Abstract
Objective This study was aimed to summarize and analyze the quality of the available evidence in systematic reviews (SRs) of repetitive transcranial magnetic stimulation (rTMS) on the non-motor cortex (non-M1) for neuropathic pain (NP) through an evidence mapping approach. Methods We follow the Global Evidence Mapping (GEM) methodology. Searches were conducted in PubMed, EMBASE, Epistemonikos, and the Cochrane Library. The study type was restricted to SRs with or without meta-analysis. All literature published before January 23, 2021, were included. The methodological quality of the included SRs was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2). Data were extracted according to a defined population-intervention-comparison-outcome (PICO) framework from primary studies that included SRs. The same PICO was categorized into PICOs according to interventions (stimulation target, frequency, number of sessions (short: 1–5 sessions, medium: 5–10 sessions, and long: >10 sessions)) and comparison (sham rTMS or other targets). The evidence mapping was presented in tables and a bubble plot. Results A total of 23 SRs were included. According to the AMSTAR-2, 20 SRs scored “very low” in terms of methodological quality, 2 SRs scored “low,” and 1 SR scored “high.” A total of 17 PICOs were extracted. The dorsolateral prefrontal cortex (DLPFC) is the most studied of the non-motor cortex targets. PICOs of DLPFC, premotor cortex (PMC), frontal cortex, and secondary somatosensory cortex (S2) were mainly categorized with a “potentially better” conclusion. High-frequency (5–20 Hz) rTMS of non-M1 usually lead to “potentially better” conclusions. Conclusions DLPFC, PMC, frontal cortex, and S2 seem to be promising new targets for rTMS treatment of certain NP. Evidence mapping is a useful and reliable methodology to identify and present the existing evidence gap that more research efforts are necessary in order to highlight the optimal stimulation protocols for non-M1 targets and standardize parameters to fill the evidence gaps of rTMS. Further investigation is advised to improve the methodological quality and the reporting process of SRs.
Highlights
Neuropathic pain (NP) is a chronic pain caused by lesions or dysfunction of the peripheral or central nervous system; it is often characterized by persistent pain, hyperalgesia, or even spontaneous pain [1]
Following the classification criteria for interventions, this evidence mapping has described and organized existing evidence for non-M1 targets for NP. e majority of nonM1 targets reported as “potentially better” were dorsolateral prefrontal cortex (DLPFC), probably due to DLPFC can coordinate the interaction between the cognitive pathway and the “pain matrix”, or play a direct role in promoting or inhibiting pain through the nociceptive downstream inhibitory pathway [25, 47]
The premotor cortex (PMC), the left frontal cortex, and the S2 seem to be promising therapeutic targets. ese targets are importantly involved in nociceptive modulation; they share some common mechanisms, such as the involvement in altering human temperature pain thresholds [50], inducing striatal dopamine release that modulates pain [51], and causing cerebral hemodynamic changes in broader cortical regions [52]
Summary
Neuropathic pain (NP) is a chronic pain caused by lesions or dysfunction of the peripheral or central nervous system; it is often characterized by persistent pain, hyperalgesia, or even spontaneous pain [1]. E mechanisms of NP are still unclear, which lead to the challenge of NP prevention and management. NP disturbs daily activities, work, and sleep and increases the incidence of emotional disorders such as patient depression and anxiety [2]. Pathological changes such as spontaneous activity in damaged non-nociceptive fibers, peripheral and central, hyperactivity in nociceptors, and changes in central neuroplastic may be the possible reasons for NP [3, 4]. Pharmacological treatments provide less satisfaction with pain relief in many patients. Us, the treatment of NP remains a major unmet need, and the exploration of alternative approaches, especially evidence-based non-pharmacological interventions, is important Drugs cause many adverse effects and even lead to drug dependence and abuse [7], wherein recommendation levels are not high [2, 8]. us, the treatment of NP remains a major unmet need, and the exploration of alternative approaches, especially evidence-based non-pharmacological interventions, is important
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