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 effect of administering low doses (0.5-1.5 micrograms) of the mu-opioid receptor agonist fentanyl into the right brachial plexus sheath of the rat was examined using the vocalization threshold to paw pressure test. Both forepaws were tested in each rat. Fentanyl injected into the right brachial plexus sheath at 0.5-1.5 micrograms/kg produced a localized, dose-dependent, potent and long lasting antinociceptive effect, as gauged on the right forepaw. At the lower dose used (0.5 microgram/kg of fentanyl), the antinociceptive effect was restricted to the right forepaw and lasted for more than 2 h. Increasing doses of fentanyl (1 and 1.5 micrograms/kg) induced potent effects, lasting up to 5-6 h or even longer. In complete contrast, fentanyl administered i.v. at the dose of 1 microgram/kg had a very transient effect, only lasting up to 25 min. The results of injection of low doses of the opioid antagonist naloxone when administered either i.v. or locally into the paw, on the effect of fentanyl suggest the involvement of a peripheral site of action of the opioid. The present findings suggest that, as already observed in patients in clinical situations, low doses of opiates delivered using this administration route may provide prolonged regional analgesia, with the potential of avoiding centrally mediated side effects.
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PMID:Potent and long lasting antinociceptive effects after injection of low doses of a mu-opioid receptor agonist, fentanyl, into the brachial plexus sheath of the rat. 217 42

Mice treated chronically with opioid antagonists have increased receptor density in brain and are supersensitive to the pharmacodynamic action of morphine. In the present study mice were implanted subcutaneously with naltrexone or placebo pellets for 8 days. During implantation mice received daily injections of morphine (100 or 250 mg/kg) or saline. Morphine analgesia was completely blocked in mice that were implanted with naltrexone at the low dose of morphine; while some analgesic action was observed at the higher dose. Mice implanted with placebo were analgesic following the daily morphine treatment. At the end of 8 days the pellets were removed and 24 h later some mice were tested for morphine analgesia while others were examined in binding studies. Naltrexone treatment increased [3H]naloxone, 3H[D-Ala2-D-Leu5]enkephalin (DADLE) and 3H[D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) binding compared to controls and increased the analgesic potency of morphine. Daily treatment with morphine did not alter brain opioid binding or naltrexone-induced receptor upregulation. Mice injected daily with morphine were significantly less sensitive to morphine (tolerant) than their respective saline control group for both the placebo and the naltrexone-treated groups. However, naltrexone-treated mice were more sensitive to morphine than placebo controls regardless of whether they were injected daily with morphine or not. These results indicate that if naltrexone-induced opioid receptor upregulation occurs in the presence of repeated agonist administration, the new binding sites mediate tolerance via desensitization to morphine.
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PMID:Simultaneous development of opioid tolerance and opioid antagonist-induced receptor upregulation. 217 26

The effects of tifluadom, a benzodiazepine-kappa-opioid-receptor agonist, on cholecystokinin-octapeptide (CCK-8)-induced antinociception were investigated in the mouse writhing test. When given alone, tifluadom produced pronounced, dose-dependent analgesia. The antinociceptive effect of intracerebroventricularly injected CCK-8 was potentiated by high doses of tifluadom. In contrast, when tifluadom was applied at low doses which did not induce antinociception, the antinociceptive effect of CCK-8 was completely antagonized. It is concluded that tifluadom acts both as kappa-opioid receptor agonist and as an antagonist at CCK receptors mediating CCK-induced antinociception.
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PMID:The influence of tifluadom on cholecystokinin-induced antinociception. 236 2

The role of neural histamine in morphine-analgesia and in morphine-induced potentiation of stress analgesia was studied. Pretreatment of rats with alpha-fluoromethylhistidine (alpha-FMH) (200 micrograms i.c.v./rat; daily for five days) increased the analgesic potency of morphine, centrally or peripherally injected, in the tail-flick assay. This increase was significantly blocked by i.c.v. or i.p. beta-funaltrexamine (beta-FNA) a mu selective irreversible opioid receptor antagonist, whereas i.c.v. injected naltrexone did not block the increased analgesic potency of the i.c.v. morphine. Rats subjected to cold-restrained stress (60 min at 4 degrees C) showed increased tail-flick latency, compared to the unstressed group. The analgesic potency of morphine was significantly greater in rats subjected to restraint with respect to unstressed rats. However, the inhibition of histamine biosynthesis by alpha-FMH significantly reduced cold-restraint analgesia in controls, and also inhibited the analgesic efficacy of the opiate. These results indicate that neural histamine may be responsible for pain response modifications observed in rats subjected to cold-restraint conditions, and of morphine-potentiation of stress analgesia. The data also suggest a close association between increased analgesic potency of morphine and inhibition of histaminergic effects, possibly implying a functional supersensitivity and an increase in opioid receptors.
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PMID:Peripheral and central opioid activity in the analgesic potency of morphine. 237 23

