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)

Substance P produces analgesia when administered to mice in very small doses by the intraventricular route (1.25 to 5 nanograms per mouse). The analgesic effect can be blocked by naloxone. At higher doses (greater than 50 nanograms per mouse), this activity is lost. At these higher doses, however, substance P produced hyperalgesia when combined with naloxone and analgesia when combined with baclofen [beta-(4-chlorophenyl)-gamma-aminobutyric acid]. Substance P may have dual actions in brain, releasing endorphins at very low doses and directly exciting neuronal activity in nociceptive pathways at higher doses.
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PMID:Dual actions of substance P on nociception: possible role of endogenous opioids. 20 12

The intracerebroventricular (i.c.v.) injection of antisera directed against different sequences of Gs alpha to mice enhanced the antinociceptive potency of the opioids morphine, beta h-endorphin-(1-31) and of the alpha 2-agonist clonidine when studied 24 h later in the tail-flick test. The activity of DAGO, DADLE, DPDPE and [D-Ala2]-Deltorphin II remained unchanged after that treatment. Cholera toxin (0.5 microgram/mouse, i.c.v.), agent that impairs the receptor regulation of Gs transducer proteins promoted comparable changes in the supraspinal analgesia induced by these substances. Six days after a single i.c.v. injection (0.5 microgram/mouse) of pertussis toxin the antinociceptive activity of all the opioids and clonidine appeared diminished. It is concluded that opioids and clonidine promote analgesia after binding to receptors functionally coupled to Gi/G(o) proteins, moreover, the activity of morphine, beta-endorphin and clonidine in this test seems to be counteracted by a process involving activation of Gs alpha transducer proteins.
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PMID:Intracerebroventricular injection of antibodies directed against Gs alpha enhances the supraspinal antinociception induced by morphine, beta-endorphin and clonidine in mice. 144 47

Cholera toxin, an agent that impairs the function of Gs transducer proteins, was injected (0.5 microgram/mouse, icv) and the antinociceptive activity of opioids and clonidine was studied 24h later in the tail-flick test. In these animals, an enhancement of the analgesic potency of morphine, beta-endorphin and clonidine could be observed. Cholera toxin did not modify the antinociception evoked by the enkephalin derivatives DAGO and DADLE. Pertussis toxin that catalyses the ADP ribosylation of alpha subunits of Gi/Go regulatory proteins was given icv (0.5 microgram/mouse). This treatment reduced the analgesic effect of opioids and clonidine. However, while the analgesia elicited by DAGO, DADLE and clonidine was greatly decreased, the effect of morphine and beta-endorphin was reduced to a moderate extent. It is concluded that Gi/Go regulatory proteins functionally coupled to opioid and alpha 2 receptors are implicated in the efficacy displayed by opioids and clonidine to produce supraspinal analgesia. Moreover, these two receptors are susceptible to regulation by a process that might involve a Gs protein.
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PMID:Cholera toxin and pertussis toxin on opioid- and alpha 2-mediated supraspinal analgesia in mice. 185 Apr 93

The possible analgesic effects of i.c.v. administration of several aminoglycoside antibiotics were evaluated in mice using hot plate and tail flick tests. Neomycin (10-80 micrograms/mouse), gentamicin (40-160 micrograms/mouse) and kanamycin (80-320 micrograms/mouse) produced dose-dependent increases in the latencies to forepaw licking and jumping in hot plate test. These drugs also produced dose-dependent increases in the percentage of animals showing analgesia in tail flick test. The order of potency of these aminoglycoside antibiotics in both tests was neomycin greater than gentamicin greater than kanamycin, which is exactly the same order that these drugs show as N-type calcium channel blockers. Bearing in mind this fact and the well known analgesic activity of several drugs which decrease neuronal calcium availability, we suggest that the mechanism of aminoglycoside-induced antinociception may be related to the capacity of these antibiotics to block N-type calcium channels and decrease neuronal calcium availability.
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PMID:Analgesic effects of centrally administered aminoglycoside antibiotics in mice. 186 86

