刺激隐神经C类纤维诱发体感皮层电反应(平均诱发电位)

当猫的隐神经A类纤维单独兴奋时,可引起同侧脊髓背表面电位 A-SSP(潜伏期 2.6±0.4ms)和对侧体感皮层诱发电位 A-CEP。A-CEP由早成分(潜伏期 9.6±1 1ms)和晚成分(203.0±10.gms)组成。当 C类纤维选择性传入时,出现特异的 C-CEP(潜伏期 134.4±25.9ms)和C-SSP(115.8±15.6ms)。C-CEP的幅值较A-CEP 小,并随C类纤维传入的数量而改变。C-CEP的最大幅值位于后乙状回一定部位,多为负或正-负电位,在皮层深层其相位倒转。与A-CEP相比,C-CEP的中枢延搁时间较长,跟随频率较低,对镇痛药较敏感。表明C-CEP不同于A-CEP,它是由C类传入所引起的,是在体感皮层内产生的。当A类和C类纤维同时传入时,只有A-CEP和A-SSP出现,而不出现C-CEP和C-SSP。在阻断电流逐渐增强过程中,C-CEP较C-SSP后出现;而在撤销阻断过程中,则C-CEP较C-SSP先消失。提示C类传入在中枢可能被A类传入所抑制,这种抑制可以发生在脊髓和脊上水平,后者可能更强。     

刺激大脑皮层联合区对C类纤维传入诱发皮层电反应的影响

电刺激猫大脑皮层前外侧回联合区(ALA)能使隐神经 C 类纤维传入引起的体感皮层(S(?)区)诱发电位(C-CEP)的幅值明显变小,并有后作用,表明 ALA 对 C-CEP 有抑制作用;切断ALA 与 SI 区之间的皮层内纤维联系后,ALA 对 C-CEP 的抑制作用明显减弱,抑制时程缩短;侧脑室微量注射阿片受体拮抗剂纳洛酮后,电刺激 ALA 对 C-CEP 的抑制作用明显减弱,表明 ALA 对 C-CEP 的抑制作用的作用途径之—可能是通过 ALA 与 SI 区之间的皮层内神经径路;可能与内源性阿片样物质的释放有关。提示大脑皮层联合区可能对体感皮层 C-CEP 有调制作用。     

γ—氨基丁酸在联合皮层抑制C类纤维皮层诱发电位效应中的作用

电刺激猫大脑皮层前外侧回联合区(ALA)对隐神经C类纤维传入引起的体感皮层(SI)诱发电位(C-CEP)有明显的抑制作用;侧脑室注射γ-氨基丁酸(GABA)能使C-CEP的幅值显著变小,潜伏期延长,表明GABA对C-CEP也有抑制作用;侧脑室注射GABA受体拮抗剂荷包牡丹硷后,电刺激ALA对C-CEP的抑制作用明显减弱,提示内源性GABA的释放可能参与大脑皮层联合区对C-CEP的调制过程。     

脊髓背部电刺激对延脑内侧网状结构诱发电位抑制效应的分析

实验在46只急性麻痹清醒的猫上进行。以每秒100次的重复电脉冲刺激脊髓背部(L_1)可以抑制刺激腓肠神经在延脑内侧网状结构所引起的诱发电位,抑制后效应可持续5—10分钟。在12只动物上进行了脊髓部分横断的分析,在腰2水平切断刺激部位以下的两侧侧索靠近背角部分的纤维(简称背外侧索),上述抑制作用大大减弱。如再在刺激部位上、下(胸13及腰2)分别切割背索,则抑制效应完全消失。在刺激部位以上切断两侧背外侧索并不影响抑制效应的出现。在10只动物上将背索及背外侧索从脊髓本体上分离,以观察直接刺激的效应。结果表明,分别刺激两侧背外侧索或背索对延脑诱发电位都有抑制效应,前者的作用大于后者。如同时刺激分离的背外侧索及背索则诱发电位在整个刺激期间完全被抑制,其效应与背部电刺激相似,只是所需要的电流强度较弱。上述观察证明,脊髓背部电刺激对延脑网状结构诱发电位的抑制作用是通过背外侧索的下行通路和背索的上行及下行通路而实现的。背外侧索的作用大于背索,抑制作用主要发生在脊髓水平。     

阻断5—HT下行抑制通路后电刺激体感Ⅱ区对束旁核痛反应的…

Ｃ类纤维传入引起的丘脑束旁核诱发电民痛关系密切,电刺激ＳⅡ区,可明显抑制Ｃ－ＰｆＥＰ。用赛庚啶在脊髓阻断５－ＨＴ能下行抑制通路后,电刺激ＳⅡ区对Ｃ－ＰｆＥＰ抑制作用明显减弱,但仍然存在。     

