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)

The D-amino acids (DAA), D-phenylalanine and D-leucine, produce naloxone reversible analgesia; electroacupuncture (EA) also produces analgesia which is blocked by naloxone. Combining the two treatments produces an additive effect with a larger analgesia than that produced by either treatment given alone; this combined effect is also blocked by naloxone. Moreover only 62% of the mice show EA analgesia and 53% show D-amino acid (DAA) analgesia; 80% of the animals show marked analgesia with both EA plus DAA treatment. Perhaps the combination of EA with DAA will provide a potent method for the treatment of clinical pain.
Pain 1980 Apr
PMID:A combined treatment with D-amino acids and electroacupuncture produces a greater analgesia than either treatment alone; naloxone reverses these effects. 740 86

Bone marrow cells of various animal species and men produce a group of bioregulatory peptides called myelopeptides (MPs). A highly purified MP fraction and some individual molecules have been isolated from the supernatant of porcine bone marrow cell cultures by reverse phase chromatography. MPs have a wide spectrum of functional activities: immunoregulatory, differentiating and opiate-like. They evoke 2.5-fold stimulation of antibody production to various antigens. They correct some immune defects in MRL/lpr mice with spontaneous autoimmune disorders that results in 2-fold prolongation of the life span of these mice. MPs influence the differentiation of bone marrow and peripheral blood cells derived from healthy and leukemic donors. They induce terminal differentiation in the leukemic human HL-60 cell line. MPs also show an effect on pain sensitivity. A new immunocorrective drug Myelopid has been developed on the basis of MP mixtures. This drug is effectively used in Russia both in medicine and veterinary practice for prophylaxis and treatment of diseases accompanied by immunodeficiency. Two individual MPs were isolated and identified: Phe-Leu-Gly-Phe-Pro-Thr (MP-1) and Leu-Val-Val-Tyr-Pro-Trp (MP-2). MP-1 displays immunoregulatory activity; MP-2 abolishes the inhibitory effect of leukemic cells on T-lymphocyte functional activity. MPs seem to provide not only immunoregulation but also to participate in complex interactions between different systems in the organism.
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PMID:Myelopeptides: bone marrow regulatory mediators. 764 88

The effects were investigated of cysteamine--a well known somatostatin depletor--on the pain induced by chemical stimuli in mice. Cysteamine injected intraperitoneally 4 h before the test at doses of 50 and 100 mg/kg reduced the second phase of the licking response which was induced by formalin injected into the hind paw. Furthermore, cysteamine administered at the doses of 10, 50 and 100 mg/kg reduced the writhing induced by acetic acid. Naloxone, yohimbine and CGP 35348 administered in cysteamine-pretreated animals were not able to change the cysteamine antinociceptive effects in the formalin test. Intrathecally injected somatostatin was able to revert the cysteamine antinociceptive effects in the second phase of the formalin test and in the writhing test, whereas intracerebroventricularly injected somatostatin reduced the antinociceptive effects induced by cysteamine in the second phase of the formalin test. Intrathecally injected cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl])--a reported somatostatin antagonist--increased cysteamine antinociceptive effects in the second phase of the formalin test and in the writhing test. These results suggest that somatostatin is involved in the effects of cysteamine on the nociceptive threshold.
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PMID:Effects induced by cysteamine on chemically-induced nociception in mice. 790 12

Hybrids of amino-poly(ethylene glycol) (aPEG) and [D-Ala2,(N-Me)Phe4] enkephalin analogs, H-Tyr-D-Ala-Gly-(Me)Phe-aPEG, H-Tyr-D-Ala-Gly-(Me)Phe-Leu-aPEG and H-Tyr-D-Ala-Gly-(Me)Phe-D-Leu-aPEG, were prepared by the solution method and their antinociceptive properties were examined in comparison with those of the peptides. H-Tyr-D-Ala-Gly-(Me)Phe-OH and H-Tyr-D-Ala-Gly-(Me)Phe-Leu-OH themselves at intracerebroventricular (i.c.v.) doses of 10-30 nmol/animal produced an antinociceptive effect which was less potent than that of i.c.v. morphine, 3 micrograms/animal, and H-Tyr-D-Ala-Gly-(Me)Phe-D-Leu-OH did not have any marked effect. However, the antinociceptive effects of H-Tyr-D-Ala-Gly-(Me)Phe-Leu-OH and H-Tyr-D-Ala-Gly-(Me)Phe-D-Leu-OH were remarkably potentiated by hybrid formation with aPEG to levels higher than that of 3 micrograms/mouse of morphine, and the effect lasted at least 120 min. In contrast, the effect of H-Tyr-D-Ala-Gly-(Me)Phe-OH was rather diminished by hybrid formation. In view of the low toxicity and weak immunogenic properties of aPEG, the hybrids could be useful in therapy of patients for relieving chronic and severe pain.
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PMID:Amino acids and peptides. XXIV. Preparation and antinociceptive effect of [D-Ala2,(N-Me)Phe4]enkephalin analog-poly(ethylene glycol) hybrids. 795 39

