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

Antisera against two mammalian peptides related to the molluscan cardioexcitatory peptide Phe-Met-Arg-Phe-NH2 were used to locate immunoreactive neurons in the rat brain, nerve fibres and terminals in the spinal cord, sympathetic ganglion cells and adrenal chromaffin cells. Immunoreactivity for the newly characterised octa- and octadecapeptide was detected in nerve cell bodies in the hypothalamic area, including parts of the dorsomedial, periventricular and paraventricular nuclei, and in the nucleus tractus solitarii. Nerve terminals in the superficial laminae of the spinal cord were also immunoreactive for these peptides, while the sensory ganglia were nonreactive. Some principal ganglion cells in the superior cervical ganglia exhibited bright immunofluorescence for the peptides, and a few adrenal medullary cells were immunoreactive. The presence of these peptides in the substantia gelatinosa of the spinal cord suggests that they may be involved in sensory neurotransmission, especially in the mechanisms mediating pain. In the hypothalamo-hypophysial system these peptides may be involved in the regulation of hormonal systems. They may also act as co-transmitters in the sympathetic nervous system.
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PMID:Neuroanatomy of morphine-modulating peptides. 365 12

Polymorphonuclear leukocyte (PMN) aggregation and chemotaxis were studied in 27 patients with sickle cell disease (SCD). Pain-free patients with SCD had a significantly impaired aggregation response to stimulation with n-formylmethionyl-leucyl-phenylalanine (FMLP) with or without cytochalasin B (CB), compared with normal volunteers (p less than 0.001). Patients with SCD in vaso-occlusive crisis had PMN aggregation induced by FMLP with or without CB that was significantly increased compared with the cohort of pain-free SCD patients (p less than 0.001). PMN from pain-free patients had normal chemotaxis, whereas patients in vaso-occlusive crisis had a significant impairment in PMN chemotaxis. PMN chemotaxis was inversely related to the PMN aggregation response to FMLP with CB (r = -0.75). Thus, the PMN from pain-free patients with SCD appears to have normal or decreased "stickiness" and to develop increased stickiness during vaso-occlusive crisis. The mechanisms responsible for these changes need further elucidation. Alterations in PMN function may be responsible, in part, for the increased risk of infection noted in individuals with SCD and may play a role in the development of the acute chest syndrome.
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PMID:Vaso-occlusive crisis-associated neutrophil dysfunction in patients with sickle-cell disease. 366 21

The purpose of this study was to determine the effects of ingestion of L-tryptophan or phenylalanine on burning pain threshold using a double blind, pretest-posttest control group design. Sixty healthy, female student volunteers were assigned randomly to L-tryptophan, phenylalanine, or placebo groups, (Groups 1-3, respectively). The pretest radiant heat tolerance was determined for all subjects. Burning pain tolerance was defined as the amount of time in seconds from the initial exposure of the left fifth distal phalanx to a 250-W infrared lamp until the subject's detection of an "intense burning sensation." The subjects in Groups 1 and 2 ingested four 500-mg tablets of phenylalanine or L-tryptophan a day for 14 days. The placebo group ingested four placebo tablets a day for 14 days. Immediately after the 14th day, the radiant heat pain tolerance of all subjects was remeasured. The results of a one-way analysis of covariance showed no significant difference in the posttest pain tolerance values of the three groups.
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PMID:Effect of L-tryptophan and phenylalanine on burning pain threshold. 380 44

New compounds were designed to fully inhibit the in vitro metabolism of enkephalins, ensured by three different metallopeptidases. For this purpose, bidentate ligands as hydroxamate and N-hydroxy-N-formylamino groups were selected as highly potent metal coordinating agents and introduced on Phe-Gly and Phe-Ala related structures. Compounds corresponding to the general formula HC(O)N(OH)CH2CH(CH2Ph)CONHCH2COOH (compound 7) and HN(OH)C(O)CH2CH(CH2Ph)CONHCH(R)COOH (compound 11, R = H; compound 13, R = CH3) behave as full inhibitors of the three enzymes, with IC50's in the nanomolar range for enkephalinase, from 0.3 microM to 1 nM for dipeptidylaminopeptidase, and in the micromolar range for a biologically relevant aminopeptidase. Two diastereoisomers of the most active inhibitor 13 were separated by HPLC and their stereochemistry was assigned by 1H NMR spectroscopy. Both isomers were efficient as enkephalinase blockers, but only the RS isomer, designated kelatorphan, was able to strongly inhibit aminopeptidase and dipeptidylaminopeptidase. Intracerebroventricular injection in mice of these mixed inhibitors, especially kelatorphan, led to naloxone reversible analgesic responses (hot-plate test) that were slightly better than those produced by a mixture of thiorphan and bestatin, two potent inhibitors of enkephalinase and aminopeptidase, respectively. Kelatorphan was also more efficient in potentiating the analgesia induced by a subanalgesic dose of Met-enkephalin. All these results support a physiological role in pain transmission for enkephalinase and a probably synaptic aminopeptidase M.
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PMID:New bidentates as full inhibitors of enkephalin-degrading enzymes: synthesis and analgesic properties. 389 41

