Direct spinal effect of intrathecal and extradural midazolam on visceral noxious stimulation in rabbits.

We measured alterations in a noxious visceromotor reflex in rabbits subjected to intestinal distension, after i.m., extradural or intrathecal injection of midazolam or saline. Spinal catheters were inserted and tunnelled surgically and the animals allowed to recover for 2 weeks. A balloon catheter was placed in the distal part of the descending colon, in the awake rabbit. Intraluminal pressures were increased continuously by water instillation until a sudden withdrawal of the pelvis was observed. Pressure values at withdrawal threshold were recorded immediately before the injection and after 5, 15 and 30 min. Pain thresholds were unaltered after saline. Extradural midazolam 12.5-250 micrograms kg-1 produced a dose-dependent increase in the percent maximum possible effect ranging from 7% after the smallest dose to 80%. Similar dose-dependent effects were observed after intrathecal injection of midazolam 25-62.5 micrograms kg-1. Extradural and intrathecal, but not i.v. injection of flumazenil 25 micrograms kg-1 (a benzodiazepine receptor antagonist) reduced the antinociceptive effect of extradural and intrathecal midazolam to pretreatment levels. A segmental effect of intrathecal midazolam was demonstrated using transcutaneous electrical stimulation in the areas of the neck and the lower back. The effect of intrathecal midazolam 62.5 microrgrams kg-1 was restricted to the lumbar region, demonstrating a selective action on the spinal cord. Thus extradural and intrathecal midazolam produced a dose-dependent effect on the reflex response to visceral distension in rabbits. This effect is caused by a direct spinal action on benzodiazepine receptors in the spinal cord.

Chronic catheterization of the epidural space in rabbits: a model for behavioural and histopathological studies. Examination of meptazinol neurotoxicity.

A technique of epidural catheterization in rabbits is described. Twelve albino rabbits received a totally implanted epidural catheter system. The system was implanted surgically, and the functioning of the system tested for a period of 3 months. X-ray examinations following epidural contrast injections showed a distribution up to Th4 following 1.5 ml and Th8-9 following 1.0 and 1.25 ml. Epidural injection of lidocaine throughout the study period proved the system to be functioning for all 3 months. Another 12 rabbits were included for the neurotoxicological examinations following epidural catheterization, without any injections (three rabbits), epidural injections of saline (four rabbits) and meptazinol (five rabbits) once a day for 14 days. Histopathological examinations showed a fibrous cocoon, at the tip of the catheter, in all rabbits. In the group of rabbits which did not receive any injections, the cocoon was slightly infiltrated with leukocytes and local depression of the spinal cord was observed in one rabbit. In the saline-injected group this infiltration was more pronounced and in one rabbit it extended into the meninges. Three rabbits showed local depression of the spinal cord and local myelopathy of the white matter in the area adjacent to the cocoon. In the group of rabbits receiving meptazinol, three out of five had local depression and myelopathy of the white matter. In this group these findings were more pronounced. In two rabbits the myelopathy extended transversely through the white matter into the grey matter of the spinal cord. The number of pathological changes in the group receiving meptazinol was significantly higher compared to the control and placebo groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct spinal effect of intrathecal acetaminophen on visceral noxious stimulation in rabbits.

The aim of this study was to investigate the effect of intrathecal acetaminophen on visceral and somatic noxious stimulation in the intact, non-anesthetized rabbit. Sixteen rabbits had intrathecal catheters implanted surgically. Visceral noxious stimulation was induced by intestinal distension of the distal colon and somatic stimulation with increasing electrical current through skin electrodes placed in either the cervical or the lumbar area. The effect on visceral noxious stimulation was assessed following intrathecal injection of 0.5, 2.5 and 5 mg of acetaminophen and following 10 and 50 mg acetaminophen intravenously. Naloxone 0.2 mg and yohimbine 0.1 mg were administered intrathecally prior to intrathecal injection of acetaminophen 5 mg. A dose-dependent effect of intrathecal acetaminophen against the visceromotor reflex produced by intestinal distension was shown. No effects on thresholds to lumbar or cervical electrical stimulation or intestinal distension were observed following i.v. administration. Thresholds to noxious electrical stimulation were only significantly elevated at the lumbar level following i.t. injection of 5 mg acetaminophen. Naloxone failed to antagonize the effect of intrathecal acetaminophen, whereas intrathecal yohimbine attenuated the effect of intrathecal acetaminophen in both tests. In conclusion, a spinal, dose-dependent, naloxone-irreversible, and yohimbine-reversible effect of intrathecal acetaminophen on electrical and visceral noxious stimulation was demonstrated.

Intestinal distension test, a method for evaluating intermittent visceral pain in the rabbit.

Behavioural response to intestinal distension was studied in 12 female New Zealand albino rabbits under various conditions. On increasing intraluminal pressures, the rabbits elicited uniform behavioural responses within discrete pressure ranges, notably a sudden pelvic withdrawal at 30-50 mmHg. The pressure provoking pelvic withdrawal was chosen as the test parameter and proved to be individually reproducible, irrespective of fasting/non-fasting or the time of day and with no signs of adaptation in six days consecutive measurements. Morphine modified the pressure response in a dose-dependent manner, whereas isotonic saline or pentobarbital had no effect. In conclusion, the intestinal distension test is reproducible and mimicks intermittent visceral pain in the rabbit. This allows for paired observations in small animal populations with a minimum of discomfort to the animals, which offers a major advantage when comparing with the existing visceral pain tests.

