氯胺酮预先给药对慢性炎性痛大鼠急性吗啡耐受的影响

目的 探讨氯胺酮预先给药对慢性炎性痛大鼠急性吗啡耐受的影响.方法 健康成年雄性SD大鼠24只,体重180～200 g,随机分为3组(n=8):吗啡组(M组)、氯胺酮组(K组)和氯胺酮+吗啡组(KM组).于左后足底皮下注射完全弗氏佐剂0.125 ml制备慢性炎性痛模型.注射完全弗氏佐剂后3 d,M组腹腔注射吗啡5 mg/kg,K组腹腔注射氯胺酮10 mg/kg,KM组腹腔注射氯胺酮10mg/kg,10 min后腹腔注射吗啡5 mg/kg,1次/d,连续3 d.于制模前(基础状态)、注射氯胺酮前(T1)、注射氯胺酮后15 min(T2)、30 min(T3)、60 min(T4)及120 min(T5)时测定机械痛阈和热痛阈.结果 与基础值比较,各组T1时机械痛阈及热痛阈均降低(P<0.01).第1次注射情况:与11时比较,M组和KM组T2-5时机械痛阈及热痛阈升高(P<0.05或0.01).第2次注射情况:与T1时比较,M组T2时机械痛阈升高(P<0.05),KM组T3-5时机械痛阈和热痛阈升高(P<0.05或0.01).第3次注射情况:与T1时比较,KM组T4时热痛周升高(P<0.05);与M组第3次注射时比较,KM组T3,5时机械痛阈及T3-5时热痛阈升高(P<0.05).结论 氯胺酮10 mg/kg预先给药可减轻慢性炎性痛大鼠急性吗啡耐受.

Effect of ketamine pretreatment on acute morphine tolerance in rats with chronic inflammatory pain

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.