Effects of morphine sulfate on dorsal-horn neuronal responses to graded noxious thermal stimulation in the decerebrate cat.

Effects of morphine sulfate upon activity of the neurons of dorsal-horn lamina V as evoked by graded noxious thermal stimuli applied on the receptive field were studied in spinal cord-transected, decerebrate cats utilizing an extracellular microelectrode recording technique. All single units studied (n = 30) responded to noxious thermal as well as to noxious mechanical stimulation. Their spontaneous discharge frequency was 9.7 +/- 1.5 (mean +/- 1 SE) impulses/sec (IPS), the threshold skin temperature was 44.8 +/- 0.2 C, and a linear correlation existed between skin temperature and discharge frequency at 6.7 +/- 0.6 IPS/degree C. Morphine, 1 and 2 mg/kg, iv, suppressed spontaneous activity by 53 +/- 6 and 84 +/- 6 per cent, respectively; increased threshold skin temperature to 46.5 +/- 0.3 and 47.9 +/- 0.5 C, respectively, and maintained the linear correlation between skin temperature and discharge frequency but depressed the mean slope of the regression line to 4.5 +/- 0.7 and to 2.4 +/- 0.4 IPS/degree C, respectively. Naloxone, 0.02--0.04 mg/kg, iv, reversed all of these changes produced by morphine. The results of the present study are, to the authors' knowledge, the first demonstration of the suppressive effect of morphine on the spinal nociceptive neurons in Rexed lamina V as they respond to graded noxious thermal stimuli. These results may explain the analgesic action of morphine at the spinal level.     

咪唑安定对大鼠丘脑束旁核感受伤害性刺激神经元的干预反应研究

目的 研究咪唑安定对大鼠丘脑束旁核感受伤害性神经元对感受外周伤害性刺激的干预反应。方法 微电极探查束旁核神经元（n=6），对找到的每个感受伤害性刺激神经元均实施以下步骤：（1）记录基础放电（A组）。（2）记录基础的伤害性刺激的放电反应（B组）。（3）平静5min后（原则上放电恢复到刺激前水平），静脉给予咪唑安定0.2mg,2min后记录伤害性刺激下的放电反应（C组）。（4）5min后，静脉给入咪唑安定的特异性拮抗剂吗泽尼0.05mg,2min后记录伤害性刺激的放电反应（D组）。结果 A组和B组差异有显著性，符合外周伤害性刺激使中枢痛敏神经元兴奋的正常重量反应。C组与B组差异有显著性，与A组差异无显著性，提示在咪唑安定的干预下，外周的伤害性刺激不能使中枢痛敏神经元兴奋，即咪唑安定对痛觉有抑制作用。D组与C、A组有显著性差异，而与B组无显著性差异，提示氟吗泽尼拮抗了咪唑安定的抑痛作用后，使中枢痛敏神经元恢复对外周伤害性刺激的敏感性。结论 咪唑安定可以显著性的抑制大鼠丘脑束旁核感受伤害性神经元对外周伤害性刺激的兴奋反应。     

Changes in properties of substantia gelatinosa neurons after surgical incision in the rat: in vivo patch-clamp analysis

BACKGROUND: Noxious information through A delta and C afferent fibers is transmitted to substantia gelatinosa, a process that plays an important role in plastic changes of nociceptive processing in pathophysiological conditions. In this study, changes in properties of substantia gelatinosa neurons and their sensitivity to systemic administration of lidocaine after surgical incision were investigated using the in vivo patch-clamp technique. METHODS: Under urethane anesthesia, in the current clamp mode, spontaneous activities and responses of substantia gelatinosa neurons to nonnoxious air-puff stimuli and noxious pinch stimuli were recorded before and after 1-cm-long incisions had been made in hairy skin of the hindquarters of rats. Systemic administration of lidocaine (2 mg/kg) was applied at 30 min after the incision. RESULTS: Stable recordings for 30 min or more after the incision were obtained from 18 substantia gelatinosa neurons that were classified as multireceptive (n = 8), nociceptive (n = 5), and subthreshold (n = 5) neurons. Action potential firing disappeared immediately after completion of the wound closure in most multireceptive and nociceptive neurons, and sustained spontaneous action potential firing was observed in 23% of these substantia gelatinosa neurons. Responsiveness of these substantia gelatinosa neurons, but not that of subthreshold neurons, increased after the incision. Systemic administration of lidocaine suppressed spontaneous firings of action potentials of the substantia gelatinosa neurons and reversed the increased responsiveness of the neurons. CONCLUSIONS: The results suggest that (1) changes in properties of substantia gelatinosa neurons after incision vary depending on the classification of substantia gelatinosa neurons and (2) systemic administration of lidocaine can reverse increased responsiveness of substantia gelatinosa neurons after incision injury.     

