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Stress-produced analgesia and morphine-produced analgesia: lack of cross-tolerance.

Animals exposed to cold-water swims, rotation, inescapable shocks, abrupt food deprivation and other stressors display temporary analgesia. Since repeated exposures result in adaptation of this analgesia in much the same way that repeated administration of opiates results in tolerance, the possibility of cross-tolerance between cold-water stress-induced and morphine-induced analgesia was investigated. Flinch-jump thresholds were determined in ten experimental groups of six rats each. Three groups showed dose-dependent analgesia following single injections of morphine at 5, 10 and 15 mg/kg, respectively. A fourth group, subjected to a single cold-water swim at 2 degrees C for 3.5 min, displayed analgesia comparable to that produced by 10 mg/kg of morphine. Groups subjected either to 14 daily cold-water swims or to 14 daily morphine injections at 10 mg/kg showed normal thresholds on the 14th day indicating that adaptation and tolerance had developed, respectively. The cross-over groups were exposed to either 13 days of could-water swims followed by morphine or the reverse arrangement. Both groups showed profound analgesia instead of cross-tolerance, suggesting that a non-opiate neural mechanism may mediate stress-induced analgesia.

Analgesia

Extradural analgesia--the preferred method of analgesia for vaginal breech delivery.

A prospective trial was designed to study the effect of extradural analgesia on the management of breech delivery. From a study of 51 patients, it was concluded that the duration of labour was not lengthened, the frequency of breech extraction was decreased and the condition of the infant was improved, as shown by foetal blood sampling and Apgar scores. Therefore we recommend strongly that extradural analgesia should be used in the management of all breech deliveries.

Anesthesia, Epidural

Cardiovascular effects of epidural analgesia. I. Thoracic epidural analgesia. An experimental study in sheep of the effects on central circulation, regional perfusion and myocardial performance during normoxia, hypoxia and isoproterenol administration.

Some circulatory effects of thoracic epidural analgesia (TEA) were investigated in splenectomized, open-chest sheep during normoxia, hypoxia and isoproterenol administration. During normoxia, TEA caused comparatively marked reductions in systemic arterial blood pressure, total peripheral resistance and cardiac output. A fall in heart rate was not compensated for by any rise in stroke volume. Myocardial contractility (LV dd/dt/IP) was not affected by TEA. The proportion of cardiac output diverted to the blocked area was markedly increased. Compensatory vasoconstriction was not observed within the unblocked area in six out of nine animals. Myocardial blood flow showed a pronounced reduction in accordance with the calculated changes of heart work, so that myocardial oxygen extraction remained unchanged. Studies under hypoxia revealed that cardiac responses to hypoxia in the sheep are mediated chiefly by neurogenic factors. TEA abolished the hypoxia-induced rise in heart rate but did not affect the increase in pulmonary vascular resistance caused by hypoxia. The administration of isoproterenol during TEA increased systemic arterial blood pressure, but due to further fall in total peripheral resistance it was not fully normalized. Cardiac output and heart rate increased markedly. Myocardial oxygen consumption and blood flow increased but did not reach control levels.

Anesthesia, Epidural

[Pneumoencephalotomography under diaz-analgesia and narco-analgesia].

The authors reported 92 observations of anesthesia for gaseous encephalotomography interest the adult. The contrast produce is air. 49 under diazanalgesia and myoresolution. Diazepam, +Fentanyl, pancuronium bromide N2O to 60 p. 100. 25 under diazanalgesia and myoresolution. Diazepam, +Fentanyl, succinylcholine, N2O to 60 p. 100. 18 under narco-analgesia and myoresolution. +Fentyl, pancuronium bromide N2O to 60 p. 100. The conditions of the study are described in the first part. The results and their analysis permit the appreciation of: - the patient confort, the quality of the examination; -the respect of the hemodynamics for this examination, reputed to be "difficult"; -the immediatly noticeable diminution of side effects; -the absence of side effects; -the justification and interesting of the control ventilation; -the quality of waking up. In the conclusion the authors underline the interest of their different techniques and the possibility of using them in operations in sitting position in neurosurgery, and all important chirurgical intervention.

Adolescent

Enhancement of morphine analgesia and brain levels by methamphetamine in mice.

