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Effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin on cold water swimming stress-induced antinociception in the mouse.

1. The cold (4 degrees C) water swimming stress (CWSS) for 3 min significantly increased the inhibition of the tail-flick response in ICR mice. 2. Pertussis toxin (PTX, 0.05-0.5 microgram) in mice pretreated intrathecally (IT) for 6 days attenuated the inhibition of the tail-flick response induced by CWSS. However, intracerebroventricular (ICV) pretreatment with PTX at the same doses did not affect CWSS-induced inhibition of the tail-flick inhibition. 3. 3-Isobutyl-1-methylxanthine (IBMX, 0.01-1 ng) in mice pretreated IT for 10 min dose-dependently attenuated the inhibition of the tail-flick response induced by CWSS. However, IBMX in mice ICV pretreated ICV at the same doses was not effective in attenuating the CWSS-induced inhibition of the tail-flick response. 4. Neither IT nor ICV pretreatment with cholera toxin (CTX, 0.05-0.5 microgram) for 24 hr affected the inhibition of the tail-flick response induced by CWSS. 5. The ICV or IT injection of PTX, CTX, or IBMX did not affect the basal tail-flick response latency. 6. It is concluded that spinal, but not supraspinal, PTX-sensitive G-proteins and cAMP phosphodiesterase may be involved in the antinociception produced by CWSS. However, neither spinal nor supraspinal CTX-sensitive G-proteins appear to be involved in mediating the antinociception induced by CWSS.

1-Methyl-3-isobutylxanthine↗

Effect of spinal manipulation duration on low threshold mechanoreceptors in lumbar paraspinal muscles: a preliminary report.

STUDY DESIGN: Electrophysiologic recordings were obtained from low threshold primary afferent neurons innervating lumbar multifidus and longissimus muscles in the anesthetized cat. OBJECTIVE: The purpose of this study was to classify sensory nerve endings in lumbar paraspinal muscles and characterize their responses to biomechanical loads applied over a range of durations that encompass those occurring during spinal manipulation. SUMMARY OF BACKGROUND DATA: Neural responses arising from the mechanical input during spinal manipulation are thought to contribute to this maneuver's therapeutic effects. Because manual therapies are distinguished to a large extent on the basis of the speed with which they are applied, it is important to understand how their rate of application affects the signaling properties of primary afferent neurons innervating paraspinal tissues. If alterations in sensory input do contribute to the mechanism of spinal manipulation's therapeutic effect, it seems reasonable to expect that these primary afferents would respond to spinal manipulation in some unique fashion. METHODS: Experiments were performed on 6 adult cats. A L4-L5 laminectomy was performed and the L6 dorsal roots exposed. The L6-L7 vertebrae and associated paraspinal tissues remained intact bilaterally, including lumbodorsal fascia, multifidus, longissimus, iliocostalis muscles, and deeper tissues. Forceps were clamped tightly onto the lateral surfaces of the L6 spinous process through a thin narrow, slit in the lumbodorsal fascia. Single unit afferent activity was recorded from fine filaments teased from the L6 dorsal root. Instantaneous discharge frequency was calculated. Afferents were classified based on von Frey threshold, conduction velocity, and responses to direct muscle stimulation and to succinylcholine injection. Spinal manipulative-like loads were applied to the L6 vertebra (posterior to anterior) using a programmable electronic feedback control system. Force-time profiles were half-sine waves with durations of 25, 50, 100, 200, 400, and 800 milliseconds delivered at constant magnitudes of 33%, 66%, or 100% body weight. RESULTS: The 6 afferents were classified as low threshold mechanoreceptors based on von Frey thresholds being less than 6 g. Five afferents were Group I or II muscle proprioceptors and one afferent was a Group III muscle mechanoreceptor. The receptive field for 2 of the 6 afferents was in the multifidus muscle and the receptive field of the remaining 4 afferents was in the longissimus muscle. In general, the mean instantaneous discharge frequency for all 6 afferents increased abruptly as the duration of the impulse approached 100 milliseconds. An increase in loading magnitude (33% vs. 66% vs. 100% body weight) did not appear to systematically affect the discharge from the 6 low threshold mechanoreceptors. CONCLUSIONS: This preliminary report suggests that abrupt changes in neural discharge (instantaneous frequency) of low threshold muscle mechanoreceptors of the lumbar spine occur as the duration of a biomechanical load approaches that typically used during spinal manipulation. These changes could comprise part of the mechanism contributing to this intervention's physiologic effects. Further studies are warranted to better understand the signaling properties of a wider range of sensory receptors as well as determine the central effects of these high frequency discharges.