The contribution of opioid receptor to lappaconitine (LA) induced analgesia was investigated by in vivo and in vitro methods. The antagonistic effects of naloxone (NLX) on the analgesic actions of LA (s.c.) and morphine (MOR, s.c.) were determined by the tail pressure method, the hot plate method and the acetic acid-induced writhing method in mice. The ED50 values of MOR in the absence of NLX were 3.82, 0.50 and 0.33 mg/kg, respectively, but in the presence of NLX, the analgesic effect of MOR was decreased and the ED50 values were changed to 41.6, 4.40 and 5.97 mg/kg, respectively. However, NLX did not affect the analgesic activity of LA. The ED50 values of LA in the three methods were 9.12, 3.34 and 1.70 mg/kg in the absence of NLX and 12.1, 4.19 and 2.88 mg/kg in the presence of NLX, respectively. The inhibitory effect of the LA on the electrically evoked contractions of isolated guinea-pig ileum was weaker than that of MOR, and differently from MOR, its effect was not antagonized by NLX. Additionally, LA did not abolish the electrically evoked contractions of isolated rabbit and mouse vas deferens. In conclusion, the results suggest that the opioid receptor was not involved in the analgesic activity of LA.
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PMID:Pharmacological studies of lappaconitine. Occurrence of analgesic effect without opioid receptor. 253 50

We evaluated the ability of mu [morphine, Tyr-Pro-N-MePhe-D-Pro-NH2 (PLO17)], delta (Tyr-D-Pen-Gly-Phe-D-Pen) (DPDPE) and kappa [U50,488H, (trans-3,4-dichloro-N-methyl-N-(2-(1-pyr-rolidinyl) cyclo-hexyl)benzeneacetamine)] opioid receptor selective agonists to inhibit diarrhea induced by castor oil (0.6 ml p.o.) in mice after supraspinal (i.c.v.) and peripheral (s.c.) administration. The antidiarrheal potency of each compound was compared to its analgesic and gastrointestinal antitransit potency when given by the same route of administration. When administered i.c.v., morphine, PLO17 and DPDPE inhibited diarrhea in a dose-related fashion. The mu agonists, morphine and PLO17, given i.c.v, inhibited diarrhea at doses much lower than those needed to produce analgesia or to inhibit gastrointestinal transit. DPDPE (i.c.v.) was equipotent in inhibiting diarrhea and in eliciting analgesia, but did not effect the rate of transit. U50,488H (i.c.v.) inhibited diarrhea only at extremely high doses which also caused profound postural-motor incapacitance. U50,488H given i.c.v. had no effect on transit at any dose. When given peripherally, morphine, PLO17, DPDPE and U50,488H all inhibited diarrhea in a dose-related fashion. All four compounds inhibited diarrhea at doses much below those needed to cause analgesia. Morphine s.c. and PLO17 s.c. both inhibited diarrhea at doses lower than those required to inhibit transit. DPDPE s.c. and U50,488H s.c. had no effect on transit at any dose. The antidiarrheal effects of i.c.v. morphine, i.c.v. PLO17 and i.c.v. DPDPE were antagonized by pretreatment with 1 microgram i.c.v. of naltrexone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antidiarrheal properties of supraspinal mu and delta and peripheral mu, delta and kappa opioid receptors: inhibition of diarrhea without constipation. 254 Mar 24

