内源性大麻素类似物NAGly对大鼠脊髓胶状质神经元的突触传递的抑制作用

目的:探讨内源性大麻素类似物N-花生四烯酰甘氨酸(N-arachidonylglycine,NAGly)对脊髓后角II层胶状质(SG)神经元突触兴奋性的影响。方法:选用生后4~6周雄性SD大鼠,深麻醉后蔗糖人工脑脊液快速心脏灌注处死,取脊髓腰膨大段,制备保留脊髓腰膨大处一侧后根的脊髓矢状切片。利用膜片钳技术,对脊髓后角II层SG神经元进行全细胞记录,通过分析后根刺激诱发的兴奋性突触后电流(eEPSC)的变化情况,观察NAGly(20μmol/L)对SG神经元突触传递兴奋性的影响,以及对自发性兴奋性突触后电流(sEPSC)的发放频率及幅度的影响。结果:通过诱发刺激的强度、潜伏期以及纤维传导速度我们将记录到的SG神经元分为Aδ纤维/C纤维投射神经元,NAGly对Aδ纤维和C纤维介导的eEPSC的幅度都有明显的抑制作用(P0.001),并且这种作用可以被洗脱。NAGly对SG神经元的sEPSC的频率有明显的抑制,但不明显改变其幅度,提示其作用部位在突触前。结论:内源性大麻素类似物NAGly可以抑制脊髓后角浅层Aδ纤维及C纤维介导的突触传递,并通过突触前机制抑制SG神经元的兴奋性。提示内源性大麻素类似物NAGly可通过抑制伤害性C和A纤维介导的突触传递发挥镇痛作用。     

内源性大麻素含量升高可激活脊髓背角星形胶质细胞并导致机械性触诱发痛

目的:观察丁高大鼠鞘内大麻素水平后实验动物的疼痛行为学变化及脊髓背角星形胶质细胞的激活状态,探讨内源性大麻素参与触诱发痛的可能机制。方法:成功建立大鼠鞘内置管模型后,分别鞘内注射外源性大麻素2-AG、大麻素受体激动剂CP55940、大麻素水解酶抑制剂JZL195。使用Von-frey纤维丝观察给药后不同时间点大鼠机械性缩足反射阈值的变化,运用共聚焦显影观察脊髓背角星形胶质细胞的激活状态。结果:(1)鞘内注射2-AG、CP55940、JZLl95后1 d即产生明显的触诱发痛(P0.01)并至少持续到给药后第21 d(P0.001);(2)鞘内注射2-AG、CP55940和JZLl95后第5 d即有明显的星形胶质细胞激活(P0.01),并可持续到给药后第21 d(P0.01)。结论:升高鞘内大麻素水平可能通过激活星形胶质细胞导致触诱发痛。     

大鼠硬膜外双电极脊髓电刺激模型的建立

目的:为研究脊髓电刺激(spinal cord stimulation,SCS)镇痛作用的机制提供方便、实用和有效的SD大鼠脊髓硬膜外双电极刺激模型。方法:选取250~350 g雄性SD大鼠,结扎其左侧L5脊神经制作神经病理性痛模型。在此基础上,将制作的电极置入脊髓背侧硬膜外间隙(T11~T12),电极尾端经皮下隧道从颈后部引出、并固定于皮肤。术后恢复5 d,行脊髓电刺激测试。用电子Von Frey测试仪测量建模前后大鼠后肢的机械性缩足阈值,评估硬膜外双电极刺激对其术侧后肢机械性缩足阈值的影响。SCS测试后第2 d,在大鼠腹腔内注射大麻素1型受体(CB1)的拮抗剂AM251,然后观察AM251对大鼠SCS镇痛作用的影响。结果:大鼠左侧后肢机械性缩足的基础阈值为49.37±6.99 g,L5脊神经结扎及硬膜外电极置入术后机械性缩足的阈值为19.23±5.12 g,行SCS(20 Hz,150~200 mV)30 min后术侧机械性缩足阈值为35.62 g±7.27 g,与给予SCS刺激前比较具有显著性差异(P0.01);而与手术对侧(右侧)相比,机械性缩足阈值无明显变化(P0.05)。腹腔注射AM251可翻转SCS的镇痛作用(15.00±1.01 g,P0.01)。结论:硬膜外双电极植入方法取材容易,简单易行,与当前临床普遍应用的电刺激装置极为相似,为进一步研究脊髓电刺激的镇痛机理提供了可靠的模型,并为其他领域脊髓硬膜外电刺激实验动物模型的制作提供了参考。本文结果还提示内源性大麻素CB1受体可能参与SCS的镇痛机制。     