Changes in Properties of Substantia Gelatinosa Neurons after Surgical Incision in the Rat: In Vivo Patch-clamp Analysis

Background: Noxious information through A[delta] and C afferent fibers is transmitted to substantia gelatinosa, a process that plays an important role in plastic changes of nociceptive processing in pathophysiological conditions. In this study, changes in properties of substantia gelatinosa neurons and their sensitivity to systemic administration of lidocaine after surgical incision were investigated using the in vivo patch-clamp technique.

Methods: Under urethane anesthesia, in the current clamp mode, spontaneous activities and responses of substantia gelatinosa neurons to nonnoxious air-puff stimuli and noxious pinch stimuli were recorded before and after 1-cm-long incisions had been made in hairy skin of the hindquarters of rats. Systemic administration of lidocaine (2 mg/kg) was applied at 30 min after the incision.

Results: Stable recordings for 30 min or more after the incision were obtained from 18 substantia gelatinosa neurons that were classified as multireceptive (n = 8), nociceptive (n = 5), and subthreshold (n = 5) neurons. Action potential firing disappeared immediately after completion of the wound closure in most multireceptive and nociceptive neurons, and sustained spontaneous action potential firing was observed in 23% of these substantia gelatinosa neurons. Responsiveness of these substantia gelatinosa neurons, but not that of subthreshold neurons, increased after the incision. Systemic administration of lidocaine suppressed spontaneous firings of action potentials of the substantia gelatinosa neurons and reversed the increased responsiveness of the neurons.     

Isoflurane depresses windup of C fiber-evoked limb withdrawal with variable effects on nociceptive lumbar spinal neurons in rats

Windup is a progressive increase in responses of nociceptive spinal cord neurons to repeated electrical C fiber stimulation. We hypothesized that isoflurane would depress windup at approximately the minimum alveolar anesthetic concentration (MAC) required to suppress purposeful movement in response to noxious stimulation. We recorded windup responses in single lumbar spinal neurons (n = 17) to a series of 15 repetitive electrical stimuli delivered at 1 Hz to the hindpaw at C fiber strength; hindpaw withdrawal force was simultaneously recorded. The total number of action potentials per 15 stimuli (mean +/- sem as a percentage of each neuron's maximal response) was 83% +/- 5%, 84% +/- 5%, 67% +/- 7%, and 57% +/- 8% at 0.7, 0.9, 1.1, and 1.4 MAC, respectively. The 0.9 and 1.1 MAC values differed significantly from each other, whereas the 0.7 and 0.9 MAC values differed from the 1.4 MAC value (P < 0.05). The reduced firing was attributed to a depression of the initial C fiber-evoked responses in most units, and a reduction in windup slope over the initial 5 stimuli in 6 units. Muscle force was 67%, 11%, and 4% of the 0.7 MAC value at 0.9, 1.1, and 1.4 MAC, respectively. Isoflurane depressed excitability and variably affected windup of lumbar spinal cord neurons, while uniformly depressing windup of limb withdrawals in a concentration-dependent manner.     

Effect of intravenous epinephrine on uterine artery blood flow velocity in the pregnant guinea pig

The purpose of the present study was to determine the effect of intravenously administered epinephrine on the maternal cardiovascular response and uterine artery blood flow velocity (UBFV) in the pregnant guinea pig. Epinephrine (0.2, 0.5, and 1.0 micrograms/kg) and lidocaine (0.4 mg/kg, with and without 0.2 micrograms/kg of epinephrine) were administered intravenously to seven chronically instrumented pregnant guinea pigs near term. Lidocaine without epinephrine did not significantly alter maternal heart rate (MHR), maternal mean arterial pressure (MMAP), or UBFV. Epinephrine, with and without lidocaine, resulted in a transient decrease in MHR. Further, epinephrine, with and without lidocaine, resulted in significant elevations in MMAP and significant, dose-related reductions in UBFV. Mean (+/- SEM) UBFV was 72 +/- 4%, 56 +/- 4%, and 40 +/- 5% of baseline at 30 s after administration of epinephrine, 0.2, 0.5, and 1.0 micrograms/kg, respectively. It is concluded that these small intravenous boluses of epinephrine result in significant, although transient, reductions in UBFV in the pregnant guinea pig.     

