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)

Central (i.c.v.) effects of D-Tyr-D-Leu-[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(1DME)Y8Fa] and D-Tyr-D-Leu-D-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(3D)Y8Fa], synthetic analogs of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 on intestinal myoelectric activity and nociception were studied and compared to that of D-Ala2-Met5-enkephalinamide in rats. The duration of disruption of intestinal migrating myoelectric complexes, induced by p.o. administration of a test meal was significantly shortened (P < .01) by (1DME)Y8Fa and (3D)Y8Fa (8, 40 and 80 micrograms/kg) and D-Ala2-Met5-enkephalinamide (40 and 80 micrograms/kg). The coadministration of any two of these drugs, at doses of nonmeasurable effect when given alone (2 micrograms/kg), has also reduced the duration (P < .01) of the postprandial intestinal motor profile. Both separate and combined effects of drugs were antagonized by naloxone (1 mg/kg s.c.). In contrast, in the tail-flick test, analgesia induced by D-Ala2-Met5-enkephalinamide (40 micrograms/kg i.c.v.) was blocked by (1DME)Y8Fa, (3D)Y8Fa (8 micrograms/kg) and naloxone (1 mg/kg s.c.). The coadministration of (1DME)Y8Fa and (3D)Y8Fa at doses of no proper effect when given alone (8 micrograms/kg) has significantly (P < .01) reduced the latency time. This effect was not blocked by naloxone (1 mg/kg s.c.). It is concluded that the Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs, (1DME)Y8Fa and (3D)Y8Fa, when given i.c.v. exert effects similar to opiate agonists and antagonists on intestinal myoelectrical activity and on nociception, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative action of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs on intestinal motility and nociception in rats. 847 35

The effect of microinfusion into the nucleus raphe dorsalis (DR) of neuropeptide FF (NPFF) analogs on the antinociceptive effects of morphine was evaluated in rats, using the tail-immersion test. infusion of morphine into the DR induced a dose-dependent analgesia significantly reversed by co-infusion of 2.5 nmol opioid antagonist, naloxone. Similarly, 2.5 nmol NPFF and (1DMe)Y8Fa(D-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2) or (3D)Y8Fa(D-Tyr-D-Leu-D-Phe-Gln-Pro-Gln-Arg-Phe-NH2), two neuropeptide FF analogs, inhibited morphine analgesia, although these peptides had no effect on nociceptive thresholds. This anti-opioid effect is indirect since NPFF analogs displayed no significant affinity towards mu and delta opioid binding sites in the DR. After intracerebroventricular infusion, morphine produced the same degree of analgesia as that measured after infusion into the nucleus raphe dorsalis and both NPFF analogs reversed morphine antinociception. This result is the first direct evidence that neuropeptide FF may act on opioid system at the DR and that several nuclei are involved in the suppression of morphine-induced antinociception.
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PMID:Effects of neuropeptide FF analogs on morphine analgesia in the nucleus raphe dorsalis. 857 40

Analgesia has been reported to be facilitated by supraspinal nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In the rostromedial medulla, an important pain-suppressing region, iontophoretically delivered 8-bromo-cGMP excited most single recorded cells (9/10), and methylene blue (a guanylyl cyclase inhibitor) inhibited all cells (7/7). Nitrite and ferrous ions together, shown voltammetrically ex vivo to yield nitric oxide (NO), excited some cells (14/28) and inhibited others (7/28). Methylene blue blocked excitation (3/3) but not inhibition (4/4) by the putative NO. Spontaneous or glutamate-evoked firing was gradually inhibited (23/32) or unaffected by N omega-nitro-L-arginine (a NO synthase inhibitor), but was mostly inhibited by L-arginine (the NO precursor) (23/26), although a rapid onset militated against elevated NO production. These substances, excepting L-arginine, produced changes consistent with an excitatory cGMP-NO cascade contributing to analgesia.
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PMID:Excitation of cells in the rostral medial medulla of the rat by the nitric oxide-cyclic guanosine monophosphate messenger system. 858 98

