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J Pharmacol Exp Ther. 2001 Jul;298(1):257-63.

Blockade of opioid receptors in rostral ventral medulla prevents antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS).

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Physical Therapy Graduate Program, College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.


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 microg/1 microl), naltrindole (5 microg/1 microl), or vehicle (1 microl) microinjected into the RVM. The selectivity of naloxone and naltrindole doses was tested against the mu-opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) (20 ng, 1 microl) and the delta2-opioid receptor agonist deltorphin (5 microg, 1 microl) 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 mu- and delta-opioid receptors, respectively. Hence, low-frequency and high-frequency TENS produces antihyperalgesia by activation of mu- and delta-opioid receptors, respectively, in the RVM.

[Indexed for MEDLINE]

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