Attenuation of Ascending Nociceptive Signals to the Rostroventromedial Medulla Induced by a Novel α2-Adrenoceptor Agonist, MPV-2426, following Intrathecal Application in Neuropathic Rats

Background: In the current study, the potency and spread of the antinociception induced by MPV-2426, a novel [alpha]2-adrenoceptor agonist, was characterized in neuropathic and non-neuropathic animals.

Methods: Neuropathy was induced by unilateral ligation of two spinal nerves in the rat. After lumbar intrathecal or systemic administration of MPV-2426, thermally and mechanically evoked responses of nociceptive neurons of the rostroventromedial medulla were recorded during pentobarbitone anesthesia. To obtain a behavioral correlate of neurophysiologic findings, nocifensor reflex responses evoked by thermal and mechanical stimuli were assessed in unanesthetized neuropathic and control animals.

Results: After intrathecal administration, MPV-2426 and dexmedetomidine produced a dose-related antinociceptive effect, independent of the submodality of the noxious test stimulus or the pathophysiologic condition. This antinociceptive effect was spatially restricted to the inputs from the lower half of the body, and it was reversed by atipamezole, an [alpha]2-adrenoceptor antagonist. After systemic administration in non-neuropathic animals, MPV-2426 had no antinociceptive effect on responses to rostroventromedial medulla neurons, whereas systemically administered dexmedetomidine produced a dose-related suppression of nociceptive signals to the rostroventromedial medulla, independent of the site of test stimulation. In a behavioral study, intrathecal MPV-2426 produced a dose-dependent suppression of nocifensor responses evoked by noxious mechanical or heat stimuli, whereas systemic administration of MPV-2426 had no effects.     

Halothane suppression of spinal sensory neuronal responses to noxious peripheral stimuli is mediated,in part,by both GABA(A) and glycine receptor systems

BACKGROUND: A major effect of general anesthesia is lack of response in the presence of a noxious stimulus. Anesthetic depression of spinal sensory neuronal responses to noxious stimuli is likely to contribute to that essential general anesthetic action. The authors tested the hypothesis that gamma-aminobutyric acid receptor type A (GABA(A)) and strychnine-sensitive glycine receptor systems mediate halothane depression of spinal sensory neuronal responses to noxious stimuli. METHODS: Extracellular activity of single spinal dorsal horn wide dynamic range (WDR) neurons was recorded in decerebrate, spinal cord transected rats. Neuronal responses to noxious (thermal and mechanical) and nonnoxious stimuli were examined in the drug-free state. Subsequently, cumulative doses (0.1-2.0 mg/kg) of bicuculline (GABA(A) antagonist) or strychnine (glycine antagonist) were administered intravenously in the absence or presence of 1 minimum alveolar concentration (MAC) of halothane. RESULTS: Halothane, 1.1%, depressed the response of WDR neurons to both forms of noxious stimuli. Antagonists, by themselves, had no effect on noxiously evoked activity. However, bicuculline and strychnine (maximum cumulative dose, 2.0 mg/kg) partially but significantly reversed the halothane depression of noxiously evoked activity. Similar results were seen with most, but not all, forms of nonnoxiously evoked activity. In the absence of halothane, strychnine significantly increased neuronal responses to low threshold receptive field brushing. CONCLUSION: Halothane depression of spinal WDR neuronal responses to noxious and most nonnoxious stimuli is mediated, in part, by GABA(A) and strychnine-sensitive glycine systems. A spinal source of glycine tonically inhibits some forms of low threshold input to WDR neurons.     

Halothane Suppression of Spinal Sensory Neuronal Responses to Noxious Peripheral Stimuli Is Mediated, in Part, by Both GABAA and Glycine Receptor Systems

Background: A major effect of general anesthesia is lack of response in the presence of a noxious stimulus. Anesthetic depression of spinal sensory neuronal responses to noxious stimuli is likely to contribute to that essential general anesthetic action. The authors tested the hypothesis that [gamma]-aminobutyric acid receptor type A (GABAA) and strychnine-sensitive glycine receptor systems mediate halothane depression of spinal sensory neuronal responses to noxious stimuli.

