Prolonged Continuous Theta Burst Stimulation to Demonstrate a Larger Analgesia as Well as Cortical Excitability Changes Dependent on the Context of a Pain Episode

Abstract

A series of neuropathic pain conditions have a prevalence in older adults potentially associated with declined functioning of the peripheral and/or central nervous system. Neuropathic pain conditions demonstrate defective cortical excitability and intermissions, which raises questions of the impact of pain on cortical excitability changes and when to deliver repetitive transcranial magnetic stimulation (rTMS) to maximize the analgesic effects. Using prolonged continuous theta-burst stimulation (pcTBS), a relatively new rTMS protocol to increase excitability, this study was designed to investigate pcTBS analgesia and cortical excitability in the context of pain. With capsaicin application, twenty-nine healthy participants received pcTBS or Sham stimulation either in the phase of pain initialization (capsaicin applied) or pain ascending (20 min after capsaicin application). Pain intensity was measured with a visual-analogic scale (VAS). Cortical excitability was assessed by motor-evoked potential (MEP) and cortical silent period (CSP) which evaluates corticospinal excitability and GABAergic intracortical inhibition, respectively. Our data on pain dynamics demonstrated that pcTBS produced a consistent analgesic effect regardless of the time frame of pcTBS. More importantly, pcTBS delivered at pain initialization induced a larger pain reduction and a higher response rate compared to the stimulation during pain ascending. We further provide novel findings indicating distinct mechanisms of pcTBS analgesia dependent on the context of pain, in which pcTBS delivered at pain initialization was able to reverse depressed MEP, whereby pcTBS during pain ascending was associated with increased CSP. Overall, our data indicate pcTBS to be a potential protocol in pain management that could be delivered before the initialization of a pain episode to improve rTMS analgesia, potentially through inducing early corticospinal excitability changes that would be suppressed by nociceptive transmission.

Evaluation of Relationships between Corticospinal Excitability and Somatosensory Deficits in the Acute and Subacute Phases of Stroke

“…Although the motor cortex is predominantly involved in mo-tor control, it is also responsible for somatosensation via its anatomical and functional connections with somatosensory cortices and the thalamus [19]. In fact, motor cortex rTMS has a clear impact on the transmission of sensory information from the body parts [20][21][22]. This argument is also consistent with findings that motor recovery following stroke is positively associated with sensory functioning [2].…”

“…Somatosensory deficits following stroke are associated with the impairment of somatosensory pathways (e.g., the medial lemniscal pathway for discriminative touch and proprioception, the spinothalamic pathway for pain and temperature) [25][26][27], which transmits sensory signals from body parts. Our group has previously demonstrated that bottom-up sensory transmission is able to inhibit corticospinal excitability measured by motorevoked potential (MEP) and cortical silent period (CSP) [21]. MEP amplitude provides a simple and direct measurement of the excitation of corticospinal pathways.…”

A randomised sham-controlled study evaluating rTMS analgesic efficacy for postherpetic neuralgia

“…The presence of long-term effects in our data and others (Attal et al, 2021) also indicate neuroplastic changes induced by repetitive sessions of TMS. Indeed, there are quite some studies that reported neuroplastic changes following motor cortex rTMS in neuropathic pain (Lefaucheur et al, 2006;Hosomi et al, 2013;Liu et al, 2021;Teixeira et al, 2021).…”

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

“…Antal and Paulus, and Borckardt et al found that iTBS of the motor cortex did not induce a significant reduction in acute pain perception. However, most studies indicated that one-session high-frequency rTMS can decrease pain sensitivity ( Ciampi et al, 2014 ; Moisset et al, 2015 ; De Martino et al, 2019 ; Liu et al, 2021 ). An explanation could be related to differences in the methodology used to assess pain thresholds.…”