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)

We have recently reported that, in SH-SY5Y cells, mu-opioid receptor occupancy activates phospholipase C via a pertussis toxin-sensitive G-protein. In the present study we have further characterized the mechanisms involved in this process. Fentanyl (0.1 microM) caused a monophasic increase in inositol 1,4,5-trisphosphate mass formation, with a peak (20.5 +/- 3.6 pmol/mg of protein) at 15 s. Incubation in Ca(2+)-free buffer abolished this response, while Ca2+ replacement 1 min later restored the stimulation of inositol 1,4,5-trisphosphate formation (20.1 +/- 0.6 pmol/mg of protein). In addition, nifedipine (1 nM-0.1 mM), an L-type Ca(2+)-channel antagonist, caused a dose-dependent inhibition of inositol 1,4,5-trisphosphate formation, with an IC50 of 60.3 +/- 1.1 nM. Elevation of endogenous beta/gamma subunits by selective activation of delta-opioid and alpha 2 adrenoceptors failed to stimulate phospholipase C. Fentanyl also caused a dose-dependent (EC50 of 16.2 +/- 1.0 nM), additive enhancement of carbachol-induced inositol 1,4,5-trisphosphate formation. In summary, we have demonstrated that in SH-SY5Y cells activation of the mu-opioid receptor allows Ca2+ influx to activate phospholipase C. However, the possible role of this mechanism in the process of analgesia remains to be elucidated.
 ...
PMID:Mu-opioids activate phospholipase C in SH-SY5Y human neuroblastoma cells via calcium-channel opening. 783 76

The involvement of calcium in nicotine-induced analgesia in male rats was explored using the tail-flick test. A single dose of nicotine (1 mg/kg SC) produced a maximal effect on tail-flick latency (15 s) within 8-10 min, which lasted for 4 min. Pretreatment with the calcium chelator, EDTA (250 microM/kg SC four injections at 15 min intervals), before the single dose of nicotine accelerated the onset and prolonged the duration of the nicotine-induced analgesia. The maximal effect on tail-flick latency occurred within 2 min and lasted for 10-20 min. Conversely, pretreatment with calcium chloride (1.5 mM/kg IP) attenuated nicotine-induced analgesia. It is suggested that nicotine may exert its antinociceptive effects via modulation of calcium fluxes across the neural membrane.
 ...
PMID:Modulation of nicotine-induced analgesia by calcium agonist and antagonist in adult rats. 787 Sep 21

Neuropeptide FF (NPFF), an FMRFamide-like peptide with antiopioid properties, inhibits morphine-induced analgesia but also produces hyperalgesia. In the present study, the mechanisms of NPFF release were investigated in an in vitro superfusion system with rat spinal cord slices. The opening of voltage-sensitive Na+ channels with veratridine (20 microM) induced calcium-dependent NPFF release, which was abolished by tetrodotoxin (1 microM), suggesting that NPFF release depends on nerve impulse activity. We also showed that NPFF release was a function of the extent of depolarization and was calcium dependent. The 30 mM K(+)-induced release was blocked by Co2+ or Ni2+ (2.5 mM) but was unaffected by Ca2+ channel blockers of the L type--Cd2+ (100 microM), nifedipine or nimodipine (10 microM), diltiazem (20 microM), or verapamil (50 microM)--or the N type--omega-conotoxin GVIA (1 microM). In contrast, omega-agatoxin IVA (1 microM) led to a 65% reduction in NPFF release, suggesting that P-type Ca2+ channels play a prominent role. The 35% remaining release resulted from activation of an unknown subtype. The NPFF-like material in superfusates recognized spinal NPFF receptors, suggesting that NPFF release in the spinal cord has a physiological role.
 ...
PMID:Release of neuropeptide FF, an anti-opioid peptide, in rat spinal cord slices is voltage- and Ca(2+)-sensitive: possible involvement of P-type Ca2+ channels. 789 Oct 84