内源性大麻素系统在妇科肿瘤研究中的新进展

近年来研究发现,内源性大麻素系统（ECS）已成为多种病理条件下的潜在靶点,尤其在癌症治疗领域引起了广泛的关注。在妇科肿瘤中,ECS各组分的表达都发生了明显变化,ECS通过抑制癌细胞的增殖、迁移和血管生成来抑制癌症进展,与肿瘤的诊断和预后相关,可成为对抗癌症进展的新靶标。尽管仍需进一步研究完全确定ECS对肿瘤进展的影响,但现阶段已提供了足够的证据将ECS作为妇科癌症治疗的新方向。     

大麻素CB_1受体活化对神经病理性疼痛大鼠脊髓背角嘌呤能P2X_2受体表达的抑制作用

目的:观察脊髓背角大麻素CB_1受体(CB_1R)在坐骨神经缩窄性损伤(CCI)所致的神经病理性疼痛中的作用及其对嘌呤能P2X_2受体表达的调节。方法:7~8周龄SD大鼠分为4组:(1)sham组;(2)CCI组;(3)CP55940+CCI组;(4)AM251+CP55940+CCI组。分别于CCI术前1 d,术后1、3、5、7、10、14 d测定热缩足反射潜伏期(TWL);免疫印迹技术检测各组大鼠损伤侧L_4~L_6段脊髓背角P2X_2受体表达。结果:CCI术后大鼠出现热痛敏,TWL明显缩短;鞘内给予非选择性大麻素受体激动剂CP55940可明显延长CCI大鼠TWL(P0.05);预先鞘内注射CB_1R拮抗剂AM251(0.05 mg/kg)可显著降低CP55940的镇痛效果(P0.05)。免疫印迹实验结果显示:CCI大鼠脊髓背角P2X_2受体在术后7、14 d表达明显增加(P0.05);鞘内给予CP55940可显著降低P2X_2受体表达(P0.05),而预先给予AM251可降低CP55940抑制P2X_2受体表达的效应(P0.05)。结论:脊髓背角CB_1受体激活对CCI所致的神经病理性疼痛具有良好的镇痛作用,其镇痛效应可能与抑制CCI大鼠嘌呤能P2X_2受体表达有关。     

曲古抑菌素A通过抑制脊髓背角内的炎症反应减轻大鼠神经病理性痛

目的:观察曲古抑菌素A (TSA)对脊神经结扎(SNL)大鼠镇痛效果及分子机制。方法:40只健康雄性Sprague Dawley(SD)大鼠随机分为假手术组(sham)、曲古抑菌素A处理组(TSA)、脊神经结扎组(SNL)和SNL+TSA组(SNL+TSA)。采用L5脊神经结扎(SNL)的方法建立神经病理性痛模型,鞘内注射TSA进行干预,通过von Frey丝和热板实验检测大鼠的痛敏,应用免疫荧光染色方法观察大鼠脊髓背角内HDAC1的表达情况;应用Western Blot方法观察大鼠脊髓背角内胶质纤维酸性蛋白(GFAP)和离子钙接头蛋白分子1(Iba-1)的表达水平;应用real time RT-PCR方法检测大鼠脊髓背角内TNF-α、IL-1β和IL-6的mRNA表达水平。结果:SNL模型大鼠术后机械性痛阈值和热痛阈值均显著降低(P <0.05),鞘内给予TSA能够明显缓解大鼠患侧后足机械性痛敏和热痛敏; SNL模型大鼠脊髓背角内HDAC1的表达较对照组明显增加,而鞘内注射TSA可显著抑制其表达; SNL术后脊髓背角内GFAP和Iba-1的表达显著升高(P <0.05),...     

