ACh对正常大鼠和吗啡成瘾大鼠海马CA1区痛反应电活动的影响

目的 研究ACh对正常大鼠和吗啡成瘾大鼠海马CA1区痛兴奋神经元(pain-excitation neurons,PEN)和痛抑制神经元(pain-inhibitation neurons,PIN)电活动的影响,进一步探讨ACh对正常和吗啡成瘾状态下CA1区痛觉调制的作用及机制.方法 电刺激坐骨神经作为伤害性电刺激,在细胞外用玻璃微电极记录CA1区PEN和PIN的放电,观察ACh对正常大鼠和吗啡成瘾大鼠CA1区PEN和PIN电活动的影响.结果 伤害性刺激能够增强PEN的电活动,而减弱PIN的电活动.正常大鼠中,ACh使PEN的痛诱发放电频率降低,PIN的放电频率增加;ACh的作用在注射后4 min达到峰值.吗啡成瘾大鼠中,ACh同样也抑制了PEN的电活动,兴奋PIN的电活动,但是作用的高峰出现在注射后6min.胆碱能受体拮抗剂阿托品可阻断ACh的作用.结论 海马CA1区内的胆碱能神经元和毒蕈碱受体参与了伤害性信息的处理,并且起到了镇痛作用.吗啡成瘾可以降低CA1区痛反应神经元对伤害性刺激的敏感性.     

多巴胺对正常和吗啡成瘾大鼠疼痛相关电活动的不同作用

目的研究多巴胺对正常大鼠和吗啡成瘾大鼠中枢的伤害性刺激的传递的影响。方法在给予坐骨神经伤害性刺激后,记录中枢痛兴奋神经元的电活动,观察多巴胺对正常大鼠和吗啡成瘾大鼠中枢痛兴奋神经元电活动的影响。结果正常大鼠中,多巴胺使尾核痛兴奋神经元的痛诱发放电潜伏期缩短,说明多巴胺可使正常大鼠尾核痛兴奋神经元的活动增强,多巴胺受体拮抗剂氟哌利多可以阻断这种作用。吗啡大鼠中,多巴胺使尾核痛兴奋神经元的痛诱发放电潜伏期延长,说明多巴胺可使吗啡大鼠尾核痛兴奋神经元的活动减弱。结论脑室注射多巴胺后,正常大鼠和吗啡成瘾大鼠的尾核对痛刺激的反应存在着差异。     

多巴胺对正常和吗啡成瘾大鼠疼痛相关电活动的不同作用(英文)

目的研究多巴胺对正常大鼠和吗啡成瘾大鼠中枢的伤害性刺激的传递的影响。方法在给予坐骨神经伤害性刺激后,记录中枢痛兴奋神经元的电活动,观察多巴胺对正常大鼠和吗啡成瘾大鼠中枢痛兴奋神经元电活动的影响。结果正常大鼠中,多巴胺使尾核痛兴奋神经元的痛诱发放电潜伏期缩短,说明多巴胺可使正常大鼠尾核痛兴奋神经元的活动增强,多巴胺受体拮抗剂氟哌利多可以阻断这种作用。吗啡大鼠中,多巴胺使尾核痛兴奋神经元的痛诱发放电潜伏期延长,说明多巴胺可使吗啡大鼠尾核痛兴奋神经元的活动减弱。结论脑室注射多巴胺后,正常大鼠和吗啡成瘾大鼠的尾核对痛刺激的反应存在着差异。     

L-365,260对吗啡成瘾大鼠尾核中痛兴奋神经元电活动的影响

目的观察八肽胆囊收缩素(CCK-8)B受体拮抗剂L-365,260对正常及吗啡成瘾大鼠尾核(Cd)中痛兴奋神经元(PEN)电活动的影响,从而进一步探讨中枢CCK-8和尾核在吗啡成瘾大鼠痛觉调制中的作用。方法以电脉冲刺激大鼠坐骨神经作为伤害性痛刺激,用玻璃微电极记录尾核中PEN的放电,观察Cd内注入L-365,260对PEN电活动的影响。结果 L-365,260可降低吗啡成瘾与正常大鼠尾核中PEN的兴奋性,使PEN痛诱发放电频率减少,潜伏期延长。结论 L-365,260对吗啡成瘾及正常大鼠尾核中PEN均呈抑制作用。L-365,260是通过作用于尾核内CCK-B受体增强吗啡镇痛作用。间接证明CCK-8确实参与了大鼠中枢痛觉的调制,CCK-8主要通过激活大鼠尾核中CCK-B受体来下调吗啡镇痛作用的。     