The ability of nimodipine, a calcium-channel blocker, to enhance morphine analgesia and/or modify the development of tolerance was studied in patients with cancer pain who had needed successive increments of morphine for periods ranging from 21 to 780 days. Assessment of daily morphine consumption was the primary effect parameter. Nimodipine succeeded in reducing the daily dose of morphine in 16 of 23 patients (oral, n = 13; intrathecal, n = 3), and failed to modify it in 2 patients. Total oral daily dose was reduced by nimodipine (120 mg/day) from 282.6 +/- 47.7 mg to 158.7 +/- 26.2 mg (n = 15, P < 0.001). Intrathecal morphine was also reduced by 1-5 mg/day. Nimodipine was withdrawn in 5 patients during the first week of treatment due to intolerance (n = 3) or aggravation of the disease (n = 2). These preliminary results support experimental findings showing that pharmacological interference with Ca(2+)-related events may modify chronic opioid effects, including the expression of tolerance.
 ...
PMID:Enhancement of opiate analgesia by nimodipine in cancer patients chronically treated with morphine: a preliminary report. 797 Aug 35

The analgesic effect of protopine (Pro), an alkaloid isolated from Papaveraceae, was confirmed by tail-pinch and hot-plate tests when given sc 10-40 mg.kg-1, and 20-40 mg.kg-1 inhibited the spontaneous movements of mice. Pro 40 mg.kg-1 increased the sleeping rate, prolonged the sleeping duration, and shortened the sleeping latency in mice hypnotized by ip pentobarbital sodium 30 mg.kg-1. Pro 10-40 mg.kg-1 did not affect the inflammatory reaction induced by xylene and egg white. An icv injection of Pro 20-200 micrograms/mouse showed a remarkable analgesic effect in mice. The icv pretreatment of naloxone 2 micrograms blocked the analgesic effect completely. CaCl2 40 micrograms/mouse (ICV) or methotrexate 10 mg.kg-1 (ip), an agonist of Ca2+ channel, showed a complete blockade of the analgesia, while nifedipine 100 mg.kg-1(po), a blocker of Ca2+ channel, enhanced the analgesic effect. The ip pretreatment of reserpine 4 mg.kg-1 reduced the Pro analgesia. Phentolamine 10 mg.kg-1(ip), an alpha-adrenergic blocker, tended to weaken the analgesia, but propranolol 10 mg.kg-1(ip), a beta-blocker, did not affect it. These results suggest that Pro displays its analgesic effect mainly through the opioid and calcium systems and partly through the adrenergic mechanism.
 ...
PMID:Opioid, calcium, and adrenergic receptor involvement in protopine analgesia. 801 45

The effects of pertussis toxin, forskolin, and cAMP analogues on the antinociceptive action of nicotine were examined to investigate the possible involvement of adenylate cyclase and G-proteins in nicotine's antinociceptive effect. Intrathecal injection of pertussis toxin (0.25 and 0.50 micrograms) in mice inhibited nicotine-induced antinociception in the tail-flick test. The effect of the toxin was dose and time dependent. Forskolin, a potent adenylate cyclase activator, and 8-(-4-chlorophenylthio) adenosine-3':5' monophosphate, cyclic (8-CPT-cAMP), a cAMP analogue, inhibited the antinociceptive effects of nicotine in a dose-dependent manner. EGTA reversal of 8-CPT-cAMP's inhibitory effects suggests that calcium may to be involved. These data implicate the possible involvement of a G-protein and a second messenger system (activation of a cAMP-dependent protein kinase and increase in cyclic AMP levels) in nicotine-induced analgesia in mice.
 ...
PMID:Nicotine-induced antinociception in mice: role of G-proteins and adenylate cyclase. 802 3

Opioids inhibit the voltage-dependent calcium channel conductance, which is one of the mechanisms of opioid analgesia on the opioid receptor. According to the hypothesis that calcium antagonists can potentiate the analgesic effect of opioids, we designed a study to investigate the effects of KB-2796, a new calcium channel blocker, on the antinociception of fentanyl at the level of the spinal cord in rats. PE-10 catheters were chronically implanted in the lumbar intrathecal space of the rats. Tail-flick test was used to assess the nociceptive sensitivity. Fentanyl (1 microgram) and KB-2796 (50, 150 or 250 micrograms) were tested individually as well as in combination. Dimethyl sulfoxide (10%) was used as a control. All drugs were injected intrathecally. Fentanyl alone produced a significant but short duration (15-30 minutes) of antinociception. KB-2796 by itself did not show any antinociception at any of the doses tested. However, when KB-2796 at the higher doses (150 and 250 micrograms) was administered with fentanyl, the antinociceptive effect was significantly (P < 0.05) enhanced over that of fentanyl alone from 30 to 180 minutes after the injection. In conclusion, our results suggest that KB-2796 potentiates the analgesic effect of fentanyl at the spinal level. These data also support our hypothesis that calcium channel blockers may involve in the antinociception of opioids.
 ...
PMID:Enhancement of antinociceptive effect of fentanyl by KB-2796 at spinal level. 803 73

