Title: Multiplex microneurography: a pathway to stratified pain generator diagnostics.
Funder: Versus Arthritis

Abstract: Chronic pain is a major health concern in the UK with up to 50% of the population suffering during their lifetimes. Our aim is to be better able to diagnose and hence treat this pain. Effective treatment is hampered by an inability to identify the pain mechanisms at play in an individual patient. A crucial distinguishing diagnosis is of the relative contribution of central vs. peripheral pain generator(s). Current guidelines for chronic pain cannot take this key difference into account, even though currently treatments would be deployed differently if this information were known. Evidence from patient populations shows that many types of chronic pain are associated with abnormal activity in pain sensing nerves (nociceptors) i.e. a peripheral pain generator. Microneurography is the only technique through which recordings can be made from human nociceptors. It was microneurography that revealed the abnormal nociceptor activity in patients. Unfortunately, this technique is unsuitable for clinical diagnostics in its current form: data yields are low; the size of the nociceptor signal is small in comparison to the recording noise; and it is very labour intensive. The technology of microneurography has changed relatively little over the last 50 years despite great advances in computing power, software versatility and electrode construction. We have recently validated the use of ultrasound guidance and of cost effective, open source hardware and software to improve microneurography in terms of data yields, generalisability to other nerves and enabling its use in laboratories without specialised equipment. The standard recording approach uses a single needle electrode – sampling data from one single point in a nerve. Our aim, within 18 months, is to develop and test novel multi-contact microneurography electrodes that will allow recordings from multiple nociceptors concurrently. We believe this will improve the signal:noise ratio and enable real-time identification of many nociceptors simultaneously. If successful this will bring microneurography a step closer to the point at which it can be deployed as a diagnostic tool. Dr. Whittaker and Prof O'Neill’s group at Newcastle University have developed fabrication processes to produce multi-contact electrodes for EMG recordings. These electrodes have been conceived and built to be suitable for percutaneous use, just like microneurography electrodes. In the first part of the project we will modify the electrode fabrication to ensure the geometry is appropriate for intra-neural recordings. Simultaneously at the University of Bristol we will work up a pre clinical testing process in rodents focusing on the online analysis and ‘clustering’ methods for nociceptor identification. We will then perform a sequential, iterative process of optimisation of the performance of the electrodes before finally testing their efficacy in healthy volunteers. This work will generate crucial ground breaking data to support translation of these electrodes into the clinic to guide the care of patients with chronic pain and will also provide novel methods for pre-clinical pain science. In so doing we will also launch the pain research career of Jim Dunham into a translational direction and train a talented junior scientist (Anna Sales) in state-of-the-art pain research methods.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM;MUSCULOSKELETAL