Modulating Brain Rhythms of Pain Using Transcranial Alternating Current Stimulation (tACS) - A Sham-Controlled Study in Healthy Human Participants

Abstract

Chronic pain is a major health care problem. A better mechanistic understanding and new treatment approaches are urgently needed. In the brain, pain has been associated with neural oscillations at alpha and gamma frequencies, which can be targeted using transcranial alternating current stimulation (tACS). Thus, we investigated the potential of tACS to modulate pain and painrelated autonomic activity in an experimental model of chronic pain in 29 healthy participants. In 6 recording sessions, participants completed a tonic heat pain paradigm and simultaneously received tACS over prefrontal or somatosensory cortices at alpha or gamma frequencies or sham tACS. Concurrently, pain ratings and autonomic responses were collected. Using the present setup, tACS did not modulate pain or autonomic responses. Bayesian statistics confirmed a lack of tACS effects in most conditions. The only exception was alpha tACS over somatosensory cortex where evidence was inconclusive. Taken together, we did not find significant tACS effects on tonic experimental pain in healthy humans. Based on our present and previous findings, further studies might apply refined stimulation protocols targeting somatosensory alpha oscillations.Trial registration: The study protocol was pre-registered at ClinicalTrials.gov (NCT03805854). Perspective: Modulating brain oscillations is a promising approach for the treatment of pain. We therefore applied transcranial alternating current stimulation (tACS) to modulate experimental pain in healthy participants. However, tACS did not modulate pain, autonomic responses, or EEG oscillations. These findings help to shape future tACS studies for the treatment of pain.

Aftereffects of alpha transcranial alternating current stimulation over the primary sensorimotor cortex on cortical processing of pain

“…Nevertheless, the changes in pain ratings did not differ between real α-tACS and sham stimulation conditions, indicating that α-tACS of SM1 did not overwhelmingly affect perceptual responses to suprathreshold painful stimuli. The lack of an α-tACS effect was consistent with a recent study reporting that α-tACS did not successfully modulate tonic experimental pain in healthy human participants 33 but was inconsistent with a study reporting the analgesic effects of α-tACS. 3 Nevertheless, differences in both tACS stimulation protocols and pain assessments should be noted when comparing results from this study and these previous studies.…”

“…Subjective pain perception in response to mechanical pain has been shown to attenuate during the application of somatosensory α-tACS, provided that the intensity of painful stimulation is uncertain. 3 By contrast, using an experimental model of tonic pain among healthy participants, May et al 33 reported that pain or pain-related autonomic activity was not significantly affected by somatosensory α-tACS. These 2 studies thus reported inconsistent results regarding how experimental pain perception was affected during the application of sensorimotor α-tACS (ie, “online effects” during stimulation).…”

Pain control based on oscillatory brain activity using transcranial alternating current stimulation: An integrative review

“…The authors showed that alpha-tACS over bilateral sensorimotor cortices can reduce subject-reported pain when the intensity of an upcoming pain was uncertain. However, another study reported that alpha-tACS over bilateral sensorimotor cortices had no effect on experimental heat pain in healthy participants ( May et al, 2021 ). Clinical studies have investigated whether tACS modulates pain intensity in patients with chronic low back pain.…”

“…Few tACS studies have adapted conditions other than somatosensory alpha oscillations to modulate pain. A recent study investigated whether gamma-tACS over bilateral prefrontal cortices modulates experimental heat pain ( May et al, 2021 ). Gamma oscillations in prefrontal areas encode pain intensity during experimental heat pain in healthy participants ( Schulz et al, 2015 ; Nickel et al, 2017 ) and are associated with ongoing back pain intensity ( May et al, 2019 ).…”

Non-invasive brain stimulation for osteoarthritis

“…Single-pulse TMS uses frequent sites of action, such as the primary motor cortex (M1) ( Savoie et al, 2020 ). tDCS and tACS cathode and anode positions: contralateral orbit (SO), primary sensory cortex (S1) ( Marlow et al, 2013 ; May et al, 2021 ). tRNS: cerebral cortex.…”