Evidence-Based Umbrella Review of Non-Invasive Neuromodulation in Chronic Neuropathic Pain

Background and objective: Non-invasive neuromodulation techniques (NIN), such as transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS), have been extensively researched for their potential to alleviate pain by reversing neuroplastic changes associated with neuropathic pain (NP), a prevalent and complex condition. However, treating NP remains challenging due to the numerous variables involved, such as different techniques, dosages and aetiologies. It is necessary to provide insights for clinicians and public healthcare managers to support clinical decision-making. This umbrella review aims to consolidate existing evidence on the effectiveness of various NIN in managing chronic NP.

Databases and data treatment: A systematic search was conducted in the PubMed/MEDLINE database, including meta-analyses of controlled trials comparing NIN techniques with sham interventions for NP treatment. The quality of included studies was assessed using the AMSTAR-2 tool and the GRADE system, with effect sizes adjusted to the standard mean difference (SMD).

Results: The review included 22 meta-analyses comprising 8151 participants from 214 controlled trials. The most investigated NIN techniques were tDCS and rTMS, with primary targets being the motor cortex and dorsolateral prefrontal cortex. The findings suggest that excitatory protocols, particularly high-frequency rTMS and anodal tDCS, are effective in reducing pain intensity in individuals with NP. However, the overall quality of evidence was rated low, primarily due to heterogeneity among studies and small sample sizes.

Conclusion: NIN techniques show promise in managing NP, with potential benefits in pain reduction. However, further high-quality research is needed to establish optimal protocols and long-term effects.

Significance statement: This paper consolidates the evidence regarding non-invasive neuromodulation for the treatment of neuropathic pain, including differentiating the most effective techniques based on the aetiology of pain, and provides clinicians with easy access to this critical information. It also highlights key aspects that require further research in the field of non-invasive neuromodulation and neuropathic pain.