Modulation between high- and low-frequency transcutaneous electric nerve stimulation delays the development of analgesic tolerance in arthritic rats

Abstract

Objective: To investigate whether repeated administration of modulating frequency transcutaneous electric nerve stimulation (TENS) prevents development of analgesic tolerance.

Design: Knee joint inflammation (3% carrageenan and kaolin) was induced in rats. Either mixed or alternating frequency was administered daily (20min) for 2 weeks to the inflamed knee under light halothane anesthesia (1%-2%).

Setting: Laboratory.

Animals: Adult male Sprague-Dawley rats (N=36).

Intervention: Mixed- (4Hz and 100Hz) or alternating- (4Hz on 1 day; 100Hz on the next day) frequency TENS at sensory intensity and 100micros pulse duration.

Main outcome measures: Paw and joint withdrawal thresholds to mechanical stimuli were assessed before induction of inflammation, and before and after daily application of TENS.

Results: The reduced paw and joint withdrawal thresholds that occur 24 hours after the induction of inflammation were significantly reversed by the first administration of TENS when compared with sham treatment or to the condition before TENS treatment, which was observed through day 9. By the tenth day, repeated daily administration of either mixed- or alternating-frequency TENS did not reverse the decreased paw and joint withdrawal thresholds.

Conclusions: These data suggest that repeated administration of modulating frequency TENS leads to a development of opioid tolerance. However, this tolerance effect is delayed by approximately 5 days compared with administration of low- or high-frequency TENS independently. Clinically, we can infer that a treatment schedule of repeated daily TENS administration will result in a tolerance effect. Moreover, modulating low and high frequency TENS seems to produce a better analgesic effect and tolerance is slower to develop.

Fig. 1

Bar graphs representing mechanical thresholds of the ipsilateral (A) paw and (B) knee joint from animals before and after knee joint inflammation in the groups mixed, alternating, and sham TENS. Plot represents mean values, error bars represent the standard error of the mean (SEM). *Significantly different from before knee joint inflammation (P<.05).

Fig. 2

Bar graphs representing mechanical thresholds of the ipsilateral paw from animals that received (A) mixed-frequency TENS, (B) alternating-frequency TENS, or (C) sham TENS for the time before (black bars) and after (white bars) application of TENS. Striped bar represents time before knee joint inflammation. Plot represents mean values, error bars represent the SEM. *Significantly different from before application of TENS; †significantly different from before inflammation (P<.05).

Fig. 3

Bar graphs representing mechanical thresholds of the ipsilateral knee joint from animals that received (A) mixed-frequency TENS, (B) alternating-frequency TENS, or (C) sham TENS for the time before (black bars) and after (white bars) application of TENS. Striped bar represents time before knee joint inflammation. Plot represents mean values, error bars represent the SEM. *Significantly different from before application of TENS; †significantly different from before inflammation (P<.05).

Fig. 4

Line graphs representing mechanical thresholds of the (A) ipsilateral paw and (B) knee joint from animals that received mixed- and alternating-frequency TENS, and sham TENS. Baseline corresponds to time before the induction of knee inflammation. Error bars represent the SEM. *Significantly different from baseline; †mixed- and alternating-frequency TENS significantly different from before TENS treatment; ‡mixed-and alternating-frequency TENS significantly different from sham TENS (P<.05).