Low frequency TENS is less effective than high frequency TENS at reducing inflammation-induced hyperalgesia in morphine-tolerant rats

Eur J Pain. 2000;4(2):185-93. doi: 10.1053/eujp.2000.0172.


Both transcutaneous electrical nerve stimulation (TENS) and morphine are commonly used for relief of pain. Extensive research has been done on the effectiveness of each of these two methods for pain relief when given independently. However, very little literature exists examining the effectiveness of their combined use. Systemically administered morphine activates mu opioid receptors and when administered for prolonged periods results in analgesic tolerance. Low (4 Hz) and high (100 Hz) frequency TENS activate mu- and delta-opioid receptors, respectively, It is thus possible that TENS would be less effective in morphine-tolerant subjects. The current study investigated the effectiveness of high- and low-frequency TENS in the reversal of hyperalgesia in inflamed rats that were morphine-tolerant. Morphine tolerance was induced by subcutaneous implantation of morphine pellets over 10 days. Knee joint inflammation was induced by injection of kaolin and carrageenan into the knee joint cavity. Secondary heat hyperalgesia was tested by measuring the paw withdrawal latency to radiant heat (1) before pellet implantation (either morphine or placebo), (2) after pellet implantation and before inflammation, (3) after inflammation and (4) after TENS. Both high (100 Hz) and low (4 Hz) frequency TENS caused nearly 100% inhibition of secondary hyperalgesia in animals receiving placebo pellets. In contrast, the hyperalgesia in morphine-tolerant animals with knee joint inflammation was unaffected by low frequency TENS but fully reversed by high frequency TENS. These results suggest that patients who are tolerant to morphine may respond better to high frequency TENS than to low frequency TENS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrageenan
  • Drug Tolerance
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Irritants
  • Kaolin
  • Male
  • Morphine / pharmacology*
  • Morphine Dependence*
  • Narcotics / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, delta / physiology
  • Receptors, Opioid, mu / physiology
  • Spinal Cord / chemistry
  • Spinal Cord / physiology
  • Synovitis / chemically induced
  • Synovitis / complications
  • Transcutaneous Electric Nerve Stimulation / methods*


  • Irritants
  • Narcotics
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Kaolin
  • Morphine
  • Carrageenan