Methods: Extracellular activity of single spinal dorsal horn wide dynamic range (WDR) neurons was recorded in decerebrate, spinal cord transected rats. Neuronal responses to noxious (thermal and mechanical) and nonnoxious stimuli were examined in the drug-free state. Subsequently, cumulative doses (0.1-2.0 mg/kg) of bicuculline (GABAA antagonist) or strychnine (glycine antagonist) were administered intravenously in the absence or presence of 1 minimum alveolar concentration (MAC) of halothane.

Results: Halothane, 1.1%, depressed the response of WDR neurons to both forms of noxious stimuli. Antagonists, by themselves, had no effect on noxiously evoked activity. However, bicuculline and strychnine (maximum cumulative dose, 2.0 mg/kg) partially but significantly reversed the halothane depression of noxiously evoked activity. Similar results were seen with most, but not all, forms of nonnoxiously evoked activity. In the absence of halothane, strychnine significantly increased neuronal responses to low threshold receptive field brushing.     

Attenuation of ascending nociceptive signals to the rostroventromedial medulla induced by a novel alpha2-adrenoceptor agonist, MPV-2426, following intrathecal application in neuropathic rats

BACKGROUND: In the current study, the potency and spread of the antinociception induced by MPV-2426, a novel alpha2-adrenoceptor agonist, was characterized in neuropathic and non-neuropathic animals. METHODS: Neuropathy was induced by unilateral ligation of two spinal nerves in the rat. After lumbar intrathecal or systemic administration of MPV-2426, thermally and mechanically evoked responses of nociceptive neurons of the rostroventromedial medulla were recorded during pentobarbitone anesthesia. To obtain a behavioral correlate of neurophysiologic findings, nocifensor reflex responses evoked by thermal and mechanical stimuli were assessed in unanesthetized neuropathic and control animals. RESULTS: After intrathecal administration, MPV-2426 and dexmedetomidine produced a dose-related antinociceptive effect, independent of the submodality of the noxious test stimulus or the pathophysiologic condition. This antinociceptive effect was spatially restricted to the inputs from the lower half of the body, and it was reversed by atipamezole, an alpha2-adrenoceptor antagonist. After systemic administration in non-neuropathic animals, MPV-2426 had no antinociceptive effect on responses to rostroventromedial medulla neurons, whereas systemically administered dexmedetomidine produced a dose-related suppression of nociceptive signals to the rostroventromedial medulla, independent of the site of test stimulation. In a behavioral study, intrathecal MPV-2426 produced a dose-dependent suppression of nocifensor responses evoked by noxious mechanical or heat stimuli, whereas systemic administration of MPV-2426 had no effects. CONCLUSIONS: Intrathecal MPV-2426 has spatially limited antinociceptive properties in neuropathic and non-neuropathic conditions because of its action on spinal alpha2-adrenoceptors. These properties may be advantageous when designing therapy for spatially restricted pain problems.     

The influence of a right-to-left cardiac shunt on lidocaine pharmacokinetics

The pharmacokinetics of lidocaine were studied in 1-2-month-old lambs with surgically created, intracardiac right-to-left shunts (RLS) and in age-matched control lambs. Shunts were prepared by anastomosing the pulmonary artery to the left atrial appendage to achieve arterial oxygen saturation of 65-75%. Catheters were implanted both in the right atrium for drug infusion and in the ascending aorta for blood sampling. Lidocaine, 1 mg/kg, injected as a rapid bolus, or 12 mg/kg, injected as a continuous infusion over 15 min, was delivered into the right atrium. Serial samples of arterial blood were obtained every 2.5 s for 1 min following the bolus injection and up to 4 h following the continuous infusion. Samples were analyzed for lidocaine by gas chromatography. Peak arterial whole blood concentration of lidocaine in the shunted animals was 37.0 +/- 2.1 micrograms/ml compared to 21.1 +/- 0.1 microgram/ml in the control animals; P less than .01. The peak arterial concentrations during the lidocaine infusion were 12.6 +/- 3.5 micrograms/ml in the RLS and 5.8 +/- 1.5 micrograms/ml in the controls. Total body clearance of lidocaine was decreased in the shunted animals to 30.7 +/- 13.2 ml.kg-1.min-1 from 68.1 +/- 12.1 ml.kg-1.min-1 in the control animals; P less than .001. The steady-state volume of distribution was also decreased in the shunted animals, 1.0 +/- 0.2 l/kg versus 2.0 +/- 0.7 l/kg in the controls; P less than .02. To induce convulsions 4.75 +/- 0.46 mg/kg of lidocaine was required in the shunted animals and 7.37 +/- 0.44 mg/kg in the control animals (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Subarachnoid Bupivacaine Block on Anesthetic Requirements for Thiopental in Rats

