Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of the L-arginine-NO-cGMP pathway in morphine-induced central analgesia was investigated in two nociceptive tests: PGE2-induced hind paw hyperalgesia and tail-flick. The central analgesic effect of morphine was potentiated by MY5445, a specific cGMP phosphodiesterase inhibitor. I.c.v. injections of morphine or carbachol caused dose-dependent analgesia, which was prevented by methylene blue, an inhibitor of guanylate cyclase. The NO synthase inhibitor, N-iminoethyl-L-ornithine, prevented carbachol-induced analgesia, but did not affect morphine-induced analgesia. Our results suggest that activation of cGMP may underlies analgesia induced by morphine and carbachol. The activation of guanylate cyclase by carbachol seems to depend on the L-arginine-NO pathway, but that caused by morphine remains to be further characterized.
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PMID:The molecular mechanism of central analgesia induced by morphine or carbachol and the L-arginine-nitric oxide-cGMP pathway. 133 72

The Asu-AVT (1,6-aminosuberic acid -8-arginine-vasotocin) in an analogue of 8-arginine-vasotocin (AVT) which is one of pineal hormones. The effect of Asu-AVT on the pain threshold and EA analgesia was studied in rats. An increase of 16.2-41.5% in pain threshold was observed within 70 min. after ivc of Asu-AVT (75ng), while the Asu-AVT injection in combination with EA produced a significant increase of 164.6-309.1% in pain threshold, which was much higher than that in the saline-EA group (p < 0.05-0.01). The effect of Atu-AVT is analogous to that of oxytocin and arginine-vasopressin. The data indicate ivc of ASu-AVT not only elevates the pain threshold, but also enhances the EA analgesia. These results suggest that the pineal hormone, AVT may play a role in the EA analgesia.
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PMID:[Effect of Asu-AVT on electroacupuncture (EA) analgesia]. 133 26

Four analogues of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, a mammalian FMRFamide-like peptide with antiopiate properties, were synthesized with N-terminus modifications and were shown to have high affinity for F8Famide binding sites. The degradation rate of these analogues in mouse brain slices was 3 times lower than that of the natural peptide. One analogue, (2DME)Y8Fa (D.Tyr-D.Leu-[N-Me]Phe-Gln-Pro-Gln-Arg-Phe-NH2), produced a clear hyperalgic effect and inhibited morphine analgesia in the mouse tail-flick test at lower doses than did the parent compound. (3D)Y8Fa (D.Tyr-D.Leu-D.Phe-Gln-Pro-Gln-Arg-Phe-NH2) and (2D)Y8Fa (D.Tyr-D.Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) in contrast did not decrease morphine analgesia but were analgesic alone. The analgesic effects of 22 nmol (2D)Y8Fa and (3D)Y8Fa were decreased by (1DME)Y8Fa (D.Tyr-Leu-[N-Me]Phe-Gln-Pro-Gln-Arg-Phe-NH2) or (2DME)Y8Fa and were reversed by naloxone. These results indicate opioid modulating properties of F8Famide. These analogues may prove to be useful tools for studying the modulation of pain by F8Famide.
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PMID:Analogues of F8Famide resistant to degradation, with high affinity and in vivo effects. 146

General pharmacological properties of cefepime (CFPM), a new injectable semisynthetic cephalosporin and its metabolite N-methylpyrrolidine-N-oxide (NMP-N-oxide) were studied in laboratory animals. The results obtained are summarized as follows: 1. CFPM reduced spontaneous locomotor activity but potentiate the anesthesia at the highest dose in mice. Furthermore, significant hypothermia and analgesia were observed at the same dose in mice. No effects were found on the other CNS function in mice and rats or on EEG activities in rabbits. 2. Muscle relaxant activity was not observed in mice treated with CFPM even at the highest dose. 3. CFPM had no effect on the intestinal smooth muscle and did not show any antagonism against some smooth muscle contracting drugs. 4. The respiration, blood pressure, heart rate and ECG were affected by CFPM. Those changes, however, might have been principally caused by L-arginine blended with CFPM product. 5. No effect of CFPM on the intestinal movement or gastric secretion was found even at the highest dose of CFPM. 6. The pH neutralizer L-arginine caused alterations in the renal function and electrolyte metabolism but CFPM did not. 7. Whole blood clotting time tended to be lengthened by CFPM at the highest concentration but this effect seemed to have been caused by L-arginine. Other parameters of the coagulation system or red blood cell resistance were not affected by CFPM. 8. NMP-N-oxide, a metabolite of CFPM, had almost no effect on any of the tested parameters except for its slight effect on the circulatory system. These findings indicate that CFPM has scarcely any pharmacological properties which might be leading to severe adverse reactions in clinical use.
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PMID:[General pharmacology of cefepime]. 150 98

