Functional Cerebral Neurovascular Mapping During Focused Ultrasound Peripheral Neuromodulation of Neuropathic Pain.

Abstract

Nociceptive pain is required for healthy function, yet, neuropathic pain (disease or injury) can be severely debilitating. Though a wide-array of treatment options are available, they are often systemic and/or invasive. As a promising neuromodulation treatment, Focused ultrasound (FUS) is a noninvasive and highly spatially-targeted technique shown to stimulate neural activity, yet, effects on pain signaling are currently unknown. Develop and validate a method for studying FUS nerve stimulation modulation of pain-evoked neural responses in vivo. We developed a high-resolution functional ultrasound (fUS) method capable of mapping cortical responses in healthy and neuropathic pain mice in response to FUS neuromodulation treatment. FUS-evoked hemodynamic responses are correlated with the intensity of peripheral neuromodulation. We confirm functional connectivity is altered in neuropathic mice and demonstrate that FUS can modulate neuropathic pain-evoked hemodynamics. The findings presented herein provides evidence for an FUS-based nerve pain method and validates the fUS technique developed for monitoring pain-evoked hemodynamics. We anticipate that the findings presented herein describe a noninvasive and flexible nerve modulation technique for pain mitigation, furthering evidence for clinical translation.