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)

To investigate whether ATP participates in spinal nociceptive transmission, effects of intrathecally applied P2-purinoceptor antagonists and agonists in the tail-flick and the formalin test were studied in rats. In the tail-flick assay, the P2 antagonists suramin (12-120 micrograms), Evans blue (0.1-10 micrograms), Trypan blue (1-30 micrograms) and Reactive blue 2 (1-30 micrograms) but not pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 0.03-30 micrograms) caused moderate antinociception up to a doubling of the response latency. In contrast, the P2 agonists alpha,beta-methylene ATP (alpha,beta-mATP, 0.3-30 micrograms) and 2-methylthio-ATP (3-30 micrograms) decreased the tail-flick latency by up to about 50%. When co-injected with alpha,beta-mATP, suramin (120 micrograms) or Evans blue (10 micrograms) prevented the effect of alpha,beta-mATP 3 micrograms but not of alpha,beta-mATP 30 micrograms. In the formalin test, pretreatment with suramin (3-90 micrograms) 60 min prior to testing caused significant antinociception by decreasing the weighted pain intensity score by up to about 80%. alpha,beta-mATP (30 micrograms), applied 30 min prior to testing, was without effect. The results indicate that endogenous ATP, acting through P2-purinoceptors, may contribute to nociceptive information processing in the spinal cord.
 ...
PMID:Antinociceptive effect of intrathecally administered P2-purinoceptor antagonists in rats. 788 28

In order to assess the acute metabolic effects of an intra-arterial infusion of nucleotide-nucleoside-mixture (NNM), 31P-mr-spectroscopy at the site of m. gastrocnemius and metabolite determinations from blood of the femoral artery and vein were carried out in 10 patients with PAOD stage II during ergometric calf exercise to the claudication pain limit. The spectroscopic measurements revealed a greater exercise-induced fall of PCr and a higher increase of Pi in calf muscles during supply of NNM compared with control ergometry. Post-exercise recovery of PCr was distinctly delayed during infusion of NNM. The anaerobic production of energy, however, was sufficient to maintain the ATP concentration to the same extent as under control ergometry. On the other hand, intramuscular lactate acidosis developed to a lower degree with NNM infusion than without NNM. A reduced muscular release of lactate, pyruvate, ammonia and alanine followed from the evaluation of the arteriovenous balance of these metabolites in the femoral vessels indicating a favourable global metabolic effect of NNM infusion in the extremity. The apparent contradiction in the spectroscopic and analytic-biochemical findings can be explained by local blood shunts induced by maximum vasodilation. Noninvasive mr-spectroscopy allows to detect directly and continuously the metabolic impact of ischemia in the calf muscles afflicted by arterial occlusion, whereas the metabolite concentrations in femoral blood are altered by afflux from non-ischemic areas. The known clinical benefit of frequently repeated intra-arterial infusions of NNM is thought to be due to an expansion of collateral circulation and to a favourable influence on endothelial functions.
 ...
PMID:[Effects of a nucleotide-nucleoside mixture on ischemic muscle metabolism in patients with stage II peripheral arterial occlusive disease. MR spectroscopic and biochemical analytic results]. 803 45

There have been hints over the years about the involvement of purines in pain, and we now have direct evidence with the cloning and characterisation of extracellular receptors for ATP (P2X-purinoceptors) on nociceptive sensory neurons. In this article, a hypothesis is put forward about the sources of ATP released to activate these receptors in three different pain conditions--as a cotransmitter from sympathetic nerves in causalgia and reflex sympathetic dystrophy; from endothelial cells in vascular pain, including migraine and angina; and from tumour cells in cancer. These findings are leading to an active search for selective P2-purinoceptor antagonists to alleviate pain.
 ...
PMID:A unifying purinergic hypothesis for the initiation of pain. 866 73

The recent discovery of a P2X purinoceptor (a ligand-gated ion channel triggered by ATP) that is selectively expressed by small-diameter sensory neurons has led to the exploration of the sources of ATP involved in the initiation of different types of nociception and pain, including sympathetic nerves, endothelial cells and tumour cells. In addition, the anti-nociceptive actions of adenosine via prejunctional P1(A1) purinoceptors in the spinal cord and the pain-enhancing actions of adenosine via P1(A2) purinoceptors in the periphery have generated great interest in the development of P1 agonists and antagonists, as well as P2X antagonists as potential analgesic drugs.
 ...
PMID:Purinergic receptors: their role in nociception and primary afferent neurotransmission. 879 2