Anesthesia↗

Inhibition of cyclic guanosine 5'-monophosphate-dependent protein kinase I (PKG-I) in lumbar spinal cord reduces formalin-induced hyperalgesia and PKG upregulation.

Nitric oxide-mediated nociception has been suggested to involve formation of cyclic guanosine 5'-monophosphate (cGMP) and activation of cGMP-dependent protein kinase (PKG). To further evaluate this pathway we assessed the effects of the PKG-inhibiting cGMP analog Rp-8-Br-cGMPS in the rat formalin assay and analyzed the regulation of PKG expression in rat lumbar spinal cord. Spinally delivered Rp-8-Br-cGMPS (0.1-0.5 micro mol i.t.) reduced the nociceptive behavior in a dose-dependent manner. Similar effects were achieved with Rp-8-Br-PET-cGMPS (0.5 micro mol i.t.), another PKG-inhibitory cGMP analog. In contrast, Rp-8-Br-cAMPS (0.5 micro mol i.t.), an inhibitor of protein kinase A, had no effect in this model. Formalin treatment resulted in a rapid (within 1h), long-lasting (up to 96h) upregulation of PKG-I protein expression. This increase was prevented in animals pretreated with Rp-8-Br-cGMPS (0.5 micro mol i.t.) or morphine (2.5-5mg/kg i.p.) 10min prior to formalin injection. Spinal delivery of 8-Br-cGMP, a PKG-activating cGMP analog, without subsequent formalin treatment also caused an increase of PKG-I protein expression. Hence, the upregulation of PKG-I might possibly be mediated by cGMP itself. Our data suggest that PKG-I activation is involved in the synaptic transmission of nociceptive stimuli in the spinal cord and that PKG-I inhibitors might be interesting novel drugs for pain treatment.

Animals↗

Postoperative analgesic effect of intrathecal neostigmine and its influence on spinal anaesthesia.

A clinical trial was conducted to evaluate the postoperative analgesic efficacy and the safety of intrathecal neostigmine in patients undergoing anterior and posterior vaginoplasty under spinal anaesthesia. Thirty-six patients were randomly divided into three groups to receive: normal saline (1 ml), morphine (100 micrograms in 1 ml of saline) or neostigmine (100 micrograms in 1 ml of saline) intrathecally just before a spinal injection of hyperbaric bupivacaine (0.5%, 4 ml). The mean [SD] time to the first analgesic (nonsteroidal anti-inflammatory drug) administration was significantly prolonged by intrathecal neostigmine (10.7 [4.3] h) and morphine (15.3 [3.0] h) compared with saline (4.5 [1.0] h). The three groups also differed in the number of patients requiring subcutaneous morphine to complement the analgesia provided by the intramuscular nonsteroidal anti-inflammatory drugs and the mean [SD] times for their administration: eight patients in the saline group (8.0 [3.8] h), one patient in the morphine group (18 h) and two patients in the neostigmine group (8 and 12.9 h). The morphine and neostigmine groups showed similar analgesic effectiveness. The characteristics of spinal anaesthesia were not modified by intrathecal morphine or neostigmine. Severe nausea and vomiting, sweating and distress during surgery were the most obvious adverse effects of intrathecal neostigmine. On the other hand, less hypotension was observed in the neostigmine group. The usefulness of intrathecal neostigmine as the sole postoperative analgesic may be restricted by the severity of its adverse effects.

Adult↗

Effectiveness of intravenous ephedrine infusion during spinal anaesthesia for caesarean section based on maternal hypotension, neonatal acid-base status and lactate levels.