RB101 (N-((R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl dithio]-1-ox-opropyl)-L-phenylalanine benzyl ester) is a recently developed full inhibitor of the enkephalin-catabolizing enzymes able to cross the blood-brain barrier, whereas RB38A ((R)-3-(N-hydroxycarboxamido-2-benzylpropanoyl)-L-phenylalanine) is as potent as RB101 but almost unable to enter the brain. In this study, we have investigated the effects of systemic administration of morphine, RB101 and RB38A on nociception induced by pressure on inflamed peripheral tissues. Antinociceptive test was performed between 4 and 5 days after injection into the rat left hindpaw of Freund's complete adjuvant to produce localized inflammation. Morphine (1, 2 and 4 mg/kg, i.v.) induced antinociception in inflamed paws at all the doses used, and only at the highest dose in non-inflamed paws. RB101 (10 and 20 mg/kg, i.v.) induced an antinociceptive response only in the inflamed paws. RB38A, also induced an antinociceptive effect in the inflamed paws, but only at the highest dose (20 mg/kg, i.v.). The responses induced by morphine and the inhibitors of enkephalin catabolism were antagonized by the systemic administration of naloxone (1 mg/kg) or methylnaloxonium (2 mg/kg) which acts essentially outside the brain. Central injection (i.c.v.) of methylnaloxonium (2 micrograms) blocked the effect of morphine only in non-inflamed paws, and slightly decreased the response induced by RB101 on inflamed paws. These results indicate that the endogenous opioid peptides, probably enkephalins, are important in the peripheral control of nociception from inflamed tissues.
Pain 1994 Jul
PMID:Antinociceptive response induced by mixed inhibitors of enkephalin catabolism in peripheral inflammation. 797 Aug 41

The effects of pretreatment with the selective cholecystokinin (CCK) B antagonists (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl)-N1-(3-methylphenyl urea (L-365,260), 4-([2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[tricyclo[3.3, 1.1(3.7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-1-phenylethyl] amin)-4-oxo-[R-(R*,R*)]butanoate-N-methyl-D-glucamine (PD-134,308) and N-(2-adamantyloxycarbonyl)-D-alpha-methyltryptophanyl-[N-(2- (4-chlorophenyl)ethyl)]glycine (RB 211), on the naloxone-reversible, antinociceptive responses induced by systemic (i.v.) administration of the complete inhibitor of the enkephalin-catabolizing enzymes, N-((R,S,)-2-benzyl-3[(S)-(2-amino-4-methylthio)butyldithio]-1- oxopropyl)-L-phenylalanine benzyl ester (RB 101), were determined in rat tail-flick and mouse hot-plate tests. L-365,260 (0.12, 0.25 and 0.5 mg/kg s.c.), PD-134,308 (0.3, 1 and 3 mg/kg i.p.) and RB 211 (0.5, 1 and 1.5 mg/kg i.p.) strongly potentiated the antinociceptive effects induced by RB 101 in the rat tail-flick test, in which spinal control of nociception is predominant. Thus, the antinociception observed after the association of L-365,260 (0.5 mg/kg), RB 211 (1.5 mg/kg) or PD-134,308 (3 mg/kg) with RB 101 (5 mg/kg) was, respectively, 300, 500 and 800% higher than that observed with RB 101 given alone. This facilitatory effect was partially blocked by the administration of naloxone (1 mg/kg s.c.). Under the same conditions the potentiation of the antinociceptive response produced by morphine (0.1-4 mg/kg s.c.) was inferior to 250%. In the mouse hot-plate test, L-365,260 (0.02 and 0.1 mg/kg i.p.) and PD-134,308 (0.3, 1 and 3 mg/kg i.p.) also enhanced endogenous enkephalin induced antiociception, but this potentiating effect, completely reversed by administration of naloxone (0.1 mg/kg s.c.), was about 2 times less effective than in the tail-flick assay. The present findings demonstrate an opposing physiological role of endogenous CCK, acting on CCK B receptors, and opioid peptides in the control of pain perception at both spinal and supraspinal levels. These results could have important clinical applications because a combination of a CCK B antagonist and RB 101, which has been showed to be almost devoid of morphine side effects, would increase the overall antinociceptive efficacy into a range that will be more clinically useful.
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PMID:Cholecystokinin B antagonists strongly potentiate antinociception mediated by endogenous enkephalins. 803 45