Background: Subarachnoid bupivacaine blockade has been reported to reduce thiopental and midazolam hypnotic requirements in patients. The purpose of this study was to examine if local anesthetically induced lumbar intrathecal blockade would reduce thiopental requirements for blockade of motor responses to noxious and nonnoxious stimuli in rats.

Methods: After intrathecal and external jugular catheter placement, rats were assigned randomly to two groups in a crossover design study, with each rat to receive either 10 micro liter of 0.75% bupivacaine or 10 micro liter of normal saline intrathecally. The doses of intravenously administered thiopental required to ablate the eyelid reflex, to block the withdrawal reflex of a front limb digit, and to block the corneal reflex were compared. In two separate groups of animals, hemodynamic parameters and concentrations of thiopental in the brain were compared between intrathecally administered bupivacaine and saline.

Results: The thiopental dose required to block the described responses was decreased with intrathecally administered bupivacaine versus intrathecally administered saline from (mean +/- SD) 40 +/- 5 to 24 +/- 4 mg/kg (P < 0.001) for the eyelid reflex, from 51 +/- 6 to 29 +/- 6 mg/kg (P < 0.005) for front limb withdrawal, and from 67 +/- 8 to 46 +/- 8 mg/kg (P < 0.01) for the corneal reflex. The concentration of thiopental in the brain at the time of corneal reflex blockade for the group given bupivacaine was significantly lower than in the group given saline (24.1 vs. 35.8 micro gram/g, P = 0.02).     

Thiopental directly depresses lumbar dorsal horn neuronal responses to noxious mechanical stimulation in goats

BACKGROUND: Thiopental has hypnotic actions in the brain, but it also depresses nociceptive transmission. In this study we examined whether thiopental had direct (spinal) and/or indirect (supraspinal) effects on the responses of single lumbar dorsal horn neurons to noxious mechanical stimulation, using a method to deliver thiopental differentially to either the torso or cranial circulation in goats. METHODS: Goats (n=10) were anesthetized with isoflurane and neck dissections performed to permit cranial bypass. A lumbar laminectomy was made to permit single-unit recording of lumbar dorsal horn neuronal activity (1-2 neurons/animal). Isoflurane was maintained at 0.8+/-0.1% to both head and torso throughout the study. During cranial bypass, thiopental was separately administered to the torso (low dose, 1.5+/-0.5 mg/kg; high dose, 3.7+/-0.5 mg/kg) or cranial (low dose, 0.12+/-0.03 mg/kg; high dose, 0.2 mg/kg) circulation. RESULTS: Thiopental administered to the torso significantly depressed dorsal horn neuronal responses to noxious stimulation at the high dose: 757+/-471 to 392+/-305 impulses/min at 1 min post-injection, P<0.006 (n=14); evoked responses recovered at 5 min post-injection. At the low dose, there was a similar numerical decrease, but this did not reach significance: 876+/-780 to 407+/-499 impulses/min at 1 min post-injection, P>0.05 (n=6). No significant change was observed when thiopental was administered to the cranial circulation: low dose, 1061+/-1167 to 965+/-874 impulses/min at 1 min post-injection, P>0.05 (n=10); high dose, 864+/-331 to 917+/-525 impulses/min at 1 min post-injection, P>0.05 (n=8). CONCLUSION: Thiopental has a direct (spinal) depressant effect on dorsal neuronal responses to noxious stimulus, but no significant supraspinal effect.     

Effect of Systemic Morphine on the Responses of Convergent Neurons to Noxious Heat Stimuli Applied over Graded Surface Areas

Background: Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord.

Methods: Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2).

Results: The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11 +/- 4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159 +/- 36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42 +/- 24% of control values; P < 0.05) than was observed with the smaller stimulus.     

Placental transfer of lidocaine: effects of fetal acidosis.

