This research theme is interested in peripheral and central pain mechanisms, meaning what happens in the nerves and in the brain. We explore these mechanisms through different types of imaging techniques (scans), as well as a technique called microneurography, which involves reading electrical signals directly from small nerve fibres.
Peripheral nerve imaging
Magnetic resonance imaging (MRI) can reveal detailed structural properties of nerves. It has shown that diabetic and entrapment neuropathies cause changes in these structural properties, which correlate with sensory function and physiology. The PAINSTORM teams at Imperial College London and the University of Oxford have been pioneering peripheral nerve imaging at both 3 and 7 Tesla (these are units describing the strength of the magnets in a scanner), which will be used to determine structural phenotypes in neuropathic pain. We have developed sciatic nerve imaging at Imperial College London and median nerve imaging at the University of Oxford. We will study these imaging metrics in relation with other measures in well-phenotyped patients with different types of neuropathies.
Microneurography
Microneurography is the only neurophysiological technique that records neuronal activity directly from nociceptors in awake patients. We must understand better how changes in peripheral nociceptive fibre properties in disease states (e.g. diabetes) contribute to neuropathic pain. With deep phenotyping, microneurography, and peripheral nerve imaging, we will be able to compare the excitability profile of each nociceptive fibre subclass and their responses to external stimuli between study participants with painful and painless diabetic polyneuropathy.
We will also look at how changes in nociceptive fibre properties correlate with clinical variables, such as neuropathy severity or diabetic control, and peripheral nerve imaging metrics. We will stratify patients into sensory profiles to determine whether these correlate with microneurography.
Spinal cord, brainstem, and whole brain neuroimaging
Neuropathic pain involves central and peripheral mechanisms. A central theme to our work has been to prove that an endogenous dysfunctional descending pain modulatory system is a key pathophysiological mechanism in chronic pain. Scaling up this observation and better understanding what drives this dysfunction is the next key goal. This will be enabled by linking to Work Package 3 outcomes.
We have built on early work in learning/prediction errors in pain to show similar learning-related effects in the spinal cord. Building on our track record of neuroimaging innovation, we will take subsets of patients to further verify DRG-dorsal horn functional connectivity and dorsal horn activity as metrics of aberrant peripheral nerve activity and dorsal horn sensitisation, respectively.
We will collaborate with Work Packages 2 and 3 to better determine imaging endophenotypes of these psychosocial processes that powerfully contribute to the development, exacerbation and maintenance of persistent pain.