Changes in lappaconitine levels in blood, brain and spinal cord following subcutaneous (s.c.) injection were correlated with the analgesic activity at intervals up to 90 minutes after injection. In the mouse, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections of amounts corresponding to ED50 values in the tail pinch method (i.c.v.: 2333 ng/mouse; i.t.: 1127 ng/mouse) gave peak lappaconitine levels of 1300 ng/g brain and 761 ng/g spinal cord, respectively. However, injection of lappaconitine at ED50 by the s.c. route (7 mg/kg) gave lower peak lappaconitine levels of 320 ng/g brain and 214 ng/g spinal cord. The responses to i.c.v., i.t. and combined i.c.v. plus i.t. administration of lappaconitine were evaluated by the determination of ED50 values, which were plotted as an isobologram. The experimental point is not significantly different from the theoretical additive ED50 point. When a dose equal to the experimental additive ED50 value (i.c.v., i.t. = 620, 413 ng/mouse) was injected, peak lappaconitine levels reached 344 ng/g brain and 241 ng/g spinal cord. Thus, the equianalgesic doses of lappaconitine (ED50 by the s.c. route and additive ED50 by the i.c.v. plus i.t. route) gave closely similar concentrations of the drug in brain and spinal cord. These results indicate that a simultaneous action of lappaconitine on supraspinal and spinal sites is likely to be important for the analgesia produced by systemically administered lappaconitine.
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PMID:Pharmacological studies of lappaconitine: supraspinal-spinal interaction in antinociception. 188 28

1. The analgesic effects of diltiazem and verapamil, both per se and together with morphine, were studied using subcutaneous (s.c.) and intracerebroventricular (i.c.v.) administrations, in the hot-plate test in mice. 2. The i.c.v. injection of verapamil (15-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) induced dose-dependent analgesic effects. 3. The i.c.v. administration of verapamil (30-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) significantly enhanced, in a dose-dependent way, the analgesic effects of morphine and produced a parallel displacement to the left of the morphine log dose-response line. 4. When these calcium channel blockers were administered subcutaneously at doses of 40 and 80 mg/kg, they exerted no analgesic actions, but dose-dependently potentiated the analgesic effects of morphine, producing a parallel shift to the left of the morphine log dose-response line. 5. These results suggest that inhibition of calcium entry through calcium channels induced by verapamil and diltiazem may play a role in analgesia development.
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PMID:Analgesic effects of diltiazem and verapamil after central and peripheral administration in the hot-plate test. 227 85

1. The effect of atropine on the nociceptive system was examined in mice and rats by use of the hot-plate, writhing and tail-flick tests. 2. Atropine dose-dependently produced analgesia, no effect and hyperalgesia. Analgesia was observed in both species with doses ranging from 1 to 100 micrograms kg-1 while hyperalgesia was obtained with 5 mg kg-1. 3. Atropine antinociception was prevented by pirenzepine (0.1 microgram per mouse, i.c.v.), dicyclomine (10 mg kg-1, i.p.), atropine-methylbromide (0.5 microgram per mouse, i.c.v.) and hemicholinium-3 (1 microgram per mouse, i.c.v.). Naloxone (1 mg kg-1, i.p.), alpha-methyl-p-tyrosine (100 mg kg-1, s.c.) and reserpine (2 mg kg-1, i.p.) were ineffective. 4. The site of atropine analgesia is in the CNS since it exerts its antinociceptive effect also when injected i.c.v. (1-10 ng per mouse). Moreover drugs which do not cross the blood-brain barrier, such as hemicholinium-3, pirenzepine and atropine methylbromide, were unable to antagonize atropine analgesia if administered i.p. 5. Atropine also in vitro, showed a biphasic action on electrically-evoked guinea-pig ileum contractions. Concentrations between 10(-14) and 10(-12) M increased electrically and nicotine-evoked contractions but did not affect acetylcholine- and oxotremorine-evoked contractions. Concentrations above 10(-9) M inhibited both electrically- and drug (acetylcholine, nicotine and oxotremorine)-evoked contractions while they were ineffective on unstimulated ileum. 6. On the basis of the above findings, amplification of cholinergic transmission by very low doses of atropine is postulated, through a selective blockade of presynaptic muscarinic autoreceptors, as the likely mechanism of action. 7. Atropine antinociception, unlike oxotremorine antinociception, was obtained without any impairment of mouse rota-rod performance. 8. The antagonism by pirenzepine and dicyclomine of oxotremorine and atropine antinociception suggests that M1 muscarinic receptor subtypes are responsible for cholinergic analgesia.
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PMID:Investigation into atropine-induced antinociception. 228 66