The pharmacological effects of a purified neurotoxin from king cobra (Ophiophagus hannah) venom were studied. Using the hot-plate test, it is shown that this neurotoxin increased latency time dose-dependently when administered i.p. Similar analgesic action was observed when it was administered p.o. or i.c.v. The rota-rod performance, which is a good index for neurological deficits including sedation, muscle relaxant and impairment of motor activity and coordination, was not significantly affected in the dose range of 16-32 ng/g that caused analgesia. The toxin did not increase the convulsion threshold in the dose range of 8-64 ng/g in the maximal electroshock seizure tests. These results demonstrated that this neurotoxin produced analgesia in the dose range of 16-32 ng/g (i.p.) without causing any neurological or muscular deficits. It is further shown that such analgesic action was blocked by naloxone and L-NG-nitro-arginine methyl ester, suggesting the possible involvement of the opioid and nitric oxide systems, respectively. In view of the source of this neurotoxin (O. hannah) and its potent analgesic action, it is proposed that this toxin be named hannalgesin.
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PMID:A novel analgesic toxin (hannalgesin) from the venom of king cobra (Ophiophagus hannah). 874 82

The possible participation of nitric oxide (NO) in pain modulation and stress analgesia was studied in adult Wistar rats. Cerebral citruline as a coproduct of NO from L-arginine increased from the mean value 5.6 +/- 0.4 nM/mg.Pt. to 8.9 +/- 0.5 nM/mg.Pt. in acute restraint stress. In high doses (50 mg/kg body weight), intraperitoneal administration of L-arginine caused a small and transient decrease of the tail-flick latencies to the thermal stimulus, without significant changes of the stress analgesia induced by restraint stress. In animals pretreated with N-nitro-L-arginine methyl ester (NAME) a progressive increase of the latency time was obtained and the increased latencies induced by acute immobilization appeared significantly potentiated. These results offer new indirect evidence in favour of the modulatory role of NO in thermoalgesic sensitivity and stress-induced analgesia.
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PMID:Possible involvement of the L-arginine-nitric oxide pathway in the modulation of stress-induced analgesia. 874 43

The effects of L-NG-nitro arginine methyl ester (L-NAME), L-NG-monomethyl arginine (L-NMMA), L-arginine and D-NG-nitro arginine methyl ester (D-NAME) on morphine antinociception were studied in the mouse using two nociceptive assays, the abdominal constriction and tail flick tests. In the abdominal constriction test, L-arginine and D-NAME (20 mg/kg) had no effect on the number of abdominal constrictions, nor did they affect the responses due to morphine (1 mg/kg). L-NAME and L-NMMA (10 mg/kg) exhibited marked antinociception when administered on their own, and morphine antinociception was enhanced in mice pretreated with these two agents. In the tail flick test, similar doses of L-NAME, L-NMMA, L-arginine and D-NAME had no effect on their own. D-NAME had no effect on morphine analgesia, L-NAME and L-NMMA enhanced morphine antinociception, and L-arginine attenuated morphine antinociception. Therefore, increasing the levels of NO attenuates morphine antinociception, while lowering the levels enhances it. These results suggest that NO may play an important role in pain perception, and probably in the antinociceptive responses to morphine.
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PMID:Effects L-NG-nitro arginine methyl ester (L-NAME), L-NG-monomethyl arginine (L-NMMA) and L-arginine on the antinociceptive effects of morphine in mice. 878 70

The effects of NG-nitro-L-arginine (L-NNA) and NG-monomethyl-L-arginine (L-NMMA), two potent inhibitors of nitric oxide synthase (NOS) on the development of tolerance to the analgesic action of [D-Ala2, Glu4] deltorphin II (deltorphin II), a delta 2-opioid receptor agonist, and morphine, a mu-opioid receptor agonist, were determined in mice. Male Swiss-Webster mice were rendered tolerant to deltorphin II by twice daily ICV injections of the drug for 4 days. Tolerance to morphine was induced by twice daily s.c. injections of the drug for 4 days. Multiple injections of deltorphin II (20 micrograms/mouse) or morphine (15 mg/kg) resulted in the development of tolerance to their analgesic action as evidenced by decreases in the response in comparison to mice injected with vehicle. Concurrent administration of L-NNA or L-NMMA (2,4, or 8 mg/kg, i.p.) had no effect on the development of tolerance to the analgesic action of deltorphin II. However, the same doses of L-NNA or L-NMMA inhibited the development of tolerance to the analgesic action of morphine. Acute treatment with L-NNA or L-NMMA did not modify deltorphin II- or morphine-induced analgesia in mice. It is concluded that NOS inhibition attenuates tolerance to the analgesic action of morphine but not to that of deltorphin II, a delta 2-opioid receptor agonist, in the mouse.
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PMID:Nitric oxide synthase inhibition attenuates tolerance to morphine but not to [D-Ala2, Glu4] deltorphin II, a delta 2-opioid receptor agonist in mice. 880 71