A number of compounds have been shown to inhibit the degradation of enkephalins. As expected, these compounds produce naloxone reversible analgesia and potentiate the analgesia produced by enkephalins and by acupuncture. One of these, D-phenylalanine, is also anti-inflammatory. D-phenylalanine has proven to be beneficial in many human patients with chronic, intractable pain. It is proposed the enkephalinase inhibitors may be effective in a number of human "endorphin deficiency diseases" such as depression, schizophrenia, convulsive disorders and arthritis. Such compounds may alleviate other conditions associated with decreased endorphin levels such as opiate withdrawal symptoms.
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PMID:D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application. 612 72

Met5-enkephalin, tyr-gly-phe-met, is an endogenous pentapeptide, with morphine agonist activity. In this study, we demonstrated that met5-enkephalin was degraded with the release of tyrosine by resting human PMN, whereas it was degraded as well as oxidized to its sulfoxide derivative, met5-(O)-enkephalin, by phagocytosing PMN. PMN also degraded met5-(O)-enkephalin but to a lesser extent. Bacitracin at 1 gm/L inhibited the degradation and oxidation of met5-enkephalin without affecting the production of superoxide and viability of PMN. The oxidation of met5-enkephalin by phagocytosing PMN was inhibited by catalase or NaN3 but not by SOD. This suggests that the oxidation of met5-enkephalin by phagocytosing PMN was, at least in part, dependent on the MPO system (MPO-H2O2-halide). Using purified canine MPO, we further demonstrated that MPO-H2O2-CI- oxidized met5-enkephalin to met5-(O)-enkephalin. The MPO-mediated oxidation of met5-enkephalin was inhibited by methionine but not by methionine sulfoxide, tyrosine, glycine, or phenylalanine, confirming that it was the methionine moiety of met5-enkephalin which was oxidized. Since both the sulfoxide derivative and the degradation products met5-enkephalin have reduced opiate agonist activity, oxidation and degradation of met5-enkephalin by PMN may contribute to the pain at the site of inflammation. (J Lab Clin Med 99:418, 1982.)
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PMID:Degradation and oxidation of methionine enkephalin by human neutrophils. 627 80

D-phenylalanine has been shown to possess opiate-like effects upon pain perception. The present study examined whether it would have similar opiate-like effects upon food intake in deprived rats. The first experiment demonstrated that food intake of rats deprived for 24 h prior to injection was significantly reduced for 2 h following a 250 mg/kg dose of D-phenylalanine. However, intake over a 24 h period following injection was significantly increased following a 125 mg/kg dose of D-phenylalanine. The second experiment revealed that 0.3, 1.0, 3.0 and 10.0 mg/kg doses of naloxone dose-dependently reduced intake for 2 h in deprived rats when paired with a vehicle injection. However, the inhibitory actions of the two lower naloxone doses were significantly attenuated when paired with an injection of a 250 mg/kg dose of D-phenylalanine. These results are discussed in terms of whether D-phenylalanine possesses direct or indirect opiate-like effects upon ingestion.
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PMID:Modulation of deprivation-induced food intake by D-phenylalanine. 632 75

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

The analgesic responses following morphine and cold-water swims (CWS) can be dissociated from each other. Indeed, certain manipulations in rats such as hypophysectomy or D-phenylalanine injections decrease CWS analgesia while increasing morphine analgesia. The present study examined the reciprocal notion, namely whether a manipulation that decreases morphine analgesia would increase CWS analgesia. Naloxazone, an opiate antagonist which selectively inhibits the high affinity binding site in a long-acting manner, was administered intracerebroventricularly and assessed for its effects upon morphine analgesia and CWS analgesia as measured by the jump test. While intracerebroventricular injections of naloxazone reduced morphine analgesia at 0.5 and 24 hr following microinjection, the same 50 micrograms dose significantly increased CWS analgesia at 0.5 hr after injection, suggesting a mechanism of collateral inhibition between opioid and non-opioid pain-inhibitory systems.
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PMID:Naloxazone and pain-inhibitory systems: evidence for a collateral inhibition model. 716 50

Methionine- and leucine-enkephalin produce mild and transient analgesic effects, presumably because of enzymatic degradation. Administration of high (250 mg/kg) doses of D-phenylalanine retards the degradation process and elicits analgesia which is reversed by naloxone and which summates with electroacupuncture analgesia. The present study evaluated D-phenylalanine's dose-dependent effects upon a non-opioid analgesic treatment, cold-water swims (CWS), and compared this with morphine. following determination of flinch-jump baselines, three groups of rats received respectively either 25, 50 or 100 mg/kg of D-phenylalanine intraperitoneally in three conditions: alone, with CWS (2 degrees C for 3.5 min), and with morphine (5 mg/kg, SC). Parallel controls with saline were also tested. Simultaneous exposure with each minimally analgesic dose of D-phenylalanine reduced significantly the analgesic, but not hypothermic effects of CWS. By contrast, morphine analgesia was unaffected by D-phenylalanine. These data provide further support that different pain-inhibitory systems mediate CWS and morphine analgesia and suggest that activation of one system is capable of exerting collateral inhibition upon the other.
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PMID:Antagonism of stress-induced analgesia by D-phenylalanine, an anti-enkephalinase. 720 49


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