EPIONE: Effective Pain Interventions with Neural Engineering

Chronic pain is one of the great unmet needs in medicine. The scale of the problem is illustrated by several data fundamentals: it is the leading global cause of disability; it has an economic burden estimated to exceed heart disease and cancer combined; and it is a root cause of the opioid crisis, killing 130 people per day in the US alone. Importantly, chronic pain is a disease in its own right and often emerges as a maladaptation of the brain’s intrinsic machinery for bodily protection and recovery from disease and injury. Conventional research has focused on drug discovery, but there have been few major breakthroughs in pain drugs for several decades. The EPIONE programme aims to use engineering to support a new generation of therapeutic technologies to solve the problem. The programme adopts a control systems approach, bringing together an interdisciplinary expert team from different domains of engineering, with neuroscientists, clinicians, and lived-experience partners. The team will work together to identify new technological strategies to reduce symptomatic pain by directly modulating information processing in the brain. This approach builds a technological framework that combines sensor systems, different interventions to control brain activity (invasively and non-invasively), adaptive control algorithms, and precise pain network targeting. Several key features distinguish the programme from what has been previously attempted, highlighting the state-of-the-art innovations that underscore the strength of the team. This includes: i) developing new methods to modulate brain activity; ii) the use of computer models of the pain system to guide points of intervention; iii) developing the ability to target multiple parts of the brain at once; and iv) the use of closed-loop systems that continually adjust therapy according to patient specific needs. The work-packages themselves focus on four core interventional approaches: invasive (i.e. surgically implanted) deep brain stimulation (built on our Picostim-DyNeuMo system), programmed drug delivery systems (using implanted microfluidic ion pumps), non-invasive focused ultrasound and transcranial magnetic stimulation, and neurofeedback systems. These are bound together by two cross-cutting themes: computational models and simulation platforms to simulate and model the processing and control of pain information in neural circuits; and systems integration to combine multiple elements to design holistic, realisable treatments. In this way, the whole team are united behind the common goal to create the capability for a new generation of personalized systems that fundamentally reduce or abolish pain. Each of the team members are world-renown in their own field, and the programme is unique in bringing this level of expertise to work together closely on such a highly integrated project. The programme also actively and strongly supports next generation principal investigators within the core project team, incorporates an explicit early career researcher development strategy, and exploits an active and expansive infrastructure for lived-experience involvement and co-design. The team fully adheres to principles of responsible innovation, and are committed to safe, ethical, inclusive, and open research practices. Whilst the long-term vision is to support transformational healthcare technologies, there is a clear vision to deliver impact within the lifespan of the programme. ‘World-first’ deliverables include the development of an adaptive brain implant for networked pain modulation set for clinical study deployment, a translation-ready closed-loop programmed drug delivery system, and several integrated systems with the ability to non-invasively target multiple brain regions simultaneously.