A well-functioning sense of pain is critical for safely traversing the world around us. However, neuropathic pain, resulting from injury or disease to our peripheral nervous system (PNS), can significantly hinder our ability to perform daily tasks, especially in chronic conditions. With a current estimated chronic pain prevalence of 20.4% in adults and a gradually aging population, effective methods for pain management and treatment are essential.
Noninvasive displacement-guided Focused Ultrasound (FUS) neuromodulation has shown potential as a promising neurostimulation technique, offering great spatial selectivity together with high penetration depth. Despite this potential, it remains unclear how to best adapt such a system to treating PNS neuropathic pain. Functional ultrasound (fUS) neuroimaging can map somatosensory-evoked responses with high spatiotemporal resolution, correlating cerebral blood volume (CBV) changes with neurovascular responses. This study seeks to use fUS imaging to elucidate the effects of FUS peripheral neuromodulation on the brain and its potential for treating neuropathic pain.
We developed a high-resolution fUS methodology operating at 40 MHz enabling the visualization of microvasculature without contrast agents and the measurement of CBV changes following various stimuli. Our findings confirm that FUS nerve stimulation evokes measurable cerebral hemodynamic responses which can be correlated with FUS activation intensity and success rate. We demonstrate the capability of differentiating CBV responses at distinct cortical neuronal layers.
Using a spared-nerve injury (SNI) mouse model of neuropathic pain, we demonstrate the feasibility of recording functional connectivity biomarkers as well as measuring the response to electrically-evoked pain. Specifically, we observed a decrease of CBV following electrical stimulation when FUS was applied in stark contrast to a 20% increase in sham sonicated mice. Taken together, the methodology outlined in this study presents a promising step forward in the development of noninvasive analgesic treatments providing quantitative biomarkers in mapping pain registration in the brain.