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 calcium entry blocker, verapamil, enhanced morphine analgesia, but neither methadone nor propoxyphene analgesia was affected by verapamil in the mouse hot-plate test. To explain this, it was hypothesized that methadione and propoxyphene differ from morphine because they, like verapamil, block calcium channels and subsequent studies were done to confirm this. Verapamil, methadone and propoxyphene all depressed barium-induced bovine adrenal catecholamine release and KCl-induced contractions of guinea pig ileum, which are known to be calcium-dependent events. Calcium reversed opioid-induced inhibition in both tissues. Morphine did not affect either catecholamine release or ileal contractions. Procaine also did not influence catecholamine release or ileal contraction. Therefore, local anesthesia was eliminated as a mechanism for the inhibitory action of methadone and propoxyphene in these tissues. Opioids which block calcium channels should, like verapamil, produce bradycardia and hypotension. In the spinal vagotomized rat, methadone, propoxyphene, and verapamil produced bradycardia and hypotension, whereas, morphine produced tachycardia and (at low doses) hypertension. The results of this work suggest that methadone and propoxyphene, in contrast to morphine, block calcium channels in a manner similar to verapamil, and that some pharmacological and especially toxicological differences between these drugs are due to different degrees of verapamil-like calcium channel blockade.
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PMID:Calcium channel blockade by certain opioids. 666 95

Organic calcium (Ca++) channel antagonists enhance opiate-induced analgesia and antagonize respiratory depression produced by morphine in rodents. Our preliminary data indicated that verapamil reduces the subjective effects of morphine in humans. We therefore assessed morphine-verapamil interactions in 12 experienced, male polydrug users with histories of heroin abuse by using a double-blind, cross-over study design. Treatments consisted of two drug infusions. Either verapamil, 2.5 or 10 mg, or saline was infused, 30 ml i.v. over 2 min; half way through this infusion either 10 mg of morphine or saline was infused, 3 ml i.v. over 10 sec, via a second catheter. Autonomic parameters, responsiveness to pain and subjective self-reports of mood and feeling state were measured over 4 hr. Analgesia was measured using a finger pressure test and hand immersion in ice water. Respiration was measured by using respiratory inductive plethysmography and transcutaneous CO2 levels. The Addiction Research Center Inventory (ARCI) was used to measure the subjective effects. Morphine had a liminal effect on pain threshold, but verapamil potentiated this effect to elevate pain threshold significantly. Verapamil did not affect the ability of morphine to increase pain endurance or to produce respiratory depression. Morphine produced positive affective responses, as demonstrated by elevated scores on the Morphine-Benzedrine Group subscale of the ARCI. Verapamil alone produced no effects on any ARCI subscales; however, 10 mg of verapamil significantly reduced morphine-elevated MBG scores over a 3-hr period. The results suggest the euphorigenic and analgesic effects of opioids may be differentiated by using Ca++ channel blockers.
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PMID:Effects of verapamil on morphine-induced euphoria, analgesia and respiratory depression in humans. 826

We evaluated the opioid antinociceptive mechanism of the calcium channel blockers verapamil and flunarizine in groups of mice with the hotplate test. Both produced a naloxone-sensitive dose-dependent analgesia. The antinociceptive effect of both was reversed by beta-FNA, (mu1 and mu2 antagonists), and both enhanced the antinociceptive activity of morphine, implying a role for mu receptors. Furthermore, since the analgesic effect of flunarizine, but not verapamil, was reversed by naloxonazine (mu1 antagonist), we suggest that the mu1 subtype is involved in flunarizine analgesia, but not in verapamil analgesia. Studies with the selective delta opioid agonist DPDPE and the selective antagonists naltrindole indicated that the antinociceptive activity of verapamil is also mediated by delta receptor agonistic activity (primarily following i.c.v. administration); flunarizine, by contrast, exhibited antagonistic activity at this receptor. Verapamil amplified the antinociceptive activity of kappa1 (U50,488H) and kappa3 (nalorphine) agonists, but its known analgesic activity was inhibited only partially by the kappa1 antagonist Nor-BNI, indicating partial involvement of kappa1 receptor. Flunarizine, however, demonstrated antagonistic activity at both kappa1 and kappa3 receptors, with more prominent inhibitory activity at the latter one. These findings suggest that verapamil and flunarizine elicit analgesia at both the spinal and supraspinal levels. Verapamil's analgesia was explained by agonistic activity at the mu, delta and may also be kappa3 receptor subtypes. Flunarizine exhibited a mixed agonistic-antagonistic opioid activity as shown by its agonistic activity at the mu1 receptor and antagonistic activity at delta, kappa1 and kappa3 receptor subtypes.
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PMID:Pharmacological interaction of the calcium channel blockers verapamil and flunarizine with the opioid system. 1008 3

