Portable Neurostimulation System for Chronic Migraine Pain

Portable Neurostimulation System for Chronic Migraine Pain Portable Neurostimulation System for Chronic Migraine Pain The proposed project addresses a pressing need for therapeutic devices for treating chronic migraine (CM). Migraine affects 12% of the world population and chronic migraine affects around 1.4-2.2% of world population. Chronic migraine (CM) is a life-changing disorder characterized by chronic pain, sensory amplification, autonomic and affective disruptions that is highly debilitating. CM patients can suffer for as often as 15 days or more in a month resulting in significant debilitation and decreased productivity. Current treatments result in significantly high refractory cases. As a result, a number of different approaches, such as botox injections, nerve blocks, and neurostimulation are being used. In recent years, a new line of medication has been developed specifically for migraines and the trigeminal pain pathway. These therapeutics act as CGRP antagonists, and a first-in-class oral medication was approved in late 2019. Despite their approval, most people don't have access to these medications yet. Other concerns with the pharmacological therapy include long-term side-effects, costs etc. Occipital nerve stimulation (ONS) has been demonstrated in several clinical studies to have beneficial effects for treating migraine, cluster headaches, transformed migraine, chronic migraine and occipital neuralgia. However, current technologies involve batteries and invasive leads that lead to instabilities in the neuronal interface and stimulation efficacy. Non-invasive stimulation of the trigeminal nerve and the vagal nerve have also been attempted (with 4 FDA approved devices - Cefaly, eNeura, Nerivio and Gammacore). However, the lack of spatial precision in the non-invasive neurostimulation technologies have led to variable outcomes and poor adoption with additional issues of high cost, reimbursement and coverage (based on physician feedback). Therefore, there is a clinical need for a non-invasive or minimally invasive neuromodulation therapy that has the spatial precision comparable to implanted neurostimulation leads. The overall concept of this proposal is to develop a hand-held patient administered neurostimulation system that includes a non-invasive ultrasound transducer and millimeter scale, ultrasound-powered devices called wireless, injectable neurostimulators (WINS) to stimulate the occipital nerve (ON) to mitigate pain during an episode of CM. We intend to develop this technology to be portable and easy to use, capable of being administered as needed by the patient episodically for a few minutes at a time. The injectable WINS modules will be placed next to the occipital nerve by a neurosurgeon in an outpatient procedure and powered by an external ultrasound transducer when needed to stimulate the ON. The proposed WINS technique will provide the spatial precision of implanted microscale leads with the added benefits of the system being wireless and battery-less. The proposed WINS system has been demonstrated to successfully stimulate rodent motor cortical neurons and the sciatic nerve in chronic experiments in our laboratories at ASU. As part of the Flinn seed grant, we propose to develop and test the WINS technique for ONS to mitigate pain in rat models of ONS. Further, the proposed effort will de-risk the WINS technologies and its different configurations through carefully sequenced optimization and testing in rodent experiments. The resulting optimized technology will be licensed from ASU through the formation of a startup company, which will take it through the regulatory process leading to clinical trials. The team involves 2 experienced neural engineers from ASU and one neurosurgeon from BNI. The proposed effort is highly synergistic with the Barrow-ASU initiative for innovation in neuroengineering that seeks to promote innovations in devices, technology, therapies and research to improve brain and spinal cord function.