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

Indomethacin, a typical cyclo-oxygenase inhibitor, acts as an analgesic by preventing the hyperalgesia induced by prostaglandins during inflammation. Analgesics of the dipyrone type directly block the sensitization of nociceptors. In the present investigation, the analgesic effect of diclofenac was compared with that of indomethacin in two algesimetric tests which permit discrimination between the two types of analgesic: the rat knee joint incapacitation and the rat paw hyperalgesia tests. The analgesics were given either pre- or posttreatment relative to the induction of hyperalgesia with carrageenin or prostaglandin E2. In both tests intraperitoneal pretreatment with indomethacin was equally or slightly more potent than diclofenac. Posttreatment with diclofenac was more effective than posttreatment with indomethacin. This was particularly evident in the paw hyperalgesia test in which posttreatment with indomethacin was not effective while diclofenac caused dose-dependent analgesia. When nociception was induced by PGE2 in both tests, the administration of indomethacin directly into the knee joint or rat paw had no effect while diclofenac continued to cause dose-dependent analgesia. Thus, diclofenac has a direct effect on ongoing hyperalgesia in addition to its ability to block cyclo-oxygenase. Naloxone and N-methyl-nalorphine did not affect diclofenac analgesia, thus indicating that the analgesic effect of the latter is independent of a central or peripheral opioid effect. Local administration of agents which inhibit the formation of nitric oxide (NG-monomethyl-L-arginine) or inhibit the activation of guanylate cyclase by nitric oxide (methylene blue) abolished diclofenac-induced analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Mechanism of diclofenac analgesia: direct blockade of inflammatory sensitization. 790 38

The cold water tail-flick test in the rat is somewhat unique in that it is sensitive to the analgesic effects of delta- and kappa- in addition to mu-opioid agonists. The present study was designed to test whether a component of morphine-induced analgesia in this test might be mediated by delta- or kappa-opioid receptors. Morphine was administered icv in combination with the non-selective opioid antagonist naloxone (NLX), as well as the mu-, delta- and kappa-selective antagonists, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr (CTAP), naltrindole (NTI) and norbinaltorphimine (norBNI), respectively. Morphine induced analgesia in a dose related manner. Administration of NLX (1-10 micrograms) or CTAP (1 microgram) antagonized morphine in a competitive fashion. Neither NTI (1-10 micrograms) nor norBNI (0.1 microgram) had any effect on the morphine dose-effect curve. Thus, morphine appeared to be a selective mu agonist in the cold water tail-flick test, at least by the icv route.
 ...
PMID:Receptor selectivity of icv morphine in the rat cold water tail-flick test. 795 48

The study was undertaken to evaluate the role of nitric oxide (NO) in pretectal (PTN)-induced analgesia in rats. Microinjection of varying concentrations of L-arginine (1 nM to 1 microM) produced a quick, long-lasting and concentration-dependent analgesic response, whereas similar concentrations of D-arginine failed to produce analgesia. Moreover pretreatment with N-nitro-L-arginine methyl ester (L-NAME, 1 microM) significantly prevented L-arginine induced analgesia. Further, pretreatment of animals with methylene blue, a known guanylate cyclase inhibitor also prevented the development of analgesia. Our study suggests that L-arginine caused production of NO, which in turn activates pretectal analgesic system involving cyclic GMP.
 ...
PMID:Evidence for involvement of nitric oxide in pretectal analgesia in rat. 810 59

The effects of intrathecal injections of F8Famide (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, 0.05-17.5 nmol) and FMRF-amide (Phe-Met-Arg-Phe-NH2, 0.002-25 nmol), known as anti-opioid agents, were investigated by using noxious thermal (tail flick) and mechanical (paw pressure) tests in the rat. Both peptides produced significant long-lasting (24-48 h) analgesia in both tests without causing detectable motor dysfunction. Pretreatment with systemic naloxone (5.5 mumol/kg i.p.) attenuated the initial antinociceptive effects (first hour) induced by both peptides (8.8 nmol) in the tail flick test and only by FMRFamide in the paw pressure test. A subeffective dose of F8Famide (0.05 nmol) enhanced both the intensity and the duration of spinal morphine (6.6 nmol) analgesia in both tests. In contrast, a subanalgesic dose of FMRFamide (0.002 nmol) decreased the intensity and enhanced the duration of the effect of morphine. These results show that, besides acting as antinociceptive agents in the spinal cord, F8Famide and FMRFamide could differentially modulate spinal opioid functions.
 ...
PMID:Antinociceptive effects of intrathecally administered F8Famide and FMRFamide in the rat. 810 75

