Email this article Effectiveness of low dose physostigmine for dose reduction of morphine in pain management
Abstract
Background: This is an interventional study, undertaken in the experimental animal models for the evaluation of the antinociceptive potential of Physostigmine and its combination with Morphine at their sub-analgesic doses. The objective of the study was to evaluate the antinociceptive potential of Physostigmine alone and in combination with morphine.
Methods: Antinociceptive effect of Physostigmine in three graded doses (50, 100 and 200 μg/kg) and combination of Physostigmine at low dose (50 μg/kg) with sub-analgesic dose of Morphine (0.1 mg/kg) and Morphine in analgesic dose (1 mg/kg) was evaluated by using Hot Water Bath method in albino rats.
Results: Comparison of maximal possible effect in percentage (MPE in %) between groups at 90 minutes in control, Morphine, Physostigmine in 50, 100, 200 μg/ kg doses and combination group respectively, demonstrated significant difference (p <0.001) when compared by one way ANOVA test. There was no much increase in maximal possible effect in the tail withdrawal latency in Physostigmine 50 μg/kg (SC) treatment at 90 min (5.50±0.88) in comparison to control (NS) treatment group. Combination treatment of low doses of both Physostigmine 50 μg/kg + Morphine 0.1 mg/kg increased in maximal possible effect the tail withdrawal latency 90 min (53.87±1.38) in-comparison to control (NS) treatment group (6.17±0.92).
Conclusions: Physostigmine is more potent antinociceptive than Morphine and Physostigmine potentiated the antinociceptive activity of low dose of standard drug Morphine.
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Balmer HG, Nunn TJ. Intramuscular ketamine with hyaluronidase. Nineteen daily anaesthetics administered to a child for radiotherapy. Anaesthesia. 1977;32(7):636-8.
Barash, Paul G, Cullen, Bruce F, Stoelting, Robert K. Clinical Anesthesia. 5th Ed. Philadelphia: Lippincott Williams & Wilkins; 2006:1405-1412.
Yang XF, Xiao Y, Xu MY. Both endogenous and exogenous ACh plays antinociceptive role in hippocampus CA1 of rats. J Neural Transm. 2008 Jan 1;115(1):1-6.
Mojtahedin A, Tamaddonfard E, Zanbouri A. Role of central muscarinic cholinergic receptors in the formalin-induced pain in rats. Indian J Pharmacol. 2009 Jun;41(3):144.
Flodmark S, Wramner T. The analgetic action of morphine, eserine and prostigmine studied by a modified Hardy-Wolff-Goodell method. Acta Physiol Scand. 1945;9:88-96.
Pedigo NW, Dewey WL. Comparison of the antinociceptive activity of intraventricularly administered acetylcholine to narcotic antinociception. Neurosci Lett. 1981;26:85-90.
Pedigo NW, Dewey WL, Harris LS. Determination and characterization of the antinociceptive activity of intraventricularly administered acetylcholine in mice. J Pharmacol Exp Ther. 1975;193:845-52.
Metys J, Wagner N, Metysova J. Studies of the central antinociceptive action of cholinomimetic agents. Int J Neuropharmacol. 1969;8:413-25.
Oliveira MA, Prado WA. Antinociception and behavioral manifestations induced by intracerebroventricular or intra-amygdaloid administration of cholinergic agonists in the rat. Pain. 1994 Jun 1;57(3):383-91.
Hayes RL, Katayama Y, Watkin LR. Bilateral lesions of dorsolateral funiculus of the cat spinal cord: effects on basal nociceptive reflexes and nociceptive suppression produced by cholinergic activation of the pontine parabrachial region. Brain Res. 1984;311:267-80.
Terenzi MG, Prado WA. Antinociception elicited by electrical or chemical stimulation of the rat habenular complex and its sensitivity to systemic antagonists. Brain Res. 1990;535:18-24.
Ireson JD. A comparison of the antinociceptive actions of cholinomimetics and morphine-like drugs. Br J Pharmacol. 1970;40:92-101.
Pleuvry BJ, Tobias MA. Comparison of the antinociceptive activities of physiostigmine, oxotremorine and morphine in the mouse. Br J Pharmacol. 1971;43:706-14.
Lipman JJ, Spencer PSJ. A comparison of muscarinic cholinergic involvement in the antinociceptive effects of morphine and clonidine in the mouse. Eur J Pharmacol. 1980;64:249-58.
Cozanitis DA, Friedman T, Furst S. Study of the analgesic effect of galantamine, a cholinesterase inhibitor. Arch Int Pharmacodyn Ther. 1983;266:229-38.
Lawrence D, Livingston A. The effect of physostigmine and neostigmine on ketamine anaesthesia and analgesia. Br J Pharmacol. 1979;67:427.
Romano J, Shih TM. Cholinergic mechanisms of analgesia produced by physostigmine, morphine and cold water swimming. Neuropharmacol. 1983;22:827-33.
Pert A. The cholinergic system and nociception in the primate: interactions with morphine. Psychopharmacol. 1975 Jan 1;44(2):131-7.
Nemirovsky A. The effect of M-cholinomimetics on nociceptive transmission in the spinal cord. Farmakol Toksikol. 1985;48:36-9.
Nemirovsky A. The effect of anticholinesterases on nociceptive transmission in the spinal cord. Farmakol Toksikol. 1988;51:12-4.
Kharkevich DA, Nemirovsky A. Antinociceptive activity of muscarinomimetic agents. Ann Ist Super Sanita. 1990;26:11-5.
Gillberg PG, Hartvig P, Gordh T. Behavioral effects after intrathecal administration of cholinergic receptor agonists in the rat. Psychopharmacol. 1990;100:464-9.
Smith MD, Yang X. Antinociceptive effect of spinal cholinergic stimulation: interaction with substance P. Life Sci. 1989;45:1255-61.
Vogel HG. Drug Discovery and Evaluation Pharmacological Assays. 2nd ed. Germany: Springer; 2002:697.
Nemirovsky A. The effect of M-cholinomimetics on nociceptive transmission in the spinal cord. Farmakologiya I Toksikologiya. 1985;48:36-9.
Gillberg PG, Gordh T Jr, Jansson I. Characterization of the antinociception induced by intrathecally administered carbachol. Pharmacol Toxicol. 1989;64:340-3.
Gordh JT, Jansson I, Hartvig P. Interactions between noradrenergic and cholinergic mechanisms involved in spinal nociceptive processing. Acta Anesthesiol Scand. 1989;33:39-47.
Yaksh TL, Dirksen R, Harty GJ. Antinociceptive effects of intrathecal injection cholinomimetic drugs in the rat and cat. Eur J Pharmacol. 1985;117:81-8.
Yaksh TL, Grafe MR, Malkmus S, Rathbun ML, Eisenach JC. Studies on the safety of chronically administered intrathecal neostigmine methylsulfate in rats and dogs. Anesthesiology. J American Society Anesthesiol. 1995 Feb 1;82(2):412-27.
Petersson J, Gordh TE, Hartvig P, Wiklund L. A double-blind trial of the analgesic properties of physostigmine in postoperative patients. Acta Anaesthesiol Scand. 1986;30:283-8.
Beilin B, Bessler H, Papismedov L, Weinstock M, Shavit Y. Continuous physostigmine combined with morphine‐based patient‐controlled analgesia in the postoperative period. Acta Anaesthesiol Scand. 2005;49(1):78-84.
