The effect of galanin on wide-dynamic range neuron activity in the spinal dorsal horn of rats

The present study investigated the effect of galanin on wide-dynamic range (WDR) neuron activity in the dorsal horn of the spinal cord of rats. The evoked discharge of WDR neurons was elicited by transdermic electrical stimulation applied on the ipsilateral hindpaw of rats. Galanin was administered directly on the spinal dorsal surface of L3-L5. The evoked discharge frequency of the WDR neurons decreased significantly after the administration of galanin and the effect lasted for more than 30 min. Furthermore, the inhibitory effect of galanin on the evoked discharge frequency of WDR neurons was blocked by following administration of the galanin antagonist galantide, indicating that the inhibitory effect of galanin on the activity of WDR neurons was induced by activating galanin receptors in the dorsal horn of the spinal cord. The results suggest that galanin has an inhibitory role in the transmission of presumed nociceptive information in the dorsal horn of the spinal cord in rats.     

Calcitonin gene-related peptide 8-37 inhibits the evoked discharge frequency of wide dynamic range neurons in dorsal horn of the spinal cord in rats.

The present study was performed to explore the effect of calcitonin gene-related peptide 8-37 (CGRP8-37) on the electrical stimulation-evoked discharge frequency of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord in rats. The discharge frequencies of WDR neurons were evoked by transdermic electrical stimulation applied on the ipsilateral hindpaw. CGRP8-37 was applied directly on the dorsal surface of the L3 to L5 spinal cord. After the administration of 3 nmol of CGRP8-37, the evoked discharge frequency of WDR neurons decreased significantly, an effect lasting more than 30 min. The results indicate that CGRP receptors play an important role in the transmission of presumed nociceptive information in the dorsal horn of the spinal cord.     

Distinct effects of D-serine on spinal nociceptive responses in normal and carrageenan-injected rats

Single unit extracellular recordings from dorsal horn neurons were performed with glass micropipettes in pentobarbital-anesthetized rats. A total of 60 wide dynamic range (WDR) neurons were obtained from 34 rats. In normal rats (20/34), spinally administered D-serine (10 nmol), a putative endogenous agonist of glycine site of NMDA receptors, significantly enhanced the C- but not Abeta-, and Adelta-fiber responses of WDR neurons in the spinal dorsal horn. When 1 nmol of the glycine site antagonist 7-chlorokynurenic acid (7-CK) was co-administered with 10 nmol D-serine, the facilitation of D-serine on C-fiber response was completely blocked. 7-CK (1 nmol) alone failed to influence Abeta-, Adelta-, and C-fiber responses of WDR neurons. In contrast, in carrageenan-injected rats (14/34), 10 nmol D-serine had no effect on C-fiber response, while 1 nmol 7-CK per se markedly depressed C-fiber response of WDR neurons. These findings suggest that under physiological conditions, glycine sites in the spinal cord were available but became saturated following peripheral inflammation. Thus, increased endogenous d-serine or glycine may be involved in nociceptive transmission by modulating NMDA receptor activities. The glycine site of NMDA receptors may become a target for the prevention of inflammatory pain.     

刺激大鼠外侧缰核对脊髓背角神经元伤害性反应的影响

电刺激大鼠一侧外侧缰核可对脊髓疹角广动力型神经元的伤害性放电产生明显抑制;这种抑制效应可部分地被静脉注射赛庚啶及酚妥拉明所阻断,电解损毁ＬＨｂ对ＷＤＲ神经元的放电无影响,本文结果表明,ＬＨｂ参与了脊髓上结构对脊髓背角ＷＤＲ神经元伤害性反应的下行抑制,这种下行抑制为位相性抑制。     

Role of calcitonin gene-related peptide and its antagonist on the evoked discharge frequency of wide dynamic range neurons in the dorsal horn of the spinal cord in rats.

The present study was performed to explore the effect of calcitonin gene-related peptide (CGRP) and its antagonist CGRP8-37 on the evoked discharge frequency of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord in rats. Recording was performed with a multibarrelled glass micropipette and the chemicals were delivered by iontophoresis. The discharge of WDR neurons was evoked by transdermic electrical stimulation applied on the ipsilateral hindpaw. (1) Iontophoretic application of CGRP at an ejection current of 100 nA increased the discharge frequency of WDR neurons significantly. (2) Iontophoretic application of CGRP8-37 at an ejection current of 80 or 160 nA induced significant decreases in the discharge frequency of WDR neurons, but not at 40 nA. (3) Iontophoretic application of CGRP8-37 not only antagonized the CGRP-induced increase in the evoked discharge frequency of WDR neurons but also induced a significant decrease in the evoked discharge frequency of WDR neurons compared to basal levels. The results indicate that CGRP and its receptors play a facilitary role on the transmission and/or modulation of nociceptive information in the dorsal horn of the spinal cord in rats.     