Maternal cardiovascular changes and neonatal acid-base status, including lactate levels, were assessed in 30 healthy women undergoing elective caesarean section under spinal anaesthesia. Patients were allocated randomly to receive IV ephedrine infusion (n = 15) (5 mg.min(-1) immediately after the spinal injection or bolus administration of IV ephedrine (n = 15) (10 mg) in case of development of hypotension. Maternal and neonatal blood pressure, heart rate and acid-base status including lactate levels were compared between the groups. Systolic blood pressure in the bolus group was significantly lower when compared to the infusion group. Nausea was observed in one patient (6%) in the infusion group and nausea and vomiting were observed in 10 patients (66%) in the bolus group. Although umbilical arterial pH values were significantly lower in the bolus group, lactate levels were similar In conclusion, ephedrine infusion prevented maternal hypotension, reduced the incidence of nausea and vomiting and led to improved umbilical blood pH during spinal anaesthesia for caesarean section.

Acid-Base Equilibrium↗

Intrathecal morphine reduces breakthrough pain during labour epidural analgesia.

BACKGROUND: When using the combined spinal-epidural (CSE) technique for labour analgesia, parturients often experience breakthrough pain after the spinal medication has receded. We tested the hypothesis that a small dose of intrathecal morphine would reduce breakthrough pain. METHODS: This was a randomized, double-blind, placebo-controlled trial. Subjects were randomized to receive either 100 microg of morphine (MS) or placebo (PLCB) with the spinal injection of bupivacaine and fentanyl. Assessments included need for supplementation during labour analgesia, use of pain medications for 24 h after delivery, and side-effects. The primary end-point was the rate of breakthrough pain. RESULTS: Sixty subjects were enrolled, 55 subjects completed the trial. The MS group had a significantly lower rate of breakthrough pain than the PLCB group [0.6 (0.6) vs 1.1 (0.8) episodes per patient; P < 0.01], and longer time to first episode of breakthrough pain (300 vs 180 min; P = 0.03). The MS group used 75% less opioid medications during the subsequent 24 h, but had a 17% incidence of nausea. CONCLUSIONS: The addition of small dose of morphine to the spinal component of the CSE technique improved the effectiveness of epidural labour analgesia and reduced the need for pain medications over 24 h, but resulted in a small increase in nausea.

Adult↗

Role of the electrogenic Na/K pump in disinhibition-induced bursting in cultured spinal networks.

Disinhibition-induced bursting activity in cultures of fetal rat spinal cord is mainly controlled by intrinsic spiking with subsequent recurrent excitation of the network through glutamate synaptic transmission, and by autoregulation of neuronal excitability. Here we investigated the contribution of the electrogenic Na/K pump to the autoregulation of excitability using extracellular recordings by multielectrode arrays (MEAs) and intracellular whole cell recordings from spinal interneurons. The blockade of the electrogenic Na/K pump by strophanthidin led to an immediate and transient increase in the burst rate together with an increase in the asynchronous background activity. Later, the burst rate decreased to initial values and the bursts became shorter and smaller. In single neurons, we observed an immediate depolarization of the membrane during the interburst intervals concomitant with the rise in burst rate. This depolarization was more pronounced during disinhibition than during control, suggesting that the pump was more active. Later a decrease in burst rate was observed and, in some neurons, a complete cessation of firing. Most of the effects of strophanthidin could be reproduced by high K+-induced depolarization. During prolonged current injections, spinal interneurons exhibited spike frequency adaptation, which remained unaffected by strophanthidin. These results suggest that the electrogenic Na/K pump is responsible for the hyperpolarization and thus for the changes in excitability during the interburst intervals, although not for the spike frequency adaptation during the bursts.

Action Potentials↗

Effects of posture and baricity on spinal anaesthesia with 0.5% bupivacaine 5 ml. A double-blind study.

