Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate coronary flow reserve during cardiac catheterization, intracoronary adenosine and papaverine have been used in the clinical setting. Although papaverine maximizes coronary blood flow, it induces several toxic side effects that reduce its desirability as a coronary dilator. This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model. In dogs (n = 34), we studied the effects of each agent on hemodynamics, regional myocardial blood flow, contractility (sonomicrometric and echocardiographic), metabolism (coronary arterial and venous lactate and tissue high-energy phosphates), and electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine anesthesia/analgesia was induced, and a left thoracotomy was performed. An arterial shunt was created from the left carotid artery to the left anterior descending coronary artery. Two separate groups were studied: group 1 (n = 16) for regional myocardial blood flow and mechanical function and group 2 (n = 18) for biochemical measurements. Adenosine (67 +/- 2 micrograms/min) or papaverine (6 +/- 1 mg/min) was infused into the coronary shunt at a rate of 0.5 + 0.1 ml/min for a maximum duration of 3.5 minutes. Regional myocardial blood flows were determined at control (predrug) and maximal coronary flow using radiolabeled microspheres. All hemodynamic, wall motion, biochemical, and electrocardiographic parameters were also measured at these times. Both drugs produced comparable increases in total and regional coronary blood flows (adenosine, 1.21 +/- 0.15 to 4.83 +/- 0.36 ml/min/g; papaverine, 1.21 +/- 0.05 to 4.89 +/- 0.28 ml/min/g) upon infusion into the left anterior descending coronary artery. Papaverine produced significant (p less than 0.05) changes in subendocardial ST segment electrocardiogram (-2.5 mm), QT prolongation (8 +/- 2%), myocardial creatine phosphate (47% decrease), and coronary sinus serum lactate (277% increase) compared with control. In addition, intracoronary papaverine induced an abnormal contractile pattern. No significant changes in any of these parameters (i.e., ST segment, QT prolongation, myocardial creatine phosphate level, or lactate level) were observed with intracoronary adenosine infusions. We conclude that intracoronary adenosine is comparable to papaverine for maximizing coronary blood flow without the deleterious properties observed with intracoronary papaverine.
 ...
PMID:Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism. 198 87

The effect of adenosine, S-phenylisopropyladenosine (S-PIA) and dipyridamole (an adenosine reuptake inhibitor) on the analgesic action of morphine in mice and rats was investigated in the hot-plate (56 degrees C) and tail immersion (52 degrees C) tests. Adenosine, 50 and 100 mg/kg, induced analgesia in mice and rats in the hot-plate test and potentiated the action of morphine (particularly in mice). The analgesic effects of adenosine were completely abolished by caffeine (10 mg/kg in mice and rats), and partially inhibited by naloxone (1 mg/kg, only in mice). S-PIA given alone (0.6 mg/kg) produced in mice some analgesic effect in the hot-plate test: the effect was abolished by caffeine and partially by naloxone. The effect of S-PIA on the action of morphine depends on the dose and the animal species. Dipyridamole alone did not affect the reactivity of animals in tests for analgesia, but potentiated the action of morphine.
 ...
PMID:The effect of adenosine receptor agonists on analgesic effects of morphine. 228 Oct 16

Adenosine-mediated analgesia and interactions between opioids and adenosine in the brain have been observed by several researchers. Our investigations were designed to examine opioid-adenosine interactions at spinal sites and possible modulation of opioid-stimulated descending antinociceptive pathways by adenosine in the spinal cord. Methylxanthines administered intrathecally (i.t.) were used as adenosine receptor antagonists to determine possible interactions between opioids and endogenous adenosine. Theophylline administered i.t. dose-dependently antagonized analgesia induced by morphine administered i.t. or i.c.v. as measured by tail-flick and hot-plate assays. Analgesia induced by i.t. injections of 2-chloroadenosine, an adenosine agonist, was also antagonized by theophylline. However, doses of naloxone (i.t.) that antagonized analgesia induced by i.t. injections of morphine had no effect on 2-chloroadenosine (i.t.)-induced analgesia. These data support morphine-stimulated release of adenosine in the spinal cord. Antagonism of morphine (i.c.v.)-induced analgesia by theophylline was mimicked by caffeine and isobutylmethylxanthine. The results could not be explained as a consequence of effects on phosphodiesterease enzymes, drug-induced hyperalgesia or spinal redistribution of i.c.v. administered morphine. Therefore, our studies suggest that endogenous adenosine in the spinal cord is involved in analgesia mediated by opioid-stimulated descending antinociceptive pathways.
 ...
PMID:Spinal adenosine modulates descending antinociceptive pathways stimulated by morphine. 242 75

