Effect of sevoflurane on spinal dorsal horn WDR neuronal activity in cats

The effects of sevoflurane (0.5%, 1.5%, and 2.5%) on the spinal dorsal horn wide dynamic range (WDR) neuronal activity were studied in either spinal cord intact or spinal cord-transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind foot pads of intact cats or decerebrate and spinal cord-transected (L 1-2) cats. The experiment was divided into two sections. When bradykinin (BK) 10 micrograms was injected into the femoral artery contralateral to the recording site as a noxious test stimulus in the spinal cord-transected cat, 7 of 15 WDR neurons gave inhibitory responses which were depressed by 0.5%, 1.5%, and 2.5% sevoflurane. On the other hand, when the injection of BK 10 micrograms into the femoral artery contralateral to the recording site was used in the spinal cord-intact cat, all of 7 WDR neurons gave inhibitory responses, which were significantly depressed by 0.5%, 1.5%, and 2.5% sevoflurane. The results suggest that sevoflurane reduces the inhibition of dorsal horn WDR neuronal activities induced by BK injection in spinal cord-intact cats as well as in spinal cord-transected cats.     

Enflurane reduces the excitation and inhibition of dorsal horn WDR neuronal activity induced by BK injection in spinal cats

The effects of enflurane (0.5%, 1.5% and 2.5%) on the excitation and inhibition of dorsal horn wide dynamic range (WDR) neuronal activity induced by bradykinin (BK) injection was studied in spinal cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind paw foot pads of decerebrate, spinal cord transected (L_1–2) cats. When 10µg of BK was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus, 24 of 26 WDR neurons (92%) gave excitatory responses and 2 (8%) gave inhibitory resposes. On the other hand, when the injection of 10µg of BK into the femoral artery contralateral to the recording site was used as the noxious test stimulus, 7 of 12 WDR neurons (58%) gave inhibitory responses, 3 (25%) gave excitatory responses, and 2 (17%) showed no response. The excitatory neuronal activity in WDR neurons was not depressed by 0.5% or 1.5% enflurane but was depressed significantly by 2.5%. However, the inhibitory neuronal activity in WDR neurons was significantly depressed by 0.5%, 1.5% and 2.5% enflurane. We have found that enflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection. These results suggest that the reduction of excitatory and inhibitory responses produced by noxious stimulation is likely to be the fundamental basis of the enflurane-induced anesthetic state in terms of WDR neurons.(Nagasaka H, Nakajima T, Takano Y et al.: Enflurane reduces the excitation and inhibition of dosal horn WDR neuronal activity induced by BK injection in spinal cats. J Anesth 4: 102–109, 1990)     

Intrathecal clonidine suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats

The analgesic effectiveness of perispinal clonidine administration prompted us to evaluate clonidine effects on spinal dorsal horn wide dynamic range neurons. Intrathecal clonidine produced a dose-dependent (10 and 30 micrograms), yohimbine-reversible suppression of noxiously evoked activity in decerebrate, spinal cord-transected cats. In addition, combining ineffective intrathecal doses of morphine (25 micrograms) and clonidine (5 micrograms) produced statistically significant, reversible suppression of noxiously evoked activity. The time course of suppression was similar to that observed behaviorally. These results support the role of spinal alpha 2-adrenergic receptors in clonidine analgesia.     

Spinally administered epinephrine suppresses noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord

This study was designed to determine if spinally administered epinephrine is capable of suppressing noxiously evoked activity of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord. Extracellular activity was recorded from single WDR neurons in the dorsal horn of decerebrate, spinal cord-transected (T-12) cats. Activity was evoked by the presentation of a noxious radiant heat stimulus (51 degrees C) to the cells' receptive fields on the hind paws. Evoked activity was monitored both before and after the spinal administration of either 50 micrograms (n = 6) or 100 micrograms (n = 6) epinephrine. Both doses of epinephrine produced a significant suppression of noxiously evoked activity, which was dose-dependent. In addition, the 100-microgram dose produced a suppression that was of longer duration than that seen following the 50-microgram dose. Recovery from suppression was recorded following both the 50- and 100-microgram dose. These results indicate that spinally administered epinephrine is capable of suppressing noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord. Since WDR neurons have been identified as cells of origin for the spinothalamic tract, such an action may block the central transmission of afferent pain information. This may be a mechanism by which spinally administered epinephrine enhances the duration or intensity of spinal anesthesia produced by local anesthetics and may also explain spinal analgesia resulting from the spinal administration of adrenergic agonists. Interactions between spinally administered epinephrine and spinally administered opioids also were studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of halothane and isoflurane on hyperexcitability of spinal dorsal horn neurons after incision in the rat