Delivery through the blood-brain barrier of opioid peptide-based therapeutic agents may be achieved with the use of conjugation of avidin and blood-brain barrier transport vectors. However, this drug delivery strategy requires that 1) the peptide is monobiotinylated and 2) the peptide is biologically active after cleavage of a disulfide linker and peptide release from the avidin-vector conjugate. Whether these criteria may be successfully fulfilled was examined in the present studies. The highly mu receptor-specific dermorphin analog, Tyr-D-Arg-Phe-Lys-NH2 (DALDA), was selectively monobiotinylated at the epsilon-NH2 group of Lys4 with the cleavable biotin linker, sulfosuccinimidyl-2-(biotinamidoethyl) 1,3'-dithioproprionate to obtain biotinylated DALDA (bio-DALDA). The N-terminal alpha-NH2 group of the peptide was protected during biotinylation with the N-9-fluorenylmethoxycarbonyl group. Cleavage of the disulfide bridge yielded the desbiotinylated derivative, desbio-DALDA. The identity of these peptides was verified by secondary ion mass spectrometry. In receptor binding assays with 3H-Tyr-D-Ala-Gly-Phe-(N-Me)-Gly-ol, the Kis of DALDA, bio-DALDA and desbio-DALDA for mu opioid receptors were determined to be 2.3 +/- 0.4, 6.5 +/- 1.1 and 4.0 +/- 0.9 nM, respectively. Binding of bio-DALDA to avidin resulted in a Ki of 14.5 +/- 2.4 nM. The i.c.v. administration of DALDA and desbio-DALDA induced potent and long-lasting analgesia in the rat tail-flick assay. It was found that 1 microgram of DALDA was equipotent to 3 micrograms of desbio-DALDA and 20 micrograms of morphine. The analgesic effect could be blocked by naloxone pretreatment. In conclusion, these studies 1) described methods for the preparation of a biologically active monobiotinylated mu opioid receptor-specific ligand and 2) demonstrated the advantages of using cleavable biotinylation of opioid peptides because the affinity of desbio-DALDA for the receptor approximated the affinity of DALDA and had a 3- to 4-fold higher affinity than did the bio-DALDA-avidin complex.
 ...
PMID:Synthesis and bioactivity of monobiotinylated DALDA: a mu-specific opioid peptide designed for targeted brain delivery. 811 91

Antinociceptive activity of seven pentapeptide fragments of human adenovirus type 2 (Ad2) virion proteins: Thr-Val-Pro-Pro-Arg (1), Thr-Arg-Pro-Pro-Arg (2), Thr-Gly-Pro-Pro-Thr (3), Pro-Arg-Pro-Pro-Thr (4), Phe-Val-Pro-Pro-Arg (5), Ala-Arg-Pro-Pro-Ala (6), Tyr-Gly-Pro-Pro-Lys (7)--analogs of known tuftsin inhibitor Thr-Lys-Pro-Pro-Arg, was measured by hot-plate procedure. Also two tuftsin-like fragments of epitopes of HIV-1 and HIV-2: Thr-Lys-Ala-Lys (8), Thr-Lys-Glu-Lys (9), and tuftsin analog Thr-Lys-Asp-Lys (10) were tested. In the control experiments the effects of tuftsin and pentapeptide tuftsin inhibitor were also studied. The peptides 2, 4 and 5 were found to produce very strong analgesia after the icv injection. It was observed that pretreatment with peptide 8 remarkably diminished the antinociceptive effect induced by tuftsin.
 ...
PMID:The analgesic activity of some tuftsin- and tuftsin inhibitor-like fragments of the viral coat proteins. 822 Jun 60

