Morphine antinociception on thermal sensitivity and place conditioning in male and female rats treated with intraplantar complete freund's adjuvant

The experience of pain is characterized by the presence of a noxious sensory stimulus combined with negative affect, which is often treated clinically through administration of drugs such as morphine or other opioids. This study investigated the effects of morphine one and seven days after intraplantar administration of complete freund's adjuvant (CFA) in male and female rats. Hargreaves test for thermal nociception and conditioned place preference (CPP) were performed following subcutaneous administration of saline or morphine (1.0, 4.0, 8.0, 12.0 mg/kg). Hargreaves test results revealed that male rats were more sensitive to morphine antinociceptive actions as compared to female rats one day after CFA treatment; however, this sex difference was not detected seven days after CFA treatment. One day after CFA treatment, morphine doses of 8.0 and 12.0 mg/kg produced a CPP in male rats, while female rats exhibited CPP with only the 12.0 mg/kg dose. Seven days after CFA treatment, both male and female rats exhibited a CPP with morphine doses of 4.0 mg/kg and higher. These results reveal sexually dimorphic properties of morphine in the paw withdrawal latencies and conditioned place preference models, representing reflexive and non-reflexive behavioral assays employed to examine inflammatory nociception. Our findings also suggest that antinociceptive effects of morphine are dynamic across early and later periods of CFA-induced inflammatory pain.