BACKGROUND: The aim of this study was to determine whether halothane and isoflurane used during and after surgical injury attenuate subsequent hyperexcitability of spinal dorsal horn (SDH) neurons by preventing development of central sensitization. METHODS: Activity of a wide-dynamic-range neuron of the SDH was isolated in decerebrate-spinal Sprague-Dawley rats, and neuronal activity (receptive field size and responses to nonnoxious and noxious stimuli) was recorded. A 1-cm-long incision was made through the skin, fascia, and muscle under anesthesia with halothane (1.1% or 2.2%) and isoflurane (1.4% or 2.8%). Anesthesia was discontinued just after the incision had been made or was continued until 30 min after the incision, and activity of the SDH neurons was measured for up to 2 h after the incision. In a control group, the incision was made without anesthesia. RESULTS: In the control group, the incision resulted in maximum excitation in the SDH neurons during surgery; spontaneous activity significantly increased for up to 30 min after the incision (P < 0.05) but did not significantly increase thereafter, returning to the preincision value. Halothane and isoflurane suppressed excitation of the neurons during the incision in a concentration-related manner. Administration of 2.2% halothane and 2.8% isoflurane during the incision and for up to 30 min after the incision almost abolished activity of the neurons for 30 min after the incision. The magnitude of neuronal activity 2 h after the incision was not significantly different among all groups, including the control group. CONCLUSIONS: The results demonstrate that administration of halothane and isoflurane does not attenuate development of hyperexcitability of SDH neurons despite the fact that excitation and spontaneous activity during and after the incision were greatly suppressed by administration of halothane and isoflurane.     

Differential effects of halothane and isoflurane on lumbar dorsal horn neuronal windup and excitability

Background. Windup of spinal nociceptive neurones may underlietemporal summation of pain, influencing the minimum alveolarconcentration (MAC) of anaesthetics required to prevent movementto supramaximal stimuli. We hypothesized that halothane andisoflurane would differentially affect windup of dorsal hornneurones. Methods. We recorded 18 nociceptive dorsal horn neurones exhibitingwindup to 1 Hz electrical hindpaw stimuli in rats. Effects of0.8 and 1.2 MAC isoflurane and halothane were recorded in thesame neurones (counterbalanced, crossover design). Windup wascalculated as the total number of C-fibre (100–400 mslatency) plus afterdischarge (400–1000 ms latency) spikes/20stimuli (area under curve, AUC) or absolute windup (C-fibreplus afterdischarge–20xinitial response). Results. Increasing isoflurane from 0.8 to1.2 MAC did not affectAUC, but increased absolute windup from 429 (62) to 618 (84)impulses/20 stimuli (P<0.05) and depressed the initial C-fibreresponse from 14 (3) to 8 (2) impulses (P<0.05). Increasinghalothane from 0.8 to1.2 MAC depressed AUC from 690 (79) to537 (65) impulses/20 stimuli (P<0.05) and the initial responsefrom 18 (2) to 13 (2) impulses (P<0.05), but absolute windupwas not affected. Absolute windup was 117% greater during 1.2MAC isoflurane compared with 1.2 MAC halothane. Conclusions. Windup was significantly greater under isofluranethan halothane anaesthesia at 1.2 MAC, whereas the initial C-fibreresponse was suppressed more by isoflurane. These findings suggestthat these two anaesthetics have mechanistically distinct effectson neuronal windup and excitability.     

咪唑安定对大白鼠脊髓后角广动力范围神经元伤害性刺激反应影响的研究

目的研究咪唑安定对大白鼠脊髓腰膨大部位广动力范围神经元(WDR neuron)对伤害性刺激反应的影响。方法在脊髓表面使用不同剂量的眯唑安定(M5组5μg、M10组1μg、M：。组20μg)，用微电极记录和观察脊髓后角广动力范围神经元对伤害性刺激诱发放电频率的变化，并观察氟马西尼是否能逆转此抑制作用。结果M10、M20组咪唑安定对伤害性刺激诱发的脊髓后角广动力范围神经元放电反应有抑制作用；氟马西尼对咪唑安定抑制广动力范围神经元放电反应的作用具有拮抗效应。结论经脊髓表面使用一定剂量的咪唑安定对脊髓后角广动力范围神经元对于伤害性刺激诱发的放电反应具有抑制作用；此作用可能由脊髓内苯二氮蕈类受体介导。     