In four groups of 10 patients, 0.5% bupivacaine 5 ml was used in spinal anaesthesia for gynaecological surgery. Group 1 received plain solution in the sitting position, group 2 plain solution in the lateral position, group 3 hyperbaric solution in the sitting position and group 4 hyperbaric solution in the lateral position. All patients were returned to the horizontal supine position, the sitting subjects 2 min after, and the lateral subjects immediately after, spinal injection. In each group the mean height of block was to the mid-thoracic segments, but there was no significant difference between the groups. There was, however, considerable scatter within each group. Posture had some effect on the speed of onset of the analgesia, but no significant effect on the final outcome. The use of 0.5% bupivacaine as a test dose in extradural blockade is discussed.

Adult↗

[Dmt(1)]DALDA is highly selective and potent at mu opioid receptors, but is not cross-tolerant with systemic morphine.

The clinical effectiveness of morphine is limited by several side effects, including the development of tolerance and dependence. Most of these side effects are believed to be mediated by central opioid receptors; therefore, hydrophilic opioids, which don't cross the blood-brain barrier, may have advantages over morphine in some clinical applications. We recently synthesized several analogues of DALDA (Tyr-D-Arg-Phe-Lys-NH2), a highly hydrophilic peptide derived from the endogenous opioid peptide dermorphin; all of them, particularly [Dmt(1)] DALDA (Dmt - 2',6'-dimethyl tyrosine), had high potency and selectivity at mu receptors, the target of morphine, in activity assays. Here we report the pharmacological characterization of [Dmt(1)] DALDA in the whole animal. [Dmt(1)]DALDA was 40 times more potent than morphine in inducing antinociception in mice when both drugs were given s.c., and 6-14 times more potent than DAMGO, a selective m agonist, when both drugs were given it. However, [Dmt(1)]DALDA showed poor cross-tolerance to morphine; thus chronic morphine treatment of animals increased the antinociceptive AD(50) of systemic [Dmt(1)]DALDA two fold or less, as compared to an 8-9-fold increase for morphine and a 4-5-fold increase for DAMGO. The antinociceptive activity of [Dmt(1)]DALDA (i.t) was blocked by CTAP, a selective mu antagonist, but not by TIPP psi, a selective delta antagonist, nor by nor-BNI, a selective kappa antagonist. [Dmt(1)]DALDA-induced antinociception was also blocked by naloxone methiodide, an antagonist that does not cross the blood-brain barrier, when agonist and antagonist were given i.t. or i.c.v., but not when they were given s.c. We conclude that [Dmt(1)] DALDA is a highly potent analgesic acting at mu receptors. Though it appears to penetrate the blood-brain barrier, it exhibits low cross-tolerance to morphine, suggesting that it may have advantages over the latter in certain clinical applications.

Analgesics, Opioid↗

Sympathetic reflexes after depletion of bulbospinal catecholaminergic neurons with anti-DbetaH-saporin.

We examined the effects of destroying bulbospinal catecholaminergic neurons with the immunotoxin anti-dopamine beta-hydroxylase-saporin (anti-DbetaH-Sap) on splanchnic nerve activity (SNA) and selected sympathetic reflexes in rats. Anti-DbetaH-Sap was administered into the thoracic spinal cord with the retrograde tracer fast blue. After 3-5 wk, anti-DbetaH-Sap eliminated most bulbospinal C1 (>74%), C3 ( approximately 84%), A5 ( approximately 98%), and A6 cells. Noncatecholaminergic bulbospinal neurons of the rostral ventrolateral medulla and serotonergic neurons were spared. Under chloralose anesthesia, mean arterial pressure and heart rate of anti-DbetaH-Sap-treated rats (3-5 wk) were normal. Resting SNA was not detectably altered, but the baroreflex range and gain were reduced approximately 40% (P < 0.05). Phenyl biguanide-induced decreases in mean arterial pressure, heart rate, and SNA were unchanged by anti-DbetaH-Sap, but the sympathoexcitatory response to intravenous cyanide was virtually abolished (P < 0.05). Rats that received spinal injections of saporin conjugated to an anti-mouse IgG had intact bulbospinal C1 and A5 cells and normal physiological responses. These data suggest that C1 and A5 neurons contribute modestly to resting SNA and cardiopulmonary reflexes. However, bulbospinal catecholaminergic neurons appear to play a prominent sympathoexcitatory role during stimulation of chemoreceptors.

Amidines↗

Muscarinic-mediated analgesia.