The opioid activity and the selectivity for opioid receptor (subtypes) of newly synthesized fluorinated enkephalin (Enk) analogues, [2R, 4R], [2R, 4S], [2S, 4S] and [2S, 4R] trifluoro-Leu5-Enk (KKF-31, 32, 33 and 34) were investigated. The inhibitory effect of KKF-compounds on the electrically induced contractions of guinea-pig ileum (GPI) and mouse vas deferens (MVD) were dose-dependent but relatively lower than that of L-Leu5-Enk, except that KKF-34 was rather slightly more potent than L-Leu5-Enk in MVD preparations. In GPI preparations, the pA2 values of naloxone for these compounds were higher than those of naltrindole while the values of naltrindole for KKF-compound were higher than those of naloxone in MVD preparations. Intracerebroventricular KKF-31 and KKF-32 at doses of 20 and 10 nmol/mouse, respectively, produced analgesia comparable to 0.1 nmol Tyr-D-Arg-Phe-Lys-NH2 and 100 nmol Tyr-D-Thr-Gly-Phe-Leu-Thr; however, neither KKF-33 nor 34 produced analgesia up to the doses of 100 nmol/mouse. Both naloxone, 1 mg/kg, i.p., and naltrindole, 10 mg/kg, i.p., antagonized KKF-31- and KKF-32-induced analgesia. The results suggest that the introduction of trifluoromethyl group in Leu5 results in the alternation of the opioid activity and receptor selectivity. Although KKF-33 and KKF-34 possessed a more potent in vitro inhibitory effect than KKF-31 and KKF-32, mediated through mu- and delta-opioid receptors in both preparations, they did not show any appreciable analgesic effect. KKF-31 and KKF-32 produce naloxone- and naltrindole-reversible analgesia irrespective of in vitro mu- and delta-opioid activity.
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PMID:The opioid activity and receptor selectivity of fluorinated Leu5 enkephalin analogues in vitro and in vivo. 165 91

We have previously described the peripheral analgesic effect of dibutyryl cyclic GMP, acetylcholine (ACh) and morphine (Mph) injected into the rat paws. Since ACh induces nitric oxide (NO) release from endothelial cells which is though to stimulate guanylate cyclase (GC) we investigated if NO-cyclic GMP pathway was involved in the analgesia by those agents. Using a modification of the Randall-Selitto rat paw test, it was found that sodium nitroprusside, which releases NO non-enzymatically, blocked rat paw PGE2 induced hyperalgesia. The peripheral analgesic effect of sodium nitroprusside, ACh and morphine was enhanced by intraplantar injection of an inhibitor of cyclic GMP phosphodiesterase (MY5445) and blocked by a GC inhibitor, methylene blue (MB). Peripheral analgesia induced by ACh and morphine, but not by sodium nitroprusside, was blocked by NG-monomethyl-L-arginine (L-NMMA) an inhibitor of the formation of NO from L-arginine. Central effect of morphine as tested by the rat paw and by the tail flick tests was inhibited by intraventricular injection of methylene blue. In addition, the central morphine analgesia was potentiated by My5445. In contrast, with the periphery, the central effect of morphine was not blocked by L-NMMA. Our results demonstrate that NO causes peripheral analgesia via stimulation of GC and supports the suggestion that at this site morphine and acetylcholine analgesia is subsequent to NO release. In the mechanism of the central analgesic effect of morphine, the cGMP system is activated but via NO release, probably by a direct stimulation of the receptors. This is the first demonstration that links peripheral and central analgesic effect of morphine to the stimulation of GC system.
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PMID:Molecular base of acetylcholine and morphine analgesia. 167 74