It has been found that the metal salts MnCl2, NiCl2, GdCl3 and LaCl3 in doses up to 30, 20, 5 and 10 micrograms, respectively, potentiate the analgesic effect of intracisternally injected morphine (2 micrograms per mouse). The ability of the metal salts to potentiate the affinity of opiate ligands to the appropriate receptors is effectuated via interaction of metal cation with the specific opiate receptor site. It is suggested that one of the possible mechanisms of the potentiating effect of some metal salts on the morphine-induced analgesia involves the enhancement of morphine affinity for mu-receptors in the brain.
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PMID:[Potentiating action of bi- and trivalent metal salts on the analgesic effect of morphine]. 299 78

Jimpy (B6CBA-A W-J/A-Ta jp) mice, which are known to be deficient in neuronal cerebroside sulfate (a putative component of the mu opioid receptor), were non-responsive in the tail flick test (compared to littermate controls and a standard Swiss strain of mouse) to analgesic doses of two mu opioid receptor agonists, morphine sulfate and [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO). However, the jimpy mice responded normally (compared to controls) to the analgesic effects of the selective delta opioid receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE). These results suggest (1) that delta opioid receptors can mediate analgesia and (2) that cerebroside sulfate is not necessary for delta opioid receptor activation.
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PMID:[D-Pen2,L-Pen5]enkephalin induced analgesia in the jimpy mouse: in vivo evidence for delta-receptor mediated analgesia. 303 73

Intraperitoneal injection of zymosan (1 mg in 0.5 ml saline) in mice induces a transient writhing response accompanied by the synthesis of small amounts of prostaglandin E2(PGE2, less than 2 ng) and larger amounts of PGI2 (200 ng per mouse), measured as its non-enzymatic breakdown product, 6-keto-PGF1 alpha. Although both centrally-acting analgesics (morphine, clonidine) and prostaglandin biosynthesis inhibitors (aspirin, indomethacin, ibuprofen) blocked the writhing response to intraperitoneal injection of zymosan, only the latter reduced prostaglandin levels in the peritoneal cavity. The writhing response correlated equally well with PGE2 levels and 6-keto-PGF1 alpha levels when data from mice treated with centrally-acting analgesics were excluded. However, intraperitoneal injection of PGI2, but not PGE2, reversed the analgesia induced by indomethacin in zymosan-injected mice. Centrally-acting agents, but not ibuprofen, blocked the ability of PGI2 to reverse the analgesic activity of indomethacin. PGI2 (2 micrograms per mouse), injected intraperitoneally in otherwise untreated mice, induced writhing. These data indicate that PGI2 is the prostaglandin involved in mediation of the writhing response to zymosan and that prostaglandin biosynthesis inhibitors, but not centrally-acting analgesics, exert their analgesic activity by reducing the peritoneal level of PGI2. It is possible that PGI2 may have the ability to stimulate pain receptors directly in the mouse peritoneal cavity, in addition to its previously recognized ability to sensitize pain receptors to other pain-producing stimuli.
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PMID:The role of prostaglandins in the nociceptive response induced by intraperitoneal injection of zymosan in mice. 359 81


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