Supraspinal neural mechanisms of the analgesic effect produced by transcutaneous electrical nerve stimulation

Although the analgesic effects of conventional transcutaneous electrical nerve stimulation (TENS) and acupuncture-like TENS are evident, their respective neural mechanisms in humans remain controversial. To elucidate and compare the supraspinal neural mechanisms of the analgesic effects produced by conventional TENS (high frequency and low intensity) and acupuncture-like TENS (low frequency and high intensity), we employed a between-subject sham-controlled experimental design with conventional, acupuncture-like, and sham TENS in 60 healthy human volunteers. In addition to assessing the TENS-induced changes of subjective ratings of perceived pain, we examined the TENS associated brainstem activities (fractional amplitude of low frequency fluctuations, fALFF) and their corresponding resting state functional connectivity (RSFC) with higher-order brain areas using functional magnetic resonance imaging. The analgesic effect of conventional TENS was only detected in the forearm that received TENS, coupled with decreased pons activity and RSFC between pons and contralateral primary somatosensory cortex. In contrast, acupuncture-like TENS produced a spatially diffuse analgesic effect, coupled with increased activities in both subnucleus reticularis dorsalis (SRD) and rostral ventromedial medulla (RVM), and decreased RSFC between SRD and medial frontal regions as well as between SRD and lingual gyrus. To sum up, our data demonstrated that conventional TENS and acupuncture-like TENS have different analgesic effects, which are mediated by different supraspinal neural mechanisms.