神经病理性痛大鼠脊髓背角缝隙连接蛋白表达变化及鞘内注射甘珀酸的镇痛作用

目的 研究慢性神经病理性痛大鼠脊髓背角内缝隙连接蛋白家族(Cx)中Cx43和Cx32的表达变化,以及鞘内注射缝隙连接阻断剂甘珀酸（CBX）的镇痛作用。 方法 成年SD大鼠50只,分为正常对照组、假手术组和坐骨神经分支选择性损伤组(SNI)。手术前1d、术后3d、5d、10d、20d和30d,观察大鼠行为并检测机械刺激缩足反射阈值(PWMT)。15只大鼠于术后10d、20d、30d取脊髓腰段进行免疫印迹检测,另15只大鼠于术后10d、20d、30d取脊髓腰段进行免疫荧光染色,检测腰段脊髓背角内Cx43和Cx32表达的变化。有10只大鼠先进行鞘内插管,后行SNI手术,术后20d向鞘内注射生理盐水或CBX,观察大鼠PWMT的变化。 结果 SNI大鼠手术侧PWMT阈值较非手术侧或假手术组明显降低,术后20d达最低值。SNI大鼠手术侧脊髓背角内Cx43、32表达增多,明显高于非手术侧和假手术组背角。鞘内注射CBX 3h后,PWMT平均阈值由(2.5±1.0)g上升到(20.0±3.2)g,有抑制效应, 而生理盐水组则无抑制效应。 结论 脊髓背角内的缝隙连接在因外周神经损伤引起的神经病理性痛中起重要作用。     

异氟醚通过海马内源性大麻素调节条件恐惧大鼠恐惧记忆

目的:探讨异氟醚早期干预对条件恐惧大鼠恐惧记忆及海马内源性大麻素水平的影响。方法:以巴甫洛夫条件恐惧反射理论为基础,建立大鼠条件恐惧模型,模拟大鼠创伤后应激障碍(posttraumatic stress disorder,PTSD)恐惧记忆,高效液相色谱质谱分析和RT-PCR方法检测模型大鼠海马内源性大麻素2-AG(2-arachidonoylglycerol)、AEA(N-arachidonoylethanolamine)含量,行为学方法分析大鼠僵立时间,行为检测前给予异氟醚干预对海马内源性大麻素水平及大鼠僵立时间的影响,然后海马或者腹腔给予内源性大麻素受体1拮抗剂AM281,再次记录大鼠行为学表现。结果:条件恐惧模型大鼠的僵立时间与正常大鼠相比明显增加(P0.05)AEA水解酶FAAH(fatty acid amide hydrolase,FAAH)和2-AG合成酶DAGL(diacylglycerol lipase,DAGL)mRNA水平与正常大鼠比较无差别(P0.05),而2-AG水解酶MAGL(monoacylglycerol lipase,MAGL)mRNA水平明显升高(P0.05);异氟醚干预提高了模型大鼠海马2-AG水平(P0.05),减少了应激大鼠的僵立时间(P0.05)。海马内或者腹腔给予AM281均可抑制异氟醚对应激大鼠僵立时间的影响。结论:异氟醚通过海马内源性大麻素2-AG干预创伤后应激障碍模型大鼠的恐惧记忆的形成。     