谷氨酸对抗吗啡对丘脑束旁核痛反应神经元放电的影响

目的 研究脑室注射谷氨酸(Glu)对吗啡引起的大鼠两侧丘脑束旁核痛反应神经元电活动的影响。方法 以电脉冲刺激右侧坐骨神经作为伤害性刺激，同时用两根玻璃微电极细胞外记录两侧丘脑束旁核神经元的放电。结果 (1)腹腔注射吗啡(10mg／kg)可抑制痛兴奋神经元(PEN)和加强痛抑制神经元(PIN)的电活动；(2)脑室注射Glu(1．5μg／10μl)能对抗吗啡引起PEN放电的抑制作用和PIN电活动的加强作用；(3)Glu可同时对抗吗啡所引起束旁核中PEN和PIN的电变化。结论 Glu对吗啡引起的镇痛效应有明显的对抗作用，提示Glu在中枢伤害性信息整合方面发挥重要作用。     

蓝斑核注射乙酰胆碱对大鼠蓝斑核痛反应神经元电活动的影响

[摘要] 目的 观察蓝斑核（LC）注射乙酰胆碱(ACh)后,蓝斑核（LC）中痛反应神经元的放电变化,研究ACh与LC在痛觉信息通路中的作用。 方法 以电脉冲刺激坐骨神经作为伤害性刺激,用玻璃微电极引导LC中痛反应神经元的电变化。结果 ① LC内注入ACh能够使大鼠LC中痛兴奋神经元（PEN）痛诱发放电频率增加、潜伏期缩短;痛抑制神经元（PIN）痛诱发放电频率减少、完全抑制时程延长;② LC内注入ACh 的M受体拮抗剂阿托品能够阻断ACh的上述效应。结论 ACh可使正常大鼠LC中痛反应神经元对伤害性刺激的反应增强,表现为致痛效应;揭示了ACh和LC在痛觉调制中具有非常重要的作用。     

谷氨酸对丘脑束旁核痛兴奋神经元放电的影响

目的：观察脑室注射谷氨酸（Glu)对大鼠丘脑束旁核（PF）痛兴奋神经元（PEN）电变化的影响。方法：以电脉冲刺激右侧坐骨神经作为伤害性痛刺激，用玻璃微电极细胞外记录神经元放电的变化。结果：（1）伤害性刺激使大鼠丘脑PF的PEN诱发放电频率增加；（2）脑室注射Glu(1.5μg/10μl）加强PEN的电活动，使PEN放电频率的净增值增加，潜伏期缩短；（3）这种作用可被Glu的NMDA受体拮抗剂MK－801（0．17μg/0.5μl)所阻断。结论：Glu在中枢痛沉调制中可能起兴奋作用，而NMDA受体参与介导中枢伤害性信息的传递过程。     

大鼠丘脑束旁核痛反应神经元放电与甩尾痛反应的联合观察

本实验以辐射热照射大鼠尾部做为伤害性刺激，可同时引起丘脑束旁核中痛兴奋神经元（painexcitatoryneurons，PEN）放电增加，痛抑制神经元（paininhibitoryneurons，PIN）M电减少和甩尾反射．放电变化发生在先，甩尾反射发生在后，束旁核中PEN和PIN放电变化与甩尾反射呈显著正相关．电针“足三里”可使PEN放电频率减少，PIN的抑制时程缩短，以及甩用反射潜伏期延长．在中枢神经元放电和整体反射水平上同时呈现出镇痛效应。     

GABA对大鼠伏隔核痛反应神经元电活动的影响

目的在50只成年Wister大鼠上，观察了侧脑室(icv)注射GABA(γ-氨基丁酸)后，伏隔核(NAc)痛反应神经元放电的变化和荷包牡丹碱(Bic)对GABA作用的阻断效应，从而进一步研究GABA与NAc在痛觉调制中的作用。方法采用icy注射，电脉冲强直刺激坐骨神经作为伤害性痛刺激，玻璃微电极细胞外记录痛反应神经元放电的变化。结果(1)icv注入GABA能够使正常大鼠NAc中痛兴奋神经元(PEN)痛诱发放电频率减少、潜伏期延长，而使痛抑制神经元(PIN)痛诱发放电频率增加、诱发放电完全抑制时程缩短；(2)icv注入GABAA受体拮抗剂Bic能够阻断GABA的上述效应。结论(1)外源性GABA可使正常大鼠NAc中痛反应神经元对伤害性刺激的反应减弱，表现为镇痛效应；(2)GABA的这种镇痛作用主要是通过GABAA受体介导的。该结果揭示，GABA和NAc在痛觉调制中具有非常重要的作用。     

