A mechanistic neuroimaging study to determine brain changes with auricular stimulation and auriculotherapy in healthy volunteers and chronic low back pain patients

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Abstract

Project Summary - Abstract There is a critical unmet need for effective low-cost, non-invasive, opioid-sparing treatments for chronic pain, particularly chronic low-back pain (CLBP). Auriculotherapy (AT) is a promising alternative treatment for chronic pain that is underutilized, in large part due to lack of demonstration of systems-neuroscience changes that provide a mechanistic explanation for the beneficial clinical effects. Our overall objective in this proposal is to determine the neural signatures of experimental stimulation (stim) and durable modulation of brain network connectivity following AT treatment, using multi-modal neuroimaging. Aim 1 involves a basic experimental study in pain-free volunteers that will evaluate, using functional near-infrared spectroscopy (fNIRS), whether nontherapeutic touch stim with von-Frey filaments applied to different ear points will cause distinct activations in the primary somatosensory cortex and prefrontal cortex, testing assumptions about the accepted auricular cartography used for AT practice. Aims 2 and 3 involve a 1:1 randomized double-blind sham-controlled mechanistic clinical trial in CLBP patients, who will return after a 2-month washout period for crossover condition. The filament stim fNIRS paradigm described for Aim 1 and whole-brain resting-state functional MRI will be performed both before and 5-7 days after verum/sham AT. For AT, we will use compressed gas (Cryo-AT) to provide focal, needle-free, persistent stim of AT points. Cryo-AT is barely perceptible, allowing patient blinding and rigorous sham control by using a device with an empty canister at the same AT points. Cryo-AT has been shown to be as effective and well-tolerated as needles, and we have previously demonstrated long-lasting effectiveness for cryo-AT. In Aim 2 fNIRS stim data will be used to test the hypothesis that low-back AT points are sensitized or pathologically imbalanced in CLBP. Stim of the low-back AT point is expected to elicit a greater magnitude fNIRS response compared to the pain-free cohort of Aim 1 and compared to stim of AT points representing pain-free body areas in CLBP patients. When repeating the fNIRS stim paradigm 5-7 days later, significantly smaller fNIRS responses from low-back AT points are expected when patients receive Cryo-AT treatment compared to sham, demonstrating resolution of the pathologic imbalance. In Aim 3 fMRI data will be analyzed for long-lasting changes in network connectivity. We expect significantly greater connectivity change following Cryo-AT treatment, as the primary outcome. In a secondary analysis, changes in pain, anxiety, and depression will be regressed against the connectivity-change contrast for individual anatomical regions of interest, to localize changes in pain and mood to specific brain areas with connectivity changes after Cryo-AT. Overall Impact: Our world-class multidisciplinary team, with expertise in AT, fNIRS, MRI, and clinical pain research, from an excellent environment, will expeditiously complete this study and provide mechanistic neuroscientific insights into the beneficial effects of AT. This will increase the adoption of AT in routine clinical care to improve pain relief and mood, while avoiding excess opioid use in millions of Americans with CLBP.