Methamphetamine and morphine were approximately equipotent in producing analgesia in mice using the tail-flick assay. The ED50 for morphine analgesia was significantly reduced when 3.2 mg/kg of methamphetamine was given 5 or 60 min before morphine. Methamphetamine pretreatment increased the peak effect but did not alter the duration of morphine analgesia. Enhancement of morphine analgesia was apparent when methamphetamine was given up to 60 min before morphine and it did not coincide with analgesia produced by methamphetamine alone. Brain levels of morphine were found to be significantly higher in methamphetamine- compared to saline-pretreated mice, at times when enhanced analgesia was observed. Further studies showed that morphine brain levels were increased by methamphetamine pretreatment in an apparent dose-dependent manner. The analgesia observed at several morphine brain levels was compared in order to determine whether enhanced analgesia resulted from increased morphine brain levels. Methamphetamine administration 5 or 60 min before morphine shifted the log morphine brain level-response curves for morphine analgesia to the left and the morphine brain level at a given percent analgesia was significantly lower in methamphetamine- than in saline-pretreated mice. In addition, methamphetamine pretreatment enhanced methadone analgesia but had no effect on methadone brain levels.

Analgesia

The analgesic efficacy of intrathecal morphine compared to peripheral regional analgesia in total hip arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Following elective total hip arthroplasty, pain continues to be a significant problem. Intrathecal morphine or peripheral regional analgesia, that is local infiltration analgesia or peripheral nerve block, are common analgesic modalities, but it is still not known which is superior. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: The following electronic databases were searched from inception to 24 March 2026: CENTRAL; Ovid Embase; Ovid MEDLINE; Scopus; and Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials that compared intrathecal morphine to peripheral regional analgesia in patients scheduled for elective total hip arthroplasty under general or spinal anaesthesia. RESULTS: Eight trials and 471 patients were included. The peripheral regional analgesia was peripheral nerve block in six trials and local infiltration analgesia in two trials. No difference was demonstrated between intrathecal morphine and peripheral regional analgesia in regard to the first coprimary outcome, the pain score at rest at 24 h. The quality of evidence was moderate. Intrathecal morphine was found to be superior to peripheral regional analgesia with respect to the second coprimary outcome, the cumulative intravenous morphine equivalent consumption at 24 h. Mean difference (95% CI) was 11.38 mg (4.31-18.45; P  = 0.002, I2  = 81%). The quality of evidence was low. Intrathecal morphine was revealed to be superior to peripheral regional analgesia at 8-12 h for the pain score at rest, 1.24 (0.60-1.88); P  = 0.0001, I2  = 68%; pain score on movement, 1.15 (0.12-2.17), P  = 0.03, I2  = 65%; but the rate of in hospital pruritus was reduced with peripheral regional analgesia, 0.31 (0.17-0.58), P  = 0.0002, I2  = 0%. No differences in functional status were shown. CONCLUSIONS: We found no difference between intrathecal morphine and peripheral regional analgesia in regard to pain score at rest at 24 h. Intrathecal morphine may lead to a favourable effect on some but not all analgesic indices compared to peripheral regional analgesia in elective total hip arthroplasty. The quality of evidence for these positive effects was low. Intrathecal morphine reduced the systemic opioid consumption, but is not in itself an opioid free strategy. This notion is supported by the increased incidence of in hospital pruritus with intrathecal morphine. The quality of evidence for this was high. In view of the quality of evidence, high quality randomised controlled trials are required to substantiate these results.

Humans

[Clinical basis of acupuncture analgesia (author's transl)].

Based on 249 observations acupuncture analgesia has been studied in its clinical picture and its abilities in surgery. Clinically, whatever may be the acupuncture sites, the first appearance of analgesia is noticed on the hands, the feet, the vertex, the auricles of the ears. Then, from these areas the propagation of analgesia extends towards the trunk where analgesia zones are to meet. A generalized analgesia may be obtained on the whole body with non specific, even arbitary acupuncture sites. It is incomplete, not so efficient as analgesia with novocaine. It involves only superficial layers of the skin, the buccal muquous membrane and that of the pharynx, the cornea, the teeth... Deep layers of tissues, muscles, nerves, deep viscera... are not affected by analgesia. Sixty four operations of all kinds have been performed with the view to test acupuncture analgesia. Progressive and late appearance of analgesia seems to favour the hypothesis of a humoral way in the mechanism of acupuncture analgesia.