γ-氨基丁酸对吗啡成瘾大鼠中枢神经系统痛觉的调制

目的 观察γ-氨基丁酸(γ-aminobutyric acid,GABA)对吗啡依赖大鼠中枢神经系统伏隔核(nucleus accumbens,NAc)痛兴奋神经元(pain-excited neurons,PEN)电活动的影响.方法 脑室或NAc中注射GABA或荷包牡丹碱(bicuculline,Bic),电脉冲刺激右侧坐骨神经作为伤害性疼痛刺激,用玻璃微电极在细胞外记录中枢神经系统伏隔核痛兴奋神经元电活动的变化.结果 脑室及NAc中注入GABA均能使吗啡依赖大鼠NAc中PEN潜伏期延长、痛诱发放电频率减少;GABAA受体拮抗剂Bic能够阻断GABA的上述效应.结论 外源性GABA在中枢痛觉调制中起抑制作用,GABA及GABAA受体参与介导中枢伤害性信息的传递过程.     

Both endogenous and exogenous ACh plays antinociceptive role in the hippocampus CA1 of rats

Summary. The present study examines the effect of acetylcholine (ACh), muscarinic acetylcholine receptors (mAChRs) agonist pilocarpine and mAChRs antagonist atropine on the pain-evoked response of pain-excited neurons (PEN) and pain-inhibited neurons (PIN) in the hippocampal CA1 of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The discharges of PEN and PIN in the hippocampal CA1 were recorded by glass microelectrode. The results showed that intrahippocampal microinjection of ACh (2 μg/1 μl) or pilocarpine (2 μg/1 μl) decreased the frequency of discharge of PEN, and increased the frequency of discharge of PIN evoked by the noxious stimulation in the hippocampal CA1, while intrahippocampal administration of atropine (0.5 μg/1 μl) produced opposite response. On the basis of the above findings, we can deduce that ACh and mAChRs are involved in the modulation of nociceptive information transmission in the hippocampal CA1. Correspondence: Man-Ying Xu, Department of Physiology, Harbin Medical University, Harbin 15 0081, Heilongjiang Province, China     

The effect of acetylcholine on pain-related electric activities in the hippocampal CA3 of rats

Acetylcholine (ACh) regulates pain perception in the central nervous system. However, the mechanism of action of ACh on pain-related neurons in the hippocampal CA3 is not clear. The present study aimed to determine the effect of ACh, muscarinic ACh receptors (mAChRs) agonist pilocarpine and mAChRs antagonist atropine on the pain-evoked responses of pain-excited neuron (PEN) and pain-inhibited neuron (PIN) in the hippocampal CA3 of normal rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The electric activities of PEN or PIN in the hippocampal CA3 were recorded by using a glass microelectrode. Our results showed that, in the hippocampal CA3, the intra-CA3 microinjection of ACh (2 μg/1 μl) or pilocarpine (2 μg/1 μl) decreased the discharge frequency and prolonged firing latency of PEN, and increased the discharge frequency and shortened firing inhibitory duration (ID) of PIN, i.e. exhibiting the analgesic effect of ACh or pilocarpine. The intra-CA3 administration of atropine (0.5 μg/1 μl) produced an opposite effect. On the basis of the above-mentioned findings, we can deduce that ACh and mAChRs in the hippocampal CA3 are involved in the modulation of nociceptive response by regulating the electric activities of PEN and PIN.     

Cholecystokinin‐8 antagonizes electroacupuncture analgesia through its B receptor in the caudate nucleus

Objectives: The analgesic effect of electroacupuncture (EA) stimulation has been proved. However, its mechanism of action is not clear. It has been well‐known that cholecystokinin‐8 (CCK‐8) is a neuropeptide which is mainly related to the mediation of pain. The caudate nucleus was selected to determine if the release of CCK and the neural activity in this nucleus were involved in producing EA analgesia. Materials and Methods: Radiant heat focused on the rat‐tail was used as the noxious stimulus. The pain threshold of rats was measured by tail‐flick latency (TFL). EA stimulation at the bilateral Zusanli (ST 36) acupoints of rats was used to investigate the effects of EA analgesia. The electrical activities of pain‐excited neurons (PEN) and pain‐inhibited neurons (PIN) in the caudate nucleus were recorded with a glass microelectrode. The present study examined the antagonistic effects of the intracerebral ventricular injection of CCK‐8 on EA analgesia and reversing effects of CCK‐B receptor antagonist (L‐365,260) injection into the caudate nucleus on CCK‐8. Results: The radiant heat focused on the tail of rats caused an increase in the evoked discharge of PEN and a reduction in the evoked discharge of PIN. EA stimulation at the bilateral ST 36 acupoints of rats resulted in the inhibition of PEN, the potentiation of PIN, and prolongation of TFL. The analgesic effect of EA was antagonized when CCK‐8 was injected into the intracerebral ventricle of rats. The antagonistic effect of CCK‐8 on EA analgesia was reversed by injection of CCK‐B receptor antagonist (L‐365,260) into the caudate nucleus of rats. Conclusions: Our results suggest that CCK‐8 antagonize EA analgesia through its B receptor.     

