Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine administered to humans has been reported to induce pain after intravenous administration. On the other hand adenosine analogues have been shown to possess antinociceptive effects after peripheral and intrathecal administration in animals. The aim of the present study was to investigate the effect of peripheral administration of adenosine agonists with different affinities for the A1 and A2 adenosine receptors on a persistent pain stimulus using the formalin test. The drugs chosen were, R-phenylisopropyl-adenosine (R-PIA) with high affinity for the A1 receptor, N-ethylcarboxamide-adenosine (NECA) with almost equal affinity for the A1 and A2 receptor and 2-(2-aminoethylamino)-carbonylethylphenylethylamino-adenosin e (APEC) with high affinity for the A2 receptor. The drugs were mixed with formalin and administered subcutaneously into the dorsal hind paw in mice to study the local effects. They were also injected separately from the formalin solution in different paws to evaluate the systemic effect. The total time of licking the injected paw during the first 5 min. was recorded. In high doses all compounds reduced the licking activity, but a low dose of APEC (1 microM) injected together with the formalin solution had an algesic effect. All effects were antagonized by theophylline. These results suggests that A1 adenosine receptors mediate a local peripheral antinociceptive effect and the involvement of local peripheral A2 receptors in the enhancement of the algesic response.
 ...
PMID:Local antinociceptive and hyperalgesic effects in the formalin test after peripheral administration of adenosine analogues in mice. 143 21

Intravenous (i.v.) bolus administration of adenosine causes increased ventilation and an angina pectoris-like chest pain. Whether adenosine per se or one of its metabolites such as inosine mediates these effects is not clear. Bolus doses of adenosine, inosine, or saline were administered i.v. blindly to six volunteers. Spirometry, ECG recordings, and pain ratings were taken. Adenosine induced both an increase in tidal volume and respiration rate, a dose-dependent chest pain and, at higher doses, various degrees of atrioventricular (AV) block. None of these effects were noted after equimolar injections of inosine or saline. The findings indicate that the angina pectoris-like pain and increased ventilation is induced by adenosine per se and is not produced by adenosine metabolites.
 ...
PMID:Intravenous adenosine but not its first metabolite inosine provokes chest pain in healthy volunteers. 169 61

In this pilot study some cardiac effects of exogenous adenosine on the denervated heart were studied in a patient with transplanted heart since 3 years. He was instrumented with catheters into the left coronary artery, the coronary sinus and the right ventricle. Adenosine was given in increasing doses intracoronarily, into the aorta at the diaphragmal level and into a peripheral vein. When given into the aorta pain was provoked dose-dependently and not different from a reference group. When given intracoronarily no pain was provoked except at the highest dose when a slight discomfort of the chest was provoked. After intravenous injection no pain was provoked in the chest or in adjacent structures. Coronary sinus flow increased dose-dependently and not different from the reference group. No increased heart rate response occurred after intravenous or intracoronary injections. Extensive degrees of sinus and AV nodal blockade occurred. In conclusion, the results are in keeping with a role for adenosine as a messenger between myocardial ischaemia and angina pectoris and cardiac sympathetic pressure response. The importance of innervation for proper sinus and AV nodal function was also illustrated.
 ...
PMID:Effects of exogenous adenosine in a patient with transplanted heart. Evidence for adenosine as a messenger in angina pectoris. 207 41

During myocardial ischemia, malignant arrhythmias and acceleration of cell damage may be induced by sympathetic overstimulation of the heart. This stimulation is due to excessive concentrations of catecholamines within the underperfused myocardium, in combination with enhanced myocyte sensitivity to adrenergic stimuli. Various mechanisms may account for local accumulation of catecholamines in the extracellular space of the ischemic but still viable myocardium. In early myocardial infarction, plasma noradrenaline and adrenaline concentrations are enhanced, reflecting increased activity of the whole sympathetic nervous system, rather than local activity in the heart. In uncomplicated infarction, these concentrations are only five times the normal levels at rest, and there are no convincing data that these mildly increased levels of plasma catecholamines directly induce a major deterioration of myocardial function during the ischemic process. Of more importance is the reflex increase in cardiac sympathetic nerve activity that is induced by pain, anxiety, and a fall in cardiac output or arterial blood pressure and that is accompanied by local exocytotic release of noradrenaline from sympathetic nerve endings of the heart. Excessive accumulation of the neurotransmitter, however, is prevented by at least three mechanisms: 1) Released noradrenaline is rapidly removed so long as neuronal catecholamine reuptake is functional. 2) Adenosine accumulating in the ischemic myocardium effectively suppresses exocytotic noradrenaline release by stimulating presynaptic A1-adenosine receptors. 3) Exocytotic catecholamine release ceases when the sympathetic neurons become depleted of adenosine triphosphate since this release mechanism requires high-energy phosphates. However, with progression of ischemia (i.e., greater than 10 minutes), the myocardium is no longer protected against excess adrenergic stimulation since local metabolic release mechanisms become increasingly important. This release, which is independent of both central sympathetic activation and extracellular calcium, occurs in two steps. First, catecholamines escape from their storage vesicles and accumulate in the cytoplasm of the neuron. In the second, rate-limiting step, noradrenaline is transported across the axolemma from the cytoplasm to the interstitial space via the neuronal uptake carrier in reverse of its normal transport direction. As a consequence of this nonexocytotic local metabolic release, extracellular noradrenaline reaches 100-1,000 times its normal plasma concentrations within 30 minutes of ischemia. Concentrations of this magnitude are capable of producing myocardial necrosis, even in the nonischemic heart, and may play an important role in the pathogenesis of ventricular fibrillation in early ischemia.
 ...
PMID:Catecholamines in myocardial ischemia. Systemic and cardiac release. 220 58