大麻素受体2参与神经病理性疼痛的研究进展

神经病理性疼痛(Neuropathic Pain)是由于躯体感觉系统产生疾病或受到者损伤后,机体受到的有害或者无害的刺激被病理性的放大后所致.周围神经性痛是起源于周围神经系统受到机械创伤、代谢性疾病、神经化学毒物等影响.而中枢神经性痛一般都是由于脊髓损伤、中风或者多发性硬化引起的[1].然而到目前为止,神经病理性痛确切的发病机制仍不清楚,临床上治疗神经病理性疼痛的措施仍停留在对于原发疾病或损害的处理上,而现有的一些药物治疗(如阿片类药物、抗抑郁药和抗惊厥药物等),存在疼痛缓解不足或一些有害的副作用,药物用量受到限制,治疗效果一直不佳.近年来有研究表明大麻素受体2 (cannabinoid receptor 2,CB2)在选择性激动剂激活下能够有效地抑制急性、炎性疼痛而不产生中枢神经系统的副作用[2-5],因此其可能作为未来治疗神经病理性疼痛的一个治疗靶点.关于大麻素受体2在神经病理性疼痛中的作用的报道也越来越多,本文对其近几年的研究进展综述如下.     

脊髓背角HCN通道在神经病理性疼痛中的作用

目的:观察脊髓背角超极化激活环核苷酸门控阳离子通道(HCN通道)在坐骨神经缩窄性损伤(CCI)所致的慢性神经病理性疼痛中的作用。方法:8周龄成年雄性SD大鼠48只随机分为6组:(1)sham组(假手术组)、(2)CCI组(鞘内注射生理盐水)、(3)~(6)ZD7288+CCI(鞘内分别注射1,10,30,50μg ZD7288),每组8只。CCI及CCI+ZD7288组大鼠在鞘内置管5 d后行CCI术,术后鞘内给药,每日两次,连续14 d;sham组大鼠不进行鞘内置管,仅游离坐骨神经,不结扎。分别于CCI术前1 d,术后1、3、5、7、10、14 d鞘内给药2 h后测定热缩足潜伏期(TWL);术后第7、14 d处死大鼠,取术侧L4~L6脊髓背角,采用Western Blot技术检测脊髓背角HCN1,3,4及磷酸化蛋白激酶A(P-PKA)表达的变化。结果:大鼠CCI术后即形成稳定的热痛敏,TWL明显缩短;与CCI组相比,鞘内给予HCN通道阻滞剂ZD7288可明显延长CCI大鼠的TWL(P0.05)。Western Blot结果显示,与假手术组相比,CCI组大鼠在术后7、14 d术侧脊髓背角HCN1,3,4及P-PKA表达显著增加(P0.05);鞘内给予ZD7288可显著降低CCI大鼠HCN1,3,4及P-PKA的表达(P0.05)。结论:脊髓背角HCN通道的激活可促进CCI所致的神经病理性痛的发生与维持,HCN通道阻滞剂ZD7288具有良好的镇痛效应,ZD7288的镇痛作用可能与其抑制PKA的活性密切相关。     

瑞芬太尼诱导大鼠脊髓背角痛觉过敏及利多卡因的抑制作用

目的探讨大鼠脊髓背角细胞蛋白激酶Cγ(PKCγ)膜转位/激活在瑞芬太尼诱导痛觉过敏中的作用及利多卡因的抑制作用。方法将大鼠随机分为4组:(1)丙泊酚组(P组),(2)瑞芬太尼组(R组),(3)瑞芬太尼-利多卡因组(RL组)及(4)利多卡因组(L组)。比较4组麻醉后累积疼痛评分和机械性刺激缩足阈值。用免疫印迹(每组n=8)和免疫荧光法测量脊髓背角PKCγ膜转位/激活。结果 (1)累积疼痛评分P、RL和L组相似;R组18(15-20.75)高于P组11.5(8-13.5)、RL组11(9-14)和L组8.5(11-16.25)(P<0.05)。(2)手术侧机械性刺激缩足阈值R组39.2(39.2-68.6)mN低于P组117.6(58.8-137.2)mN、RL组588(588-588)mN和L组588(588-588)mN组(P<0.05)。(3)蛋白免疫印迹显示脊髓背角PKCγ膜转位/激活R组(假手术组153%±35%,手术对侧为160%±41%,手术侧为157%±36%)高于其他3组,R组PKCγ免疫阳性显色在细胞边缘增强。术后短时间内,未发现组织损伤对脊髓背角PKCγ膜转位/激活的影响。结论脊髓背角PKC...     