单胺类受体阻断剂和纳洛酮对家兔脊髓下行性抑制作用的影响

实验在27只麻痹的清醒家兔上进行。用玻璃微电极记录丘脑束旁核单位对腓总神经伤害性刺激发生的痛敏放电情况。这种痛敏放电活动均能无例外地被模拟的下行性抑制、即用弱电流刺激分离的脊髓背侧1/2外周端所抑制。在27个单位中,静注α-肾上腺能受体阻断剂酚妥拉明后,有16个单位的脊髓刺激的抑制效应被明显削弱,11个单位的脊髓刺激效应基本无变化。在5个酚妥拉明有效的单位,待药物作用消失之后,其脊髓刺激效应均能被纳洛酮所阻断。在5个脊髓刺激效应不受酚妥拉明影响的单位,静注5-羟色胺受体阻断剂賽庚啶后,有4个单位的脊髓刺激效应被明显削弱;而另外一个单位的脊髓刺激效应依然存在。以上实验结果提示,经由脊髓背侧下行、在脊髓水平对痛信号进行调制的下行通路可能主要包括两类纤维系统,一类以去甲肾上腺素(通过α受体发挥作用)和内源性吗啡样物质为递质或/和调制物,另一类则以-5羟色胺为递质。这两类纤维可能分别影响不同的脊髓背角上行投射神经元。     

阻断5－HT下行抑制通路后电刺激体感Ⅱ区对束旁核痛反应的影响

Ｃ类纤维传入引起的丘脑束旁核诱发电位（ＣＰｆＥＰ）与痛关系密切,电剌激ＳⅡ区,可明显抑制ＣＰｆＥＰ［１］。用赛庚啶在脊髓阻断５ＨＴ能下行抑制通路后,电剌激ＳⅡ区对ＣＰｆＥＰ抑制作用明显减弱,但仍然存在。提示ＳⅡ区可能一方面通过５ＨＴ能下行性抑制通路来影响Ｃ类纤维传入上传,继而抑制ＣＰｆＥＰ;另一方面还可能通过其它抑制途径。     

刺激大鼠“涌泉”穴诱发的脊髓背表面电位

刺激大鼠“涌泉”穴诱发的节段性背表面电位(Y-sCDP),在远节段(L3-T7)逐渐消失,而在更远节段(C6)又记录到一个背表面电位(Y-dCDP),该电位为一慢电位正波(P波),高位横断脊髓后Y-dCDP完全消失,说明它来源于脊髓上结构,当电解损毁中脑导水管周围灰质(PAG)后,P波幅值显著降低(P<0.05),说明刺激“涌泉”穴产生的Y-dCDP为激活PAG等痛觉调制核团下行诱发的脊髓背表面电位。     

C类纤维传入诱发体感皮层电反应的脊髓上传通路

实验用猫,在氯醛糖和三碘季铵酚处理下进行。以强电脉冲刺激腓浅神经,结合极化电流阻滞A类纤维的传入后,选择性引起C类纤维传入时,在对侧大脑皮层体感Ⅰ区记录到特异的C类纤维皮层诱发电位(G-CEP)。观察到损毁脊髓胸11节段对侧腹外侧索后,C-CEP的幅值明显衰减;损毁同侧背索后,G-CEP的幅值也明显衰减;保留同侧背索,损毁脊髓其他部份后,C-CEP仍出现,但幅值变小;同时损毁上述两索后,C-CEP完全消失。提示C类纤维传入诱发C-CEP的脊髓上传通路位于同侧背索和对侧腹外侧索。     

刺激下丘脑弓状核对丘脑束旁核单位痛诱发放电的影响和初步分析

1.电刺激大鼠下丘脑弓状核(ARC)对外周伤害性刺激引起的丘脑束旁核(PF)单位的痛诱发放电有明显的抑制作用,这种抑制作用可被纳洛酮所翻转。2.切断脊髓背半部后,刺激ARC对PF单位痛诱发放电的抑制作用依然存在。3.腹腔注射对氯苯丙氨酸(色氨酸羟化酶抑制剂)后,刺激ARC 的抑制作用消失。4.从ARC到PF存在着一条有内源性阿片样物质(可能是β-内啡肽)和5-羟色胺参与的上行痛觉调制通路。     

家兔若干与下行抑制有关的中枢部位中去甲肾上腺素、5-羟色胺和脑啡肽在针刺镇痛中的变化

应用推挽灌流技术、去甲肾上腺素(NA)放射酶学法和亮-脑啡肽放射免疫法观察不同脑区 NA 和脊髓背角亮-脑啡肽的释放。应用分子筛柱层析分离家兔不同脑区的5-羟色胺(5-HT)和5-羟吲哚乙酸(5-HIAA),并对它们进行荧光微量测定。以此来阐明针刺镇痛时 NA、5-HT 和亮-脑啡肽在下行抑制中的作用。1.家兔电针20 min,痛阈显著提高,此时中脑导水管周围灰质(PAG)和中缝大核(NRM)的 NA 释放显著减少,而 Al 核团和脊髓背角的 NA释放显著增加。2.电针镇痛时,PAG、延脑中缝核区和脊髓的5-HT 和5-HIAA 含量均有显著增加,除 PAG 外,这种增加的出现较 NA 为晚。提示可能在针刺镇痛的下行抑制中,NA 的参予较5-HT 为早。3.针刺镇痛时脊髓背角亮-脑啡肽的释放也明显增加。     

