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Vol. 298, Issue 1, 257-263, July 2001

Blockade of Opioid Receptors in Rostral Ventral Medulla Prevents Antihyperalgesia Produced by Transcutaneous Electrical Nerve Stimulation (TENS)

A. Kalra, M. O. Urban and K. A. Sluka

Physical Therapy Graduate Program (A.K., K.A.S.), Neuroscience Graduate Program (K.A.S.), and Department of Pharmacology (M.O.U.), College of Medicine, University of Iowa, Iowa City, Iowa

Although transcutaneous electrical nerve stimulation (TENS) is used extensively in inflammatory joint conditions such as arthritis, the underlying mechanisms are unclear. This study aims to demonstrate an opiate-mediated activation of descending inhibitory pathways from the rostral ventral medulla (RVM) in the antihyperalgesia produced by low- (4 Hz) or high-frequency (100 Hz) TENS. Paw withdrawal latency to radiant heat, as an index of secondary hyperalgesia, was recorded before and after knee joint inflammation (induced by intra-articular injection of 3% kaolin and carrageenan) and after TENS/no TENS coadministered with naloxone (20 µg/1 µl), naltrindole (5 µg/1 µl), or vehicle (1 µl) microinjected into the RVM. The selectivity of naloxone and naltrindole doses was tested against the µ-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) (20 ng, 1 µl) and the delta 2-opioid receptor agonist deltorphin (5 µg, 1 µl) in the RVM. Naloxone microinjection into the RVM blocks the antihyperalgesia produced by low frequency (p < 0.001), but not that produced by high-frequency TENS (p > 0.05). In contrast, naltrindole injection into the RVM blocks the antihyperalgesia produced by high-frequency (p < 0.05), but not low-frequency (p > 0.05) TENS. The analgesia produced by DAMGO and deltorphin is selectively blocked by naloxone (p < 0.05) and naltrindole (p < 0.05), respectively. Thus, the dose of naloxone and naltrindole used in the current study blocks µ- and delta -opioid receptors, respectively. Hence, low-frequency and high-frequency TENS produces antihyperalgesia by activation of µ- and delta -opioid receptors, respectively, in the RVM.

0022-3565/01/2981-0257$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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