维普资讯 http://www.cqvip.com BI BLI D:I SSN 0253- 9756 Ac口phar r namk笔I ca Si ni c a 中 国药理 学报 1997 J ul ;1 8(4):37 7—379 K etam i ne- induced peri pheral analgesi a i n rats BAI Li ,ZHAO Zhi — Qi (Shanghai Br ai n Re s e arc h I ns t i t ut e,Chi nes e Ac ademy o f Sci enc e s,Shanghai 200031,Chi t n) i ket m' ni ne; el e ct ri c s t i mul at i on; (Sha ̄ ghm Ani mal Cent er. Chi nes e Ac ade my 0f Sci ence s) ehct m myogr aphy; pa i n n ̄ ea su_ v e r ne nt; a l ml ge s  ̄; we r e a ne s t he t i z e d wi t h u r e t h a ne(1. 1’ g‘k g ,i p,i ni t i a l l y) ml oxone n d f a i xed i n a st er eot axi c f r ame KEY W ORDS Body t e m per at ure, t he ml or of t e pl h ant ar reCi c ̄. and bl ood pr es sur e w AI N :To e xan1 i r l e whet 上 1 e r kemmi ne may di r et c l y ac t at per i phe r al noe i e pt c or s t o pr oduc e a 1 1 al nmi nl mne d i t w hi n nor r r m【I i mi t s. As a no e i e e pt i v e f lex i on r e f l e x (FR), t e f h i r i ng 。f a_ Ⅳ匝T}I (I DS: W i s t ar r at s we . 1  ̄ ane st het i ze d wi t h ur et l ume. As anoe i e ept i vef le xi on r ef l ex(FR),C r e s ponse s f r om t he p0劬 。I bi c eps s emi t endi ne e us ( pma T)mt mc l ewa s e v o ke dbyde e t r i c a l s t i mu l a t i on ( 2 r ns,80 V ,2—3 pI l l £ 8 ,0, 5}k)vi a a pa i r cf de ct r c xnyogra phy (EMG ) f r r ma t he I : ost e ri c ̄ bi c eps s e rni t endi nosus (PBST ) mus cl e wan e voke d by dect r i caI s mnul at l ce l(2 ,80 V,0. 5 Hz,2— 3 pul s es.at 5一 mi n i nt er val s) vi a a pai r of s t ai nl ss e st e el nee dl e s i ns ert ed s ub c u t a ne o us l y t o t e h t wo t o e s o f i ps i l a t e r l a hi n dp a w【 r0 obt a i n a st abl e re cor di ng.ur et hane wa s s uppl ement d " e t o keep s t ai nl e s s st ee l ne edl e s i ns er t e d s ubc ut ane ous l y a st abl ea n e st hes i a. Th e f i r i ng of EM G wa s ave rage d a" t 5 a ppl i d t e o t he t、 ∞ mi n i nt e rv al s n d a a s t bl a e bas el i neⅥ as e s t abl i she d f 呵 a" t 1 e日 5 t oe s of i ps l t at er al hi ndpaw. RESULTS;Su ̄ nanmusi nj ct e i on of ket ami ne(36 mr r  ̄l・L ,5 止 ) i nt o t he i ps i t at er al hi ndp sw 20 mi nh ef or e me di cat ion. The dr ugswe r ei nj ect d sci e n" t o pr oduc ed R n i bi t i on of C r es pons es. At 9 r ai n ke- t a mi ne on FR wa n expr es se d a n - the cha r 窖e i n " t he r ef l ex a f t er appl i c at ion f o ke t a mf ine, m gni nJ de∞ m pa eet i on of m l mmne (1% ,5止 )i nt ot he鼬l I l e ar ea annul l edket  ̄ni ne- n duc i e di nl ' ibi f ion. c0N口LUS 0N:Ket f ami ne a s a di s s oci at eane s t he t i cac1 . sonper i pher alnoc i e pt c om t o t he paw e" h t wee  ̄ the " t wo hi nd— 0 st imul at d . T he e ef f ect of 王 ± a n d ana ly ̄ R ESULTS pr oduc e a 1 l aI g目i a,whi ch i s r e l at e d t o a ct i vi t y of per ipher alor  ̄oi d r e cept or s. t o bas eh e The dat a w盯 e。中r e龉d as by t t st e The fi ri ng of EM G i n PBST refl ex by el ectr ic st l m ul ati on of hi nd- di gl ts exhi bi te d two c omp o n. ents, t he A resp o nse with a short l at ency and C Ketar ni ne as a di ss oci ate anest het i c at very l ow dos e(0. 