脊髓刺激术对神经病理性痛模型大鼠痛行为和脊髓背角内小胶质细胞激活的影响

目的:探讨脊髓刺激术(spinal cord stimulation,SCS)对神经病理性痛(neuropathic pain,NP)模型大鼠痛行为及脊髓背角内小胶质细胞激活的影响。方法:成年大鼠20只,随机分为4组:(1)正常对照组(control组);(2)SCS组:正常大鼠给予SCS刺激;(3)脊神经结扎(spinal nerve ligation,SNL)假刺激组(SNL+shamSCS组):SNL且植入SCS装置,但不刺激;(4)SNL+SCS组:SNL且给予SCS刺激。术前连续3 d、术后第5 d检测各组大鼠足底机械痛敏阈值(mechanical withdrawal threshold,MWT)。SCS组和SNL+SCS组术后第2-5 d给予SCS刺激,每d持续8 h;且在每次给予SCS 8 h刺激前进行90 min行为学测试,即SCS刺激30 min,以及刺激结束后的60 min内(共90 min),每15 min测量一次MWT。在第5 d给予SCS 8 h刺激结束后处死动物,利用免疫组织化学染色结合平均光密度(average optical density,AOD)分析的方法检测各组大鼠腰5节段脊髓背角内小胶质细胞特异性标志物OX-42的表达情况。结果:(1)行为学结果显示:术后第5 d,SNL+shamSCS组和SNL+SCS组大鼠手术侧后爪的MWT由术前26.00±0.0 g分别降至5.50±0.96 g和6.40±0.40 g(P<0.05);SNL+SCS组给予SCS刺激30 min后大鼠手术侧后爪的MWT明显有所提高,达16.20±2.60 g,与刺激前(6.40±0.40 g)相比有显著性差异(P<0.05);但停止SCS刺激60 min后,大鼠的MWT明显有所下降,与刺激前几乎没有明显差别。(2)免疫组化染色结果显示:术后第5 d,SNL+SCS组脊髓背角内OX-42的表达明显弱于SNL+shamSCS组,但二者都强于control组和SCS组;AOD结果也证实:SNL+SCS组大鼠脊髓背角内OX-42的AOD(1.29±0.28)明显低于SNL+shamSCS组(2.66±0.38),但仍高于control组(0.14±0.21)和SCS组(0.24±0.08)。结论:SCS对SNL模型大鼠的神经病理性痛有较好的镇痛效果;该作用可能与SCS刺激显著抑制脊髓背角内小胶质细胞的激活密切相关。     

Electroacupuncture reduces the evoked responses of the spinal dorsal horn neurons in ankle-sprained rats

Acupuncture is shown to be effective in producing analgesia in ankle sprain pain in humans and animals. To examine the underlying mechanisms of the acupuncture-induced analgesia, the effects of electroacupuncture (EA) on weight-bearing forces (WBR) of the affected foot and dorsal horn neuron activities were examined in a rat model of ankle sprain. Ankle sprain was induced manually by overextending ligaments of the left ankle in the rat. Dorsal horn neuron responses to ankle movements or compression were recorded from the lumbar spinal cord using an in vivo extracellular single unit recording setup 1 day after ankle sprain. EA was applied to the SI-6 acupoint on the right forelimb (contralateral to the sprained ankle) by trains of electrical pulses (10 Hz, 1-ms pulse width, 2-mA intensity) for 30 min. After EA, WBR of the sprained foot significantly recovered and dorsal horn neuron activities were significantly suppressed in ankle-sprained rats. However, EA produced no effect in normal rats. The inhibitory effect of EA on hyperactivities of dorsal horn neurons of ankle-sprained rats was blocked by the α-adrenoceptor antagonist phentolamine (5 mg/kg ip) but not by the opioid receptor antagonist naltrexone (10 mg/kg ip). These data suggest that EA-induced analgesia in ankle sprain pain is mediated mainly by suppressing dorsal horn neuron activities through α-adrenergic descending inhibitory systems at the spinal level.     

