中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2010年
4期
476-482
,共7页
吉小莉%颜玲娣%周培岚%董华进%宫泽辉%黄培堂
吉小莉%顏玲娣%週培嵐%董華進%宮澤輝%黃培堂
길소리%안령제%주배람%동화진%궁택휘%황배당
ω-SO3%吗啡%炎性疼痛%镇痛%耐受%交叉耐受%自发活动
ω-SO3%嗎啡%炎性疼痛%鎮痛%耐受%交扠耐受%自髮活動
ω-SO3%마배%염성동통%진통%내수%교차내수%자발활동
ω-SO3%morphine%inflammatory pain%antinociception%tolerance%cross tolerance%locomotor activity]
目的 评价单次及连续鞘内给药ω-SO3对福尔马林致大鼠炎性疼痛的镇痛作用.方法 采用福尔马林致大鼠炎性疼痛模型,通过大鼠鞘内置管术分别单次及多次鞘内给药,观察ω-SO3对炎性疼痛急性期和持续期的镇痛强度和有效时间以及连续给药对其镇痛作用可能的影响;通过大鼠自发活动实验评价ω-SO3单次鞘内给药可能引起的中枢副反应.结果 在大鼠福尔马林炎性疼痛模型上,单次鞘内给药ω-SO3产生剂量及时间依赖性的镇痛作用,其抑制炎性疼痛急性期和持续期的ED_(50)值分别为1.79和0.41 ng·g(-1),比吗啡的镇痛作用强并且有效时间长;以ED80剂量每日鞘内给药2次连续5 d后,ω-SO3仍然产生与单次给药类似的镇痛强度,而吗啡的镇痛作用降低,说明产生镇痛耐受,更有意义的是ω-SO3对吗啡镇痛耐受大鼠仍具有镇痛作用.在上述镇痛剂量范围内,ω-SO3单次鞘内给药对大鼠自发活动没有明显的影响.结论 ω-SO3对福尔马林致炎性疼痛的急性期和持续期均具良好的镇痛作用,其镇痛作用强,有效时间长,连续给药不产生自身镇痛耐受,并且对吗啡不产生交叉耐受.
目的 評價單次及連續鞘內給藥ω-SO3對福爾馬林緻大鼠炎性疼痛的鎮痛作用.方法 採用福爾馬林緻大鼠炎性疼痛模型,通過大鼠鞘內置管術分彆單次及多次鞘內給藥,觀察ω-SO3對炎性疼痛急性期和持續期的鎮痛彊度和有效時間以及連續給藥對其鎮痛作用可能的影響;通過大鼠自髮活動實驗評價ω-SO3單次鞘內給藥可能引起的中樞副反應.結果 在大鼠福爾馬林炎性疼痛模型上,單次鞘內給藥ω-SO3產生劑量及時間依賴性的鎮痛作用,其抑製炎性疼痛急性期和持續期的ED_(50)值分彆為1.79和0.41 ng·g(-1),比嗎啡的鎮痛作用彊併且有效時間長;以ED80劑量每日鞘內給藥2次連續5 d後,ω-SO3仍然產生與單次給藥類似的鎮痛彊度,而嗎啡的鎮痛作用降低,說明產生鎮痛耐受,更有意義的是ω-SO3對嗎啡鎮痛耐受大鼠仍具有鎮痛作用.在上述鎮痛劑量範圍內,ω-SO3單次鞘內給藥對大鼠自髮活動沒有明顯的影響.結論 ω-SO3對福爾馬林緻炎性疼痛的急性期和持續期均具良好的鎮痛作用,其鎮痛作用彊,有效時間長,連續給藥不產生自身鎮痛耐受,併且對嗎啡不產生交扠耐受.
목적 평개단차급련속초내급약ω-SO3대복이마림치대서염성동통적진통작용.방법 채용복이마림치대서염성동통모형,통과대서초내치관술분별단차급다차초내급약,관찰ω-SO3대염성동통급성기화지속기적진통강도화유효시간이급련속급약대기진통작용가능적영향;통과대서자발활동실험평개ω-SO3단차초내급약가능인기적중추부반응.결과 재대서복이마림염성동통모형상,단차초내급약ω-SO3산생제량급시간의뢰성적진통작용,기억제염성동통급성기화지속기적ED_(50)치분별위1.79화0.41 ng·g(-1),비마배적진통작용강병차유효시간장;이ED80제량매일초내급약2차련속5 d후,ω-SO3잉연산생여단차급약유사적진통강도,이마배적진통작용강저,설명산생진통내수,경유의의적시ω-SO3대마배진통내수대서잉구유진통작용.재상술진통제량범위내,ω-SO3단차초내급약대대서자발활동몰유명현적영향.결론 ω-SO3대복이마림치염성동통적급성기화지속기균구량호적진통작용,기진통작용강,유효시간장,련속급약불산생자신진통내수,병차대마배불산생교차내수.
Aim To evaluate the antinociception of ω-SO3,a novel Omega-superfamily conotoxin,in rat formalin test.Methods Potency and duration of ω-SO3 antinociception compared with morphine were investigated in rat formalin test after acute intrathecal administration.Development of tolerance or cross tolerance to analgesia of ω-SO3 and morphine was tested in formalin test after chronic intrathecal administration.Locomotor activity of rat after acute intrathecal administration was tested to evaluate possible central side effects.Results In rat formalin test after intrathecal bolus injection,ω-SO3 produced dose-and time-dependent antinociception by suppressing acute(ED_(50),1.79 ng·g~(-1))and tonic phases(ED_(50),0.41 ng·g~(-1)),which was approximately 10-fold potency and twice longer-acting of morphine in blocking tonic phase responses.After repeated intrathecal injections twice daily for 5 consecutive days,ω-SO3 produced analgesia without loss of potency whereas morphine produced analgesia tolerance in rat formalin test;further,ω-SO3 still produced potent analgesia in morphine-tolerant rats.No changes in motor function were seen in rats receiving above antinociceptive doses.Conclusion sNovel ω-SO3 produces potent and long-acting spinal antinociception without observable motor dysfunction and after chronic intrathecal administration.ω-SO3 produces neither tolerance nor cross-tolerance to morphine analgesia.
