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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandins are highly potent derivatives of unsaturated fatty acids with multiple biological activities. They are synthesized and metabolized in almost all tissues studied so far. The E- und F-type prostaglandins may be regarded as local modulators of hormonal effects on cell function and--in some cases (kidney, uterus-corpus luteum)--as regional or tissue hormones. Thus they seem to be involved in the regulation of neurotransmission, kidney function, triglyceride metabolism in adipose tissue and progesterone biosynthesis. Apart from their influence on renal blood flow prostaglandins of the A-type possibly have an additional function as circulatory hormones regulating blood pressure. Second messenger-systems (cAMP, Ca++-cGMP) which mediate the effects of most non-steroidal hormones are also involved in the action of prostaglandins, at least of the E-and F-types. Disturbances in prostaglandin metabolism (increased or decreased biosynthesis) are discussed to play a role in the pathogenesis of inflammation, pain, fever, hypertension, bronchial asthma and gastric or duodenal ulcer formation. Drugs with antiinflammatory, analgesic and antipyretic activity have been shown to be potent inhibitors of prostaglandin formation. The correlation of a local prostaglandin deficit or the therapeutic use of single effects of prostaglandins by administration of exogenous compounds (natural prostaglandins or modified derivatives) has so long been less satisfactory because of their large number of biological actions which lead to undesired side effects. Extensive experience have been obtained in the successful induction of therapeutic abortion. This effect is based on the stimulatory action of E- and F-type prostaglandins on the smooth muscles of the pregnant uterus which is resistent to the influence of other stimuli, e. g. oxytocin. Here the incidence of side effects could be reduced by local administration of low doses of prostaglandins into the uterine cavity. A general improvement of the therapeutic usefulness of prostaglandins will however only be achieved, if modified derivatives with more specific actions on the desired "target" tissues are available.
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PMID:[Biology of prostaglandins with reference to therapeutic aspects]. 16

The dibutyryl derivative of guanosine 3',5'-monophosphate (cyclic GMP), administered centrally, totally abolishes response to noxious stimuli without depressing the central nervous system. Analgesic properties of the nucleotide are not reversed by naloxone. Microinjected intracerebrally into different sites, dibutyryl cyclic GMP does not mimic the action of morphine. Pharmacological effects of dibutyryl cyclic GMP suggest that endogenous cyclic GMP modulates an inhibitory pain pathway distinct from that on which morphine acts.
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PMID:Guanosine 3',5'-monophosphate: a central nervous system regulator of analgesia. 20 29

Levels of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) have been investigated in joint fluid in inflammatory arthropathies. A disturbed balance between cAMP and cGMP due to a depressed level of cAMP was found in rheumatoid arthritis (RA) and Reiter's syndrome, in comparison with patients with osteoarthritis. No correlation could be demonstrated between the absolute levels of cAMP or cGMP and the degree of local inflammatory activity, white cell count, or lysosomal enzyme activity in the joint fluid. Intra-articular injection of epinephrine showed just as good an effect on local pain as betamethasone (Cellestona), but the steriod reduced the swelling more effectively. An increase in intracellular levels of cAMP at 20 min was observed following injection of epinephrine with a slight change in cGMP. Intra-articular injection of dibutyryl-cAMP (db-cAMP) produced a marked easing of local pain and swelling in each of the 4 patients so treated. It is concluded that stimulation of the beta-adrenergic system or injection with db-cAMP may be beneficial in rheumatoid inflammation.
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PMID:Cyclic nucleotides in joint fluid in rheumatoid arthritis and in Reiter's syndrome. 22 70