Neuropeptide FF (FLFQPQRFamide, NPFF) is an octapeptide implicated in morphine analgesia, tolerance and dependence. Many of the behavioral effects of NPFF have also been observed with the invertebrate neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide), which binds to NPFF receptors because of its low homology to the C-terminal portion of NPFF. A competitive ligand binding assay was used to characterize NPFF receptors in rat spinal cord and a strong requirement was found for the C-terminal Arg-Phe-amide. It was found that FMRFamide (Ki = 1.8 nM) bound with lower affinity than NPFF (0.26 nM) but it was about 7-fold more potent than PQRFamide (12 nM). This finding explains the similar bioactivities of NPFF and FMRFamide. The Gln2 appeared to be the cause of the relatively low potency of PQRFamide, based on the binding specificity of NPFF receptors for a series of FMRFamide analogs. In contrast to the Arg-Phe-amide, substitutions at the first and second positions of FMRFamide were generally tolerated, with the most potent analogs being PMRFamide (Ki = 0.54 nM), FFRFamide (0.25 nM) and FWRFamide (0.42 nM). Among the most potent ligands was a pentapeptide containing a photoreactive Phe analog, D-Tyr-(p-benzoyl-Phe)-norLeu-Arg-Phe-amide (Ki = 0.23 nM). It was found that dansyl-PQRFamide and dansyl-RFamide also bound to NPFF receptors with Ki values of 6.1 and 73 nM, respectively. The radioligand binding and G-protein coupling of NPFF receptors were not altered by chronic morphine treatment.
 ...
PMID:Neuropeptide FF receptors: structure-activity relationship and effect of morphine. 822 91

Based on pharmacological evidence that inhibitory amino acids mediate vaginocervical mechano-stimulation produced analgesia (VSPA), we hypothesized that inhibitory amino acids would be released endogenously in the spinal cord in response to vaginocervical mechano-stimulation (VS). This hypothesis was tested by HPLC analysis of the amino acid content of 5-min superfusates of the spinal cord before, during and after VS (400 g force applied against the cervix) in urethane-anesthetized rats. Utilizing an in vivo push-pull superfusion method, artificial cerebrospinal fluid was continuously superfused over the spinal cord through the intrathecal space surrounding the sacral-lower thoracic region. In addition, concentrations of amino acids in the superfusate were measured in response to KCl stimulation (increasing the superfusion medium from 3.4 to 40.0 mM KCl to produce non-specific depolarization), and noxious hind paw mechano-stimulation (pinching the hind paw to produce a sustained flexor response in ipsilateral hind leg). There was a significant increase in the concentration of Gly, Tau, Asp, Glu and Lys in the superfusate in response to VS (n = 8) and to KCl (n = 8), but not to hind paw stimulation (n = 5). Also, GABA concentrations increased in response to KCl, and the concentration of Ala, Ser, Gln, Thr, Arg and Phe increased in response to VS, however, GABA levels were sometimes below the limits of detection. In contrast, there was no significant change in any amino acid concentration in response to hind paw pinch stimulation, and VS did not significantly affect the concentrations of Tyr, His, Ile, Leu, Met, Trp or Val. The present findings support our hypothesis that VS releases inhibitory amino acids in the spinal cord. Moreover, other amino acids, including 'excitatory' amino acids, are released into the superfusate. The profile of amino acid release in response to VS differs from that in response to paw pinch or KCl administration.
 ...
PMID:Release of amino acids into regional superfusates of the spinal cord by mechano-stimulation of the reproductive tract. 824 40

Intracerebroventricular injection (icv) of 1-arginine (Arg, 0.5, 5.0, 50 micrograms) produced a dose-dependent prolongation in the hot-plate latency in mice. A similar result was obtained when nitroprusside (0.1, 1.0, 10 micrograms, icv) was given. Naloxone (2 mg.kg-1, ip) failed to antagonize the effects of Arg or nitroprusside. But Arg-induced antinociception was attenuated by NG-monomethyl-arginine (NMMA, 10 micrograms). 8-Bromoguanosine 3': 5' cyclic monophosphate (bromo-cGMP, 50 micrograms) also produced an antinociceptive effect. The results suggest that Arg induces an analgesia possibly via activation of nitric oxide-cGMP pathway.
 ...
PMID:Possible involvement of nitric oxide in arginine-induced analgesia. 824 16

The purpose of the present study was to systematically investigate the effects of the mammalian neuropeptide Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF) on nociception, using the tail-flick test. We report that ICV administration of NPFF induces a rapid and short-lasting hyperesthesic effect during day or night, for doses ranging from 10 ng to 10 micrograms. During the night, this hyperesthesic effect is followed by a long-lasting analgesic effect, the magnitude of which is related to the magnitude of the hyperesthesic effect. In addition to this intrinsic effect of NPFF, we report that NPFF reverses morphine-induced analgesia and that the magnitude of the response elicited by NPFF increases as a function of morphine-induced analgesia.
 ...
PMID:Biphasic effect on nociception and antiopiate activity of the neuropeptide FF (FLFQPQRFamide) in the rat. 828 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>