右美托咪啶对慢性神经病理性痛大鼠脊髓背角神经元凋亡的影响

目的 评价右美托咪啶对神经病理性痛大鼠脊髓背角神经元凋亡的影响.方法 健康成年雄性SD大鼠72只,体重180～220 g,采用随机数字表法,将其随机分为3组(n=24):假手术组(S组)、慢性神经病理性痛组(CNP组)和右美托咪啶组(D组).S组仅分离坐骨神经但不结扎,CNP组和D组采用结扎坐骨神经的方法制备大鼠神经病理性痛模型,D组于结扎坐骨神经结束开始至处死前,腹腔注射右美托咪啶50μg/kg,1次/d,S组和CNP组注射等容量生理盐水.于术前1d、术后3、7、14 d(T0-3)时测定大鼠机械缩足阈值(MWT)和热缩爪潜伏期(TWL);于T1-3时测定痛阈后每组随机处死8只大鼠,取L4,5脊髓组织,采用免疫组化法检测脊髓背角Bcl-2及caspase-3的表达水平,采用透射电镜观察脊髓背角浅层神经元超微结构.结果 与S组比较,CNP组和D组T1-3时MWT降低,TWL缩短,脊髓背角Bcl-2和caspase-3表达上调(P＜0.05);与CNP组比较,D组T1 -3时MWT升高,TWL延长,脊髓背角Bcl-2表达上调,caspase-3表达下调(P＜0.05).脊髓背角浅层神经元超微结构:S组基本正常,CNP组细胞凋亡数目增加,D组细胞凋亡数目较CNP组减少.结论 腹腔注射右美托咪啶可减轻大鼠慢性神经病理性痛,其机制可能与抑制脊髓背角神经元凋亡有关.     

Effects of ketamine on formalin-induced activity in the spinal dorsal horn of spinal cord-transected cats: differences in response to intravenous ketamine administered before and after formalin

BACKGROUND: Although formalin has been widely used as an algesic substance in rodent studies, the unique biphasic effect seen in rats is not present in humans. Humans, like cats, have a monophasic behavioral response to formalin injection. Electrophysiologically, spinal dorsal horn neurons in cats also have what could be considered a monophasic response after the initial burst of activity following formalin injection. Although several studies of the effects of ketamine on formalin responses have been carried out in rodents, we are unaware of similar studies in cats. We hypothesize that such species differences may explain observed differences in preemptive analgesic effects. Therefore, we examined the effects of ketamine on activity of spinal wide dynamic range (WDR) neurons evoked by formalin injection in cats. METHODS: We investigated in cats the effect of ketamine on the activity of WDR neurons in the spinal dorsal horn that was evoked by formalin. In addition, we studied the effects of pre- and post-administration of ketamine on the maintained phase of the formalin response. Each dose was a subanesthetic, anesthetic or high anesthetic dose (3.0 mg x kg(-1), 10 mg x kg(-1), and 30 mg x kg(-1)). RESULTS: Intravenously administered ketamine produced a dose-dependent depression of evoked activity that was significantly greater when the drug was administered before formalin. CONCLUSION: In spite of the species differences in responses to formalin, there still appears to be a clear preemptive effect of ketamine in the cat. Species differences may not explain apparent differences between human and animal preemptive analgesia.     

5-HT3 receptors partially mediate halothane depression of spinal dorsal horn sensory neurons

We recently reported that gamma-aminobutyric acid type A- and strychnine-sensitive glycine receptor systems partially mediate halothane depression of spinal dorsal horn low-threshold neurons. Serotonin subtype 3 (5-HT(3)) receptors belong to the same ligand-activated ion-channel family as gamma-aminobutyric acid type A- and strychnine-sensitive glycine receptors, so we examined the possible involvement of 5-HT receptor systems in halothane depression of spinal sensory neurons. Extracellular recordings of spinal low-threshold neurons were obtained in decerebrate, spinally transected rats. Receptive field size and brush-induced activity were recorded in the presence or absence of 5-HT antagonists and in the presence or absence of 1.1% (1 minimum alveolar anesthetic concentration) halothane. In the absence of halothane, antagonists had no effect on receptive field size or brush-induced activity. In the presence of halothane, methysergide, a nonselective 5-HT antagonist, and tropisetron, a selective 5-HT(3) antagonist, significantly reversed the halothane-induced reduction in receptive field size but did not alter halothane depression of brush-induced activity. Methiothepin, a 5-HT(1) antagonist, and ketanserin, a 5-HT(2) antagonist, did not reverse halothane depression. These results support the hypothesis that 5-HT(3) receptors partially mediate some inhibitory effects of halothane on spinal dorsal horn neurons. IMPLICATIONS: The results of this study support the hypothesis that halothane depression of spinal sensory neuronal responses to low-intensity stimuli is mediated, to a minor extent, by serotonin subtype 3 neurotransmitter systems.     

