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, an endogenous antinociceptive compound acting in the central nervous system, was infused intravenously (50-70 micrograms/kg/min) to 2 patients with peripheral neuropathic pain. In 1 subject, spontaneous pain was alleviated, and tactile allodynia was essentially relieved during 40 min of infusion. Allodynia to warmth and touch were abolished in the other subject. In addition, hyperalgesia to pinprick was markedly attenuated as was pressure-induced allodynia. The reported effects lasted for hours after termination of the infusion. Our preliminary encouraging data call for further controlled studies of the potentially relieving effect of adenosine in painful neuropathic conditions.
Pain 1995 Apr
PMID:Systemic adenosine infusion: a new treatment modality to alleviate neuropathic pain. 764 39

In an open study a total of 53 episodes of supraventricular reentrant tachycardia in 31 infants and children were treated with intravenous adenosine at two centers. Adenosine was given as a rapid intravenous bolus injection beginning with a dose of 0.1 mg/kg. If there was persistence of the dysrhythmia dosage was increased in 0.05 mg/kg-steps up to a maximum dose of 0.3 mg/kg if necessary. The median dose required for successful termination of the tachycardias was 0.15 mg/kg. In 26 patients with 48 episodes of regular narrow-QRS-complex tachycardia adenosine was used as the therapeutic agent of first choice. In all patients a shortlasting atrioventricular block occurred within seconds after the administration of adenosine. In 42 of 48 episodes of tachycardia (87%) the dysrhythmias were converted to a stable sinus rhythm. In six episodes (13%) recurrence of the tachycardia was observed immediately. In five children adenosine was used for diagnostic purpose: in three children with wide-QRS-complex tachycardia successful termination with adenosine proved the supraventricular origin of the dysrhythmia. In two children with suspected atrial flutter adenosine-induced atrioventricular block allowed identification of flutter waves in one patient while in the other patient no effect of adenosine was seen. Side-effects such as flush, chest-pain or abdominal pain were frequent but mild and only of a few seconds' duration. No influence of adenosine on blood pressure was noted. Only in one child with previously unknown sinus node dysfunction was a relevant electrophysiologic side effect seen: a prolonged sinus arrest with asystole of 12 seconds' duration occurred after adenosine administration.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Therapeutic efficacy and diagnostic potential of adenosine in infants and children]. 773 18

Adenosine, intrathecally administered, produces antinociception in experimental studies on animals. The effect of intravenous (i.v.) adenosine on experimentally induced pain in humans has not been studied. The present single-blind, randomized, placebo-controlled study was conducted in nine healthy volunteers. The pain-reducing effects of adenosine (70 micrograms.kg-1.min-1 i.v.), morphine (0.1 mg/kg i.v.), ketamine (0.1 mg/kg i.v.), adenosine + morphine, and adenosine + ketamine were compared to each other and to placebo in random order. Ischemic pain was induced by the submaximum effort tourniquet technique. Pain was assessed using the visual analog scale (VAS, 0-100 mm). The sums of pain scores (SPS) were compared and found significantly 30%-40% lower for adenosine as well as for the other compounds and combinations (P < 0.03), compared to placebo. The number of subjects who reached VAS 100 within 30 min was significantly lower (P < 0.03) when receiving adenosine + morphine (0/9) and adenosine + ketamine (2/9) than when receiving placebo (7/9). This may indicate an additive effect on pain reduction when adenosine is given in combination with morphine or ketamine. In conclusion, the results indicate that i.v. adenosine, as well as morphine and ketamine, can reduce experimentally induced ischemic muscle pain in healthy volunteers.
 ...
PMID:The influence of adenosine, ketamine, and morphine on experimentally induced ischemic pain in healthy volunteers. 794 93

Abnormal constriction of coronary resistive vessels can induce angina and myocardial ischemia. The possibility that a microvascular vasomotor dysfunction could cause ischemia is in contrast with the well-known traditional notion that a metabolically induced vasodilation could compensate for the effect of an epicardial coronary stenosis. Vasoconstrictor stimuli can plausibly act on vessels situated immediately proximal (prearterioles) to those that can be dilated by ischemia metabolites (arterioles). This functional 2-compartment model of resistive vessels is based on the ability of different substances to cause opposite actions on resistive vessels with different sizes. The possible mechanisms of prearteriolar dysfunction, observed in patients with syndrome X, single vessel disease after a successful PTCA and in a subset of chronic stable patients include: an organic reduction of total vascular section; vascular smooth muscle hyperreactivity to heterogeneous constrictor stimuli; an impaired flow-mediated endothelium-dependent vasodilation (possibly due to a reduced NO and/or EDHF synthesis). The first and third hypothesis can only account for anginal episodes at effort while the second model could explain episodes occurring at rest and without an increase in heart rate. Those mechanisms causing an imbalance between myocardial oxygen supply and demand, induce an increased release of adenosine in order to promote a compensating vasodilation. Adenosine can possibly avoid the occurrence of ischemia but, being a powerful algogenic stimulus, causes pain. It is worth noting that the presence of patchy prearteriolar dysfunction induces areas with excessive release of adenosine. Since total vascular section is extremely large a massive adenosine spill-over can occur with a consequential boosting of algogenic and vasodilatory effect.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Mechanisms of coronary microvascular dysfunction]. 802 13

