Neural and Immune Correlates of Painful Chemotherapy-Induced Neuropathy, Feasibility, and Preliminary Efficacy of a Motor Cortex Non-Invasive Brain Stimulation Intervention: A Study Protocol

Background: More than half of patients treated with commonly used platinum- and taxane-based anti-cancer agents suffer painful chemotherapy-induced peripheral neuropathy (CIPN). Non-Hispanic black (NHB) patients have a greater risk of experiencing CIPN and consequent chemotherapy dose reductions compared to non-Hispanic white patients (NHW). Transcranial direct current stimulation (tDCS) of the motor cortex is a promising, safe, and effective intervention for neuropathic pain. Recently, we demonstrated, in a randomized experimental study in healthy individuals, that one 20 min session of motor cortex tDCS reduced capsaicin-induced mechanical hyperalgesia. The descending pain modulatory network (DPMN), a group of brain structures activated in response to painful stimuli and pain modulation, was more responsive after active versus sham stimulation. Methods: The overarching goal of this proposal is to conduct an exploratory double-blind randomized controlled trial addressing three specific aims: (1) determine the feasibility and efficacy of active tDCS targeting the motor cortex as an analgesic and anti-hyperalgesic intervention in patients with painful CIPN; (2) determine structural and functional brain correlates of painful CIPN in the DPMN in NHBs and NHWs; and (3) determine inflammatory mediators in patients with painful CIPN and their relationship to the severity of painful CIPN. Conclusions: We expect that NHB subjects will experience greater therapeutic effects of tDCS compared to NHW subjects, since NHBs have a dysregulated DPMN impacted by neuroinflammation.