Extracellular ATP elicits biological responses ranging from cell death to synaptic transmission. Recent gene-cloning efforts have uncovered a family of cell-surface ATP receptors, which are potential targets for the development of novel drugs to treat airway and cardiovascular diseases, inflammation and pain.
 ...
PMID:ATP receptors in sickness, pain and death. 880 49

Nociceptors belong to A delta and C afferents that are equipped in the periphery with receptors for detecting potentially damaging physical and chemical stimuli. This review summarizes experimental evidence that these receptors represented by ionic channels are also functionally expressed on the cell bodies of sensory neurones in short-term cultures. The nociceptors belong predominantly to the small and medium size DRG neurones in which algogens such as weak acids, capsaicin, bradykinin and scrotonin produce inward currents that can generate impulse activity. It seems likely that the neurones which are not sensitive to algogens but to GABA, ATP or glutamate, agents not producing pain in humans, belong to other categories of DRG neurones equipped for detecting other modalities of sensation. new techniques for physical stimulation of DRG neurones in culture may be of great help in the search for complementing the criteria for distinguishing nociceptors among other neurones in culture. It is suggested that such an in vitro model will be useful for studying cellular mechanisms of nociception.
 ...
PMID:Can sensory neurones in culture serve as a model of nociception? 888 18

ATP stimulates nociceptive neurons via an action on ligand-gated ion channels. Since tissue injury and inflammation result in both localized acidosis and release of ATP, we studied the effect of acid pH on ATP-gated ion channels in rat nodose ganglion neurons. Lowering pH dramatically increased membrane depolarization and action potential firing elicited by ATP. ATP-activated current was enhanced by acid pH and suppressed by alkaline pH. A pH of 7.2 produced the half-maximal effect. Acidification increased the apparent affinity of the receptor for ATP, as evidenced by a parallel shift of the ATP concentration-response curve to the left. The observations suggest that the localized acidosis associated with tissue injury may enhance pain perception via an action on ATP-gated ion channels on mammalian sensory neurons.
 ...
PMID:Acid pH augments excitatory action of ATP on a dissociated mammalian sensory neuron. 893 Sep 78

Recent reports demonstrated that K+ channels could contribute to signal transmission in the brain and spinal cord, and opioids' action may be related to K+ channels' functions. We investigated the antinociceptive effect of epidurally injected ATP-sensitive K+ channel opener, nicorandil, using tail flick test in rats. Epidural nicorandil (100 micrograms.rat-1) increased % maximum possible effect (%MPE) of epidural morphine (1, 10 micrograms.rat-1) from -3% to 40% (P < 0.05) and 46% to 65%, respectively. Epidural glibenclamide (10 micrograms.rat-1), ATP-sensitive K+ channel blocker, antagonized this effect. Epidural nicorandil alone (10 approximately 100 micrograms.rat-1) showed no antinociceptive effects. Systemic nicorandil (100 micrograms.rat-1, i.m.) did not increase the epidural morphine analgesia. These data suggest that the K+ channel opener could point the way to a new approach to pain treatment.
 ...
PMID:[Nicorandil, as ATP-sensitive K+ channel opener, potentiated morphine analgesia]. 895 67

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

The initial pain from tissue damage may result from the release of cytoplasmic components that act upon nociceptors, the sensors for pain. ATP was proposed to fill this role because it elicits pain when applied intradermally and may be the active compound in cytoplasmic fractions that cause pain. Moreover, ATP opens ligand-gated ion channels (P2X receptors) in sensory neurons and only sensory neurons express messenger RNA for the P2X3 receptor. To test whether ATP contributes to nociception, we developed a tissue culture system that allows comparison of nociceptive (tooth-pulp afferent) and non-nociceptive (muscle-stretch receptor) rat sensory neurons. Low concentrations of ATP evoked action potentials and large inward currents in both types of neuron. Nociceptors had currents that were similar to those of heterologously expressed channels containing P2X3 subunits, and had P2X3 immunoreactivity in their sensory endings and cell bodies. Stretch receptors had currents that differed from those of P2X3 channels, and had no P2X3 immunoreactivity. These results support the theory that P2X3 receptors mediate a form of nociception, but also suggest non-nociceptive roles for ATP in sensory neurons.
 ...
PMID:Distinct ATP receptors on pain-sensing and stretch-sensing neurons. 916 13


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