Clinical characteristics: Angina pectoris represents a visceral pain caused by reversible myocardial ischemia. The majority of ischemic attacks are symptomless. When pain is manifested, it appears late during the ischemic event. The pain is complex in its quality and bears little relation to the region of myocardial ischemia. Pain shows a sensitive dependence on initial conditions suggesting a mechanism with deterministic chaotic dynamics for the association between myocardial ischemia and pain. Neurophysiological substrate: Ganglia are present within the heart, particularly in epicardial fat. The blood supply of intrinsic cardiac ganglia arises primarily from branches of the proximal coronary arteries. Both afferent and efferent neurons within the intrinsic cardiac nervous system exist, while the majority of neurons in that location may be local circuit neurons. Integration takes place not only in the intrinsic cardiac nervous system, but also in mediastinal, middle cervical, and stellate ganglia. Cardiac afferent receptors are also connected to cell bodies in dorsal root and nodose ganglia, as well as intrathoracic ganglia. Myocardial regions have no spatial representation in these ganglia. Adenosine, among a number of substances, can modulate the activity generated by cardiac afferent nerve endings and intrinsic cardiac neurons. Such effects appear to be exerted at A1 receptors. Adenosine as a pain messenger: During myocardial ischemia adenosine is released in large quantities into the interstitial space. The endothelium takes up the major amount of adenosine. Thus only small increments of adenosine are detected in the blood-stream. Given as an intravenous bolus to healthy volunteers or to patients with ischemic heart disease and angina pectoris, adenosine provokes angina pectorislike pain, which is similar to habitual angina pectoris with regard to quality and location. Pain is provoked in the absence of ECG signs of ischemia. Patients with asymptomatic myocardial ischemia are less sensitive to adenosine, whereas patients with Syndrome X are more sensitive with respect to adenosine-provoked pain. When adenosine is given intraarterially, including into the coronary arteries, pain is provoked in the corresponding vascular bed. Adenosine-provoked pain and ischemic pain are counteracted by previous administration of the adenosine receptor antagonist theophylline.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Mechanisms of pain in angina pectoris--a critical review of the adenosine hypothesis. 811 Jun 16

Adenosine is known to cause pain when injected intravenously or intra-arterially. We have conducted a double-blind placebo-controlled study by injecting adenosine intradermally in 6 healthy subjects (5 male, 1 female; age: 27-34 years). Pain was assessed using the visual analogue scale. The intradermal injection of 2 mumol of adenosine produced pain significantly greater than normal saline after 15 sec (T0) (29 +/- 13 vs. 7 +/- 6 mm, P = 0.004), 1 min after T0 (13 +/- 9 vs. 0 +/- 0 mm, P = 0.002) and 2 min after T0 (4.5 +/- 5 vs. 0 +/- 0 mm, P < 0.05). There was evidence of hyperalgesia to mechanical and heat stimuli at the injection site (primary hyperalgesia). There was no evidence of mechanical hyperalgesia in the cutaneous area surrounding the injected site (secondary hyperalgesia). In all cases the intradermal injection of adenosine produced local hyperemia (mean surface are: 147 +/- 69 mm2) which was absent after placebo injection. The pre-injection of bamiphylline, a rather selective antagonist of A1 adenosine receptors, differently from placebo, completely suppressed the adenosine-induced pain after 15 sec (T0) (15 +/- 10 vs. 0 +/- 0 mm, P = 0.002) and 1 min after T0 (9 +/- 7 vs. 0 +/- 0 mm, P = 0.002). No anesthesia to heat, cold and mechanical stimuli was detected at the bamiphylline site. The adenosine-induced erythematous area was wider at the bamiphylline pre-injected site than at the placebo pre-injected site (173 +/- 114 vs. 119 +/- 85 mm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Pain 1993 May
PMID:Analgesic effect of bamiphylline on pain induced by intradermal injection of adenosine. 833 89

