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。     

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。     

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-inhibitationneurons,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。     

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.     

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。     

脑室注射吗啡对大鼠尾核神经元放电和甩尾反射的影响

浅麻醉Ｗｉｓｔａｒ大鼠４９只，用辐射热照尾部作为伤害性刺激，以痛兴奋神经元（ｐａｉｎｅｘｃｉｔａｔｉｏｎｎｅｕｏｎｓＰＥＮ）诱发放电频率减少，痛抑制神经抑（ｐａｉｎｉｎｈｉｂｉｔｉｏｎｎｅｕｒｏｎｓ，ＰＩＮ）诱发放电频率增加和甩尾反射潜伏期（ｔａｉｌｆｌｉｃｋｌａｔｅｎｃｙＴＦＬ）延长为镇痛效应，观察脑室注射不同剂量吗啡对尾核中ＰＥＮ，ＰＩＮ及ＴＦＬ的同时影响，表明，脑室注射５０μｇ／１０μｌ吗啡     

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。     

侧脑室注射α-干扰素及白细胞介素-2对大鼠丘脑束旁核痛兴奋神经元放电的影响

目的 从神经元放电的角度进一步研究α-干扰素(IFN-α)及IL-2的中枢镇痛作用。方法 以串脉冲刺激右侧坐骨神经和有齿镊子夹尾作为伤害性刺激,诱发大鼠丘脑束旁核痛兴奋神经元放电,记录在不同大鼠侧脑室注射IFN-α和IL-2对大鼠丘脑束旁核痛兴奋神经元电活动的影响。结果 IFN-α使大鼠丘脑束旁核痛兴奋神经元的放电频率降低,在给药前:PEN诱发放电秒净增值16.33±4.03;注射后6min、12min、18min,分别为7.92±0.64(P<0.01)、5.59±0.47(P<0.01)、7.44±0.59(P<0.01)。注射后20min开始恢复,24min基本恢复至注射前水平。IL-2也可使PEN放电频率降低,给药前,PEN诱发放电频率净增值为(17.16±3.94)Hz,注射后4min、8min、12min、16min 分别为(5.86±0.91)Hz、(2.81±0.96)Hz、(2.67±0.45)Hz、(4.11±0.46)Hz。此外,脑室注射IFN-α和IL-2还能使诱发放电的潜伏期延长,注射前后相比差异显著。结论IFN-α和IL-2均能使PEN的放电频率降低,潜伏期延长。     

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。     

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.     

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.     

Modulation of γ-aminobutyric acid on painful sense in central nervous system of morphine-dependent rats

OBJECTIVE: To observe the effects of gamma-aminobutyric acid (GABA) on the electric activities of pain-excited neurons (PEN) in nucleus accumbens (NAc) in central nervous system (CNS) of morphine-dependent rats. METHODS: After GABA or the GABA(A)-receptor antagonist, bicuculline (Bic), was injected into cerebral ventricles or NAc, right sciatic nerve was stimulated by electrical pulses, which was considered as traumatic pain stimulation. Extracellular recordings methods were used to record the electric activities of PEN in NAc. RESULTS: When GABA was injected into intracerebroventricle (ICV) as well as NAc, it could decrease the pain-evoked discharge frequency and prolong the latency of PEN. Bic could interdict the above effects of GABA on the electric activities of PEN. CONCLUSION: Exogenous GABA might have an inhibitory effect on the central pain adjustment. Furthermore, GABA and GABA(A) receptor participate and mediate the traumatic information transmission process in CNS.     

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.     

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.     

Electric stimulation at sciatic nerve evokes long-term potentiation of cornu dorsale medullae spinalis field potential in rats at various developmental phases

BACKGROUND: Long-term potentiation of cornu dorsale medullae spinalis field potential in adult rats has already been reported; however, there is lack of correlated researches on naenonate, infant and adult rats which have different responses to pain conduction information. OBJECTIVE: To observe the various effects of electric stimulation at sciatic nerve on long-term potentiation of evoked field potential at superficial layer of cornu dorsale medullae spinalis of rats at various developmental phases and analyze manifestations of pain conduction information at superficial layers (Ⅰ–Ⅱ) of cornu dorsale medullae spinalis in immature rats. DESIGN: Grouping controlled study. SETTING: Department of Physiology, Medical College of Wuhan University. MATERIALS: The experiment was carried out in the Laboratory of Physiology (provincial laboratory), Medical College of Wuhan University from March 2006 to May 2007. A total of 27 healthy male Sprague-Dawley (SD) rats, 17–90 days old, SPF grade, weighing 41–200 g, were provided by Experimental Animal Center, Medical College of Wuhan University. METHODS: Based on their birthdays, rats were divided into naenonate group (17–20 days old, weighing 41–52 g, n =10), infant group (35–50 days old, weighing 87–125 g, n =10) and adult group (60–90 days old, weighing 180–200 g, n =7). Left sciatic nerve was separated and stimulated with single square wave (15 V, 0.5 ms). Meanwhile, evoked field potential was recorded at superficial layers of lateral T13–L1 cornu dorsale medullae spinalis and then stimulated with high-frequent and high-intensive tetanizing current (30–40 V, 0.5 ms, 100 Hz, 1 s per bundle, 10 s in bundle interval) four times. After the operation, onset of long-term potentiation was observed; meanwhile, amplitude changes and latency of field potential were analyzed. MAIN OUTCOME MEASURES: Amplitude and latency changes of field potential at superficial layers of cornu dorsale medullae spinalis of rats in the three groups. RESULTS: A total of 27 accepted rats were involved in the final analysis. ① Amplitude changes: Electric stimulation at sciatic nerve with high-frequent and high-intensive tetanizing current could induce evoked field potential at superficial layers (Ⅰ–Ⅱ) of cornu dorsale medullae spinalis in the three groups. Long-term potentiation in the naenonate group manifested that amplitude of A-kind never fiber was raised and there was significant difference (P < 0.05). In addition, average amplitude was increased and there was obviously significant difference (P < 0.01). Long-term potentiation in the infant group manifested that amplitude of C-kind never fiber was raised and there was significant difference (P < 0.01); while, long-term potentiation in the adult group manifested that amplitude of C-kind never fiber was raised and there was significant difference (P < 0.01). Otherwise, latencies in the three groups were all shortened. ② Latency changes: Average latency of A-kind nerve fiber in the naenonate group was shortened and there was significant difference (P < 0.01); in addition, evoked potential of C-kind nerve fiber was low and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation (P > 0.05). Average latency of C-kind nerve fiber in the infant group was shortened and there was significant difference (P < 0.01); in addition, evoked potential of A-kind nerve fiber was stable and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation (P > 0.05). Average latency of C-kind nerve fiber in the adult group was shortened and there was significant difference (P < 0.01); in addition, evoked potential of A-kind nerve fiber was stable and latency was immovable. There was no significant difference before and after high-frequent and high-intensive electric stimulation. CONCLUSION: Evoked field potential at superficial layer of cornu dorsale medullae spinalis can be recorded through electric stimulation at sciatic nerve. Single stimulation and tetanizing electric stimulation can cause different characteristics of evoked field potential in rats at various developmental phases. Superficial layer of cornu dorsale medullae spinalis of naenonate rats is mainly caused by A-kind nerve fiber which participants in pain conduction and formation of pain sensitivity; however, that of infant and adult rats mainly depends on C-kind nerve fiber.     

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