The effect of serotonin on GABA synthesis in cultured rat spinal dorsal horn neurons

The spinal dorsal horn (SDH) is the first step in the integration of primary nociceptive information, which is controlled by the descending serotonin (5-HT) system as well as the principal inhibitory neurotransmitter gamma-aminobutyric acid (GABA). However, the influence exerted by 5-HT on GABA synthesis remains poorly understood. The major pathway for GABA synthesis is the enzymatic decarboxylation of glutamate by glutamic acid decarboxylase (GAD) 65 and 67. In the present research, western blotting results show a time- and dose-dependent enhancement of GAD65 and GAD67 expression induced by 5-HT treatment and a concentration of 100nM 5-HT applied for 3 days is shown to be the optimal condition for maximal expression of GAD67 and a significant expression of GAD65. Under the stimulation of such 5-HT application the phosphorylation of Akt and p42/p44 mitogen-activated protein (MAP) kinase is activated and specifically blocked by inhibitors of phosphatidylinositol 3-kinase (PI3-K) (LY294002) or the p42/p44 MAP kinase (PD98059 and U0126) pathways. Moreover, LY294002, or PD98059, or U0126 partially inhibit 5-HT-stimulated increases in GAD67 or GAD65 expression. Further, 5-HT application has no effect on the number of GAD65/GAD67-immunopositive neuronal cells; but it can induce an increase in the total area, process length and number of primary neurites of GAD65/67-positive neurons, an increase that appears to involve LY294002 and PD98059. The results of this study provide an in vitro model of the regulation of 5-HT on synthesis of GABA in the SDH that is putatively thought to occur in vivo as a result of excitatory neural activity.     

Evidence for spinal dorsal horn hyperexcitability in rats following sustained morphine exposure

Repeated or sustained exposure to opioids can not only induce analgesia but also long lasting enhancements in pain sensitivity, a phenomenon reported clinically and in animals. In rats, opioid-induced abnormal pain can be readily measured following continued delivery of morphine and the recruitment of descending facilitatory influences appears essential for the genesis of this state. Here, we provide evidence that an increased excitability develops in neurons of the deep dorsal horn (DH), following 7-10 days of sustained delivery of morphine. Electrophysiological recordings were made in halothane-anesthetised animals implanted with osmotic minipumps containing either morphine (45 microg/0.5 microl/h and 90 microg/0.5 microl/h) or saline. A separate group of na?ve animals was also used as controls. Sustained morphine exposure resulted in dose-related and modality-specific enhancements of DH neurons (C-fibre and Adelta-fibre evoked responses, non-potentiated responses) and expanded neuronal receptive fields, as mapped with low intensity mechanical punctate stimuli. Heat and mechanical stimulation of the hindpaw (brush and von Frey filaments) produced similar enhancements in morphine-treated rats compared to control rats, reflecting spinal hyperexcitability. Interestingly, wind-up itself was unaltered. These neuroadaptive changes could form the neuronal basis for the documented clinical and experimental reports of abnormal paradoxical pain after opioids. Since brainstem excitatory controls actively operate during prolonged opioid exposure, the sustained triggering of such influences may act alongside spinal mechanisms such as wind-up to enhance central sensitisation and alter CNS excitability.     