Systemic administration of cholinesterase inhibitors which cross the blood brain barrier have long been known to produce analgesia and enhance analgesia from opiates. A major site of analgesic action of cholinergic agents is the spinal cord. Muscarinic receptors are concentrated in the superficial layers of the dorsal horn of the spinal cord, an area of noxious sensory processing, and these reflect innervation primarily from cholinergic neurons with cell bodies deep in the neck of the dorsal horn. Spinal injection of cholinergic agonists results in analgesia which primarily reflects muscarinic receptor activation. Analgesia occurs in animal models of acute noxious stimulation and of chronic hypersensitivity pain. Although no cholinergic agonists have been tested for safety in humans, the cholinesterase inhibitor, neostigmine, has undergone such testing, and produces analgesia to experimental, acute postoperative, and chronic pain. Thus, muscarinic cholinergic agonists and cholinesterase inhibitors hold promise as non-opiate agents for the treatment of moderate to severe acute and chronic pain.

Acetylcholine↗

[Famotidine does not modify the plasma levels of lidocaine for spinal anesthesia. A comparative study of famotidine and cimetidine].

H2 receptor antagonists are often used to reduce gastric acidity prior to general or regional anaesthesias. However cimetidine and ranitidine have been found to increase plasma levels of local anaesthetics such as lidocaine. This study aimed to compare famotidine--another H2 receptor antagonist--with cimetidine in this respect. 33 male patients 70 years old or more, scheduled for surgery under spinal anaesthesia and randomized into 3 groups, received either diazepam 0.15 mg.kg-1 and famotidine 20 mg (group A) or diazepam and cimetidine 200 mg (group B) or diazepam only (group C) on the previous night and 90 minutes before spinal anaesthesia by hyperbaric lidocaine 5%, 3 ml. Arterial blood samples were taken 3 minutes after spinal injection then every 15 minutes unto 90 minutes after the first sampling. Lidocaine plasma levels were measured by fluorescence polarization immunoassay and the results were statistically analyzed. In famotidine group lidocaine levels were intermediate between B and C groups levels, and the increase was of lesser duration than in B group. Elimination mechanism of lidocaine with and without H2 inhibitor is briefly discussed. Therefore famotidine would appear to be more convenient than other H2 receptor inhibitors whenever antacid protective effects are sought after prior to regional anaesthesia.

Aged↗

Participation of a bulbospinal serotonergic pathway in the rat brain in clonidine-induced hypotension and bradycardia.

The effects of microinjection of clonidine (1-10 micrograms in 1 microliter) into a region adjacent to the ventrolateral surface of the medulla oblongata on cardiovascular function were assessed in urethane-anesthetized rats. Intramedullary administration of clonidine, but not saline vehicle, caused a dose-dependent decrease in both the mean arterial pressure and the heart rate. The clonidine-induced hypotension was antagonized by prior spinal transection, but not bilateral vagotomy. On the other hand, the clonidine-induced bradycardia was antagonized by prior bilateral vagotomy, but not spinal transection. Furthermore, selective destruction of the spinal 5-HT nerves, produced by bilateral spinal injection of 5,7-dihydroxytryptamine, reduced the magnitude of the vasodepressor or the bradycardiac responses to clonidine microinjected into the area near the ventrolateral surface of the medulla oblongata in rats. The data indicate that a bulbospinal serotonergic pathway is involved in development of clonidine-induced hypotension and bradycardia. The induced hypotension is brought about by a decrease in sympathetic efferent activity, whereas the induced bradycardia was due to an increase in vagal efferent activity.

5,7-Dihydroxytryptamine↗

Postoperative analgesia and antiemetic efficacy after subarachnoid neostigmine in orthopedic surgery.

