Pain-related Brain Mechanisms for Pain Catastrophizing Behavior in Response to Home-based Mindfulness-based Meditation Paired with Transcranial Direct Current Stimulation

摘要

ABSTRACT The long-term goal of this mechanism of action-focused supplement project is to develop a comprehensive understanding of how patients exert neural control over pain-related behaviors, leading to reductions in clinical pain and improved health outcomes for older adults using home-based nonpharmacological pain management approaches. Based on a behavioral activation and inhibition systems model of pain that explains pain-related behavior, this supplement will assess underlying brain mechanisms explaining pain catastrophizing behavior change following home-based nonpharmacological pain interventions in older adults with knee osteoarthritis (OA). Currently more than 14 million adults in the United States are living with symptomatic OA, one of the leading causes of chronic pain. In the parent study (R01NR019051), we are conducting a double-blind, randomized, sham-controlled phase II parallel group (1:1:1:1 for four groups defined by 2x2 factorial design) clinical trial to determine the effects of remotely supervised Mindfulness-based Meditation (MBM) paired with Transcranial Direct Current Stimulation (tDCS) at home on clinical pain and symptoms in older adults with symptomatic knee OA. The parent study did not originally posit a mechanistic clinical trial, and this supplemental study will provide invaluable mechanistic brain imaging data for pain-related behavior change building on our parent study. Recently, literatures showed that clinical pain is associated with pain catastrophizing behavior and that functional magnetic resonance imaging (fMRI) imaging responses suggested greater maladaptive changes in pain-related brain function in patients with knee OA (e.g., greater changes in resting and pain-evoked cerebral blood flow in cingulate, insula, thalamus, amygdala, periaqueductal gray, and putamen). Taken together, in this supplement study, we will collect pain catastrophizing behavior and fMRI data among 40 older adults with knee OA who will be recruited in the subsequent year in the parent study using the parent project’s existing design and recruitment plan. The central hypothesis is that home-based MBM paired with tDCS will decrease maladaptive changes in pain-related brain function, which will predict pain catastrophizing behavior and clinical pain. This hypothesis will be tested by pursuing the following specific aims: To evaluate the effects of MBM paired with tDCS on pain-related brain function (quantified by fMRI data) in older adults with knee OA (specific aim 1); and to evaluate the relationship between pain-related brain function (quantified by fMRI data) and pain catastrophizing behavior and OA-related clinical pain (specific aim 2). The proposed research is significant because this supplement study is expected to reveal underexplored causal processes (i.e., pain-related brain function via functional connectivity alterations) that can illuminate the intervention’s mechanisms of actions.