Non-invasive Brain Stimulation for Chronic Pain: State of the Art and Future Directions

Abstract

As a technique that can guide brain plasticity, non-invasive brain stimulation (NIBS) has the potential to improve the treatment of chronic pain (CP) because it can interfere with ongoing brain neural activity to regulate specific neural networks related to pain management. Treatments of CP with various forms of NIBS, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), using new parameters of stimulation have achieved encouraging results. Evidence of moderate quality indicates that high-frequency rTMS of the primary motor cortex has a clear effect on neuropathic pain (NP) and fibromyalgia. However, evidence on its effectiveness regarding pain relief in other CP conditions is conflicting. Concerning tDCS, evidence of low quality supports its benefit for CP treatment. However, evidence suggesting that it exerts a small treatment effect on NP and headaches is also conflicting. In this paper, we describe the underlying principles behind these commonly used stimulation techniques; and summarize the results of randomized controlled trials, systematic reviews, and meta-analyses. Future research should focus on a better evaluation of the short-term and long-term effectiveness of all NIBS techniques and whether they decrease healthcare use, as well as on the refinement of selection criteria.

Keywords: chronic pain; neuromodulation; non-invasive brain stimulation; rTMS; tDCS.

FIGURE 1

Neural networks related to pain. The primary cortical pain matrix (thalamus, S1, S2, posterior insula, and parietal operculum) contributes to pain perception and location. The secondary (ACC, INS, AMY, and hippocampus) represent common structures identified in the affective motivational pain pathway, such as empathy for pain. The third (PFC, MCC, and PCC) represents one component of the cognitive evaluative pain system. The arrows represent multiple cortical connections between regions and systems indicating the complex interconnectedness of brain regions involved with pain. ACC, anterior cingulate cortex; PFC, prefrontal cortex; AMY, amygdala; PAG, periaqueductal gray; RVM, rostroventral medulla; DH, dorsal horn; INS, insula; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; MCC, medial cingulate cortex; PCC, posterior cingulate cortex; PB, parabrachial nucleus.

FIGURE 2

The number of annual publications and annual citations on TMS, tDCS, tACS, tRNS, tFUS, and pain. https://www.webofscience.com/wos/alldb/basic-search; search dates from 2000 to 2021.

FIGURE 3

Different forms of non-invasive brain stimulation techniques and chronic pain conditions most amenable to treatment.

FIGURE 4

Schematic diagram demonstrating the underlying neurophysiological mechanism of rTMS involved in pain management. LTP, long-term potentiation; LTD, long-term depression.

FIGURE 5

Mechanisms and targets of transcranial direct current stimulation in pain management. DLPFC, dorsolateral prefrontal cortex; M1, primary motor cortex; INS, Insula; Th, thalamus.