2 mg・ 一 )pr oduces anal ge s i c ef f ec t i n cl i ni c[11 . Si noe ket ne i s a sel e、Ti ve cl 1 anr l ant a goni st f or N— met hyl — D— a spa r t at e (NMDA ) r e s o ns p e wi t h a l ong l at enc y (Fi g 1),whi ch wer e evoked by A—and C- af ferent i nput. respecti vel y J. In thi s st udy, noci e pt c i ve C c o m ponent i n t he lexi f on ref lex wa s t s ted. e recept or, the c e nt ral m echani sm of ketam i ne- i nduced anal ge si a may be attri but ed to bl ockade of N ~I DA recept or— m edi ated spi na l t ransm i ssi on of no ci ee[ ] ti ve i nform ati on[ 2, 31 However. i n our Ket a mi ne i nj ec t d i e nt o t he i ps i l at e r al hi ndpaw pr oduced a m arke d i nhi bi ti on of C re sp o nses i n FR . Fi ve i nut m es a f t er i ni e ct i on of ket a mi ne (36 mmol . prev ious study , i t has been shown t hat t opi cal appl i c at i on of ket ami ne t o t he per i pher a l ner ve powerful l y bl c ke o d nerve conducti on, sugge s ti ng t hat per iphera l m echani sm mi ght be i nvol ved i n ana lgesi c ef fect of ket al l r l l ne T he ai m of thi s work was t o ana lyze the peri pheral n al a gesi a of ket am i ne. ‘ L一 ,5 L), t he aver a ge d C r sp e o ns es 、 r e r d uce e d by40 % ±7 % ( = 4).whi c hr et ur ne d t o I l orma l l e vel 30 mi n af t e r i ni ect i on of ket a mi ne. I n contra s t, i psi l at era l ecti on of sal i ne or ont c r lat a er a l i nj ct e i on of ket a mi ne at t he S s 3 3 f l e dose f ai l ed to pr oduc e i nhi bi ti on ofC re sp o nse. W h吼 a hi gh dos e of ke t a mi ne(180 mmol ・L ,5 L,s c) was i ps i l at er ll a y i nj ct e d ,C r e e sp o ns e s i n FR wer e M ATERIALS AND M叮 H0DS si gni f i c nt a l y r d uc e edby 85 % ±7 % ( =4). The wi  ̄ t ar r at s( = 15 we i ghr i ng 278 ± Cor r e  ̄ ndenc e t o ZHAO Zhi — Qi ,pl a n:86 21 45 474— 8700 Re cei ved 1 99 641 1— 23 Ac ce pt ed 199741 2 -19 24 g i nhi bi t i on l st a e d over 30 mi n (Fi g 2). Dur i g the maxi n ma l i nhi bi ti on by ketam i ne, 1 % na loxone(5 L)wa s i nj ect d s e ei nt ot he 8 &! x l e 维普资讯 http://www.cqvip.com 378 ・ BI BLI D:I SSN 0253 —9 756 Ac t a Pl  ̄r mac obgi m Si t ic f a 中国 药理 学报 1 997 Jul ;18( 4) ket a mi ne — i nduc ed i nhi bi t i on W hen ket a mi ne(180 \¨0; o*■ I Y I I TI OI_ LI 1)was appl i d t e o t he c ont r a] ate r al hi nd toes. 1 ess i nhi bi ti on of C r esp o nses w as obt ai ne d (36 % ±8 % , 二 5). The r ecover yt i mewas 20 mi n. whi ch was s hort er t ha n t hat of i ps i l at e r al i n j ct e i on- i nduce d i nhi bi t i on(Fi g 3). Ti me/mi n 3. 叫 0f5肚 m 0. 1% sc 9mi n af蛔 ke伽 札I 玎e -h山 。e d- nl 枷 叫 0fC 砘 叩 0T b嚣 el " n目嘶 n  ̄ t ' l ex. , 弓-∞co4¨∞z 4 . ± . < O. 05,c p<O. 0l傩 ,  ̄al x ol( c打). To t es t l oca l anes t he t i c ef f e ct,ke t ami ne(180 眦 m I_L ) pr oduc ed a c onpl et e i nhi bi t i on of C response s wer e sel ct e d i e n t he 4 rat s. 5o 10o 150 2∞ 250 300 W hen the CU/ Te Dti nt ens i t yof st i mul at i onwas enh a nc e d ff r om Ti me/m l n 80 V ,2 pu ls es t o 1 00 V, 5 pu ls es) dur i ng t he per i od of i nhi bi t i on, C re sponses were sti l l evoke d . ng 1.  ̄ dbi t l on m C re spo ̄e of fl e ̄ m ref lex l 【 e 诅I ni ( 3 6 m mmo l - L- ,5 pL). o f4 r e s p0 m . I n c ont r a st, when C r sp e o ns e was i nhi bi t d by e pr oc ai ne(1% ,5 L)i nst e ad of ket ami ne,i ncr e as - i ng currentfai l d t e o evokeC r esp o nse. DIsI 口 J 卫0N The resul t s f i rst demonst rate d that ketam i ne di r ect l y act on the per ipher al recepti ve f i el d,w here there exi st abundant noci o pt c ors. 幻 pro d uce a nal ge si a.As ke t a r r ine f i s a ce nt r a l ane st het i c s,an i nvol vem ent of t he central act i on i n i nhi bi ti on of C r e sp o ns es woul d be o2 ) I 1 8i der e d due t 。t he di f f us i on of dr ugs. I f t hi s ca s e occ urs, t he e wou r ld b e n0 di f f er enc e b et win i ps i —a nd c ont r a- - l at er a l appl i ca- - Ti me/m i t i on of dru . ri g7 -- Ef f eci。f kt e mmbl e on C sl Ⅻ ( 4) i ec t i 吼 0fs of f , ∞d Ⅲ rdl ex o f s a l i neo r ke t n mi ne36旺 1 80 I 帅 砷l ・L-。. b P< O. 05, < O.01催 s ali ne. However, ketamine-i nduce d i nh{ bi t i on at a l ow dos e (36 mmol・L ) was pr oduc d onl e y by i t s i p ̄ <l at er a l appl i c at i on. Al t hough t he o nt c r al at er al a ppl i at c i on of ket mni ne at ar ea. Ket ar nl ne  ̄i nduced i nhi bi ti on wr i t s com pl et el y a hi gh d0s e (1 80 mmol‘L。。) al s o pr oduc ed an annul l e d 10 r ai n a f t e r i nj e ct i on of nal oxone,whe re as i nhi bi ti on of C r sp e o nse s t he r e was no e f f e ct of i nj ct e i on of s al i ne on act i ons,t he i nhi bi t i on by i psi l at e r al appl i at c i on was  ̄ , suggesti ng i ts centr al 维普资讯 http://www.cqvip.com BI BLI D:I SSN 0253. 9756 Act s P ̄ eo l gl n c a Si ni c a 中国 药理 学报 m uch p o w erf ul than th at by contral at era1. T hese data show ket am i ne-i nduced peri pheral anal gesi a. The m eehani sr r  ̄ s of ketami ne— i nduced er p iph a ml anal gesi a remai n uncl e ar. II 1 t he earl i er i vitro studi es (6 r 19 97 Jul ;18(4) dor s l a hom n ocl c e ̄ i ve neur ons f  ̄l o wi ng C ibr f e s t i mul at io n Neul o ph ar ma c ol g y 198 n 7;26:1235—8 4 SongⅪ ,gha ng JF,Ze ngYM ,ZhaoZQ Ef f e e ̄ s of t a nf ine叽 c c 0 a d uet i o n of pe nphe  ̄t n Cbi n J Pme st hes l o[199 5;1 5:446—9 bot h sodi u1 7 1 and potassi um 5 Zh a ngKM .Zhz oZQ. 8e l e et i ve bl oc k ad ebyyohi mbi ne ofl oc us cha n nds were af fected by ketami ne i n the m eml e u s- i nduc e dl t t hi bi donof n oc i ee pt i ve r e le f xbut nott h at 0fC ay r el i nat e d R xons,s ugge st i ng t at h ket a mi ne— i nducod r e s l xXt s es 0f s Dl na l d0i ¥ ham i l et u 3  ̄ bl ockage of conduct i on of the peri phera l nerve Act a Ph e a ̄mco l Si n 1994; 1 5:491— 4 . probabl y r esul te d from non— synapt i c i nhi bi t i on of Na current. Si ne a there was no eff ect of ketam i ne on i nacti vati on of Na current (6] ket am i ne s eems . l n r a t s 6 AI  ̄l l l P.Ryd gv  ̄t B Thenl e c} mnm t he myel i nal d ne r. , , e m m of ac t i