电刺激猫中脑导水管周围灰质和中缝大核对脊髓背角神经元伤害性感受反应的抑制

1.在氯醛糖麻醉的猫上,观察了电刺激中脑导水管周围灰质(PAG)和中缝大核(NRM)对脊髓腰段背角神经元传入活动的影响。2.按照对刺激的反应型式,在背角记录到非伤害性低阈值传入、广动力范围、伤害性热敏以及高阈值传入诱发的自发放电抑制等四类神经元。3.刺激 PAG和 NRM对记录到的多数背角神经元皮肤传入反应有明显抑制效应,而对自发放电抑制性神经元产生去抑制。4.比较刺激两脑区的抑制效应:NRM 作用较PAG 强;PAG 活动对背角伤害性反应抑制的选择性较 NRM强;阿片肽拮抗剂-纳洛酮拮抗NRM刺激的抑制。5.这些结果提示PAG和NRM对脊髓的下行抑制,可能有一部分是通过不同神经机制实现的。     

神经递质和调质参与导水管周围灰质痛觉调控的研究进展

导水管周围灰质(periaqueductal gray,PAG)在疼痛的调控过程中处于一个不可或缺的位置.其不仅是痛觉信息上行传递的重要部位,还是疼痛抑制系统的重要组成部分.在PAG,包括γ-氨基丁酸(γ-aminobutyric acid,GABA)、5-羟色胺(5-hydroxytryptamine,5-HT)和谷氨酸(glutamate,Glu)在内的神经递质以及内源性阿片肽(endogenous opioid peptides,EOP)和内源性大麻素(endocannabinoid,e CB)为代表的神经调质都参与了PAG对疼痛的信息传递以及调节.本文重点综述GABA、5-HT、Glu、EOP和eCB在PAG参与疼痛生理调控机制的研究进展,以期为中枢神经系统的镇痛研究提供一定的理论基础.     

Gentle Mechanical Skin Stimulation Inhibits Micturition Contractions via the Spinal Opioidergic System and by Decreasing Both Ascending and Descending Transmissions of the Micturition Reflex in the Spinal Cord

Recently, we found that gentle mechanical skin stimulation inhibits the micturition reflex in anesthetized rats. However, the central mechanisms underlying this inhibition have not been determined. This study aimed to clarify the central neural mechanisms underlying this inhibitory effect. In urethane-anesthetized rats, cutaneous stimuli were applied for 1 min to the skin of the perineum using an elastic polymer roller with a smooth, soft surface. Inhibition of rhythmic micturition contractions by perineal stimulation was abolished by naloxone, an antagonist of opioidergic receptors, administered into the intrathecal space of the lumbosacral spinal cord at doses of 2–20 μg but was not affected by the same doses of naloxone administered into the subarachnoid space of the cisterna magna. Next, we examined whether perineal rolling stimulation inhibited the descending and ascending limbs of the micturition reflex. Perineal rolling stimulation inhibited bladder contractions induced by electrical stimulation of the pontine micturition center (PMC) or the descending tract of the micturition reflex pathway. It also inhibited the bladder distension-induced increase in the blood flow of the dorsal cord at L5–S1, reflecting the neural activity of this area, as well as pelvic afferent-evoked field potentials in the dorsal commissure at the lumbosacral level; these areas contain long ascending neurons to the PMC. Neuronal activities in this center were also inhibited by the rolling stimulation. These results suggest that the perineal rolling stimulation activates the spinal opioidergic system and inhibits both ascending and descending transmissions of the micturition reflex pathway in the spinal cord. These inhibitions would lead to the shutting down of positive feedback between the bladder and the PMC, resulting in inhibition of the micturition reflex. Based on the central neural mechanisms we show here, gentle perineal stimulation may be applicable to several different types of overactive bladder.     

