Transcranial magnetic stimulation maps the neurophysiology of chronic noncancer pain: A scoping review

Abstract

Background: Chronic noncancer pain is a global public health challenge. It is imperative to identify biological markers ("biomarkers") to understand the mechanisms underlying chronic pain and to monitor pain over time and after interventions. Transcranial magnetic stimulation (TMS) is a promising method for this purpose.

Objectives: To examine differences in TMS-based outcomes between persons with chronic pain and healthy controls (HCs) and/or before versus after pain-modulating interventions and relationships between pain measures and TMS outcomes; To summarize the neurophysiological mechanisms underlying chronic pain as identified by TMS.

Methods: We searched the PubMed database for literature from January 1, 1985, to June 9, 2020, with the keywords "pain" and "transcranial magnetic stimulation." Eligible items included original studies of adult human participants with pain lasting for ≥ 6 months. We completed a narrative synthesis of the study findings stratified by chronic pain etiology (primary pain, neuropathic pain, and secondary musculoskeletal pain).

Results: The search yielded 1265 records. The final 12 articles included 244 patients with chronic pain (192 females, aged 35-65 years) and 169 HCs (89 females, aged 28-59 years). Abnormalities in TMS outcomes that reflect GABAergic and glutamatergic activities were associated with many of the disorders studied and were distinct for each pain etiology. Chronic primary pain is characterized by reduced intracortical inhibition and corticospinal excitability, chronic neuropathic pain shows evidence of increased excitation and disinhibition, and chronic secondary musculoskeletal pain involves low corticospinal excitability.

Discussion: TMS could be a useful tool for delineating the neurophysiological underpinnings of chronic pain syndromes.

Figure 1.

PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) flow chart detailing study flow in literature review.^[41]

Figure 2.

Schematic representation of (A) the “Pain Matrix” network and (B) transcranial magnetic stimulation (TMS) findings related to the primary motor cortex (M1) in chronic noncancer pain. Note: for conciseness, in panel A, the basal ganglia nuclei are not depicted; and in panel B, only cross-sectional TMS findings are reported. CSP = cortical silent period, ICF = intracortical facilitation, MEP = motor evoked potential, SICI = short-interval intracortical inhibition.