Adenosine, a modulator of pain processing in the spinal cord, is metabolized by adenosine kinase and adenosine deaminase. In this study we determined which of these mechanisms is more important for the regulation of endogenous adenosine levels in the rat spinal cord. The effects of the adenosine kinase inhibitors, 5'-amino-5'-deoxyadenosine (NH2dAD) and iodotubercidin (IOT), and the adenosine deaminase inhibitor, 2'-deoxycoformycin (DCF), on adenosine release in a spinal cord superfusion model were studied. DCF markedly increased basal adenosine levels detected in perfusates and was more potent than NH2dAD and IOT in this regard. Coadministration of DCF with NH2dAD produced an enhanced effect compared to the inhibitors alone. NH2dAD, but not DCF, potentiated morphine-evoked adenosine release. These results suggest that adenosine deaminase may be the predominant pathway for adenosine metabolism in this experimental model.
 ...
PMID:Modulation of adenosine release from rat spinal cord by adenosine deaminase and adenosine kinase inhibitors. 861 36

The analgesic potential of adenosine during myocardial ischaemia was studied in patients with coronary artery disease and exercise-limiting angina pectoris. Patients were given a low dose of adenosine or placebo in a double-blind cross-over fashion by continuous i.v. infusion before and during two exercise tests. Adenosine decreased chest pain by 45 +/- 13% (p < 0.02) while heart rate-blood pressure product and electrocardiographic signs of myocardial ischaemia did not change. Ten healthy volunteers received increasing doses of adenosine by continuous i.v. infusion. The heat pain threshold increased in skin covering the chest (p < 0.03) and also tended to increase at the left thenar eminence (p < 0.07). In conclusion, the neuromodulator adenosine can therefore act as an analgesic in myocardial ischaemia.
 ...
PMID:Analgesic effects of adenosine during exercise-provoked myocardial ischaemia. 885 12

Adenosine or adenosine analogs injected intrathecally (i.t.) induce significant antinociception. Recent studies support the existence of an endogenous spinal system that can modulate nociceptive input by releasing adenosine. Inhibition of adenosine metabolism by administration of an adenosine kinase inhibitor, in the present study, decreased behavior induced by putative pain neurotransmitters providing additional support for an endogenous purinergic system. Conversely, administration of high doses of methylxanthines (i.t.), adenosine receptor antagonists, induced behavior similar to that induced by pain neurotransmitters. Methylxanthine (i.t.)-induced behavior was partially inhibited by antagonists of receptors for pain neurotransmitters. These observations are consistent with the hypothesis that an endogenous purinergic system tonically modulates nociceptive input involving a variety of chemical mediators. Preliminary studies also revealed methylxanthine-induced allodynia and suggested spinal purinergic systems may have a broader role in discriminating sensory input.
 ...
PMID:Altered sensory behaviors in mice following manipulation of endogenous spinal adenosine neurotransmission. 889 73

1. This review focuses on the extracellular actions of ATP and adenosine, and in particular their role in cardiovascular regulation. 2. ATP serves as a co-transmitter within the sympathetic nervous system, and is also released from endothelium and aggregating thrombocytes. ATP acts on P2x purinoceptors on vascular smooth muscle cells to induce vasoconstriction. Stimulation of P2y purinoceptors on endothelial cells releases endothelium-derived relaxing factors and causes vasodilatation. This dual action of ATP may have pathophysiological importance by inducing vasospasm at sites of impaired endothelial function and thrombus formation. 3. Adenosine is generated by enzymic degradation of ATP. Its formation is enhanced during ischaemia. Adenosine inhibits noradrenaline release from sympathetic nerve endings, causes vasodilatation via endothelium-dependent and endothelium-independent actions, has important anti-arrhythmic properties and prevents deleterious sequelae of ischaemia. In humans, adenosine evokes a sympatho-excitatory reflex mediated by chemically sensitive receptors and afferent nerves in the kidney, heart and forearm. This reflex may be active during exercise and ischaemia and, because of its potential adverse consequences, it should be considered when developing new therapies to potentiate the anti-ischaemic actions of endogenous adenosine in humans. Adenosine appears to mediate ischaemia-induced pain; a reduced sensitivity to adenosine may underlie silent ischaemia. 4. New drugs that interact with adenosine formation or degradation or with adenosine receptors are under development. These have potential therapeutic application in the treatment of ischaemia and other circulatory disorders.
 ...
PMID:Cardiovascular pharmacology of purines. 903 87


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