Spinal analgesia produced by morphine is blocked by methylxanthine adenosine receptor antagonists. In biochemical studies, morphine releases adenosine from spinal cord synaptosomes prepared from the dorsal spinal cord, as well as from the intact spinal cord in vivo. Adenosine release is reduced by intrathecal and neonatal pretreatment with capsaicin but not by intrathecal pretreatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine, indicating that adenosine originates from small-diameter primary afferent neurons but not descending monoaminergic pathways. In this Viewpoint Jana Sawynok and colleagues review the evidence supporting the hypothesis that the spinal analgesic action of morphine is due to the release of adenosine from primary afferent nerve terminals and subsequent activation of A1 and A2 adenosine receptors.
 ...
PMID:Adenosine release may mediate spinal analgesia by morphine. 258 27

Treatment of mice with either a 75-mg morphine pellet (72 h) s.c. or 100 mg/kg of morphine s.c. (3.5 h) did not alter the ED50 of (-)-N6-(phenylisopropyl)adenosine (PIA) in the tail-flick assay. Under the same treatment conditions, caffeine became a more potent antagonist of PIA-induced analgesia, and the dose-response curve for the locomotor effects of caffeine was shifted to the left. There was no change from control in the distribution of caffeine to the brain in mice pretreated with morphine. Brain levels of PIA were decreased significantly at the two highest doses used to elicit analgesia in morphine-implanted mice when compared to control. Adenosine receptor binding assays, utilizing [3H]PIA and [3H]diethylphenylxanthine as agonist and antagonist ligands, respectively, revealed significant increases in the Bmax values for both ligands without changes in Kd in morphine-implanted mice when compared to control. These data suggest that there is an increase in sensitivity to drugs which interact with adenosine receptors in morphine-tolerant and -dependent mice.
 ...
PMID:Changes in adenosine receptor sensitivity in morphine-tolerant and -dependent mice. 300 48

mu-Opioid receptor agonists, e.g. morphine, produce analgesia that can be potentiated by restraint stress. Adenosine receptor agonists, e.g. 5'-N-ethylcarboxamidoadenosine (NECA), also produce analgesia. To determine if adenosine-induced analgesia is also potentiated by stress, dose- and time-effect curves for NECA (0.01-0.1 mg/kg s.c.) were generated in adult male Sprague-Dawley rats either unrestrained or restrained in Plexiglas cylinders, using the tail-flick assay. Morphine (1.0-5.6 mg/kg s.c.) was also tested for comparison. Both compounds produced dose-dependent increases in tail-flick latencies. This effect of both drugs was potentiated in restrained rats. The opioid receptor antagonist, naltrexone (1.0 mg/kg s.c.) blocked completely the effect of morphine in both groups and attenuated the stress-induced potentiation of NECA-induced analgesia. The adenosine receptor antagonist, caffeine (10.0 mg/kg s.c.), blocked the analgesic effect of NECA but not that of morphine. These results indicate that adenosine-mediated analgesia is potentiated by restraint stress and suggest a role for endogenous opioids in the mediation of stress-induced potentiation of analgesia.
 ...
PMID:Restraint stress potentiates analgesia induced by 5'-N-ethylcarboxamidoadenosine: comparison with morphine. 822 92

This is a case report of supraventricular tachycardia following initiation of epidural analgesia with use of an epinephrine test dose in a parturient during active labor. Vagal stimulatory efforts failed to interrupt the arrhythmia, but treatment with adenosine was successful. Fetal monitoring with a scalp electrode provided evidence of fetal well-being throughout the episode. Adenosine was chosen because of its safety for both the mother and the fetus and its lack of the hypotensive effect often seen with verapamil.
 ...
PMID:Adenosine treatment of supraventricular tachycardia following epidural test dose: a case study. 829 2

During pregnancy, stress and vigorous exercise often result in pronounced tachycardia. Generally, a vagal stimulatory effort will interrupt the episode; however, intrapartum supraventricular tachycardia may not respond to vagal stimulation, necessitating drug therapy. This article is a case report of idiosyncratic supraventricular tachycardia following initiation of epidural analgesia; use of epinephrine was part of the test dose protocol. Adenosine, chosen for the lack of hypotensive effect associated with verapamil, was administered intravenously with immediate results. Fetal monitoring via scalp electrode provided evidence of fetal well-being during and after the episode.
 ...
PMID:Idiosyncratic supraventricular tachycardia after epidural anesthesia. 842 91