Spinal and supraspinal contributions to central sensitization in peripheral neuropathy

We will focus on spinal cord dorsal horn lamina I projection neurones, their supraspinal targets and involvement in pain processing. These spinal cord neurons respond to tonic peripheral inputs by wind-up and other intrinsic mechanisms that cause central hyper-excitability, which in turn can further enhance afferent inputs. We describe here another hierarchy of excitation - as inputs arrive in lamina I, neurones rapidly inform the parabrachial area (PBA) and periaqueductal grey (PAG), areas associated with the affective and autonomic responses to pain. In addition, PBA can connect to areas of the brainstem that send descending projections down to the spinal cord - establishing a loop. The serotonin receptor, 5HT3, in the spinal cord mediates excitatory descending inputs from the brainstem. These descending excitatory inputs are needed for the full coding of polymodal peripheral inputs from spinal neurons and are enhanced after nerve injury. Furthermore, activity in this serotonergic system can determine the actions of gabapentin (GBP) that is widely used in the treatment of neuropathic pain. Thus, a hierarchy of separate, but interacting excitatory systems exist at peripheral, spinal and supraspinal sites that all converge on spinal neurones. The reciprocal relations between pain, fear, anxiety and autonomic responses are likely to be subserved by these spinal-brainstem-spinal pathways we describe here. Understanding these pain pathways is a first step toward elucidating the complex links between pain and emotions.     

Effects of thalamic sensory relay nucleus stimulation on the jaw-opening reflex in response to tooth-pulp stimulation in the cat

The effects of stimulation of the thalamic sensory relay nucleus (TSRN, nucleus ventralis posteromedialis) on the jaw-opening reflex (JOR) in response to tooth pulp stimulation were compared with the effects of stimulation of the periaqueductal gray (PAG) and nucleus raphe magnus (NRM) in the cat. After stimulation of the TSRN, PAG and NRM, the JOR was inhibited. However, while the inhibitory effects of PAG and NRM stimulation lasted for more than 500 ms and were antagonized by the opiate antagonist, naloxone, the inhibitory effects of TSRN stimulation lasted for approximately 100 ms and were resistant to naloxone. These findings suggest that although TSRN stimulation exerts descending inhibitory effects on segmental nociceptive activity, similarly to PAG or NRM stimulation, the descending inhibitory pathways mediating the effect of TSRN stimulation may be largely distinct physiologically as well as pharmacologically from those mediating the effect of PAG and NRM stimulation.     

Evidence for Ascending and Descending Intraspinal as Well as Primary Sensory Somatostatin Projections in the Rat Spinal Cord

Somatostatin distribution was measured quantitatively in the rat spinal cord by radioimmunoassay. Rostro-caudally, somatostatin content was about 50% higher in lumbar-sacral cord than in cervical or thoracic levels. The dorso-ventral distribution is more uneven: somatostatin is highest in the dorsal horn, where the peptide is 15 times as concentrated as it is in the ventral white matter, the region of lowest concentration. However, measurable amounts of the peptide were found in all regions studied. Dorsal root ganglionectomy decreased somatostatin levels in the dorsal cord, supporting the previously proposed role for this peptide as a primary sensory neurotransmitter or modulator; but somatostatin content also was decreased both rostral and caudal to spinal transection, indicating the presence of ascending and descending somatostatin pathways within the spinal cord. Brain levels did not change. Met-enkephalin and substance P were also measured after the above surgical manipulations. Met-enkephalin content was not altered and substance P content was lowered significantly only after ganglionectomy. Although this study confirms the primary sensory neuron as the origin of a part of spinal cord somatostatin, it further indicates the presence of ascending and descending somatostatin pathways within the rat spinal cord.     

躯体传入冲动抑制中枢性心肌缺血的脊髓机制

本工作在58只尿酯-氯醛糖麻醉,三碘季铵酚制动,人工呼吸,切断迷走神经的兔上进行。结果显示:电刺激正中神经(MN)和腓深神经(DPN)均能抑制或部分抑制下丘脑背内侧核(DMH)诱发的缺血性心电 ST 段偏移,以刺激 MN 的抑制作用更为明显。蛛网膜下腔注射(ith)吗啡(40μg)也能抑制这种缺血性心电变化。ith 纳洛酮(20μg)则可阻断刺激 MN 对中枢性心肌缺血的抑制作用。完整兔在刺激左侧 MN 或 DPN 后,用放射免疫技术测得胸 2—5(T_2-5)节段两侧中间外侧柱(IML)中亮氨酸脑啡肽(LENK)含量明显增加。在颈1(C_1)水平横断脊髓,以同样参数刺激左侧 MN,同侧胸髓 IML 中 LENK 含量明显增加,而对侧胸髓 IML 中 LENK 含量无明显改变;刺激一侧 DPN,T_(2-5)的两侧 IML 中 LENK 含量均无明显变化。上述结果表明,刺激 MN 与 DPN 均能抑制 DMH 诱发的中枢性心肌缺血,但以MN 作用较明显。我们推测这种抑制作用可能与通过脊上机制双侧性增加 IML 中 LENK 含量有关,MN 的抑制作用可能尚包括直接激活胸髓内的脑啡肽系统,增加同侧 IML 中 LENK含量,加强了对交感输出活动的抑制作用。