Increasing intensity of TENS prevents analgesic tolerance in rats

J Pain. 2012 Sep;13(9):884-90. doi: 10.1016/j.jpain.2012.06.004. Epub 2012 Aug 1.


Transcutaneous electrical nerve stimulation (TENS) reduces hyperalgesia and pain. Both low-frequency (LF) and high-frequency (HF) TENS, delivered at the same intensity (90% motor threshold [MT]) daily, result in analgesic tolerance with repeated use by the fifth day of treatment. The current study tested 1) whether increasing intensity by 10% per day prevents the development of tolerance to repeated TENS; and 2) whether lower intensity TENS (50% MT) produces an equivalent reduction in hyperalgesia when compared to 90% MT TENS. Sprague-Dawley rats with unilateral knee joint inflammation (3% carrageenan) were separated according to the intensity of TENS used: sham, 50% LF, 50% HF, 90% LF, 90% HF, and increased intensity by 10% per day (LF and HF). The reduced mechanical withdrawal threshold following the induction of inflammation was reversed by application of TENS applied at 90% MT intensity and increasing intensity for the first 4 days. On the fifth day, the groups that received 90% MT intensity showed tolerance. Nevertheless, the group that received an increased intensity on each day still showed a reversal of the mechanical withdrawal threshold with TENS. These results show that the development of tolerance can be delayed by increasing intensity of TENS.

Perspective: Our results showed that increasing intensity in both frequencies of TENS was able to prevent analgesic tolerance. Results from this study suggest that increasing intensities could be a clinical method to prevent analgesic tolerance and contribute to the effective use of TENS in reducing inflammatory pain and future clinical trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / adverse effects*
  • Animals
  • Biophysical Phenomena / physiology*
  • Carrageenan / toxicity
  • Disease Models, Animal
  • Drug Tolerance / physiology
  • Inflammation / chemically induced
  • Inflammation / complications*
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Knee Joint / drug effects
  • Knee Joint / physiopathology
  • Male
  • Pain / drug therapy*
  • Pain / etiology*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Transcutaneous Electric Nerve Stimulation / methods*


  • Analgesics
  • Carrageenan