Neurobiological mechanisms of TENS-induced analgesia

Abstract

Pain inhibition by additional somatosensory input is the rationale for the widespread use of Transcutaneous Electrical Nerve Stimulation (TENS) to relieve pain. Two main types of TENS produce analgesia in animal models: high-frequency (∼50–100 Hz) and low-intensity ‘conventional’ TENS, and low-frequency (∼2–4 Hz) and high-intensity ‘acupuncture-like’ TENS. However, TENS efficacy in human participants is debated, raising the question of whether the analgesic mechanisms identified in animal models are valid in humans. Here, we used a sham-controlled experimental design to clarify the efficacy and the neurobiological effects of ‘conventional’ and ‘acupuncture-like’ TENS in 80 human volunteers. To test the analgesic effect of TENS we recorded the perceptual and brain responses elicited by radiant heat laser pulses that activate selectively Aδ and C cutaneous nociceptors. To test whether TENS has a long-lasting effect on brain state we recorded spontaneous electrocortical oscillations. The analgesic effect of ‘conventional’ TENS was maximal when nociceptive stimuli were delivered homotopically, to the same hand that received the TENS. In contrast, ‘acupuncture-like’ TENS produced a spatially-diffuse analgesic effect, coupled with long-lasting changes both in the state of the primary sensorimotor cortex (S1/M1) and in the functional connectivity between S1/M1 and the medial prefrontal cortex, a core region in the descending pain inhibitory system. These results demonstrate that ‘conventional’ and ‘acupuncture-like’ TENS have different analgesic effects, which are mediated by different neurobiological mechanisms.

Three distinct neural mechanisms support movement-induced analgesia

“…This phenomenon fits well with our observation that the sustained analgesic effect was only observed at the stimulated side ipsilateral to hand movement. In addition, it has been demonstrated that tactile-induced analgesia can persist for up to hours in non-human animals (41,42) and humans (23), which is consistent with our observation that the analgesic effect persisted over a period of time after the execution of voluntary movement (e.g., up to 30 s in our case, Fig. 4B).…”

“…This explanation assumes the same neural mechanism of tactile-induced analgesia, in which the activation of tactile afferent nerve fibers (e.g., large-diameter Aβ fibers) inhibits the transmission of nociceptive inputs (38)(39)(40). Such an analgesic effect was maximal when tactile inputs were delivered homotopically to the same body territory of pain (23). This phenomenon fits well with our observation that the sustained analgesic effect was only observed at the stimulated side ipsilateral to hand movement.…”

“…Instead, they suggest an alternative mechanism, predicted by the gate control theory of pain. Indeed, hand shaking and its somatosensory feedback should activate large-diameter Aα and Aβ fibers, which inhibit the nociceptive volley transmitted via smalldiameter Aδ and C fibers innervating spatially adjacent skin areas (13,23).…”

“…First, according to the reafference principle, the analgesic effect should be confined to spatially adjacent skin areas innervated by the reafferent nerves and should diminish with the termination of the motor command, thus producing a spatially localized, transient and reversible analgesic effect (5,10). Second, in line with the gate control theory of pain, the analgesic effect should also be restricted to the innervating spatially adjacent skin areas, but persist after the termination of the somatosensory feedback, thus producing a spatially localized but sustained analgesic effect (14,23). Third, the supraspinal descending inhibition mechanism arising from anticipation or attention about future events or outcomes should produce a spatially diffuse and transient analgesic effect (24).…”

EEG alpha activity increased in response to transcutaneous electrical nervous stimulation in young healthy subjects but not in the healthy elderly

“…We have taken into account the alpha frequency peak and alpha bandwidth which are alpha indices in our study because previous studies reported that this indices changes based on age or stimuli (Stroganova, Orekhova & Posikera, 1999;Bazanova, 2008;Samuel et al, 2018). There are also many EEG and magnetoencephalography (MEG) studies which were evaluated evoked responses (Golding et al, 1986;Olson, 1993;Tinazzi et al, 1997Tinazzi et al, , 2000Urasaki et al, 1998;Rossi et al, 1998Rossi et al, , 2003Hoshiyama & Kakigi, 2000;Passmore, Murphy & Lee, 2014;Peng et al, 2019). Researchers analyzed evoked responses components (somatosensory evoked potentials (SEPs) and somatosensory evoked fields (SEFs)) during somatosensory stimulations (e.g., TENS).…”