The Contribution of Endogenous Modulatory Systems to TMS- and tDCS-Induced Analgesia: Evidence from PET Studies

Abstract

Chronic pain is an important public health issue. Moreover, its adequate management is still considered a major clinical problem, mainly due to its incredible complexity and still poorly understood pathophysiology. Recent scientific evidence coming from neuroimaging research, particularly functional magnetic resonance (fMRI) and positron emission tomography (PET) studies, indicates that chronic pain is associated with structural and functional changes in several brain structures that integrate antinociceptive pathways and endogenous modulatory systems. Furthermore, the last two decades have witnessed a huge increase in the number of studies evaluating the clinical effects of noninvasive neuromodulatory methods, especially transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), which have been proved to effectively modulate the cortical excitability, resulting in satisfactory analgesic effects with minimal adverse events. Nevertheless, the precise neuromechanisms whereby such methods provide pain control are still largely unexplored. Recent studies have brought valuable information regarding the recruitment of different modulatory systems and related neurotransmitters, including glutamate, dopamine, and endogenous opioids. However, the specific neurocircuits involved in the analgesia produced by those therapies have not been fully elucidated. This review focuses on the current literature correlating the clinical effects of noninvasive methods of brain stimulation to the changes in the activity of endogenous modulatory systems.

Analgesic Effect of Noninvasive Brain Stimulation for Neuropathic Pain Patients: A Systematic Review

“…HF rTMS produces excitatory effects, and is thought to enhance synapse Study of ineffective treatment is labeled gray tDCS transcranial direct current stimulation plasticity by inducing long-term potentiation (LTP). In contrast, LF rTMS generates inhibitory effects, presumably through long-term depression (LTD) [23,79,80]. rTMS may induce multiple alterations related to LTD and LTP [63].…”

Individual Traits and Pain Treatment: The Case of Hypnotizability

“…In chronic pain patients Transcranial Magnetic Stimulation (TMS) and electrical direct Transcranial Stimulation (dTCS) are efficaciously used to modulate the activity of pain-related circuits (Klein et al, 2015 ; Dos Santos et al, 2018 ; Meeker et al, 2020 ) together with vagal stimulation (Costa et al, 2019 ). Theoretically, imaginatively induced analgesia could influence cortical plasticity (Kleim and Jones, 2008 ) mimicking the effects of TMS and dTCS by suggestions aimed at modulating the activity of the pain matrix (Casiglia et al, 2020 ) and enhancing the action of descending antinociceptive pathways (Beltran Serrano et al, 2020 ).…”

Repetitive transcranial magnetic stimulation of the primary motor cortex in management of chronic neuropathic pain: a systematic review

“…The precise mechanisms of action remain incompletely elucidated [15]. Recent studies using 3D-positron emission tomography have shown that rTMS applied to M1 for pain relief activates the endogenous opioid system in a wide brain network associated with processing of pain and other salient stimuli [25,26]. The stimulation frequency and type and orientation of the stimulating coil are considered as the most crucial variables to achieve a good response [22,27].…”