The objective of this study was to investigate the site of action of dipyrone in rat paw prostaglandin-induced hyperalgesia. The intracerebroventricular (i.c.v.) injection of dipyrone had no effect on the hyperalgesic response to prostaglandins. In contrast, intraplantar (i.pl.) and intrathecal (i.t.) injections produced dose-dependent analgesic effects. The analgesia observed following the intraperitoneal (i.p.), i.t., i.pl. or combined i.t. and i.pl. administration of dipyrone was abolished by pretreating the paws with L-NMMA (a nitric oxide synthase inhibitor) or methylene blue (MB, an inhibitor of soluble guanylate cyclase). These results support the suggestion that dipyrone-mediated antinociception results from a combined spinal and peripheral effect in the primary peripheral sensory neuron via stimulation of the arginine/cGMP pathway.
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PMID:Activation of the arginine-nitric oxide pathway in primary sensory neurons contributes to dipyrone-induced spinal and peripheral analgesia. 881 64

1. The possible involvement of nitric oxide (NO) in the induction and expression of morphine tolerance and dependence was studied in mice. A two-day repeated injection regimen was used to induce morphine tolerance and dependence. Tolerance was assessed by the tail flick test and physical dependence by naloxone challenge, on the third day. 2. Two days pretreatment with L-arginine (20 mg kg-1, twice daily) or D-NG-nitro arginine methyl ester (D-NAME, 20 mg kg-1, twice daily) alone had no effect on subsequent morphine antinociception. L-NG-monomethyl arginine (L-NMMA, 10 mg kg-1, twice daily) for two days led to a slight increase (not statistically significant) in morphine antinociception; while L-NG-nitro arginine methyl ester (L-NAME, 10 mg kg-1, twice daily) for two days led to attenuation of morphine analgesia. None of the animals treated with these drugs alone showed signs characteristic of the opioid withdrawal syndrome upon naloxone challenge. 3. Induction phase L-arginine slowed the development of opioid tolerance and physical dependence, while L-NAME and L-NMMA led to a higher degree of tolerance but had no effect on the development of physical dependence. 4. L-Arginine and D-NAME had no effect on the expression of morphine tolerance and physical dependence. Expression phase L-NAME and L-NMMA, on the other hand, attenuated morphine tolerance and reduced the incidence of withdrawal signs. 5. NO may, therefore, play a role in both phases of morphine tolerance and dependence: elevation of NO levels during the induction phase delays the development of opioid tolerance/dependence, while inhibition of NO synthase accelerates the development of tolerance. Inhibition of NO attenuates the expression of both tolerance and physical dependence.
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PMID:Role of nitric oxide in the induction and expression of morphine tolerance and dependence in mice. 885 10

The i.c.v. administration of bradykinin (4, 8 and 16 micrograms) induced antinociception in mice which was resistant to naloxone; furthermore, the induction of tolerance to morphine by a single s.c. injection (100 mg/kg, 24 h before test doses of the peptide) did not affect antinociception. Since bradykinin is known to increase nitric oxide (NO) in peripheral tissues, we studied the possibility that its antinociceptive action may be related to NO effects in the central nervous system. Bradykinin effects were antagonized by previous treatment with NG-nitro-L-arginine or concomitant i.c.v. administration of bradykinin and methylene blue. The immediate precursor of NO, L-arginine, which by itself produces analgesia, also reduced bradykinin effects; moreover, tolerance to L-arginine significantly decreased the response to the peptide. These results suggest that NO is involved in antinociception induced by i.c.v. administration of bradykinin.
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PMID:Possible role of nitric oxide in the antinociceptive action of intraventricular bradykinin in mice. 888 7


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