Adenosine is formed from adenosine triphosphate within the ischaemic cells from where it is released into the coronary circulation. Adenosine exhibits several cardiovascular effects which tend to protect the ischaemic myocardium. Based on the observation that in healthy volunteers the intravenous infusion of adenosine produces angina-like chest pain, it has been recently proposed that another cardioprotective action of this substance could be provocation of angina. If this is the case adenosine should not produce chest pain in patients with silent ischaemia. To test this hypothesis we infused this substance intravenously at increasing doses of 50, 100, 150, 200, 250 and 300 micrograms kg-1 min-1 in eight patients with silent ischaemia (group A). All of them developed ST depression (1.8 +/- 0.2 mm) during exercise testing and seven also during adenosine infusion (1.1 +/- 0.8 mm). However, none of the patients had chest pain during exercise while seven had chest pain during adenosine. We then infused adenosine in eight other patients (Group B) who had painful ischaemia and an exercise tolerance similar to that of Group A patients (time to 1 mm ST depression 8.6 +/- 2.7 min and 8.4 +/- 3 min, respectively, P = NS). Adenosine induced chest pain in all Group B patients. The time to pain onset during adenosine was similar in the two groups (9.3 +/- 2.3 min in Group B and 12.4 +/- 4.9 min in Group A).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Adenosine-induced chest pain in patients with silent and painful myocardial ischaemia: another clue to the importance of generalized defective perception of painful stimuli as a cause of silent ischaemia. 324 54

In rats pretreated with indomethacin, injection of PGE1 (prostaglandin E1) with carrageenan potentiated the carrageenan paw oedema. This effect of PGE1, was maximal when it was injected together with carrageenan, there being a reduction in the action of PGE1 if carrageenan injection was delayed after PGE1 injection. PGE1 induced potentiation of increase in plasma protein leakage induced by intradermal injections of bradykinin and histamine also depended on the injection of PGE1 along with these agents. Thus oedema enhancement by PGE1 differs from its action in pain, where PGs cause a long lasting sensitization of the injected area for the actions of other algesics. Since vasodilation may be a mechanism of oedema enhancement by PGs, the ability of adenosine and papaverine to mimic PGE1 in paws and skins of rats were examined. Adenosine was active whereas papaverine was inactive in this respect. To clarify this difference, the vasodilatory properties of PGE1, adenosine and papaverine were assessed by their ability to antagonize NA response in perfused rat mesenteric blood vessels. Only papaverine was effective in antagonising the NA response. Thus, PGE1 and adenosine which potentiated the oedema inducing actions of other agents showed no vasodilatory properties and papaverine, a vasodilator, had no oedema potentiating actions.
 ...
PMID:Characteristics of prostaglandin E1 potentiation of inflammatory activity of some agents. 738 37

Adenosine is an endogenously produced substance which in animal experiments exerts anti-nociceptive effects. In humans, algesic effects have been presented following exogenous adenosine administration. A recent study on anaesthetized patients, however, suggested an anti-nociceptive effect during i.v. adenosine. We have studied the pain-reducing effect in healthy volunteers using adenosine 50-80 micrograms.kg-1.min-1 (n = 10), morphine 0.1 mg.kg-1 (n = 5), adenosine 50 micrograms.kg-1.min-1 + morphine 0.1 mg.kg-1 (n = 6), and ketamine 0.1 mg.kg-1 (n = 5); all drugs given i.v., single-blind. Quantitative sensory tests (QST) revealed a significantly increased cutaneous heat pain threshold following adenosine. No effect was seen following ketamine or morphine. Suprathreshold heat pain perception was unchanged in all subjects. Furthermore, warm and cold perception thresholds were not influenced significantly by any drug. Adenosine, morphine and ketamine produced well-known side-effects but of a mild intensity not necessitating any treatment. The present results show that i.v. adenosine can provide a modest but selective increase of cutaneous heat pain thresholds, suggesting a pain-reducing capacity of adenosine in humans.
 ...
PMID:Adenosine increases the cutaneous heat pain threshold in healthy volunteers. 748 22