To investigate whether fetal acidosis increases the placental transfer of lidocaine, resulting in higher fetal blood levels of the drug, lidocaine was infused intravenously into ten pregnant ewes to maintain plasma levels of 2-4 microgram/ml. After maternal-fetal equilibrium was reached, the fetus was made acidotic by infusing lactic acid intravenously. Fetal blood pH decreased from 7.35 to 7.10. With fetal acidemia, fetal blood lidocaine levels increased significantly from 1.60 +/- 0.11 microgram/ml to 2.72 +/- 0.26 microgram/ml. The fetal-maternal lidocaine ratio increased from 0.76 to 1.21. Correction of the acidosis by bicarbonate infusion returned the fetal-maternal ratios to control values. It is concluded that acidosis in the fetus may result in trapping of ionized lidocaine in the fetal circulation and increase the transfer of lidocaine across the placenta.     

Does Epidural Anesthesia Have General Anesthetic Effects?: A Prospective, Randomized, Double-blind, Placebo-controlled Trial

Background: Clinically, patients require surprisingly low end-tidal concentrations of volatile agents during combined epidural-general anesthesia. Neuraxial anesthesia exhibits sedative properties that may reduce requirements for general anesthesia. The authors tested whether epidural lidocaine reduces volatile anesthetic requirements as measured by the minimum alveolar concentration (MAC) of sevoflurane for noxious testing cephalad to the sensory block.

Methods: In a prospective, randomized, double-blind, placebo-controlled trial, 44 patients received 300 mg epidural lidocaine (group E), epidural saline control (group C), or epidural saline-intravenous lidocaine infusion (group I) after premedication with 0.02 mg/kg midazolam and 1 [mu]g/kg fentanyl. Tracheal intubation followed standard induction with 4 mg/kg thiopental and succinylcholine 1 mg/kg. After 10 min or more of stable end-tidal sevoflurane, 10 s of 50 Hz, 60 mA tetanic electrical stimulation were applied to the fifth cervical dermatome. Predetermined end-tidal sevoflurane concentrations and the MAC for each group were determined by the up-and-down method and probit analysis based on patient movement.

Results: MAC of sevoflurane for group E, 0.52 +/- 0.18% (+/- 95% confidence interval [CI]), differed significantly from group C, 1.18 +/- 0.18% (P< 0.0005), and from group I, 1.04 +/- 0.18% (P< 0.001). The plasma lidocaine levels in groups E and I were comparable (2.3 +/- 1.0 vs. 3.0 +/- 1.2 [mu]g/ml +/- SD).     

Effects of ketamine on nociceptive cells in the medial medullary reticular formation of the cat.

Anatomic, physiologic and behavioral evidence suggests that the neurons in the nucleus reticularis gigantocellularis of the medial medullary reticular formation may act as a relay station for the transmission of nociceptive information from the spinal cord to higher brain centers. The nucleus reticularis gigantocellularis may also be the site of action of analgesic agents, such as ketamine hydrochloride. Utilizing extracellular microelectrodes in 23 decerebrate cats, the authors measured the effect of ketamine on neurons in the nucleus reticularis gigantocellularis that were excited by electrical stimulation of peripheral nerves. The frequency of spontaneous single-unit firing activity in the nucleus reticularis gigantocellularis was suppressed by 31 +/- 11 (mean +/- 1 SE) and by 62 +/- 7 per cent with ketamine, 1.0 and 2.5 mg/kg, iv, respectively. The frequency of evoked single-unit activity was suppressed by 57 +/- 9 and 79 +/- 5 per cent with ketamine, 1.0 and 2.5 mg/kg, respectively. Ketamine produces significant depression of single-unit activity of the cells in the nucleus reticularis gigantocellularis, suggesting that this may be an important site of its analgesic action.     

