Personalized High-Definition tDCS Protocols for Chronic Pain Treatment

Innovative Neuromodulation Treatments for Chronic Pain: Assessing and Predicting the Effects of Personalized High-Definition Protocols for Transcranial Direct Current Stimulation (HD-tDCS)

This study aims to examine the use of neurostimulation as a potential adjuvant treatment for chronic pain. Among neurostimulation techniques, transcranial direct current stimulation (tDCS) represents a promising, yet not fully exploited, option. Recent methodological advances allow for increased intensity and focality of its effects through personalized high-definition tDCS protocols (HD-tDCS), enabling targeted stimulation of specific brain regions involved in pain and analgesia processing, such as the dorsal anterior cingulate cortex (dACC).

Based on this evidence, the specific objective of the study is to investigate the effect of an innovative HD-tDCS protocol (personalized using structural and functional magnetic resonance imaging (fMRI)), with stimulation applied to the dACC. The experimental design involves randomly assigning 144 patients with chronic pain to three groups, who will undergo an intensive treatment (five sessions in the same week) with cathodal, anodal, or sham (placebo) HD-tDCS.

Patient recruitment and treatment will be equally distributed between sites located in Lombardy (IRCCS Maugeri-Pavia; University of Milano-Bicocca; n=72) and Palermo (IRCCS ISMETT-Palermo; University of Palermo; n=72).

The effects of neurostimulation will be: a) evaluated using self-reported measures of physical and social functioning (Brief Pain Inventory, BPI; primary outcome) before and after treatment, and at follow-up assessments at 3 weeks and 3 months; b) interpreted in relation to underlying neurophysiological changes, as revealed by the high spatial and temporal resolution provided, respectively, by fMR) and by transcranial magnetic stimulation-evoked potentials combined with electroencephalographic recording (TMS-EEG) before and after treatment (secondary outcome).

Inclusion Criteria:

• Diagnosis of chronic pain lasting for at least six months
• Pain scores equal to or greater than 4 on Numerical Rating Scale (NRS) 0-10 on most days for the last 3 months
• Pain unresponsive to conservative treatment such as pharmacological therapy and physiotherapy, and unresponsive to minimally invasive treatments such as peripheral nerve blocks or neuromodulation or steroid epidural injections, when appropriate
• Age between 18 and 75
• Stable pain levels and willingness not to modify any ongoing pain management therapies during the study period (1 week)

Exclusion Criteria:

• History of seizure disorders
• Active malignancy
• Implanted medical devices and/or metallic implants in the head or neck region
• Cranial abnormalities
• Severe cognitive impairment (Montreal Cognitive Assessment (MoCA)<15.5)
• Neurological or psychiatric conditions, or significant comorbidities, that may interfere with tDCS
• Pregnancy
• Incompatibility with MRI and/or TMS