Diabetes, Vol 37, Issue 9 1253-1259, Copyright © 1988 by American Diabetes Association

ARTICLES

Effect of hyperglycemia on pain perception and on efficacy of morphine analgesia in rats

I Raz, D Hasdai, Z Seltzer and RN Melmed
Department of Medicine B, Hebrew University Hadassah Medical School, Jerusalem, Israel.

The effect exerted by different hyperglycemic states on the pain threshold and on the analgesic potential of morphine was studied in male Sabra rats with the hot plate device. Hyperglycemia induced by an intraperitoneal injection of 0.014 mol/kg glucose or an acute or chronic diabetic state induced by streptozocin injection did not significantly alter the pain threshold. However, states of acute and chronic diabetes markedly blunted the analgesic effect of morphine (5 mg/kg). Sabra rats maintained on a cocktail of glucose-saccharin, thought to activate the release of endogenous opioids, demonstrated an increased pain threshold and rapidly developed resistance to the analgesic effect of morphine. Previous studies have shown that glucose in high concentration may interfere with the interaction of morphine on the opiate receptor. The influence of the diabetic state on beta-endorphin synthesis and concentration in the central nervous system is another factor that might change pain perception in diabetes. We propose that in diabetes, generally, the pain threshold is adequately maintained, despite the antagonistic effect of glucose, partly due to a compensatory increased secretion of endogenous opioid peptides. We hypothesize that in patients with chronic painful diabetic neuropathy, these normal analgesic response mechanisms may be overwhelmed either by an excess of nociceptive impulses from diseased peripheral nerves or conceivably by a failure of endogenous opioid secretory response to the hyperglycemia.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Kato, K. Nemoto, K. Nakanishi, R. Morishita, Y. Kaneda, M. Uenoyama, T. Ikeda, and K. Fujikawa Nonviral Gene Transfer of Human Hepatocyte Growth Factor Improves Streptozotocin-Induced Diabetic Neuropathy in Rats Diabetes, March 1, 2005; 54(3): 846 - 854. [Abstract] [Full Text] [PDF]

				Y. Jiang, J. R. Nyengaard, J. S. Zhang, and J. Jakobsen Selective Loss of Calcitonin Gene-Related Peptide-Expressing Primary Sensory Neurons of the A-Cell Phenotype in Early Experimental Diabetes Diabetes, October 1, 2004; 53(10): 2669 - 2675. [Abstract] [Full Text] [PDF]

				S.-R. Chen and H.-L. Pan Hypersensitivity of Spinothalamic Tract Neurons Associated With Diabetic Neuropathic Pain in Rats J Neurophysiol, June 1, 2002; 87(6): 2726 - 2733. [Abstract] [Full Text] [PDF]

				C. Courteix, P. Bourget, F. Caussade, M. Bardin, F. Coudore, J. Fialip, and A. Eschalier Is the Reduced Efficacy of Morphine in Diabetic Rats Caused by Alterations of Opiate Receptors or of Morphine Pharmacokinetics? J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 63 - 70. [Abstract] [Full Text]