrain periaqueductal gray and the paraventricular nucleus of the hypothalamus.Results: Sinomenine was analgesic in both the formalin and thermal tests on animals 21 days of age.At PN7 only the highest dose elevated response latencies in the thermal test and there were no effects of sinomenine in the formalin test.Analysis of Fos expression in the sinomenine-treated animals showed no drug effect,in contrast to the behavioral results.Salvinorin A was analgesic in the formalin test only at the highest dose at 21 days of age but not in the thermal test at either age.Conclusion: The increased modest effectiveness of sinomenine in older animals and the minimum salvinorin A drug effect suggest that the compounds act on sites that develop during the preweaning period (sinomenine) or after weaning (salvinorin A).