BACKGROUND AND OBJECTIVES: The efficacy of operatively administered spinal neostigmine to provide analgesia and that of different antiemetics to prevent neostigmine-related nausea and vomiting were evaluated in patients undergoing tibial or ankle reconstruction. METHODS: One hundred patients were randomized to five groups (n = 20). The intravenous antiemetic test drug (except propofol) was given as premedication in the holding room, after intravenous midazolam, 0.05 mg/kg. The subarachnoid drugs administered were 20 mg bupivacaine (0.5%) in conjunction with 100 micrograms neostigmine, except for the saline group (S group), which received bupivacaine and saline. The S group, the neostigmine group (N group), and the propofol group (P group) received saline as the intravenous test drug. The droperidol group (D group) received intravenous droperidol 0.5 mg, and the metoclopramide group (M group) received intravenous metoclopramide 10 mg. The P group had a continuous intravenous propofol infusion (2-4 mg/kg/hr), started 10 minutes after the spinal injection. Nausea, emetic episodes, and the need for analgesic (disclofenac) or antiemetic medication were recorded for the first 24 hours following surgery and scored by a 10-cm visual analog scale (VAS). RESULTS: Subarachnoid neostigmine 100 micrograms did not affect subarachnoid bupivacaine analgesia as measured by time to first rescue analgesic in most patients, but it decreased the overall 24-hour visual analog scale (VAS) scores and the need for postoperative analgesics in 24 hours (P < .001). The incidence of intraoperative nausea and vomiting was higher in the N, D, and M groups than in the S group (P < .001). Following surgery, the 3-hour VAS assessment for emesis was higher for the N, P, and M groups than for the S group (P < .05). The overall 24-hour assessment was similar among groups. CONCLUSIONS: Subarachnoid neostigmine reduced postoperative pain scores and analgesic requirements. Whether it prolonged the duration of action of diclofenac or enhanced the mechanisms involved in spinal analgesia cannot be determined from these data. Although propofol and droperidol appeared to be more effective during and after surgery, respectively, all neostigmine groups were associated with a high consumption of antiemetics.

Adult↗

Prevention of hypotension by a single 5-mg dose of ephedrine during small-dose spinal anesthesia in prehydrated cesarean delivery patients.

UNLABELLED: To evaluate the effectiveness of prophylactic ephedrine for the prevention of hypotension associated with spinal anesthesia, 50 parturients undergoing cesarean delivery received either ephedrine 5 mg or saline IV in a double-blinded fashion immediately after the induction of spinal anesthesia. Spinal anesthesia was performed with hyperbaric bupivacaine 6.6 mg combined with sufentanil 3.3 microg as part of a combined spinal-epidural technique. All patients received 1000 mL of lactated Ringer's solution and 500 mL of hydroxyethylstarch 6% before the spinal injection. Additional ephedrine boluses (5 mg) were administered IV when the systolic blood pressure or heart rate decreased by more than 30% from baseline values, when systolic blood pressure became <100 mm Hg, or when patients complained of nausea or feeling faint. The height of the block was equal in the groups; however, more patients in the placebo group were found to develop hypotension (58% vs 25%, P < 0. 05). Only 2 (8%) patients in the ephedrine group developed hypotension with systolic blood pressure values <90 mm Hg, whereas 10 patients (42%) in the saline group experienced hypotension of this severity (P < 0.05). In addition, there was a higher incidence of nausea in the placebo-treated patients. The total amount of ephedrine administered did not differ between groups. These findings suggest that the incidence and severity of hypotension are significantly reduced by the IV administration of a prophylactic dose of 5 mg ephedrine in patients receiving small-dose spinal anesthesia for cesarean delivery. IMPLICATIONS: Ephedrine is the drug most often used to correct hypotension during spinal anesthesia for cesarean delivery in healthy patients. A single IV dose of 5 mg decreases the occurrence and limits the severity of hypotension in prehydrated subjects receiving a small-dose spinal local anesthetic-opioid combination.

Adult↗

Streptozotocin-induced diabetes selectively alters the potency of analgesia produced by mu-opioid agonists, but not by delta- and kappa-opioid agonists.

