Transcranial Direct Current Stmulation (tDCS) in Chronic Pain: Historical Perspective, Neurophysiological Machanisms and Clinical Evidences.

Abstract: Chronic pain is a highly prevalent and disabling condition and is currently recognized as a disease sustained by maladaptive neuroplasticity and dysfunction of central pain-modulating networks. Despite major advances in pharmacological therapies, a significant proportion of patients experience insufficient analgesia, functional impairment, and reduced quality of life, underscoring the need for mechanism-based, non-pharmacological treatment strategies. This review aims to summarize the historical background, neurophysiological foundations, clinical evidence, safety profile, and current limitations of transcranial direct current stimulation (tDCS) in the treatment of chronic pain, with particular emphasis on fibromyalgia and headache disorders. A narrative review of experimental and clinical literature was conducted, including randomized controlled trials, systematic reviews, meta-analyses, and international guidelines. The analysis focused on neurophysiological mechanisms of tDCS and its clinical application across major chronic pain syndromes. tDCS exerts polarity-dependent modulation of neuronal excitability by inducing subthreshold shifts in the transmembrane potential, thereby altering neuronal firing probability and promoting NMDA receptor-dependent synaptic plasticity. Importantly, its effects extend beyond local cortical modulation, influencing distributed pain-related networks involving the primary motor cortex, thalamus, insula, and cingulate cortex. Clinically, the most consistent evidence supports the use of anodal tDCS over the primary motor cortex in fibromyalgia and migraine, demonstrating moderate reductions in pain intensity, attack frequency, and disease burden. Evidence in neuropathic pain and chronic low back pain is more heterogeneous but suggests potential benefit when tDCS is applied in repeated sessions and integrated into multimodal treatment approaches. Across studies, tDCS shows a favorable safety profile, with predominantly mild and transient adverse effects. tDCS represents a safe, low-cost, and biologically grounded adjuvant therapy for chronic pain, particularly in conditions characterized by central sensitization and network-level dysfunction. While not a standalone intervention, its integration into multidisciplinary pain management strategies may enhance clinical outcomes and reduce reliance on long-term pharmacological treatments. Further large-scale, methodologically standardized trials are needed to refine stimulation protocols and identify patient subgroups most likely to benefit.