This paper used RIA method to observe 11 cases of prolapsed intervertebral disc patients, detect the change of cAMP and cGMP in the cerebrospinal fluid before and after finger pressing massage in acupuncture point Weizhong and Chengshan in order to discuss the mechanism of analgesia of finger pressing massage. The results showed that the pain was relieved after finger pressing massage. cAMP of the cerebrospinal fluid increased from 0.51 +/- 0.19 to 0.63 +/- 0.13 pm/ml, in average 32% higher than that before the therapy (P less than 0.05). Since cGMP decreased from 30.52 +/- 26.42 to 23.20 +/- 16.91 pm/ml, it showed that the mechanism of analgesia of finger pressing massage might be due to the fact that the therapy excited selectively endogenous analgesia system, caused the increase of endorphin releasing, and was accompanied by the regulation of cAMP and cGMP.
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PMID:[Influence of finger pressing massage on cAMP and cGMP in the cerebrospinal fluid in prolapsed intervertebral disc]. 216 13

Bradykinin is the prime initiator of pain and the key initial activator of the inflammatory response at the site of tissue injury. The subsequent transfer of nociceptive information (pain sensation) into the central nervous system is then mediated via afferent type C dorsal root ganglion neurons. A recently developed hybrid cell line, F-11, shows many qualities characteristic of these pain-sensitive cells. In these neuronal hybrids, we have found that bradykinin induces sequential elevation in the concentrations of several second messengers involved in neuronal activation, including inositol trisphosphate (6.5-fold), intracellular calcium (2.7-fold), and cyclic GMP (20.5-fold). Importantly, the production of these second messengers is potently inhibited by several novel bradykinin antagonists that possess no intrinsic agonist activity. The same relative rank order of potency of inhibition of bradykinin-induced second messenger production was achieved in the inositol trisphosphate, calcium, and cyclic GMP assay systems, suggesting strongly that all three messenger systems are being activated by the same bradykinin receptor. The most potent antagonist was D-Arg0-Hyp3-Thi5,8-D-Phe7-bradykinin, which inhibited in a competitive manner, with pA2 values, upon Schild plot analysis, in the nanomolar range. These potent bradykinin antagonists may be useful in the characterization of bradykinin receptors and in the clinical management of pain and inflammation.
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PMID:Bradykinin analogs antagonize bradykinin-induced second messenger production in a sensory neuron cell line. 253 66

The effects of a number of vasoactive and neurotransmitter substances on lymphocyte traffic were studied by assessing their effects on the release of lymphocytes into primary peripheral (popliteal) nodal efferent lymph of sheep following acute infusion into cannulated afferent nodal lymphatics. In a total of 23 experiments, the output of lymphocytes, small and blast, was increased by serotonin, substance P, bombesin, [met]enkephalin, isoprenaline and phenylephrine and was decreased by vasoactive intestinal peptide (VIP), neurotensin and carbachol. Substances whose actions are modulated by prostaglandins and enhanced by prostaglandin synthesis inhibitors and which elevate blood monocyte and nervous tissue levels of cyclic GMP tended to increase lymphocyte traffic through peripheral lymph nodes in sheep in vivo. The opposite effect tended to be produced by substances whose actions require or are associated with prostaglandins or histamine, and which affect blood monocytic cyclic nucleotide levels by elevation of cyclic AMP or depression of cyclic GMP. Pain and inflammation tended to increase lymphocyte traffic, while analgesics and immunomodulators tended to decrease it.
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PMID:Modification of lymphocyte traffic by vasoactive neurotransmitter substances. 614 65

20 patients with active rheumatoid arthritis were treated for 12 weeks with the prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid in the form of primrose evening oil (Efamol) and the co-factors zinc, ascorbic acid, niacin, and pyridoxin (Efavit). There was a slight fall in skin reactivity to UV light during the treatment, but no effect on plasma or urine concentrations of PGE1, cAMP or cGMP. There was no effect of the treatment on ESR, P-fibrinogen, number of tender joints, number of swollen joints, the duration of morning stiffness, or on the patient's estimation of pain.
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PMID:Treatment of rheumatoid arthritis with prostaglandin E1 precursors cis-linoleic acid and gamma-linolenic acid. 630 71

