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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics July 2001, 298 (1) 257-263;
A. Kalra
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M. O. Urban
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K. A. Sluka
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Abstract

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 δ2-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 δ-opioid receptors, respectively. Hence, low-frequency and high-frequency TENS produces antihyperalgesia by activation of μ- and δ-opioid receptors, respectively, in the RVM.

Footnotes

  • This study was supported by a grant from the Arthritis Foundation. TENS units were donated by EMPI, Inc.

  • Abbreviations:
    TENS
    transcutaneous electrical nerve stimulation
    RVM
    rostral ventral medulla
    NRM
    nucleus raphe magnus
    NGCα
    nucleus reticularis gigantocellularis pars alpha
    5-HT
    L-5-hydroxytryptophan
    PWL
    paw withdrawal latency
    DAMGO
    [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin
    DELT
    [d-Ala2]-deltorphin II
    HBC
    2-hydroxypropyl-β-cyclodextrin
    ANOVA
    analysis of variance
    PAG
    periaqeuductal gray
    • Received December 7, 2000.
    • Accepted April 6, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 298 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 1
1 Jul 2001
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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 257-263;

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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 257-263;
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