Prolonged Continuous Theta Burst Stimulation Can Regulate Sensitivity on Aβ Fibers: An Functional Near-Infrared Spectroscopy Study

Abstract

ObjectiveHigh-frequency repetitive transcranial magnetic stimulation (rTMS) induces analgesic effects in both experimental pain and clinical pain conditions. However, whether rTMS can modulate sensory and pain thresholds on sensory fibers is still unclear. Here, we compared the effects of three rTMS paradigms on sensory and pain thresholds conducted by different sensory fibers (Aβ, Aδ, and C fibers) with sham stimulation and investigate the potential brain activation using functional near-infrared spectroscopy (fNIRS).MethodsForty right-handed healthy subjects were randomly allocated into one of four groups. Each subject received one session rTMS [prolonged continuous theta-burst stimulation (pcTBS), intermittent theta-burst stimulation (iTBS), 10 Hz rTMS or sham]. Current perception threshold (CPT), pain tolerance threshold (PTT), and fNIRS were measured at baseline, immediately after stimulation, and 1 h after stimulation, respectively.ResultsSignificant differences between treatments were observed for changes for CPT 2,000 Hz between baseline and 1 h after rTMS (F = 6.551, P < 0.001): pcTBS versus sham (P = 0.004) and pcTBS versus 10 Hz rTMS (P = 0.007). There were significant difference in average HbO μm in the right frontopolar cortex (FPC) [channel 23: P = 0.030 (pcTBS versus sham: P = 0.036)], left dorsolateral prefrontal cortex (DLPFC) [channel 7: P = 0.006 (pcTBS versus sham: P = 0.004)], left FPC [channel 17: P = 0.014 (pcTBS versus sham: P = 0.046), channel 22: P = 0.004 (pcTBS versus sham: P = 0.004)] comparing four group in 1 h after stimulation in PTT 2000 Hz (Aβ-fiber).ConclusionProlonged continuous theta-burst stimulation can regulate sensitivity on Aβ fibers. In addition, single-session pcTBS placed on left M1 can increase the excitability of DLPFC and FPC, indicating the interaction between M1 and prefrontal cortex may be a potential mechanism of analgesic effect of rTMS. Studies in patients with central post-stroke pain are required to confirm the potential clinical applications of pcTBS.

Impact of repetitive transcranial magnetic stimulation on cortical activity: a systematic review and meta-analysis utilizing functional near-infrared spectroscopy evaluation

“…Among these 14 studies, one of them was a doubleblinded randomized controlled trial (RCT) [24], while the rest of the studies were observational studies including cross-over trials, cohort studies, and some without controlled groups [22,23,[27][28][29][30][31][32][33][34][35][36][37]. All studies enrolled healthy adults.…”

“…A previous review comprising nine such studies predominantly adopted a low-frequency inhibitory rTMS protocol [21]. In recent years, new studies featuring a larger number of participants, more rigorous experimental designs, and the incorporation of diverse rTMS protocols, including highfrequency facilitative protocols, have been conducted [22][23][24].…”

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients

“…It has also been shown that prolonged continuous theta burst stimulation (pcTBS) modulates the sensitivity of Aβ fibers and pain thresholds in healthy adults. Single pcTBS placed on the left M1 increases the excitability of DLPFC and FPC, suggesting that the interaction between M1 and PFC may be a potential mechanism for the analgesic effects of HF-rTMS [ 146 ]. However, studies in patients with central post-stroke pain are needed to confirm the clinical effects of pcTBS.…”

Understanding prefrontal cortex functions by decoding its molecular, cellular and circuit organization

“…Amidst the rising prevalence of chronic pain and emerging consensus that transition to chronic pain is centrally regulated, there has been little clarity about the cellular and molecular mechanisms underlying the chronification, which is key to therapeutic targeting. Previous studies have shown that transcranial stimulation of PFC could relieve chronic pain 15,84,85 . Such studies, although established a causal connection, did not provide a long-term solution for pain management owing to the deleterious effects of broad non-specific cortex-wide stimulations.…”

“…Increasing evidence indicates that disruption of this regulation is associated with the development of chronic pain, a rapidly increasing healthcare challenge that affects about 20% of the US population, exceeding cost burden of diabetes or heart disease 7,8 . Chronic pain has been associated with PFC hypoactivity, and transcranial stimulation of the PFC can induce pain relief [9][10][11][12][13][14][15] . Although projections from PFC to brainstem has been historically described in descending inhibition of pain 5,16,17 , the underlying molecular mechanism is poorly characterized.…”