Release of substance P from the spinal dorsal horn is enhanced in polyarthritic rats

Using in situ spinal dorsal horn perfusing method in decerebrated rats, we measured the release of immunoreactive substance P (iSP) in polyarthritic rats. The spontaneous release of iSP from the dorsal horn in the polyarthritic rats was significantly accelerated over that in control non-inflamed rats. Passive movements of the inflamed ankle joint evoked a significant increase in the release of iSP, while a similar movement of the non-inflamed joint led to no such increase. These results suggest that the facilitated release of iSP from the primary afferent terminals in the spinal dorsal horn in polyarthritic rats possibly plays a role in transmission of chronic pain of inflamed joints.     

Caudal end of the rat spinal dorsal horn

We have previously demonstrated that the transformation of the caudal spinal cord through the conus medullaris to the filum terminale takes place in three steps. In the conus medullaris the twin layers of CGRP-immunoreactive and IB4-labeled primary afferent fibers as well as the translucent portion of the superficial dorsal horn equivalent to the substantia gelatinosa discontinue before the complete removal of the dorsal horn. Parallel with these changes VGLUT1-immunoreactive myelinated primary afferent fibers arborize not only in the deep layers but also in the entire extension of the remaining dorsal horn, while scattered CGRP fibers still remains at the margin of and deep in the dorsal horn. PKCgamma-immunoreactive dorsal horn neurons discontinue parallel with the disappearance of the IB4-labeled nerve fibers. These observations suggest that in the dorsal horn certain neurons are linked to the substantia gelatinosa, while others are substantia gelatinosa-independent neurons.     

Response characteristics of spinal cord dorsal horn neurons in chronic allodynic rats after spinal cord injury

The physiological mechanisms of chronic pain in patients with spinal cord injury (SCI) are poorly understood. In the present study, we explored response characteristics of dorsal horn neurons of spinally injured rats exhibiting chronic pain (pain-like response to innocuous mechanical and cold stimulation). Several abnormalities were found in the distribution and response characteristics of dorsal horn neurons in chronic allodynic rats. First, 17% of the recorded neurons (vs. 0% in control animals) had no receptive field. Most of these units were located at or close to the lesioned spinal segment, and they discharged spontaneously at high frequencies. Allodynic rats also showed a significant decrease in the proportion of low-threshold (LT) neurons and an increase in the proportion of wide dynamic range (WDR) neurons. The rate of spontaneous activity of high-threshold (HT) neurons was significantly higher in allodynic compared with control rats. Moreover, HT neurons in allodynic animals showed increased neuronal responses to mechanical stimulation. WDR neurons responded with higher discharge rates to innocuous von Frey hair stimulation in allodynic compared with control rats. The percentage of WDR and HT neurons showing afterdischarges to noxious pinch was also significantly increased in the allodynic rats. The proportion of WDR and HT neurons responding to innocuous cold stimulation respectively increased from 53 and 25% in control rats to 91 and 75% in allodynic animals. These results suggest that the chronic pain-like behaviors in spinally injured rats may be generated and maintained by abnormalities in dorsal horn neurons.     

Systemic lidocaine induces expansion of the receptive field of spinal dorsal horn neurons in rats

 The effect of intravenous administration of the local anaesthetic lidocaine (1, 3 or 5 mg/kg) on the responsiveness and size of the cutaneous receptive fields of 18 lumbar dorsal horn neurons was examined in intact urethane-anaesthetized rats. Lidocaine induced expansion of the receptive field in the majority of neurons examined, particularly after the two higher doses. The expansion occurred usually within 10 min after lidocaine injection and the effect was reversible. Lidocaine also altered the responsiveness of dorsal horn neurons to peripheral mechanical stimulation. The responses of wide-dynamic-range neurons to noxious pinch were usually inhibited by lidocaine. However, some low-threshold neurons started to react to noxious mechanical stimulation and some high-threshold neurons started to respond to innocuous brushing after lidocaine injection. The present results show that moderate doses of systemic lidocaine induce complex changes in the excitability of dorsal horn neurons, including an increase in the size of the receptive field and altered response characteristics to mechanical stimulation. Received: 16 July 1997 / Accepted: 21 October 1997