Abstract
Transcutaneous electrical nerve stimulation (TENS) is commonly used for relief of pain. The literature on the clinical application of TENS is extensive. However, surprisingly few reports have addressed the neurophysiological basis for the actions of TENS. The gate control theory of pain is typically used to explain the actions of high-frequency TENS, whereas, low-frequency TENS is typically explained by release of endogenous opioids. The current study investigated the role of μ, δ, and κ opioid receptors in antihyperalgesia produced by low- and high-frequency TENS by using an animal model of inflammation. Antagonists to μ (naloxone), δ (naltrinodole), or κ (nor-binaltorphimine) opioid receptors were delivered to the spinal cord by microdialysis. Joint inflammation was induced by injection of kaolin and carrageenan into the knee-joint cavity. Withdrawal latency to heat was assessed before inflammation, during inflammation, after drug (or artificial cerebral spinal fluid as a control) administration, and after drug (or artificial cerebral spinal fluid) administration + TENS. Either high- (100 Hz) or low- frequency (4 Hz) TENS produced approximately 100% inhibition of hyperalgesia. Low doses of naloxone, selective for μ opioid receptors, blocked the antihyperalgesia produced by low-frequency TENS. High doses of naloxone, which also block δ and κ opioid receptors, prevented the antihyperalgesia produced by high-frequency TENS. Spinal blockade of δ opioid receptors dose-dependently prevented the antihyperalgesia produced by high-frequency TENS. In contrast, blockade of κ opioid receptors had no effect on the antihyperalgesia produced by either low- or high-frequency TENS. Thus, low-frequency TENS produces antihyperalgesia through μ opioid receptors and high-frequency TENS produces antihyperalgesia through δ opioid receptors in the spinal cord.
Footnotes
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Send reprint requests to: Kathleen A. Sluka, P.T., Ph.D., Physical Therapy Graduate Program, The University of Iowa, 2600 Steindeler Bldg., Iowa City, IA 52242. E-mail:kathleen-sluka{at}uiowa.edu
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↵1 This study was supported by grants from the Central Investment Fund for Research Enhancement from the University of Iowa and the Arthritis Foundation.
- Abbreviations:
- TENS
- transcutaneous electrical nerve stimulation
- PWL
- paw withdrawal latency
- ACSF
- artificial cerebral spinal fluid
- MEAP
- Met-enkephalin-Arg-Phe
- NSAID
- non-steroidal anti-inflammatory
- Received October 20, 1998.
- Accepted December 2, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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