Ventilatory response to CO2 following intravenous and epidural lidocaine

The authors determined the effects of intravenous infusion and epidural administration of lidocaine on the control of ventilation in two groups of eight healthy unpremedicated subjects. In the intravenous group, an injection of 1.5 mg/kg lidocaine was followed by an infusion at a rate of 60 micrograms X kg-1 X min-1 for 30 min. The slope of the ventilatory response to CO2 was significantly increased (P less than 0.05) from its control value (2.65 +/- 1.22 1 X min-1 X mmHg-1 [mean +/- SD]) at the end of the infusion (58%), while plasma lidocaine level was at 3.14 +/- 0.82 microgram/ml. The correlation between individual plasma lidocaine levels and the changes in the slope of the ventilatory response to CO2 was significant (r = 0.58, n = 24, P less than 0.01). In the epidural group, after the administration of 5 mg/kg of lidocaine, the slope of the ventilatory response to CO2 increased significantly (P less than 0.05) from its control value (1.52 +/- 0.75 1 X min-1 X mmHg-1) at 15 (+22%) and 25 min (+42%), while plasma lidocaine levels were at 1.79 +/- 0.42 and 2.22 +/- 0.47 microgram/ml, respectively. In both groups, resting minute ventilation and end-tidal CO2 values remained unchanged. These results suggest that epidural lidocaine has a stimulating effect on the ventilatory control mechanisms that results from the systemic effect of the drug.     

Which Spinal Cutaneous Nociceptive Neurons Are Inhibited by Intravenous Lidocaine in the Rat?

BACKGROUND AND AIMS: Intravenous lidocaine (IVL) produces analgesia in multiple painful disorders. The neurophysiological effects of IVL are not well defined, but studies in visceral nociceptive systems have shown that IVL has differential effects on subgroups of spinal neurons. The present study determined whether a similar differential effect of IVL occurs in spinal neurons excited by noxious cutaneous stimuli. METHODS: In decerebrate, cervical spinal cord-transected rats, the lumbosacral spinal cord was exposed by a laminectomy. Single-unit recordings were made of dorsal horn neurons excited by noxious cutaneous stimuli. Each neuron's response to noxious (pinch) and nonnoxious (brush) cutaneous stimuli were determined and the effect of a counterirritation stimulus (noxious skin pinch presented in the upper body) on spontaneous activity quantified. In a subset of neurons, sequential doses of IVL were administered, and responses of each neuron to repeated 50 degrees C heating of the hindpaw/tail were determined. RESULTS: IVL dose-dependently inhibited neurons excited by heating of the hindpaw/tail. IVL produced significantly greater inhibition of both spontaneous and heat-evoked activity in neurons that did not show counterirritation effects when compared with those neurons that did show counterirritation effects. Standard classification of neurons as wide-dynamic range or nociceptive-specific was less predictive of the IVL effect. CONCLUSIONS: IVL had differential inhibitory effects on 2 spinal cutaneous nociceptive neuron populations. Other drugs could also have differential effects on sensory pathways, suggesting a mechanism whereby certain drugs differentially affect different types of pain.     

Does epidural anesthesia have general anesthetic effects? A prospective, randomized, double-blind, placebo-controlled trial

BACKGROUND: Clinically, patients require surprisingly low end-tidal concentrations of volatile agents during combined epidural-general anesthesia. Neuraxial anesthesia exhibits sedative properties that may reduce requirements for general anesthesia. The authors tested whether epidural lidocaine reduces volatile anesthetic requirements as measured by the minimum alveolar concentration (MAC) of sevoflurane for noxious testing cephalad to the sensory block. METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, 44 patients received 300 mg epidural lidocaine (group E), epidural saline control (group C), or epidural saline-intravenous lidocaine infusion (group I) after premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl. Tracheal intubation followed standard induction with 4 mg/kg thiopental and succinylcholine 1 mg/kg. After 10 min or more of stable end-tidal sevoflurane, 10 s of 50 Hz, 60 mA tetanic electrical stimulation were applied to the fifth cervical dermatome. Predetermined end-tidal sevoflurane concentrations and the MAC for each group were determined by the up-and-down method and probit analysis based on patient movement. RESULTS: MAC of sevoflurane for group E, 0.52+/-0.18% (+/- 95% confidence interval [CI]), differed significantly from group C, 1.18+/-0.18% (P < 0.0005), and from group I, 1.04+/-0.18% (P < 0.001). The plasma lidocaine levels in groups E and I were comparable (2.3+/-1.0 vs. 3.0+/-1.2 microg/ml +/- SD). CONCLUSIONS: Lidocaine epidural anesthesia reduced the MAC of sevoflurane by approximately 50%. This MAC sparing is most likely caused by indirect central effects of spinal deafferentation and not to systemic effects of lidocaine or direct neural blockade. Thus, lower concentrations of volatile agents than those based on standard MAC values may be adequate during combined epidural-general anesthesia.