外源性催产素在周围神经系统中的镇痛作用研究

The Analgesic Effect of Exogenous Oxytocin on Peripheral Nervous System

背景 慢性疼痛是最为普遍的健康问题之一,而各种镇痛策略及相关机制的探索一直是医学研究的热点.催产素是一种可由自身产生的神经递质,其除了具有使妊娠末期子宫收缩和促进哺乳期排乳的作用外,其在镇痛方面的作用正日益引起人们的关注.目的 探究外源性催产素在周围神经系统中的镇痛作用.方法 2017年3月-2018年1月,将40只清洁级成年SD雄性大鼠随机分为5组(各8只)后进行造模.对照组(NOR组):不进行任何处理;模型组(INF组):右后足足掌部注射角叉菜胶;安慰治疗组(NS组):右后足足掌部注射角叉菜胶,随后即刻腹腔注射0.9% 氯化钠溶液;催产素治疗组(OT组):右后足足掌部注射角叉菜胶,随后即刻腹腔注射催产素;阳性对照组(ASP组):右后足足掌部注射角叉菜胶,随后即刻腹腔注射阿司匹林.除对照组外,其余4组均造模成功,无死亡及特殊损伤情况.5组大鼠在造模4 h后进行相关检测.采用热板实验、压板试验检测热板潜伏时间(HPL)、后足缩足潜伏期(HWL).测量造模前、造模4 h后后足周长,并计算后足肿胀程度;采用ELISA法检测外周血血清催产素、前列腺素E2(PGE2)水平及炎性组织PGE2水平.结果 造模4 h后,INF组、NS组、OT组、ASP组大鼠HPL、HWL均短于NOR组(P<0.05);OT组、ASP组大鼠HPL、HWL长于INF组、NS组(P<0.05).INF组、NS组、OT组、ASP组大鼠造模4 h后HPL、HWL均短于本组造模前(P<0.05).造模4 h后,INF组、NS组、OT组、ASP组大鼠后足周长长于NOR组(P<0.05);OT组、ASP组大鼠后足周长短于INF组、NS组(P<0.05).OT组、ASP组大鼠后足肿胀程度小于INF组、NS组(P<0.05).INF组、NS组大鼠外周血血清催产素、PGE2水平及炎性组织PGE2水平高于NOR组(P<0.05).结论 外源性催产素镇痛作用明显,其能降低外周血和炎性组织中PGE2水平,缓解炎性部位的肿胀程度,说明其可能通过抗炎和减少致痛因子而在周围神经系统发挥镇痛作用.

Background Chronic pain is one of the most common health problems.Exploring a variety of analgesic strategies and relevant mechanisms has always been the popular medical research field.Oxytocin(OT)is a self-secreting neurotransmitter.In addition to its well-known functions,such as strengthening the contraction of uterus during delivery and promoting lactation during lactation period,more and more attention has been paid to its analgesic role.Objective To explore the analgesic effect of exogenous on peripheral nerve system(PNS).Methods A total of 40 adult male SD rats were randomly divided into 5 groups(n=8 in each) during March 2017 and January 2018,control group(NOR group):with no treatment;model group(INF group):carrageenan was injected in right hind foot paw;placebo group(NS group):carrageenan was injected in right hind foot paw,followed by immediate intraperitoneal injection of 0.9% sodium chloride solution;oxytocin treatment group(OT group):carrageenan was injected in right hind foot paw,followed by immediate intraperitoneal injection of oxytocin;positive control group(ASP group):carrageenan was injected in right hind foot paw,and aspirin was injected immediately into the abdominal cavity.Except for the control group,the other four groups were successfully established without death or special injury.The rats in five groups were tested four hours after the establishment of the model.The hot-plate latency(HPL) and hindpaw withdrawal latencies(HWL) were measured by hot plate test and pressure plate test.The circumference of feet before and after modeling was measured and the swelling degree of hind feet was calculated.The levels of oxytocin,prostaglandin E2(PGE2) in peripheral blood and PGE2 in inflammatory tissue were measured by ELISA.Results Four hours after the models were made,HPL and HWL of INF,NS,OT,ASP groups were significantly shorter than those of NOR group(P<0.05);HPL and HWL of OT,ASP groups were significantly longer than those of INF,NS groups(P<0.05).HPL and HWL of the four groups(INF,NS,OT,ASP) four hours after model-making were significantly shorter than the ones before model-making(P<0.05).The circumferences of right hind paw of INF,NS,OT,ASP groups were significantly longer than that of NOR group(P<0.05);the circumferences of right hind paw of OT,ASP groups were shorter than that of INF,NS groups(P<0.05).The swelling of inflammatory paw of OT and ASP groups was smaller than that of NOR and NS groups(P<0.05).The oxytocin and PGE2 concentration in blood and the PGE2 concentration in inflammatory site of INF and NS groups were significantly higher than those of NOR group(P<0.05).Conclusion Exogenous oxytocin has significant analgesic effect,which can reduce PGE2 level in peripheral blood and inflammatory tissues and attenuate the swelling of inflammatory sites.This implicates that exogenous oxytocin plays analgesic role in the peripheral nervous system by antiinflammatory effect and reducing pain-causing factors.