异丙酚对正常大鼠脊髓背角感觉神经元反应性的抑制作用

脊髓背角感觉神经元不仅在感觉信息的传递和调节中起到重要作用,也是各种内源性和外源性药物的作用靶位.为了解静脉麻醉剂异丙酚是否对背角感觉神经元的反应性具有调节作用,本实验采用在体单细胞胞外记录技术,观察了脊髓背表面直接滴注0.5 μmol异丙酚对戊巴比妥钠麻醉大鼠脊髓背角广动力域(WDR)神经元和低阈值机械感受型(LTM)神经元反应性的影响.实验发现,异丙酚能抑制背角WDR神经元由施加于外周感受野伤害性热刺激(45、47、49和53℃,15 s)和夹捏机械刺激(10 s)诱发的反应性,与DMSO对照组比较具有显著性统计学差异(P＜0.05);同样,异丙酚对非伤害性机械刺激诱发的WDR或LTM神经元的反应性也具有显著的抑制作用(P＜0.05).本结果提示,异丙酚可直接作用于正常大鼠脊髓背角神经元,对由非伤害性和伤害性纤维介导的神经元反应性均产生抑制作用,因此异丙酚的脊髓抗伤害作用可能不是特异性的.     

Alpha-2 adrenoceptor mediating the facilitatory effect of norepinephrine on the glycine response in the spinal dorsal horn neuron of the rat

Effects of norepinephrine (NE) on the glycine-mediated inhibitory response were investigated in neurons acutely dissociated from the rat spinal dorsal horn, using nystatin perforated patch recording mode under voltage-clamp conditions. NE reversibly and concentration dependently facilitated Cl(-) current induced by 3 x 10(-5) M glycine. NE neither changed the reversal potential of the glycine response nor affected the affinity of glycine to its receptor. This effect could be mimicked by clonidine (10(-7) M) and blocked by yohimbine (10(-6) M), respectively. N-[2(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-89), an inhibitor of protein kinase A, effectively mimicked the effect of NE on glycine response, whereas chelerythrine (an inhibitor of protein kinase C) failed. NE further enhanced glycine response even in the presence of chelerythrine or stearoylcarnitine chloride (another inhibitor of protein kinase C) or chelerythrine together with stearoylcarnitine chloride. The present results suggest that alpha2-adrenoceptor is involved in the potentiation of NE on glycine response in freshly isolated spinal dorsal horn neurons. Activation of alpha2-adrenoceptor down-regulates the activity of protein kinase A that results in the potentiation of the glycinergic inhibitory effects within the spinal dorsal horn.     

刺激大脑皮层体感Ⅰ区和大脑脚对大鼠脊髓背角神经元伤害感受性反应的影响

在大鼠用玻璃微电极细胞外记录的方法,观察了刺激皮层体感Ⅰ区(SI区)和大脑脚(CP)对皮肤强电刺激诱发的脊髓背角广动力范围(WDR)神经元长潜伏期反应(C-反应)的影响。结果表明刺激SI区对背角WDR神经元C-反应的影响以抑制为主,刺激CP的作用与刺激SI区的作用相似,但刺激CP更为有效。抑制作用的持续时间在不同神经元差别很大,短者在刺激停止后仅持续400ms,长者可达10min以上。静注纳洛酮对抑制作用无明显影响,静注二甲麦角新碱在部分神经元可使抑制作用明显减弱或完全消失,提示5-HT部分参与皮层下行抑制作用的实现,而内鸦片肽则否。     

The Interstrain Differences in the Effects of D-Amphetamine and Raclopride on Dorsal Striatum Dopaminergic System in KM and Wistar Rats (Microdialysis Study)

The levels of dopamine (DA) was determined by intracerebral microdialysis in vivo in KM rats selected for high audiogenic epilepsy, and in Wistar rats selected for nonsusceptibility to loud sound. The basal level of dopamine was 25% higher in the KM rats (P < 0.05). A single amphetamine injection (1 mg/kg body weight, intraperitoneously) caused a significant increase in the DA basal level up to 250-260% in animals of both genotypes. However, in Wistar rats, the level of DA reached maximum as soon as 20 min after amphetamine administration, whereas in KM rats, this happened only after 120 min. After a single injection of the D2/D3 dopamine receptor antagonist raclopride (1.2 mg/kg of body weight, intraperitoneously), an increase in the level of DA was similar in amplitude in rats of both genotypes (up to about 210%); however, this occurred 20-30 and 100 min after raclopride administration to Wistar and KM rats, respectively. This evidence suggests that the genetic defect of KM rats, namely, the high level of audiogenic epilepsy, is caused by abnormalities of the neurotransmitter brain systems and presumably accompanied by the regulatory gene dysfunction.     

大鼠脊髓背角神经元痛放电确定性行为的年龄相关变化

为阐明脊髓背角神经元痛放电的年龄相关的动力学变化,本研究采用非线性预报方法,对两组不同年龄大鼠(成年青龄鼠3～4月龄,老年鼠＞22月龄)组织损伤诱发的脊髓背角神经元痛放电峰峰间期序列进行了确定性行为的定量分析.结果显示,皮下注入蜜蜂毒,在两组大鼠均诱发脊髓背角广动力域神经元长时程放电,而老龄大鼠的痛放电峰峰间期序列表现出更高的可确定性.本研究表明,单个神经元的痛放电动力学在整个生命过程中并不是恒定不变的,伤害性神经元活动的年龄相关动力学变化可能是老年人群中多样化痛反应的内在机制之一.