The analgesic property of the anesthetic gas N2O has long been known and used to treat pain in clinical medicine and dentistry. The present study was conducted to identify by subtype and possible location the brain opioid receptors that mediate N2O antinociception in rats. A 5-min exposure to 70% N2O consistently evoked an antinociceptive effect in the hot plate test. This drug effect was partly antagonized in dose-related fashion by i.c.v. pretreatment with naltrexone, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 and beta-endorphin, which block multiple, mu and epsilon opioid receptors, respectively. However, the N2O-evoked antinociception was unaffected by i.c.v. pretreatment with either the delta opioid antagonist naltrindole or the kappa opioid antagonist nor-binaltorphimine. When D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 was administered intracerebrally directly into the periaqueductal gray, N2O antinociception was partly antagonized in a dose-dependent manner. The antinociceptive response to N2O was uninfluenced by beta-endorphin administered into the periaqueductal gray. The findings of these pharmacological antagonism studies are consistent with the hypothesis that exposure to N2O causes a neuronal release of beta-endorphin. These results indicate that supraspinal mu and epsilon opioid receptors mediate N2O antinociception in the rat hot plate paradigm and that one central site of such mu but not epsilon opioid receptors is the periaqueductal gray.
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PMID:Antagonism of nitrous oxide antinociception in the rat hot plate test by site-specific mu and epsilon opioid receptor blockade. 818 25

Leucine enkephalin (Tyr-Gly-Gly-Phe-Leu; Leu-Enk) is a naturally occurring peptide that has been shown to have pain modulating properties. To evaluate the feasibility of using various absorptive mucosae as a route of systemic delivery, the stability of Leu-Enk and the effect of enzyme inhibitors (e.g., amastatin, EDTA, and thimerosal) on stabilization and permeation of Leu-Enk through rabbit mucosae in the presence of dihydrofusidates were investigated. Enzymes in the nasal, rectal, and vaginal mucosae were extracted and Leu-Enk (50 micrograms/mL) was added to each of the enzyme extracts and incubated to determine the kinetics and mechanism of degradation. The rate of degradation in the extracts in the absence of inhibitors followed the order: rectal > vaginal > nasal. Whereas EDTA had the best stabilizing effect on Leu-Enk, thimerosal was the best stabilizer for the degradation intermediates. A combination of amastatin (50 microM), EDTA (5 mM), and thimerosal (50 microM) had the greatest stabilizing effect on Leu-Enk and its degradation intermediates. For permeation studies, each mucosa was mounted onto a Valia-Chien permeation cell with Leu-Enk (200 micrograms/mL) in isotonic phosphate buffer (as donor solution). The enhancers used for the study were sodium tauro-dihydrofusidate (STDHF), sodium glycodihydrofusidate (SGDHF), and phosphato-dihydrofusidate (PHDHF). The greatest effect was achieved by PHDHF for all the mucosae. STDHF had a significant effect only on the rectal permeation, whereas SGDHF had significant effects on rectal and vaginal mucosae. Mechanisms by which the dihydrofusidates enhance permeating may involve micelle formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transmucosal delivery of leucine enkephalin: stabilization in rabbit enzyme extracts and enhancement of permeation through mucosae. 828 38

We report a male patient with phenylketonuria (PKU) who developed multisystem neurological manifestation in his fourth decade. He was born in 1957 when a neonatal mass screening had not been available. His neuropsychological development was entirely normal and he was a good athlete during his high school days. He was in good health until the age of 32, when his vision was blurred. In four months his gait progressively deteriorated to bind him to a wheel chair. On physical examination he had red hair and gray eyes. IQ was 68. Visual field showed concentric narrowing and his visual acuity was 0.2/0.3 (2.0/2.0). The limbs were spastic and weakened. He complained of pain in the extremities. He suffered from pollakisuria. Routine blood tests and CSF findings were normal. He was also found to be normal in peripheral nerve conduction studies and central conduction studies of SEP and VEP. EEG showed diffuse slowing in background activities. T2-weighted MRI of the head revealed widespread high-intensity areas in the deep white matter especially in bilateral occipital lobes. Serum aminogram disclosed the remarkably elevated phenylalanine (Phe) level to 1663 nmol/ml (normal range 50-90) and reduced tyrosine. Urinary secretion of endogenous tetrahydroxy-biopterin (BH4; coenzyme of Phe hydroxylase) remained in a normal range, and oral administration of 100 mg/kg of BH4 failed to normalize the serum Phe level. Despite a strict dietary control (oral intake of Phe less than 0.5 g/day), the serum Phe level remained high around 500 nmol/ml and his neurological deficits still deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Phenylketonuria with adult-onset neurological manifestation]. 829 76

Two hexapeptides affecting pain sensitivity were isolated from the bone marrow cells supernatant, shown to have primary structure Leu-Val-Val-Tyr-Pro-Trp and Phe-Leu-Gly-Phe-Pro-Thr, and synthesized by the solid phase method. In physico-chemical and biological properties the synthetic peptides were identical to the peptides isolated.
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PMID:[Isolation and structure determination of biologically active peptides from the bone marrow]. 837 52


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