To investigate the possible mechanisms of the alterations in morphine-induced analgesia observed in diabetic mice, we examined the influence of streptozotocin-induced (STZ-induced) diabetes on analgesia mediated by the different opioid receptors. The antinociceptive potency of morphine (10 mg/kg), administered s.c., as determined by both the tail-pinch and the tail-flick test, was significantly reduced in diabetic mice as compared to that in controls. Mice with STZ-induced diabetes had significantly decreased sensitivity to intracerebroventricularly (i.c.v.) administered mu-opioid agonists, such as morphine (10 micrograms) and [D-Ala2,N-Me Phe4,Gly-ol5]enkephalin (DAMGO, 0.5 micrograms). However, i.c.v. administration of [D-Pen2,5]enkephalin (DPDPE, 5 micrograms), a delta-opioid agonist, and U-50,488H (50 micrograms), a kappa-opioid agonist, produced pronounced antinociception in both control and diabetic mice. Furthermore, there were no significant differences in antinociceptive potency between diabetic and control mice when morphine (1 microgram), DAMGO (10 micrograms), DPDPE (0.5 micrograms) or U-50,488H (50 micrograms) was administered intrathecally. In conclusion, mice with STZ-induced diabetes are selectively hyporesponsive to supraspinal mu-opioid receptor-mediated antinociception, but they are normally responsive to activation of delta- and kappa-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

A comparison of bupivacaine and tetracaine in spinal anaesthesia with special reference to motor block.

Thirty-six patients received spinal anesthesia with either glucose-free bupivacaine (22.5 mg) or glucose-containing solutions of bupivacaine (20 mg) or tetracaine (15 mg). The duration of analgesia in the lower thoracic and lumbar segments was significantly longer with glucose-free bupivacaine than with the other solutions. Using a quantitative method for measuring muscle strength, the motor block was recorded for three types of movements: hip flexion, knee extension and plantar flexion of the big toe. Movements of the lower part of the thoracic cage were recorded at the same time. The length of time from spinal injection to complete motor block was short and without notable difference between all three groups. Regression of the motor block tended to start earlier for hip flexion and knee extension than for plantar flexion of the big toe. For all three movements the regression of the motor block began significantly later in the glucose-free bupivacaine group than in the other groups. During the regression phase, muscle strength returned significantly later in the glucose-free bupivacaine group than in the bupivacaine group containing glucose and knee extension returned significantly later in the glucose-free bupivacaine group than in the tetracaine group. No difference in motor block was found between the hyperbaric solutions of bupivacaine and tetracaine. For hip flexion (L1-L3), there was no noteworthy difference between the level of analgesia and the motor block segments, whereas for plantar flexion of the big toe (L5-S2) the level of analgesia lay 2-3 segments higher than the motor block segments. In seven patients, during spinal anaesthesia there was a reduction in respiratory deflections corresponding to the lower thorax.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Projections of the dorsomedial nucleus of the intercollicular complex (DM) in relation to respiratory-vocal nuclei in the brainstem of pigeon (Columba livia) and zebra finch (Taeniopygia guttata).

Injections of neuronal tracers were made into the dorsomedial nucleus of the intercollicular complex (DM) of pigeons and zebra finches in order to investigate the projections of this nucleus which has long been implicated in respiratory-vocal control. Despite the fact that pigeons are nonsongbirds and zebra finches are songbirds, the projections were very similar in both species. Most descended throughout the brainstem, taking ventral and dorsal trajectories, which merged in the medulla. Those descending ventrally terminated upon the ventrolateral parabrachial nucleus (PBvl), the nucleus infraolivaris superior, a nucleus of the rostral ventrolateral medulla (RVL), and the nucleus retroambigualis (RAm). Those taking a dorsal trajectory via the occipitomesencephalic tract terminated in the tracheosyringeal part of the hypoglossal nucleus (XIIts), the suprahypoglossal region, and nucleus retroambigualis. There were also substantial projections throughout an arc extending between XIIts and RVL rostrally, and XIIts and RAm caudally. Neurons throughout this arc, which include inspiratory premotor neurons at levels straddling the obex and expiratory premotor neurons more caudally (in RAm), were retrogradely labeled from spinal injections. The DM projections were predominantly ipsilateral, but there were distinct contralateral projections to all the homologous nuclei in both species. All but the projections to PBvl and XIIts were reciprocal. In summary, the projections of DM suggest that it is able to influence all the key motor and premotor nuclei involved in patterned respiratory-vocal activity.

Animals↗