Analgesic Effect of Epidural Capsaicin in Arthritical Rats<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

佟世义　　焦岿然
廖　旭　　薛富善
中国医学科学院中国协和医科大学整形外科医院麻醉科，北京100041
Shiyi Tong，Kuiran Jiao，
Xu Liao，Fushan Xue
Department of Anesthesiology，Plastic Surgery Hospital，Chinese Academy of Medical Sciences, Peking Union Medical college，Beijing 100041

Abstract

Objective：To evaluate the analgesic effect of epidural capsaicin using the behavioral and electrophysiological methods in arthritical rats.
　　Methods：20 adjuvant arthritical rats were equally divided into either groupⅠ，in which 0.2%capsaicin+2%lidocaine was injected into epidural space ，and group Ⅱ，in which saline was injected. After the injection ，cord dorsal potential（CDP） was determined on the 3rd day while heat pain threshold was measured each day.
　　Results：Pain threshold in the arthritical legs，which was significantly lower than that of corresponding normal legs in the arthritical rats before the epidural injection，was significantly increased in groupⅠ in the first day，but was near to that of group Ⅱ on the 2nd and 3rd day. P2 in CDP on the 3rd day was single wave，high wave in group Ⅱ，and double or three，low wave in groupⅠ. 
　　Conclusion：In arthritical rats，hyperalgesia was reversed significantly with capsaicin，but in a shorter duration of analgesia when compared with corresponding normal leg. Capsaicin could still block most of fibers C even on the 3rd day after the epidural injection.
　　Key words：Capsaicin，Heat pain threshold，Arthritical rat，Cord dorsal potential
　　Corresponding author：Fushan Xue, MD; xuebai@fescomail.net

　　本实验的目的是通过行为学和电神经生理学方法观察关节炎大鼠硬膜外间隙注射辣椒素的镇痛效果。
资料与方法
佐剂性关节炎大鼠模型的制作
　　选择健康雄性Wistar 大鼠20只，体重180～220克，采用2.5%硫喷妥钠（40 mg•kg^-1）、阿托品50μg施行腹腔注射麻醉后，将大鼠于俯卧位固定，消毒、切开背部皮肤，暴露T₁₀椎体，采用小弯针挑破黄韧带，暴露硬膜外间隙，向尾端置入PE-10聚已烯管1.5cm，固定导管，缝合伤口。手术后筛选出大鼠行为学无明显改变者进行实验。将含冻干结核菌(中国生物制品鉴定所提供)10g•L^-1的弗氏完全佐剂(用羊毛脂和腊油按1.5:8.5比例配制)0.05ml注入已置入硬膜外导管的大鼠的一侧后肢外侧踝关节周围，24h后形成急性关节炎^[1]
实验分组
　　将20只大鼠平均分成两组，Ⅰ组为辣椒素组（0.2%辣椒素+2%利多卡因）；Ⅱ组为生理盐水组。经硬膜外导管向Ⅰ组大鼠硬膜外间隙注入2%利多卡因150μl，5min后再注入0.2%辣椒素20μl；Ⅱ组仅注入生理盐水150μl，注药时体位均为头低位。
观察指标
　　分别于给药前、给药后6h、1天、2天、3天观察以下指标：
　　1. 痛阈　采用辐射热照射双后肢外踝部，测定引起缩腿反射的潜伏期，最长测定时间为10秒。
　　2. 足容积　利用排水法进行测定。
　　3. 脊髓背表面电位(CDP)　所有大鼠均于注药3天后测定CDP以2.5%硫喷妥钠（40mg•kg^-1）腹腔注射麻醉后行椎板切开术，暴露腰骶部和部分胸段脊髓，在解剖显微镜下剥离硬脊膜，暴露左侧腓肠神经并在手术部位缝制油槽，置入温度恒定在36～37℃的液体石腊，术毕移置大鼠于屏蔽箱，固定脊髓和左后肢，腹腔注射箭毒（0.2 mg•kg^-1）制动，同时行机械通气，实验中根据需要追加箭毒，维持直肠温度于37～38℃。在腓肠神经近踝关节处放置刺激电极，刺激形式为单方波，在同侧脊髓背表面放置银球电极，参考电极插入椎旁肌肉中，单极引导由腓肠神经诱发的大鼠CDP，输入SBR-I示波器并描图记录。正式记录前先沿同侧脊髓背表面纵向移动银球电极，选择出现最大N1波的部位固定为实验记录点并观测以下项目：①潜伏期：以刺激尾迹到各P₂波振幅绝对值最高点为各波型的潜伏期。②阈值：于时程为25.6ms、振幅范围为29、波宽为0.1ms时产生N1波所需的最小刺激电流为电刺激阈值。③波幅：计算在时程为512ms、振幅范围为2⁸、波宽0.5ms时能产生的最大P₂波振幅。
统计学方法
　　组间计量资料的比较采用方差分析和t检验，P<0.05有明显性差别。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

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结　果

　　关节炎大鼠硬膜外间隙注射辣椒素前、后痛阈的变化(见图1)，硬膜外间隙给药前两组大鼠患肢和健肢的痛阈无明显差别；但两组大鼠患肢痛阈均明显低于相应的健肢。Ⅰ组大鼠患肢和健肢痛阈的升高均在硬膜外间隙给药后6h最为明显（P<0.01），以后逐渐降低；给药3天后健肢痛阈仍明显高于Ⅱ组健肢；患肢痛阈在给药后6h和第1天明显高于Ⅱ组患肢（P<0.05），两组大鼠的患肢痛阈在给药后的3天内始终低于同组的健肢痛阈。
　　图2示两组大鼠足容积的变化，两组均于注射佐剂24h后出现明显的足容积增大，而且在其后的观察期内无明显改变。
　　图3示两组大鼠硬膜外间隙给药3天后的CDP改变。在Ⅱ组的全部大鼠均观测到P₂波，波型为单波；Ⅰ组有两例未观察到的P₂波，波型为双波或三波，根据潜伏期可将I组的P波分为3种类型，即a型波：潜伏期为(113.39±8.35ms)；b型波：潜伏期为(160.13±6.01ms)；c型波：潜伏期为(199.38±7.18ms)。Ⅱ组P₂波的潜伏期为(161.86±4.93ms)，与Ⅰ组的b型波接近(P＞0.05)，而与a、c型波有明显差别。Ⅰ组P₂波的3种波型中以b型波波幅最大，但仍明显低于Ⅱ组的P₂波（P<0.01）。两组的电刺激阈值无明显差别（附表）。

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