The influence of the calcium channel blockers (CCBs) nifedipine, verapamil and diltiazem, and the calmodulin antagonist trifluoperazine on the antinociceptive activity of acetaminophen was studied in male albino mice. The nociceptive response was determined by the acetic acid writhing test. Nifedipine (50 or 20 mg/kg), verapamil (20 mg/kg), diltiazem (70 mg/kg) and trifluoperazine (3 mg/kg) were administered orally alone or 1 h before acetaminophen (100 mg/kg). Nifedipine (50 mg/kg), verapamil, diltiazem and trifluoperazine administered alone demonstrated significant antinociceptive effects compared to controls. Nifedipine, verapamil, diltiazem and trifluoperazine applied 1 h before acetaminophen potentiated its antinociceptive activity, which was strongest in mice injected with verapamil and nifedipine (20 mg/kg). It was established that 1 h after nifedipine (50 mg/kg) treatment, cytochrome P450 content, NADPH cytochrome c reductase and ethylmorphine-N-demethylase (EMND) activities were increased in the liver microsomes. Verapamil, diltiazem and trifluoperazine did not change the drug metabolizing enzymes studied. It is assumed that their effect on acetaminophen analgesia is not associated with the changes in acetaminophen oxidative metabolism in the liver.
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PMID:Effects of nifedipine, verapamil, diltiazem and trifluoperazine on the antinociceptive activity of acetaminophen. 1134 95

Opioids, alpha(2)-adrenoceptor agonists and blockers of voltage-gated calcium channels (VGCCs) have been attributed antinociceptive activity in various experimental set-ups. The present study tested the ability of morphine, clonidine and drugs acting at various VGCCs to inhibit the transmission of noxious stimuli from the mesentery at the level of the spinal cord. In rats under barbiturate anaesthesia traction of 20 g was applied to a bundle of mesenteric blood vessels. This caused immediate transient changes of mean arterial pressure that were taken as indication of nociception. Similar reflexes were elicited by applying 0.6% acetic acid to the same bundle of vessels. The reflexes were dose-dependently reduced by intrathecal administration of morphine or clonidine, but were left unaltered by intrathecal administration of verapamil, Bay-K 8644 or omega-conotoxin MVIIA. Neither verapamil nor Bay-K 8644 influenced clonidine-induced analgesia. Conotoxin markedly enhanced the effectiveness of all doses of clonidine against both types of mesenteric stimuli. Verapamil, Bay-K 8644, as well as conotoxin reduced the ability of morphine to inhibit mechanically evoked reflexes, while there was no statistically significant effect in chemonociception. These data suggest that, at the spinal level, both morphine and clonidine are effective drugs to decrease the cardiovascular changes caused by acute mesenteric pain. In the dorsal spinal cord neither L-type nor N-type VGCCs are responsible on their own for the transmission of noxious stimuli from the mesentery. Inhibition of N-type channels markedly augments the action of clonidine, whereas blocking either VGCC seems to inhibit antinociceptive mechanisms induced by morphine. It is suggested that in patients the combined administration of clonidine with omega-conotoxin MVIIA might lead to effective pain control with reduced side effects.
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PMID:Role of calcium channels in the spinal transmission of nociceptive information from the mesentery. 1140 36

The aim of this study was to report the effectiveness of laser therapy applied to traumatic labial injury of patients with spastic cerebral palsy. We report two cases of patients with internal mucosa and lower lip traumatism caused by oral reflex automatism with spastic tonic bite and lower lip interposition. One patient presented extensive lower lip ulceration, loss of tissue, crusty and hemorrhagic areas, with increasing pain and spasticity. The other patient presented local congestion signs, extremely enlarged tissue growth and increased labial volume. Laser therapy was applied to all injured areas, with a low-potency diode InGaAlP laser [685 nm Quasar (Dentoflex), 190 J/ cm2, with a 24-h interval between the first and second administration, and a 7-day interval between the two subsequent ones. At first re-evaluation, 24 h later, there was a striking reduction in inflammation, a decrease in vascular congestion, and a reduction of the ulcerated area with spasticity and pain reduction. At the 14-day re-evaluation, significant clinical differences in the advanced healing process were seen. Low-intensity laser showed to be effective in traumatic soft tissue treatment in cerebral palsy patients by accelerating the healing process, reducing secondary contamination, promoting analgesia; thus, it can be an important tool in the treatment of these patients.
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PMID:Efficiency of laser therapy applied in labial traumatism of patients with spastic cerebral palsy. 1569 Jul 68