|STUDY TITLE: Brain mechanisms of pain relief by transcutaneous electrical nerve stimulation: A functional magnetic resonance imaging study
Authors: Choi JC, Kim J, Kang E, et al.
Publication Information: European Journal of Pain 2016; 20: 92–105.
Twelve men and 12 women were selected for this study. All participants had two channel TENS applied to their lower left leg skin with one cathode electrode over the fibular neck and the anode electrode from the same channel applied to the skin directly above the lateral malleolus. The other cathode electrode applied to the skin on the posterior left leg at the level of the fibular head, with the anode electrode from that second channel applied at the posterior left ankle. This allowed one channel to stimulate the common fibular (peroneal) nerve and the other to stimulate the tibial nerve. Noxious thermal stimuli at 45C were applied to the left lower leg skin through a thermode applied midway between the cathodes (fibular head level) and anodes (ankle level) with a Velcro strap. A duration of 15 seconds was selected for the study intervention because pain perception has been shown to increase over the first 10 seconds and then remain roughly constant. Subjects were placed in the MRI, and individual TENS levels that were perceived as strong, but not painful, were identified for each participant (all under 80 Hz and 60 ms pulse duration).
Each participant received the same painful stimuli in both the pain and pain+TENS conditions. In the pain+TENS condition, the participants also received TENS for 15 seconds, which was increased in a step-wise manner to overcome any habituation effect. Participants in the pain+TENS condition began with a comfortable TENS intensity (CTI) for 5 seconds, then received CTI plus 1 mA for the second 5 second period, and then CTI plus 2 mA for the third 5 second period.
Six men and six women received the pain-only condition followed by the pain+TENS condition. The other six men and six women received the pain+TENS condition first followed by the pain-only condition. All participants remained in the MRI scanner for the duration of the study.
In the pain+TENS condition, PAG functional connectivity with the lateral prefrontal cortex increased, likely activating the descending pain-inhibitory pathway. As well, the superior parietal lobe, right postcentral cortex (S1), bilateral parietal operculum (S2), supramarginal cortex, and right ventrolateral prefrontal cortex (VLPFC) were all significantly activated in the pain+TENS condition when compared to the pain-only condition. This may indicate the stimulation of large-diameter A-beta fibers, leading to reduced pain.
In the pain-only condition, the left anteroventral thalamus, bilateral rACC (rostral anterior cingulate cortex), and right hippocampal cortex were more highly activated. The anterior thalamic nuclei have many projections to the ACC, which has been shown to process the affective-motivational dimension of pain. The hippocampal cortex activates in response to noxious stimulation and may contribute to negative effect associated with pain. Left PAG functional connectivity with the left, but not the right, lateral prefrontal cortex (PFC) significantly increased as the TENS effect increased in the pain+TENS condition. Both the lateral PFC and PAG are implicated in endogenous pain inhibition. Thus, the increase in TENS effect may activate the descending pain-inhibitory pathway.
The participants reported lower perceived pain and pain-related unpleasantness in the pain+TENS condition compared to the pain-only condition.
S1, S2 and parietal cortices were activated by non-painful TENS. TENS also increased PAG functional connectivity with the lateral prefrontal cortex. This would likely result in activation of the descending pain-inhibitory pathway to produce pain relief. Increasing TENS intensity in a step-wise fashion effectively prevented temporal summation. This study suggests that TENS application is effective for pain reduction. This mirrors what many see in clinical practice. Whether this effect is physiological, or represents some degree of a placebo effect, helping our patients reduce pain levels remains the most important outcome.