It has been proposed that adenosine mediates ischaemic pain in humans. Patients with cardiac Syndrome X are hypersensitive to potential pain stimuli, including adenosine. On the other hand, recent findings suggest that low-dose adenosine infusion may have analgesic effects. Our aim was to test two hypotheses: (1) that the analgesic effect of adenosine is peripheral in origin, and (2) that part of the hypersensitivity to pain of patients with cardiac Syndrome X results from a disturbed mechanism of adenosine analgesia. A total of 12 female Syndrome X patients and eight healthy age-matched female controls were studied in a randomized, double-blind and placebo-controlled study. Adenosine (70 microg/min) or placebo was infused into the forearm via an intra-arterial catheter. After 15 min of infusion, a tourniquet on the upper arm was inflated to 225 mmHg to ensure arterial occlusion. The patient then carried out dynamic handgrip work at 60 Hz. Pain or discomfort in the forearm was estimated continuously according to the Borg CR-10 scale. After the first test, theophylline was infused for 10 min intravenously at a dose of 5 mg/kg body weight. The ischaemic forearm test was then repeated. On a second occasion, the procedure was repeated with the opposite treatment (adenosine/placebo). Only six of 12 Syndrome X patients completed the protocol because of pain during the catheterization procedure or an inability to establish an intra-arterial line. The time to onset of pain in the working, ischaemic forearm was greater for subjects treated with adenosine than for those treated with placebo, both in those Syndrome X patients who tolerated catheterization (49+/-27 s compared with 32+/-18 s; P<0.03) and in healthy controls (40+/-19 s compared with 16+/-8 s; P<0.02). The time to maximum pain, limiting ischaemic work, was also greater with adenosine pretreatment both in Syndrome X patients (137+/-28 s compared with 106+/-28 s; P<0.03) and in healthy controls (109+/-31 compared with 82+/-18 s; P<0.01). After infusion of theophylline there was no difference between adenosine and placebo in either group. Intra-arterially infused adenosine had similar peripheral analgesic effects on experimentally induced muscular ischaemia in those female Syndrome X patients who tolerated intra-arterial catheterization and in healthy controls. Thus adenosine analgesia is counteracted by theophylline, suggesting that the effect is mediated by membrane-bound peripheral adenosine receptors.
 ...
PMID:Analgesic effects of adenosine in syndrome X are counteracted by theophylline: a double-blind placebo-controlled study. 1060 Jun 54

Although significant improvement has been made in the treatment of pain in the postoperative period, many patients still experience unnecessary discomfort resulting in distress, higher morbidity and prolonged stay in hospital. The standard pillar of postoperative treatment of severe pain is the use of opioids. However, adverse reactions to opioids make their use unfavourable. A better understanding of the pathophysiology of pain has helped clinicians to a more balanced approach to postoperative pain treatment. The development of the multimodal approach to postoperative analgesia, with the use of different drugs acting via different routes to give good analgesia, with minimal side-effects, represents a major development in the treatment of postoperative pain. Early, aggressive mobilisation and feeding must follow in order to restore normal conditions quickly. Alternatives to opioids should be used as extensively as possible. Local anaesthesia, used as regional blocks or as wound infiltration, is most beneficial. Paracetamol has good basic analgesic properties, and should probably be used in dosages higher than recommended today. The combination with a NSAID results in better and longer-lasting analgesia. The intravenous form propacetamol will increase the possibilities of its use. The new concept of selective COX-2 inhibiting NSAIDs will result in analgesic and anti-inflammatory drugs with fewer side-effects. The well-known inexpensive group of corticosteroids have good analgesic and anti-emetic properties, and are especially interesting to use in patients who do not tolerate NSAIDs. The alpha2-receptor agonists like clonidine, when administered epidurally or intrathecally, are useful adjuncts, but their adverse effects on sedation and hypotension limit their use. NMDA-receptor antagonists are of limited value in the postoperative period. Adenosine and neostigimine are still on a research level but may lead to new, clinically useful analgesic drugs. In the future, cannabinoids, cholecystokinin-receptor antagonists and neurokinin-1 antagonists may become important analgesic drugs.
 ...
PMID:Non-opioid postoperative analgesia. 1106 98


1 2 3 Next >>