The effect of dopamine on pain-related neurons in the parafascicular nucleus of rats

Dopamine (DA) regulates pain perception in the central nervous system (CNS). However, the mechanism of the action of DA in pain-related neurons of the parafascicular nucleus (Pf) is not clear. The present study aimed to determine the effect of DA and its receptor antagonist, droperidol on the pain-evoked responses of the pain-excited neurons (PEN) and pain-inhibited neurons (PIN) in the Pf of rats and to analyze the mechanisms underlying this effect. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The discharges of PEN and PIN in the Pf were recorded by using a glass microelectrode. The results showed that, in the Pf, intra-Pf microinjection of DA (5 μg/0.5 μl) increased the frequency of noxious stimulation-induced discharges of the PEN and decreased the frequency of those of the PIN, while the intra-Pf administration of droperidol (0.15 μg/0.5 μl) produced an opposite effect. On the basis of the above-mentioned findings, we could conclude that DA and its receptors in the Pf are involved in the modulation of the nociceptive response by regulating the discharges of PEN and PIN.     

Effects of T-588, a newly synthesized cognitive enhancer, on hippocampal CA1 neurons in rat brain tissue slices

The effects of a newly synthesized cognitive enhancer, (-)-R-alpha-[[2-(diethylamino) ethoxy] methyl] benzo [b] thiophene-5-methanol hydrochloride (T-588), on the membrane properties of hippocampal CA1 neurons were investigated in a rat brain slice preparation. T-588 produced a slow and long-lasting depolarization of CA1 neurons with an increase in membrane resistance; this action showed close similarity to that of acetylcholine (ACh). However, the action of T-588 was not affected by atropine, tetrodotoxin or DL-2-amino-5-phosphonovalerate, while the action of ACh was blocked by atropine. The estimated reversal potential of this T-588 effect was near -90 mV which is the reversal potential of potassium ions in CA1 neurons. In the whole-cell voltage-clamp study, T-588 produced a reversible block of the outward potassium current in CA1 neurons. T-588 did not block the afterhyperpolarization evoked by an intracellular current injection, while ACh suppressed it. These results suggest that T-588 has a direct effect on CA1 neurons independent of its cholinergic activity, resulting from blockade of a conductance carried predominantly by potassium ions.     

Critical Role of Presynaptic Nicotinic ACh Receptor in the Formation of Long-Term Potentiation: Implications for Development of Anti-Dementia Drugs

Background : Since neuronal nicotinic ACh receptors are involved in the cognitive function, they have been studied as a target of anti‐dementia drugs. The present study was designed to understand the role of nicotinic ACh receptors in the expression of long‐term potentiation (LTP), a cellular model of learning and memory. Methods : The ultrastructural localization of neuronal nicotinic ACh receptors in the rat hippocampus was examined electron‐immunohistochemically using an antibody against the α7 subunit, forming a brain‐type nicotinic ACh receptor. Miniature excitatory postsynaptic currents (mEPSCs) were monitored in cultured rat hippocampal neurons. Schaffer collateral‐CA1 LTP and perforant path LTP were analyzed by recording field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) in the CA1 region and the dentate gyrus of rat hippocampal slices or in the intact mouse hippocampus. Results : α7 receptors are preferentially localized on presynaptic terminals, where the receptors are employed in the release of the excitatory neurotransmitter, glutamate. The probability of LTP development was markedly reduced in the presence of the neuronal nicotinic ACh receptor antagonists, α‐bungarotoxin and mecamylamine, in both the CA1 region and the dentate gyrus of rat hippocampal slices. Perforant path LTP was never induced in slices with selective cholinergic denervation using 192 IgG‐saporin, while it was not affected by atropine, a selective muscarinic ACh receptor antagonist, in normal slices. Nicotine facilitated hippocampal neurotransmission with the saturation occluding the potentiation induced by tetanic stimulation, and vice versa. A similar occlusion was also obtained with an intact mouse hippocampus. These types of LTP, which are dependent upon N‐methyl‐D‐aspartate (NMDA) receptors, were still induced by treatment with nicotine in the presence of D‐2‐amino‐5‐phosphonovaleric acid (APV), a selective NMDA receptor antagonist. Conclusion : The results of the present study suggest that presynaptic nicotinic ACh receptors play a critical role as a target of retrograde messengers in the formation of NMDA receptor‐dependent LTP. This may account for the involvement of nicotinic ACh receptors in cognitive function. Drugs enhancing the activity of neuronal nicotinic ACh receptors, therefore, are capable of expressing LTP, conversely, ameliorating dementia.