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)

To determine whether or not the CNS inhibitory activity of eel calcitonin (eCT) on adenylyl cyclase is the endocellular mechanism underlying the antinociceptive effect of the peptide, as shown for morphine analgesia, we administered Bordetella pertussis toxin (PTX) by intracerebroventricular (ICV) injection (0.5 microgram/rat) to block the receptor-mediated inhibition of adenylyl cyclase. In PTX-treated rats there was no change in eCT (2.5 micrograms/rat, ICV)-induced antinociceptive activity (hot-plate test) nor in eCT (100 ng/rat, ICV) inhibition of gastric acid secretion (Shay test) whereas morphine (5 micrograms/rat, ICV) analgesia was significantly reduced. In vitro studies showed no reduction of eCT binding in the CNS of rats treated with PTX in vivo. Moreover, PTX treatment did not change the inhibitory effect of eCT on adenylyl cyclase in isolated membranes from rat striatum in contrast with opiates (DAME and morphine) whose effects were lost. As PTX is known to inactivate the guanidine binding inhibitory protein Gi, these data suggest that a G protein, distinct from the Gi protein involved in the coupling of opiate receptors into a functional response, could be responsible for regulating the intracellular pathways resulting in eCT-induced antinociceptive effect and inhibition of gastric acid secretion.
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PMID:Treatment with pertussis toxin does not prevent central effects of eel calcitonin. 165 2

(+)Pentazocine antagonizes morphine analgesia as potently as its (-)-isomer, ruling out an opioid receptor mechanism of action and suggesting, which suggests a role for sigma 1 receptors. Systemic (+) pentazocine also reverses supraspinal or spinal morphine analgesia. 1,3-Di(2-tolyl)guanidine, a sigma ligand with no appreciable opioid receptor affinity, antagonizes morphine analgesia. The actions of both (+)pentazocine and 1,3-di(2-tolyl)guanidine are reversed by haloperidol, which has high affinity for both sigma and D2 receptors, but not by the D2-selective antagonist (-)sulpiride, which lacks activity at sigma sites. The antiopioid sigma system is tonically active. Haloperidol, but not (-)sulpiride, decreases morphine ED50 almost 2-fold. The antiopioid system modulates only mu analgesia. Unlike analgesia, (+)pentazocine does not influence morphine's inhibition of gastrointestinal transit or lethality. (+)Pentazocine also antagonizes kappa 1, kappa 3 and delta analgesia through sigma mechanisms in a haloperidol-sensitive manner. (-)Sulpiride is inactive. Alone, haloperidol enhances kappa 1, kappa 3 and delta analgesia more dramatically than morphine, which indicates that the sigma system is active against all opioid analgesic systems. Sigma systems are responsible for some strain differences in kappa receptor sensitivity. Unlike CD-1 mice, BALB-C mice are relatively insensitive toward the kappa 1 agent U50,488H and the kappa 3 analgesic naloxone benzoylhydrazone. Blockade of the sigma system with haloperidol eliminates these strain differences. In conclusion, sigma 1 systems functionally antagonize opioid analgesia without affecting morphine's effects on gastrointestinal transit or lethality. The antiopioid sigma system is tonically active and is more active against kappa analgesia than mu.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective antagonism of opioid analgesia by a sigma system. 799 72

Aminoglycosides (AGs) modulate nociceptors and ionic channels expressed in sensory neurons. The AG applied in situ could be useful to alleviate hyperalgesia in animal models of inflammatory pain. We tested streptomycin (ST) and neomycin (NEO) as analgesic agents applied in situ in rat paw inflammation caused by formalin or carrageenan administration. The action of ST and NEO on the action potential discharge produced by acidic stimuli in isolated dorsal root ganglion neurons was also studied in current-clamp recordings. In the formalin test, ST and NEO significantly reduced the nociceptive behaviour. ST reduced the N-(4-methyl-2-quinazolinyl)-guanidine (GMQ)-induced nociceptive behaviour, and NEO diminished the hyperalgesia to thermonociception and mechanonociception produced by CAR. In the current-clamp experiments, ST and NEO reduced the generation of action potentials when an acidic solution was applied. We conclude that ST and NEO produce analgesia to inflammatory pain, an effect that is due in part to the inhibition of ASIC activation in sensory neurons.
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PMID:Inhibition of peripheral nociceptors by aminoglycosides produces analgesia in inflammatory pain models in the rat. 2502 2