Xenon has greater inhibitory effects on spinal dorsal horn neurons than nitrous oxide in spinal cord transected cats

Xenon (Xe) suppresses wide dynamic range neurons in cat spinal cord to a similar extent as nitrous oxide (N2O). The antinociceptive action of N2O involves the descending inhibitory system. To clarify whether the descending inhibitory system is also involved in the antinociceptive action of Xe, we compared the effects of Xe on the spinal cord dorsal horn neurons with those of N2O in spinal cord-transected cats anesthetized with alpha-chloralose and urethane. We investigated the change of wide dynamic range neuron responses to touch and pinch by both anesthetics. Seventy percent Xe significantly suppressed both touch- and pinch-evoked responses in all 12 neurons. In contrast, 70% N2O did not show significant suppression in touch- and pinch-evoked responses. These results suggest that the antinociceptive action of Xe might not be mediated by the descending inhibitory system, but instead may be produced by the direct effect on spinal dorsal horn neurons. Implications: Xenon (Xe) is an inert gas with anesthetic properties. We examined the antinociceptive effects of Xe and nitrous oxide (N2O) in spinal cord-transected cats. Our studies indicate that Xe has a direct antinociceptive action on the spinal cord that is greater than that of N2O.     

Interaction between opiate subtype and alpha-2 adrenergic agonists in suppression of noxiously evoked activity of WDR neurons in the spinal dorsal horn.

Several studies have demonstrated synergistic antinociception following low-dose administration of morphine and alpha-2 adrenergic agonists at the spinal level. This study was carried out in order to identify the opiate subtypes that are likely to be involved in such synergistic suppression of noxiously evoked activity of wide-dynamic-range (WDR) neurons in the dorsal horn of the spinal cord. We also examined the effect of opiate antagonists and alpha-2 adrenergic antagonists on the suppression produced by opiate or alpha-2 adrenergic agonists. Extracellular activity of single WDR neurons in the spinal dorsal horn, which was evoked by a radiant heat stimulus (51 degrees C), was recorded in decerebrate, spinally transected cats. Agonists were administered spinally and antagonists intravenously. In the synergism study, ineffective doses of the moderately selective mu agonist morphine (25 micrograms), the delta agonist DADL (20 micrograms), and the selective delta agonist DPDPE (30 micrograms), when combined with an ineffective dose of the alpha-2 adrenergic agonist clonidine (5 micrograms) produced significant synergistic suppression of noxiously evoked WDR neuronal activity. However, the ineffective or slightly effective dose of the selective mu agonist DAGO (1 or 1.5 micrograms, respectively) did not show any synergistic action with clonidine. Furthermore, the synergism between morphine and clonidine was reversed by the selective delta antagonist ICI 174,864. We interpret these results to indicate that opiates interact at spinal delta receptors to produce a synergistic suppression of evoked WDR neuronal activity in the presence of spinal clonidine. An alternative explanation is that ICI 174,864 may interact in some way with alpha-adrenergic systems.(ABSTRACT TRUNCATED AT 250 WORDS)     

乳铁蛋白对神经病理性痛大鼠脊髓背角PKG活性的影响

目的 探讨乳铁蛋白对神经病理性痛大鼠脊髓背角cGMP依赖性蛋白激酶(PKG)活性的影响.方法 雄性SD大鼠32只,体重200～250 g,随机分为4组(n=8):假手术组仅分离坐骨神经,不结扎,鞘内注射生理盐水10μl+50%二甲基亚砜(DMSO)10μl;余3组采用结扎坐骨神经的方法制备大鼠神经病理性痛模型,神经病理性痛组鞘内注射生理盐水10μl+50%DMSO10μl;乳铁蛋白组鞘内注射乳铁蛋白100μg+50%DMS010μl;PKG抑制剂KT5823组鞘内注射乳铁蛋白100μg+KT582310μl.给药后180 min内每隔30 min以热刺激法测定大鼠缩爪潜伏期,随后处死大鼠取脊髓背角,采用免疫荧光法检测PKG活性,并行定量分析.结果 与神经病理性痛组和KT5823组相比,乳铁蛋白组缩爪潜伏期延长,乳铁蛋白组脊髓背角PKG活性升高(P＜0.05);神经病理性痛组与KT5823组上述指标比较差异无统计学意义(P＞0.05).结论 乳铁蛋白可通过抑制脊髓背角PKG活性减轻大鼠神经病理性痛.     