Adenosine is a possible mediator of cardiac pain during myocardial ischemia; however, little is known about the influence of adenosine on cardiac sympathetic afferent activity and thereby on its algogenic mechanism. In 20 anaesthetized, decerebrated, curarized and artificially ventilated cats, we studied the impulse activity of 20 single afferent sympathetic fibers with a left ventricular receptive field in relation to epicardial applications of adenosine, coronary artery occlusions and arterial pressure rises. All fibers increased their impulse activity (from 1.2 +/- 0.2 to 2.6 +/- 0.5 imp/s; P < 0.001) during slight (20 +/- 8%) rises in aortic pressure, thus exhibiting low-threshold receptor characteristics. In 10 cats, epicardial applications of three different doses of adenosine (0.1, 1 and 10 mg/ml) caused a brief increase in neural activity with dose-related responses. This response was abolished by aminophylline, a P1 purinergic inhibitor. In the other group of 10 cats, four subsequent 30-s occlusions of the coronary arterial vessel supplying the receptive fields of the fibers were performed, in control conditions and 30 s, 3 and 7 min, respectively, after the end of excitation induced by adenosine (1 mg/ml) application. During the control coronary occlusion the impulse activity increased from 1.1 +/- 0.1 to 5.5 +/- 0.7 imp/s (P < 0.0001). A similar activation was present during the second occlusion initiated 30 s after the end of adenosine-induced activation. In contrast, a significant potentiation of the response was observed (8.8 +/- 1.2 vs. 5.3 +/- 0.9 imp/s; P < 0.001) during the occlusion initiated 3 min after the end of excitation by adenosine. This effect was no longer present during the last occlusion performed after 7 min. When the protocol was repeated substituting adenosine with saline (n = 5) or after i.v. administration of aminophylline (n = 5), no potentiation was observed, even though the excitatory response to coronary occlusion was preserved. These data show that adenosine can activate cardiac sympathetic afferent fibers in a dose-related manner, and potentiate their responses to coronary occlusion, while leaving unaffected the responsiveness to a hemodynamic stimulus. The excitatory effects are likely to involve the P1 purinergic receptors. The potentiation phenomenon might play a role in the genesis of an algogenic code.
 ...
PMID:Adenosine activates cardiac sympathetic afferent fibers and potentiates the excitation induced by coronary occlusion. 756 Jul 54

In seven patients with peripheral neuropathic pain, the effect of systemic adenosine infusion on pain symptoms was evaluated in a double-blind, placebo controlled, cross-over study. The study infusions, adenosine (50 micrograms.kg-1.min-1) or placebo, were given intravenously (IV) during 45-60 min at two separate occasions. Before and during infusions, bedside examination of sensibility and quantitative sensory testing (QST), i.e., assessments of perception thresholds for touch, touch-evoked pain, cold, warmth, painful heat, and cold, were performed. In the neuropathic area, sensation magnitude was rated by a visual analog scale (100 mm VAS) using a pin and at perception threshold for touch-evoked pain using von Frey filaments. Adenosine infusion reduced spontaneous pain (P < 0.05), and caused an increase of the touch-evoked pain threshold from 10.8 +/- 5.3 to 22.2 +/- 6.9 g (P < 0.05), whereas placebo had no effect. Pain intensity at perception threshold for touch-evoked pain was, however, unaltered. Pinprick-evoked pain in the neuropathic areas was reduced from 53 +/- 11 to 29 +/- 10 mm (P < 0.05). No other sensory modality was consistently changed during adenosine infusion. In conclusion, the present study demonstrates that adenosine infusion alleviates spontaneous neuropathic pain, tactile allodynia, and pinprick hyperalgesia in patients with peripheral neuropathic disorders, probably by a central mechanism of action.
 ...
PMID:Systemic adenosine infusion alleviates spontaneous and stimulus evoked pain in patients with peripheral neuropathic pain. 757 99

Adenosine has been implicated in the pathogenesis of cardiac pain through activation of cardiac sympathetic afferents. The present study was performed to assess directly the contribution of adenosine in activating ischemically sensitive cardiac sympathetic afferents. Single-unit activity of ischemically sensitive afferents located in both ventricles was recorded from the left thoracic sympathetic chain or rami communicantes of anesthetized cats during 5 min of myocardial ischemia. Intracardiac injection (5 mg) or epicardial application (1-5 mg/ml) of adenosine onto the receptive fields failed to activate 31 ischemically sensitive A delta- and C fiber afferents, which were responsive to topical application of bradykinin (10 micrograms/ml). Intracardiac injection (5 mg) or topical application (1-5 mg/ml) of an adenosine A1 receptor agonist, N6-cyclopentyladenosine, also did not increase the discharge activity of 13 other ischemically sensitive C fiber afferents. Treatment with dipyridamole (1 mg/kg iv) to inhibit the cellular uptake of adenosine did not significantly potentiate the response of 10 separate C fiber afferents to 5 min of myocardial ischemia. Furthermore, blockade of adenosine receptors with aminophylline (5 mg/kg iv) did not significantly attenuate the response of 10 other C fiber afferents to 5 min of myocardial ischemia. The results of the present study demonstrate that exogenous and endogenous adenosine do not contribute to activation of ischemically sensitive cardiac sympathetic afferents. The findings of the present study fail to support a substantial role for adenosine and its A1 receptors in activation of cardiac sympathetic afferents during myocardial ischemia.
 ...
PMID:Lack of a role of adenosine in activation of ischemically sensitive cardiac sympathetic afferents. 763 38


1 2 3 4 5 6 7 8 9 10 Next >>