The interaction between sufentanil, a mu-opioid agonist, and the Ca2+ antagonist nimodipine on respiration and on the development of opioid tolerance in awake rats has been analyzed. Our previous work demonstrated that chronic treatment with nimodipine together with sufentanil increases the analgesic potency of the opioid 50 fold. Therefore, we have investigated whether the opioid-induced respiratory depression is potentiated in parallel with the analgesia. Ventilation was measured by the whole body plethysmographic method. In naive rats, sufentanil (10-80 micrograms/kg) consistently induced a dose-dependent respiratory depression. Pretreatment with nimodipine (200 micrograms/kg) potentiated this effect but to a lesser extent than it potentiated analgesia. After chronic administration of the opioid (2 micrograms/h, 7 days) tolerance was manifested as a reduction in both the area under the time course curve and in the maximum effect. Nimodipine (1 microgram/h) administered concurrently with sufentanil for 7 days counteracted the tolerance to respiratory depression but no additional potentiation was observed. These results demonstrate that the interaction between nimodipine and sufentanil is not limited to antinociception but also extends to respiratory depression. However, compared with analgesia, the clinical relevance of a potential increase in opioid-induced respiratory depression by nimodipine may be negligible.
 ...
PMID:Potentiation of acute opioid-induced respiratory depression and reversal of tolerance by the calcium antagonist nimodipine in awake rats. 813 6

A single electroconvulsive shock produced analgesia (expressed as prolongation of hot-plate latency) in Wistar rats 45 min after the shock. The analgesic action was prevented by administration of nifedipine, 5 mg/kg i.p., 15 min before the electroconvulsive shock, while nifedipine injection after electroconvulsive shock did not affect the analgesia significantly. At the same time single electroconvulsive shock counteracted the reduction of [3H]nitrendipine binding to cortical and hippocampal membranes from rats pretreated with nifedipine. Chronic administration of electroconvulsive shock (once daily for 8 days) produced hyperalgesia, augmented locomotor responses to low doses of apomorphine and upregulation of cortical (but not hippocampal) voltage-dependent Ca2+ channels (assessed from [3H]nitrendipine binding). In rats receiving electroconvulsive shock chronically, always 15 min after nifedipine injection, neither behavioral hyperresponsiveness nor Ca2+ channel upregulation was observed. The results suggest that the primary event in post-electroconvulsive shock analgesia depends on Ca2+ influx into neurons through voltage-dependent Ca2+ channels, and that given under conditions of Ca2+ channel blockade electroconvulsive shock is unable to trigger changes leading to Ca2+ channel upregulation, and this is possibly the reason for prevention of development of hyperalgesia and increased responsiveness to dopaminergic stimulation.
 ...
PMID:Modification of effects of chronic electroconvulsive shock by voltage-dependent Ca2+ channel blockade with nifedipine. 820 20

The issue whether an anesthesiologist can be criminally condemned for a mistaken injection by the midwife of a mixture of local anesthetics with calcium chloride into the epidural space was examined by the Criminal tribunal of Dendermonde and confirmed by the Court of Appeal of Ghent. Liability was asserted not only against the negligent midwife who did the erroneous reinjection, but also against the resident anesthesiologist who followed the rules of the anesthesia department and ordered the replacement of the syringe by telephone. The midwife was condemned not because she performed the technical act of an epidural reinjection, but because she made an obvious error in making the solution by confusing of diluting solution. The anesthesiologist was condemned because she did not directly control the midwife while she was performing her task. The current medico-legal situation in Belgium is paradoxical and even greatly inconsistent in that patients with no medical or nursing qualifications perform acts under the safety limits of the patient controlled epidural analgesia (PCEA) technique, acts which nurses or midwives are not legally permitted to perform. The author suggests that the law should be changed, allowing epidural reinjections and the replacements of the syringe of continuous epidural analgesia infusion by nurses or midwives on condition that the physician remains responsible for training and selecting his collaborators and that the injected dose does not exceed the safety limits of a spinal dose of the same anesthetic.
 ...
PMID:The anesthesiologist and the law: the criminal liability of midwives and anesthesiologists for epidural anesthetic reinjection in obstetrics. 820 24


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