可乐定对大鼠脊髓背角伤害性神经元诱发放电的影响

目的：以大鼠脊髓背角伤害性神经元的伤害刺激诱发放电作为痛指标，观察脊髓表面应用可乐定对该指标的影响。方法：选用ＳＤ大鼠３１只，随机分为５组：（１）生理盐水对照（鼠数＝５）；（２）可乐定５μｇ组（鼠数＝５）；（３）可乐定１０μｇ组（鼠数＝８）；（４）可乐定２０μｇ组（鼠数＝６）；（５）可乐定３０μｇ（鼠数＝７）。用药方式为脊髓表面滴注。结果：各剂量组可乐定均对脊髓背角伤害性神经元的伤害刺激诱发放电有抑制作用，剂量低于２０μｇ时，药效随剂量增大而增强，剂量增至３０μｇ时，药效无显著增强。结论：可乐定对大鼠脊髓背角伤害性神经元诱发放电有抑制作用，且有明显剂量－效应关系。     

The effects of hyperventilation upon spinal dorsal horn neuronal single-unit activities under nitrous oxide anesthesia

BACKGROUND: The purpose of this study is to investigate the effects of hyperventilation upon spinal dorsal horn neuronal single-unit activities under nitrous oxide anesthesia. METHODS: Eight decerebrated spinal cats with laminectomy were maintained with oxygen and pancuronium bromide. Following the control period of normocapnia, 50% nitrous oxide was administered for 30 minutes after a hypocapnia period of 20-25 mmHg for 20 minutes. The recoveries of activities followed with normocapnia and pure oxygen administration. The changes of spontaneous and evoked activities by the pinching were investigated every 5 minutes after control study. RESULTS: Inhalation of 50% nitrous oxide suppressed the WDR neuronal activities and with hyperventilation the suppressions significantly increased. CONCLUSIONS: These results were compatible with clinical reports on the effectiveness of hyperventilation as a maintenance method under N2O anesthesia.     

维拉帕米对创伤大鼠痛觉过敏及脊髓后角C-fos表达的影响

目的：观察维拉帕米对创伤大鼠痛觉过敏及脊髓后角c-fos表达的影响。方法：Wistar大鼠40只,随机分为5组,以截肢作为创伤模型。大鼠创伤后分别腹腔注射维拉帕米10mg/kg(A组n=8)、芬太尼30mg/kg(B组n=8)、芬太尼30mg/kg 维拉帕米10mg/kg（C组n=8)、生理盐水2ml(D组n=8);正常对照组不创伤、不用药（E组n=8)。于创伤后15min、30min、1h、2h观察创伤部位周围皮肤痛阈变化,2h后用免疫组织化学方法检测腰段脊髓后角I、Ⅱ层Fos蛋白的表达。结果：（1）创伤后大鼠发生痛觉过敏;（2）维拉帕米可抑制创伤部位周围皮肤的痛阈下降及脊髓后角I、Ⅱ层Fos表达,并加强芬太尼的作用。结论：维拉帕米通过对脊髓伤害传入刺激所引起的中枢敏化的抑制,产生一定的镇痛作用。     

糖皮质激素受体在慢性吗啡耐受大鼠脊髓背角神经元凋亡中的作用

目的 评价糖皮质激素受体在慢性吗啡耐受大鼠脊髓背角神经元凋亡中的作用.方法 鞘内置管成功的健康雄性SD大鼠20只,体重300～350 g,随机分为4组(n=5):对照组(C组)、慢性吗啡耐受组(M组)、吗啡+糖皮质激素受体拮抗剂组(MR组)和吗啡+糖皮质激素受体激动剂组(MD组)分别于8:00和20:00鞘内注射生理盐水10μl、吗啡10μg、吗啡10μg+RU38486 2μg、吗啡10μg+地塞米松4μg,连续6 d.于每天8:00给药后30 min行甩尾实验,给药第7天处死大鼠,取L3～L5脊髓行TUNEL染色,光镜下观察脊髓背角神经元的凋亡情况,计算凋亡率.结果 地塞米松、RU38486分别对慢性吗啡耐受的形成起促进、抑制作用.与C组比较,M组和MD组脊髓背角神经元凋亡率升高(P＜0.05);与M组比较,MR组脊髓背角神经元凋亡率降低,MD组脊髓背角神经元凋亡率升高(P＜0.05).结论 糖皮质激素受体参与了慢性吗啡耐受形成中大鼠脊髓背角神经元凋亡的过程.