The effect of intracellular modulators and ions on the analgetic action of the two tetrapeptide analogs, Tyr-D-Ala-Gly-Phe-NH2 and Tyr-D-Ala-Gly-Phe (NO) NH2, was studied in rat experiments. The threshold of pain reaction to electrical stimulation of the tail, evidenced by vocalization, was measured. PGE1, PGE2, PGE2 alpha, cAMP, and dibutyryl cAMP were shown to diminish the effect of the above-mentioned enkephalin analogs. In contrast to cAMP, cGMP was not active in this respect. Among the ions under study (calcium, lithium, rubidium, and cesium), cesium was shown to be the most active. It prevented the increase of the pain reaction threshold and shortened the duration of analgesia. Lithium had no antagonistic effect as regards the enkephalin-induced analgesia. Comparison of these findings with the previously obtained data on the antagonism of the substances under consideration with morphine suggests similarities in the mechanisms of modulation of the effects of opiates and opioids. At the same time the failure of lithium to antagonize the enkephalin analogs and the presence of morphine antagonism point out that the similarities in the mechanisms of ion regulation of exogenous analgetics and enkephalins cannot be regarded as complete enough.
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PMID:[Effect of prostaglandins, cyclic nucleotides and ions on the analgesic effect of enkephalin analogs]. 715 Jul 67

Tissue injury or the presence of foreign material initiates a series of pathophysiological events that may manifest as inflammatory pain. The physicochemical characteristics of the initiating factor trigger the release of a unique range of pain mediators that control the threshold and activation of nociceptors. It has been suggested that many nociceptors associated with inflammatory pain are dormant, and are activated by cyclo-oxygenase metabolites and sympathomimetic amines into a state of hyperalgesia. In this state, pain receptors may be activated by previously ineffective stimuli. The relative contribution of the mediators to the activation process varies with the experimental model or the pathophysiological process involved. The mechanisms that control the activity of the pain receptor are unfolding. Indeed, research has shown a central role for bradykinin (released from plasma) and cytokines (released from tissues and resident cells) in this process. The release of tumour necrosis factor-alpha (TNF-alpha) initiates the release of interleukin-1 and interleukin-8, which in turn liberate cyclo-oxygenase metabolites and sympathomimetic amines, respectively. In some models of inflammatory pain, bradykinin causes hyperalgesia via release of TNF-alpha. Drugs blocking cyclo-oxygenase (aspirin-like drugs), or those antagonising the effects of sympathomimetic amines (beta-blockers), prevent sensitisation of the pain receptors. However, during hyperalgesia only specific types of analgesics are capable of nociceptor downregulation. It is assumed that sensitisation of nociceptors is due to increased concentrations of cAMP/Ca++ in the sensory neurons. The effect of increased cAMP concentrations may be counteracted by stimulation of the arginine/nitric oxide/cGMP pathway. Peripherally acting opiates and dipyrone are examples of analgesics that act via this mechanism. The analgesic effects of glucocorticoids and nimesulide appear to be attributable to inhibition of cytokine release.
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PMID:The role of interleukins and nitric oxide in the mediation of inflammatory pain and its control by peripheral analgesics. 750 42

The addition of antidepressants to combined treatment of IHD patients aroused not only mediated psychic benefit, but also positive shifts in metabolic and mediator regulation of chronic psychoemotional stress. Antidepressants administration results in lowering of total blood cholesterol and atherogenic lipoproteins, inhibits LPO, promotes normalization of cyclic nucleotides levels (cAMP and cGMP increase and decrease, respectively). Clinical course of the disease also improved (less frequent and severe attacks of angina pectoris and associated atypical pain syndrome, of arrhythmia paroxysms; exercise tolerance increased, hemodynamics improved). The arguments in favour of antidepressant use in coronary patients with anxiodepressive symptoms and social and psychological dysadaptation are provided.
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PMID:[The effect of antidepressants on lipid metabolism and the clinical course in IHD]. 790 28


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