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

Abstract

Introduction: The objective of this review is to systematically summarize the consensus on best practices for different NP conditions of the two most commonly utilized noninvasive brain stimulation (NIBS) technologies, repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS).

Methods: PubMed was searched according to the predetermined keywords and criteria. Only English language studies and studies published up to January 31, 2020 were taken into consideration. Meta-analyses, reviews, and systematic reviews were excluded first, and those related to animal studies or involving healthy volunteers were also excluded. Finally, 29 studies covering 826 NP patients were reviewed.

Results: The results from the 24 enrolled studies and 736 NP patients indicate that rTMS successfully relieved the pain symptoms of 715 (97.1%) NP patients. Also, five studies involving 95 NP patients (81.4%) also showed that tDCS successfully relieved NP. In the included studied, the M1 region plays a key role in the analgesic treatment of NIBS. The motor evoked potentials (MEPs), the 10-20 electroencephalography system (EEG 10/20 system), and neuro-navigation methods are used in clinical practice to locate therapeutic targets. Based on the results of the review, the stimulation parameters of rTMS that best induce an analgesic effect are a stimulation frequency of 10-20 Hz, a stimulation intensity of 80-120% of RMT, 1000-2000 pulses, and 5-10 sessions, and the most effective parameters of tDCS are a current intensity of 2 mA, a session duration of 20-30 min, and 5-10 sessions.

Conclusions: Our systematically reviewed the evidence for positive and negative responses to rTMS and tDCS for NP patient care and underscores the analgesic efficacy of NIBS in patients with NP. The treatment of NP should allow the design of optimal treatments for individual patients.

Keywords: Neuropathic pain; Noninvasive brain stimulation; Repetitive transcranial magnetic stimulation; Review; Transcranial direct current stimulation.

Fig. 1

Origin and development of NIBS. NIBS is based on the interaction of electricity or magnetism with the body. The historically important events related to brain electric or magnetic stimulation were indicated

Fig. 2

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) flow diagram. A PubMed search for articles published in and after 2010 with keywords “rTMS/tDCS AND neuropathic pain” identified 237 studies from different countries. Meta-analyses, reviews, and systematic reviews were excluded. Among the 162 filtered studies, those related to animal studies or involving healthy volunteers were excluded. Finally, 29 studies covering 826 NP patients were reviewed here. Instead of using the classic central and peripheral classifications, we classified the most common (large number of cases) types of NP as typical NP (TNP), including diabetic neuropathy, stroke, spinal cord injury (SCI), and nerve injury. The remaining clinically rare types are classified as special NP (SNP), such as facial pain, phantom limb pain, cancer pain, and other types of pain

Fig. 3

Effect of NIBS on different subtypes of TNP. The figure shows the therapeutic effect of NIBS on four subtypes of typical NP (TNP) (above): (1) stroke (blue), (2) spinal cord injury (SCI) (red), (3) nerve trunk or root lesions (green), and (4) diabetes (purple). In the same subtype of data (below), the dark color represents the positive treatment results and the light color represents the negative treatment results. All NP patients can be divided into four categories: (1) rTMS-P, all NP patients with a positive analgesic effect from rTMS treatment; (2) rTMS-N, all NP patients with a negative analgesic effect from rTMS treatment; (3) tDCS-P, all NP patients with a positive analgesic effect from tDCS treatment; and (4) tDCS-N, all NP patients with a negative analgesic effect from tDCS treatment

Fig. 4

Effect of NIBS on different subtypes of SNP. The figure shows the therapeutic effect of NIBS on four subtypes of special NP (SNP) (above): (1)facial NP (FaNP) (blue), (2) phantom limb NP (PhanNP) (red), (3) cancer NP (CaNP) (green), and (4) other conditions (purple), such as malformation, and bladder pain syndrome. In the same subtype of data (below), the dark color represents the positive treatment results and the light color represents the negative treatment results. All NP patients can be divided into four categories: (1) rTMS-P, all NP patients with a positive analgesic effect from rTMS treatment; (2) rTMS-N, all NP patients with a negative analgesic effect from rTMS treatment; (3) tDCS-P, all NP patients with a positive analgesic effect from tDCS treatment; and (4) tDCS-N, all NP patients with a negative analgesic effect from tDCS treatment

Fig. 5

Common methods for targeting brain regions in NIBS. a MEP-based method was used to target M1 of the patient (left). In detail, the coil is placed over the contralateral hemisphere in the area corresponding to the M1, and the optimal stimulation site is found by moving the coil over the scalp to the site that evokes the largest MEP amplitude in the resting state of target muscle (the orange circle represents the M1 area of the brain, and the red spot represents the optimal stimulation site), and then along the central axis direction forward 5 cm is considered DLPFC region (the black spot) (right). b Picture of electrode cap on patient's head, in which the electrodes are properly distributed in the main part of the skull in a standard position (left). Schematic diagram of standard electrode placement for EEG 10/20 system (right). The position of the C3/C4 electrode is assumed to correspond to the M1 region, while the DLPFC region is targeted by placing the stimulating electrode on the scalp at F3/F4. Cz = vertex. c Schematic diagram of using neuro-navigation to target brain regions. The patient lies on the bed in a relaxed posture, and neuro-navigation is used to define the target of magnetic stimulation which is the M1 in its subdivision representing the hand