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 100μs 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.

Cholecystokinin receptors mediate tolerance to the analgesic effect of TENS in arthritic rats

“…Our previous studies show that tolerance to repeated application of high and low frequency TENS can be prevented by blockade of systemic NMDA receptors during the TENS application, and this prevents the cross-tolerance at spinal opioid receptors [36]. Further, combining high and low frequency TENS delays the onset of tolerance by one week [14]. Together with the findings that CCK receptor activation prevents tolerance to repeated TENS, these data suggest there are multiple parallel systems that contribute to tolerance.…”

“…Rats were also tested for knee joint withdrawal threshold using a pair of forceps (tweezer) applied to the knee joint as previously described [14,56]. The forceps were equipped with two strain gauges to measure force.…”

Using Tens for Pain Control: The State of the Evidence

“…Specifically blockade of NMDA-glutamate receptors or CCK receptors in the spinal cord prevents analgesic tolerance to both LF and HF TENS [45,46]. Analgesic tolerance can also be prevented by modulating between LF and HF TENS within a treatment session [47], or by increasing intensity of TENS daily [48]. Thus, animal studies suggest TENS tolerance can be delayed with pharmacological methods as well as with non-pharmacological modulation of TENS parameters.…”

Characteristics of Stimulus Intensity in Transcutaneous Vagus Nerve Stimulation for Chronic Tinnitus

“…The options to adjust the stimulation patterns or waveforms are also available in most TENS devices. A recent study reported that alternating low and high frequencies were helpful in slowing the development of tolerance in arthritic rats [17] . Thus, the modulating stimulation patterns may be an important approach for preventing tolerance.…”