The effects of 16-Me cyprenorphine (M80) on the antinociception produced by reexposing rats to a chamber associated with footshock (1 mA, 0.75 sec) 24 hr earlier was assessed with the formalin test. In Experiment 1, intracerebroventricular administration of M80 dose-dependently (0.5-8 micrograms) reversed conditional analgesia. Experiment 2 demonstrated that M80 (5 micrograms) had no effect on baseline pain sensitivity, but completely reversed conditional analgesia. Experiment 3 demonstrated that 0.25 micrograms DAGO, 3.5 micrograms DPDPE, and 28 micrograms U50,488H all produced equivalent levels of antinociception on the formalin test. The 5 micrograms dose of M80 completely reversed the antinociception produced by DPDPE but did not influence that produced by DAGO or U50,488H. These data suggest, that at the doses employed, M80 is a selective delta-opioid receptor antagonist and that delta-receptors are involved in conditional fear-induced analgesia.
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PMID:Delta opioid antagonist, 16-Me cyprenorphine, selectively attenuates conditional fear- and DPDPE-induced analgesia on the formalin test. 254 94

At the cerebral level, studies employing several experimental approaches point to an essential role of beta-endorphin in analgesia, induced by electrical stimulation of the periaqueductal grey of the midbrain. Tolerance and cross-tolerance studies suggest that mu-opioid receptors mediate this effect. The significance of sigma- and, in particular, kappa-opioid receptors in cerebral pain modulation is less well documented. At the spinal level, nociception is relayed in the dorsal horn, where opioid peptides as well as all types of opioid receptors are abundant. mu-opioid receptor-mediated anti-nociceptive processes appear to be most important in this region, but sigma-opioid receptors may also be involved. In addition, a role of kappa-opioid receptors can be demonstrated under certain conditions. Recent experiments indicate that opioids may also modulate nociception in the periphery, in particular in inflamed tissue.
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PMID:[Participation of opioids and opioid receptors in antinociception at various levels of the nervous system]. 255 24

7 alpha-bis (beta-chloroethyl) aminomethyl-6, 14-endoetheno-tetrahydro oripavine (alpha-CAM) is a new irreversible opioid receptor agonist. Its effect on isolated tissues (guinea pig ileum, mouse vas deferens, rat vas deferens and rabbit vas deferens) were studied. It was shown to be bound irreversibly to rat brain P2 membrane preparations. The ED50 of its analgesic effect in mice (icv) was found to be 0.12 nmol/mouse, and the effect may last as long as 2-3 days. It is a compound which produces the longest analgesia known up to date. A single dose (icv) of alpha-CAM was sufficient to produce dependence in mice. Thus, the compound may serve as an agent for studying the mechanism of physical dependence.
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PMID:[Pharmacological study on a new irreversible agonist of opioid receptors, 7 alpha-bis(beta-chloroethyl) aminomethyl-6, 14-endoetheno-tetrahydrooripavine]. 255 94

Selectivity for opioid receptor subtypes of enkephalin analogues (KK-1, -2, -3 and -4) of Tyr moiety on the N-terminal, and Phe-ol group on the C-terminal, connected with the methylene group (n = 1-4) were examined in isolated smooth muscle preparations and in the analgesic effect in mice. In the longitudinal muscle preparations of guinea pig ileum (GPI), morphine, U-50488H and all the enkephalin analogues inhibited electrically evoked contractions, and the inhibitory effects of morphine, KK-1, KK-2 and KK-3 were antagonized by naloxone with relatively high pA2 values, while that of U-50488H and KK-3 were preferentially antagonized by norbinaltorphimine. In the rabbit vas deferens preparations (RVD), on the other hand, U-50488H, KK-3 and KK-4 showed weak inhibitory effects and the inhibition of U-50488H and KK-3 were antagonized by norbinaltorphimine. By intracerebroventricularly (i.c.v.) injection, enkephalin analogues produced analgesia in the acetic acid (AcOH) writhing test, and the effect of KK-1 and KK-2 as well as morphine was antagonized by 1 mg/kg naloxone, while those of U-50488H and KK-3 were sensitive to 1 mg/kg Mr2266. In conclusion, enkephalin analogues with a short methylene chain between the functional groups, KK-1 and KK-2, mainly exert their effect through opioid mu-receptors, while those of longer chain, KK-3 and KK-4, act through kappa-receptors preferentially, and KK-3 is situated in the alternating point of the selectivity for mu- and kappa-receptors.
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PMID:Selectivity for opioid receptor subtypes of enkephalin analogues in isolated smooth muscle and in the analgesic effect in mice. 255 86


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