Effect of ketamine pretreatment on acute morphine tolerance in rats with chronic inflammatory pain / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of ketamine pretreatment on acute tolerance to morphine in rats with chronic inflammatory pain.Methods Twenty-four adult male SD rats weighing 180-200 g were randomly divided into 3 groups (n=8 each) group Ⅰ morphine (M) ,group Ⅱ ketamine (K) and group Ⅲ ketamine + morphine (KM). Chronic inflammatory pain was induced by subcutaneous injection of Freund's adjuvant 0.125 ml into the plantar surface of left hindpaw. Three days after Freund's adjuvant injection, the animals received intraperitoneal (IP) morphine 5 mg/kg in group M, IP ketamine 10 mg/kg in group K or IP ketamine 10 mg/kg 10 min before IP morphine 5 mg/kg in group KM once a day for 3 consecutive days respectively. The paw withdrawal threshold to yon Frey hair stimulation (PWT) and paw withdrawal latency to noxious thermal stimulation(PWLT) using the hot plate test were measured before Freund's adjuvant injection (T0, baseline), and every day before (T1) and at 15 (T2), 30 (T3), 60 (T4) and 120 min (T5) after medication for 3 days (D1,2,3).Results PWT was significantly increased after medication on D1,2,3 in group KM but only on D1,2 in group M. PWLT was significantly prolonged after medication on D1,2,3 in group KM but only on D1 in group M. Conclusion Ketamine 10 mg/kg pretreatment can decrease the acute tolerance to morphine in rats with chronic inflammatory pain.