Acupuncture Therapy

2-Deoxy-D-glucose analgesia: influences of opiate and non-opiate factors.

Acute administration of 2-deoxy-D-glucose (2-DG), an antimetabolic glucose analogue induces a powerful analgesia which adapts following repeated administration. 2-DG analgesia displays significant cross-tolerance with morphine, and like morphine analgesia, is potentiated in hypophysectomized rats. The present study examined further the role of opiates in 2-DG analgesia by examining whether the opiate antagonist, naloxone, would affect 2-DG analgesia, and whether ineffective doses of 2-DG and morphine would interact in a synergistic fashion to induce analgesia. Nociceptive thresholds were measured by the flinch-jump test. Naloxone doses of 1, 5, 10 and 20 mg/kg were all ineffective in reducing significantly 2-DG (600 mg/kg) induced pain threshold elevations. Naloxone failed to attenuate 2-DG (350 mg/kg) analgesia whether administered before or after the 2-DG injection. On the other hand, simultaneous administration of sub-analgesic doses of 2-DG (200 mg/kg) and morphine (2.5 mg/kg) summated to produce significant analgesia. This, 2-DG analgesia is similar to opiates in its tolerant and summative actions, yet dissimilar in that naloxone is ineffective in reversing its effects.

Analgesia

Lumbar sympathetic block with bupivacaine: analgesia for labor.

Forty primigravidas were given a bilateral paravertebral lumbar sympathetic block during stage I of labor using 10 cc of 0.5% bupivacaine and 1:200,000 epinephrine on each side. Good analgesia was obtained in 38 patients with maximal effect 7.5 +/- 3 minutes after blockage. Maternal mean blood pressure and pulse were unchanged, fetal well-being was not compromised, and labor progressed rapidly. Twenty-eight patients delivered prior to resolution of the block, while in the remaining 12 patients pain returned before delivery with analgesia having lasted 283 +/- 103 minutes. In the former 28 patients, analgesia for expulsion was provided by pudendal, saddle block, or infiltration analgesia, whereas continuous lumbar epidural or caudal analgesia was utilized when remission preceded stage II. In comparison to continuous lumbar epidural analgesia, the procedure is technically more difficult, generally more painful, and requires a second anesthetic for delivery. It is concluded that bilateral paravertebral lumbar sympathetic block with bupivacaine provides reliable analgesia of long duration with a low incidence of undesirable side effects. However, its primary usefulness is in cases where continuous lumbar epidural analgesia is refused or contraindicated.

Adult

Evaluation of the periaqueductal central gray (PAG) as a morphine-specific locus of action and examination of morphine-induced and stimulation-produced analgesia at coincident PAG loci.

Experiments were carried out in rats to (1) elaborate upon the sepcificity of drug action in the periaqueductal gray matter (PAG), and (2) to evaluate the posible congruence of PAG sites of morphine-induced and stimulation-produced analgesis (SPA) applied at virtually identical PAG loci. It was demonstrated that the effect of morphine intracerebrally (i,c.) administered into the PAG was not duplicated by other centrally acting agents (chlorpromazine, chlordiazepoxide, pentobarbital or naloxone) administered i.c. at the same PAG site. This selective action of morphine in the PAG was further demonstrated not to be test-bound since morphine significantly altered responding in all four of the analgesiometric tests employed. Thus, multiple i.c. injections of drugs at the same PAG locus were useful in demonstrating site specificity of drug action where behavioral and electroencephalographic methods alone had previously provided ambiguous information. Morphine-induced analgesia and SPA, evaluated at virtually coincident PAG sites, revealed only a general congruence of efficacious loci. The most effective PAG loci for morphine-induced analgesia were not the same as those for SPA; analgesia effected by one analgesia-producing manipulation did not reliably predict that analgesia would also be produced by the other analgesia-producing manipulation at the PAG sites examined. In general, the more efficacious analgesia-producing PAG loci were localized in the ventral-ventrolateral PAG.

Analgesia

Analgesia induced by cold-water stress: attenuation following hypophysectomy.