Pupillary diameter and ventilatory CO2 sensitivity after epidural morphine and buprenorphine in volunteers.

The aim of this study was to correlate pupillary diameter with respiratory depression for 20 hr after epidural administration of morphine or buprenorphine. Pupillary diameter and the ventilatory sensitivity to CO2 were measured in six healthy volunteers at various times (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 20 hr) in two sessions, separated by at least 1 week, at which either epidural morphine, 4 mg, or epidural buprenorphine, 0.15 mg, was administered randomly in a double-blind manner. Three of the six volunteers received 0.3 mg buprenorphine epidurally in a third session. Pupillary diameter was measured with a modified Essilor pupillometer. The ventilatory CO2 sensitivity was measured by a modified Read rebreathing technique. The ventilatory parameters measured were mouth occlusion pressure during the first 0.1 sec of inspiration (P0.1), end-tidal CO2 (PETCO2), tidal volume (VT) and respiratory rate (RR). Slopes of the linear regression lines (P0.1/CO2, VT/CO2, VE/CO2, and RR/CO2) and the intercept values of the regression lines and PETCO2 = 7.2 kPa (P0.1:7.2, VT:7.2, VE:7.2, and RR:7.2) were calculated. Pupillary diameter after epidural morphine was smallest at the second hour and had returned to normal after eight hours. After epidural buprenorphine there were two periods of miosis, one at 1-3 hr, the other at 10 hr. With epidural morphine, a statistically significant correlation (P less than 0.05) was found between pupillary diameter and VE/CO2, VE:7.2, P0.1:7.2, and VT:7.2. With epidural buprenorphine 0.15 mg a significant correlation was found between pupillary diameter and VE:7.2 and P0.1:7.2. With epidural buprenorphine 0.3 mg the correlations between pupillary diameter and VE:CO2, VE:7.2, and P0.1:7.2 were significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-endorphin-immunoreactive components in human cerebrospinal fluid.

Cerebrospinal fluid (CSF) from patients without neurological disorder was analyzed after Sep-Pak extraction for beta-endorphin (beta-EP)-immunoreactive components by combined reversed-phase high-performance liquid chromatography (HPLC) and radioimmunoassay. A C-terminal directed antibody detected one major immunoreactive component, probably identical with beta-EP1-31. An N-terminal directed antibody detected several immunoreactive components. One co-eluted with beta-EP1-31 but the others are probably C-terminal truncated or otherwise modified forms of beta-EP1-31. However, they eluted differently from beta-EP1-16 (alpha-endorphin), beta-EP1-26, 1-27 and alpha,N-acetyl-beta-EP1-31. Alternatively, some of the fragments may represent C-terminal extended forms of pro-enkephalin A-derived Met-enkephalin. A Met-enkephalin antiserum detected several immunoreactive components probably representing N-terminal extended forms; neither of them were identical with the beta-EP-immunoreactive components. The results illustrate the heterogeneity of the beta-EP-immunoreactive components in CSF and the need to characterize the beta-EP radioimmunoassay before its application to biological extracts.

Basophil histamine release in asthma patients after in vitro provocation with Althesin and etomidate.

Our aim was to compare the histamine-releasing effect of etomidate and Althesin on basophil leukocytes from asthmatic patients and normal persons. Blood from eight asthmatic patients and six normal persons was tested for histamine release after in vitro provocation with etomidate and althesin. In the group of asthmatic patients there was a significantly higher histamine release after provocation with althesin than after provocation with etomidate at all concentrations (P less than 0.05, P less than 0.01, P less than 0.02). There was significantly higher histamine release for asthmatic patients than for normal persons after provocation with althesin at all concentrations (P less than 0.05, P less than 0.01, P less than 0.02). There was no difference between the asthma group and the normal group after provocation with etomidate. Data were analysed using Wilcoxon's and Mann-Whitney's rank sum tests. We conclude that asthmatic patients may risk bronchospasm during induction of anaesthesia with althesin, and that etomidate may be suitable intravenous anaesthetic for asthmatic patients.

Changes in heart rate and impulse conduction after a single dose of succinylcholine.

The effect of 1 and 2 mg/kg b.w. succinylcholine on changes in cardiac rate and rhythm was studied in 40 fit, adult patients undergoing non-emergency surgery. Induction of anaesthesia consisted of atropine 0.007 mg/kg b.w., pancuronium 0.015 mg/kg b.w., thiopental 5 mg/kg and succinylcholine 1 or 2 mg/kg b.w. Succinylcholine 1 mg/kg b.w. intravenously resulted in a significant decrease in heart rate after 1 min. This decrease persisted after 2 min. The heart rate was unchanged 1 and 2 min after succinylcholine 2 mg/kg b.w. When the two groups were compared, no significant difference was found. No serious cardiac arrhythmias were seen. These results suggest that the larger single dose of succinylcholine is not more likely to cause severe bradycardia or asystole.