Blockade of NMDA receptors prevents analgesic tolerance to repeated transcutaneous electrical nerve stimulation (TENS) in rats

Priyanka M Hingne; Kathleen A Sluka

doi:10.1016/j.jpain.2007.10.010

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Blockade of NMDA receptors prevents analgesic tolerance to repeated transcutaneous electrical nerve stimulation (TENS) in rats

Journal article

Peer reviewed

Blockade of NMDA receptors prevents analgesic tolerance to repeated transcutaneous electrical nerve stimulation (TENS) in rats

Priyanka M Hingne and Kathleen A Sluka

The journal of pain, Vol.9(3), pp.217-225

03/2008

DOI: 10.1016/j.jpain.2007.10.010

PMCID: PMC2274833

PMID: 18061543

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Abstract

Repeated daily application of transcutaneous electrical nerve stimulation (TENS) results in tolerance, at spinal opioid receptors, to the antihyperalgesia produced by TENS. Since N-methyl-D-aspartate (NMDA) receptor antagonists prevent analgesic tolerance to opioid agonists, we hypothesized that blockade of NMDA receptors will prevent tolerance to TENS. In rats with knee joint inflammation, TENS was applied for 20 minutes daily at high-frequency (100 Hz), low-frequency (4 Hz), or sham TENS. Rats were treated with the NMDA antagonist MK-801 (0.01 mg/kg to 0.1 mg/kg) or vehicle daily before TENS. Paw withdrawal thresholds were tested before and after inflammation and before and after TENS treatment for 4 days. On day 1, TENS reversed the decreased mechanical withdrawal threshold induced by joint inflammation. On day 4, TENS had no effect on the decreased withdrawal threshold in the group treated with vehicle, demonstrating development of tolerance. However, in the group treated with 0.1 mg/kg MK-801, TENS significantly reversed the mechanical withdrawal thresholds on day 4, demonstrating that tolerance did not develop. Vehicle-treated animals developed cross-tolerance at spinal opioid receptors. Treatment with MK-801 reversed this cross-tolerance at spinal opioid receptors. In summary, blockade of NMDA receptors prevents analgesic tolerance to daily TENS by preventing tolerance at spinal opioid receptors. Observed tolerance to the clinical treatment of TENS could be prevented by administration of pharmaceutical agents with NMDA receptors activity such as ketamine or dextromethorphan.

Inflammation - chemically induced

Analgesics - pharmacology

Pain Threshold - physiology

Spinal Cord - drug effects

Drug Tolerance - radiation effects

Drug Tolerance - physiology

Spinal Cord - radiation effects

Male

Behavior, Animal

Dose-Response Relationship, Drug

Drug Interactions

Time Factors

Inflammation - drug therapy

Pain Threshold - drug effects

Benzamides - pharmacology

Disease Models, Animal

Pain Threshold - radiation effects

Knee Joint - drug effects

Rats

Excitatory Amino Acid Antagonists - pharmacology

Piperazines - pharmacology

Rats, Sprague-Dawley

Receptors, N-Methyl-D-Aspartate - physiology

Pain Measurement - methods

Animals

Dizocilpine Maleate - pharmacology

Dose-Response Relationship, Radiation

Transcutaneous Electric Nerve Stimulation - methods

Details

Title: Subtitle: Blockade of NMDA receptors prevents analgesic tolerance to repeated transcutaneous electrical nerve stimulation (TENS) in rats
Creators: Priyanka M Hingne - Graduate Program in Physical Therapy and Rehabilitation Science, Neuroscience Graduate Program, Pain Research Program, University of Iowa, Iowa City, Iowa 52242, USA
Kathleen A Sluka
Resource Type: Journal article
Publication Details: The journal of pain, Vol.9(3), pp.217-225
DOI: 10.1016/j.jpain.2007.10.010
PMID: 18061543
PMCID: PMC2274833
NLM abbreviation: J Pain
ISSN: 1526-5900
eISSN: 1528-8447
Publisher: Elsevier BV; United States
Grant note: KO2ARO2201 / PHS HHS R01 AR052316-03 / NIAMS NIH HHS R01 AR052316 / NIAMS NIH HHS AR052316 / NIAMS NIH HHS R01 AR052316-01A1 / NIAMS NIH HHS R01 AR052316-02 / NIAMS NIH HHS
Language: English
Date published: 03/2008
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984040389702771

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