In order to understand the role of substance P (SP) in the brain and the relationship between SP and enkephalins in the electroacupuncture analgesia (EA), we have observed the influence of SP-antagonist, (D-Arg', D-Phe5, D-Trp7.9, Leu11) -SP (DADPDTL) injected intracerebroventricularly (icv) on EA and the change of the level of SP in the brain regions of the rat during EA. We have made a further observations on the influences of the naloxone (NX) on the che change of the content of SP induced by EA and DADPDTL on the increase in Leu-enkephalins (LEK) induced by EA. The Wistar rats were used in the experiment. The latency of the tail flick, immersing the tip of rat tail (4 cm) into hot-water of 50 degrees C, was taken as the pain threshold. The drugs were injected icv via plastic cannulae implanted in the bilateral ventricles. The EA was applied to the point of "Zusanli" (S36). The contents of SP and LEK were determined radioimmunoassay in the hypothalamus, mid-brain, striatum and pons-medulla-oblongata. The pain threshold was increased by 48 +/- 9% (P less than 0.01) after EA. But icv injection of DADPDTL decreased the pain threshold by 14 +/- 7% after EA. The result suggests that DADPDTL can antagonize the effect of EA and that SP in the brain is involved in EA. After EA the contents of SP in the hypothalamus and mid-brain of the rats were decreased by 29% and 28% in comparison with that of the control group respectively (both of them, P less than 0.05), but the contents of SP in the striatum and pons-medulla-oblongata had no significant change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of substance P in electroacupuncture analgesia and its relation to enkephalins in the rat brain]. 170 61

The N-terminal tetrapeptide of substance P (SP1-4) was found to produce analgesia, after the icv injection to the rat brain, which is lower in its intensity than that produced by tuftsin (Thr-Lys-Pro-Arg tetrapeptide). Among investigated tuftsin analogues Thr-Lys-Pro-Thr and Thr-Lys-Pro-Thr-Asp (partial sequences of S-protein of HB virus) were weakly active, Thr-Arg-Pro-Arg was inactive, and Thr-Lys-Pro-Gly-Arg produced a weak hyperalgesia 30 min after the icv injection. The obtained results were compared with those obtained previously in the phagocytosis stimulation test. In the control experiments the effects of free amino acids of the tuftsin molecule (Thr, Lys, Pro, Arg) were also studied.
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PMID:Antinociceptive action of the SP1-4 tetrapeptide and of some tuftsin analogs. 171 Nov 98

Our previous pharmacological studies using animals indicated that a systemic administration of L-arginine induces an antinociceptive effect and an increase in the brain level of kyotorphin (L-tyrosinyl-L-arginine) which is an endogenous analgesic peptide and a methionine-enkephalin releaser in the brain. The aims of this study were to investigate the analgesic effect of L-arginine, a precursor of kyotorphin, in persistent pain. We selected 12 patients with various kinds of pain of at least 6 months duration. L-Arginine (10% solution, 300 ml (30 g)/patient) was administered by intravenous drip at a rate of 5 ml (0.5 g)/min during a period of 60-70 min. Pain was assessed by the patient using a 10-cm visual analogue scale (VAS), before and after the L-arginine infusion. L-Arginine treatment resulted in slight analgesia at 10-15 min after the onset of infusion and in marked analgesia at 30-40 min after that. This effect lasted for 6-24 h. L-Arginine-induced analgesia was dose-dependent and blocked by intravenous injection of naloxone. In each case, the L-arginine-induced analgesia was statistically significant as compared with the saline-induced effect. Side effects of L-arginine were a slight decrease in mean blood pressure (10-15 mm Hg), and dryness of the month. A suppressive role of a functional link between the L-arginine-kyotorphin system and the enkephalin system of the brain in persistent pain is suggested.
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PMID:Analgesic effect of L-arginine in patients with persistent pain. 182 18

Recent evidence has indicated that vasopressin (VP) can increase the pain threshold. It is not clear whether the paraventricular nucleus (PVN) of hypothalamus, which is one of the main nuclei that secrete VP in brain, is involved in the acupuncture analgesia (AA). The present study was designed to examine the role of PVN in AA. Experiments were carried out on Wistar rats using tail stimulation vocalization test to measure the pain threshold. The acupoints "Renzhong" and "Chengjiang" were selected for electroacupuncture. Electrical stimulation of PVN could increase significantly the pain threshold and enhance the effect of AA. On the contrary, electrolytical lesion of PVN could decrease the effect of AA obviously, which could be recovered by cerebroventricular injection (ICV) of 300 ng of arginine VP. Pretreatment with AVP-antiserum (ICV) could attenuate the effect of AA. These data indicated that PVN plays an important role in pain modulation and in the effect of AA. This role might be mediated by the VP-containing neurons in PVN.
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PMID:[The role of paraventricular nucleus of hypothalamus in acupuncture analgesia in rats]. 187


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