on ofke t ami neon Eu r J Phmmac d 19 86:126:245—52 7 B ̄l i otE, ̄, a / Tat l lM R,Duh ai s JM .Mi t ot o- Chi e  ̄ D. t o di le f xf r onlt hel o cal ane st he t i c s Thef ac t st at h M 钟 ha 8∞ of a ct i n of o ket m /ne i n t h e ct t r r ent a nd vo[ t  ̄ e there exi sts a di f ference between ket am i ne- and dm 【 d r a ye l i  ̄ t ed ne r f ibr e o f t h e f r o g. procai ne-i nduce d ef fe c ts and na loxone revers es ket am i ne-i nduced i nhi bi ti on i n our study supp o rt thi s vi ew . Br J Pt mrmac ol 1986}87:291—7 8 St ei nC, 蛐 A .Gramsch C,HeraA , L。c opk ̄ i d r ec e pt or s med  ̄ a t / g n mat / noc i c ep uon m i n/ / a m ma ̄ i on: e ndo genous ̄ga nds I n:Bond M R,Ch ar l am JE,w 。 a , The opi oi d r ecept or s are dens el y di str ibuted i n t he peri pheral nerve t erm i nal s and ar e i m pl i cat ed i n n ti a no ci a pti e on(8 In t he present study, r e versal . of ke t ami ne qnduced pe ipher r al ana l ge si a by na loxone st rongl y su g gests t at h the at ' l i on of ket ami ne i s cl osel y tel ated t o acti vi t y of peri pheral opi oi d recept ors. e di t or s Pr oc e ed i ngs of t he Vhh W 0r l d & w 瑚 s∞ Pai n Ar  ̄t e r dam :El s ev i e r.1 991:83— 7 9 W es dt md KN Lawa ndNB.W L I EsW D Ex ci t at or y舢 ( EAA) i n t he p er i ph er y c  ̄ mt r i bu t e t ? o t he d evdot m ̄mt of a uodyni a a nd t hem ml hypo r al ge s i a i n a r t l  ̄i t l c ra s. t 77 S — a c 氯氨酮引起的太 鼠外周镇痛作 用 As Rl enti oned i n i ntr oducti on. ket amine as a R 7/~ 2 NM DA recept or a nt agoni st produces i nhi bi ti on of noeic ept i ve r es o nses of p pa in-sensi ti ve neur on i n t he spi na l c ur dI . a c j ds (中国科学 院上 海脑 研究所 ,上海 20 0031,中 国) A recent r ep o rt showed that gl ut amate, aspar t at e a n d ar gi ni ne concent rati ons i n r at knee j oi nt e avi t y wer e i ncr e as e d wi t h i nf l a mmat or y pai n[ 9] . 关键词 氯氨酮;电捌激;肌电描记术;测痛;镇锄 痛;纳蜥 一 一 1、 her e f or e. i t s houl d b e oons i de r ed whet her NMD A r ec ept or mi ght b e 目的 ;研究 氯 氨酮是否 可 以直接 作用 于外 周 伤害 oont ri bute d 性感受器而产生镇痛 . 方法 ;一 对不 锈钢针 插入 t o ket am i ne-i nduced per ipheral n al a gesi a. 尿醇麻 醉的大 鼠一 侧后 肢 的两 足脂皮 下 ,施加 强 电流( 2 n1 s ,8 0 v,2—3脉 冲 ,0. 5} k)作 为伤 害 性 刺 激 ,在 同 一 后 肢 的后 二 头 半 腱 肌 记 录 肌 电 反 1 U ni t e d St a t e s P 仉 r qod口 I Convent i on USP DI i nf or r r mt i on f or t he hml t h ca r e pr of e v : ,  ̄o nal 1 5t h ed Roc k ̄l I( ):USPc,1988:1647 2 Song XJ, Zhao ZQ I nt e ̄di c m bet wee n s ubs t a nc e P a nd exc i t a t or y "a mi n o a ci d r e c ept or s i n mo dul at i on of no ci c ept i ve r ml xx 1 . s es of t s dor s al hor n r l eu r c  ̄  ̄ Net m ̄ i Lett 19 : 168:49— 52 3 Ⅱ c ke ns on AH . l i va n AF E dea ce f or a r ol e of NM 【 )A r ec ept or i n t he f r e quenc y depe nde nt pot  ̄l ia f ti on of de ep r at 应 。电刺 激引起 的长潜伏 期 C成 分 ,作 为 伤害 性 屈反射 的指标 , 结果 :在邻近刺激 电极 的跖部 皮 下注射氯 氨酮( 3 6 mmo l ・ L~。5正 ) 可 明显 抑箭 C 反应 ,注射 氯氨 酮 后 9分钟 ,在 同一 部 位 注射 5 ‘ ‘ L的 1%纳络酮 ,可翻转抑制效应 , 结 论 :氯氨 酮可 直接 作用 外周 伤 害性感 受器 产生镇 痛 ,并提 示可 能与外周 阿片受体 的激 活有关 ,
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