In addition to the well-known activation of the pituitary-adrenal axis, acute exposure to severe stressors includes a temporary analgesia in rats. Thus, the present study investigates whether the pituitary was involved in the mediation of analgesia induced by severe cold-water swim (CWS) stress. Flinch-jump thresholds were measured 30 min following 3.5-min swims in water temperatures ranging from 2-35 degrees C. Compared with untreated normal rats, hypophysectomized rats, receiving corticosterone and thyroxin, displayed significantly less CWS-induced analgesia, while similarly-supplemented normal rats exhibited significantly more CWS-induced analgesia. In a second experiment, operant liminal escape pain thresholds were determined following acute and chronic CWS. Whereas normal rats exhibited profound analgesia following the initial swims, the hypophysectomized rats never displayed any CWS-induced operant escape shifts. Stress-induced alterations in general activity levels and/or thermoregulation were shown to be unrelated to the diminished effectiveness of CNS to produce analgesia in hypophysectomized rats. These data imply that the pituitary is involved in the mediation of CWS-induced analgesia.

Adrenocorticotropic Hormone

Analgesia produced by microinjection of baclofen and morphine at brain stem sites.

Microinjection of either baclofen (1.5 microgram) or morphine (2.5 microgram), in equimolar doses (14 mM), at sites located in the caudal periaqueductal gray (PAG) resulted in a delay in tail flick latency (analgesia). The relative analgesic potency of baclofen among caudal PAG sites, however, did not correlate with that of morphine. Application of either drug into the caudal aspect of the cerebral aqueduct also produced analgesia, but neither agent caused analgesia when applied at PAG sites rostral to the interaural line. Baclofen also produced analgesia when microinjected in the lower brain stem at sites lateral to the midline in or near the nucleus gigantocellularis, but did not produce analgesia when applied on the midline at sites located within or near the raphe magnus. Conversely, morphine produced analgesia when applied locally at midline sites but not at sites located lateral to the midline. These data suggest that the analgesia produced by systemic administration of baclofen and morphine involves activation of different neuronal substrates.

Analgesics

Effect of Local Anesthetic Solution at Different Temperatures for Epidural Labor Analgesia on Intrapartum Fever: A Randomized Clinical Trial.

BACKGROUND: Whether heating local anesthetic solutions to core body temperature (37°C) for epidural labor analgesia reduces intrapartum fever incidence remains undefined in the current literature. METHODS: This double-blind randomized controlled trial (RCT) enrolled 220 nulliparous parturients (18-35 years, American Society of Anesthesiologists [ASA] physical status II, term singleton pregnancy). Participants were randomized to receive epidural labor analgesia with 0.075% ropivacaine + 0.5 µg/mL sufentanil at 37°C (warmed group) or 22°C (room-temperature group). Epidurals were placed at L3-L4 with a test dose of 3 mL of 1.5% lidocaine at room temperature, followed by programmed bolus epidural analgesia (initial 10 mL, 10 mL/h) and patient-controlled epidural analgesia (PCEA) 5 mL (30-minute lockout). Tympanic temperature was measured every 30 minutes from epidural initiation to delivery, defining intrapartum fever as ≥38°C. The primary outcome was fever incidence, on which the power analysis was based, and also maximum temperature and shivering. Secondary outcomes comprised analgesia onset, block level, labor durations, neonatal Apgar scores, umbilical cord blood pH and BE, and maternal adverse events. RESULTS: A total of 220 parturients were included (warmed group, n = 110; room-temperature group, n = 110). The warmed group had a lower intrapartum fever incidence (15.5% [17/110] vs 30.9% [34/110], relative risk [RR] 0.5 [95% confidence interval {CI}, 0.298-0.840]; P = .007); however, the reduction of 49.8% did not reach the preset clinically meaningful difference of 60% reduction proposed in the power analysis. The maximum body temperature was also lower in the warmed group: median (interquartile range [IQR]) 37.4 (IQR, 37.2-37.7) °C vs 37.6 (IQR, 37.3-38.0) °C, median difference -0.2 (95% CI, -0.3 to -0.1) °C ( P = .006). Shivering incidence was not different between groups (10.9% [12/110] vs 14.5% [16/110]; P = .418). No statistically significant differences were observed between groups in any of the secondary outcomes assessed, including block characteristics, local anesthetic consumption, labor duration, neonatal outcomes, and maternal adverse events. CONCLUSION: Although we found a 50% reduction in the incidence of temperature rise using warmed (37°C) local anesthetics for epidural labor analgesia, this did not reach our preset threshold of 60% reduction.

Humans