Main research interests
My broad research focus involves investigating the physiology and functional anatomy of nociceptive (pain related) and touch pathways in both health and disease (e.g. in small fibre neuropathy, fibromyalgia and central post-stroke pain).
I have three major work streams
1) Recording of single afferent nerve fibres using the technique of microneurography. We determine stimulus-response properties of afferent fibre subclasses that innervate the skin. This includes their responsiveness to mechanical, thermal and electrical skin stimulation as well as responsiveness to the application of potential ligands. Importantly the function of the recorded nerve fibres is related to perception (e.g., pain) and clinical symptoms. This work has led to the discovery of a previously unrecognised class of nerve fibre - the A-beta nociceptor (https://www.science.org/doi/10.1126/sciadv.aaw1297?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0pubmed). In collaboration with the group at Linkoping University, Sweden, our ongoing research is aims to further define the function and sub-types of these fibres and to determine their role in pain perception. In addition to microneurography studies we study the central pathways by studying alterations in sensation induced by focal spinal cord lesions (e.g., after anterolateral cordotomy).
2) Determining the functional anatomy of nociresponsive regions of primary somatosensory cortex (S1). In collaboration with Prof Susan Francis, Prof Francis McGlone and Prof Oleg Favorov we discovered a previously unrecognised region - nociresponsive Brodmann Area 3a (nBA3a) - that we believe plays a major role in the early cortical processing of C-fibre related pain. Our current work aims to determine the intrinsic cortical networks within S1 and adjacent areas that involve nBA3a and how these are altered in pain models and in pathology (e.g., central post-stroke pain). This work involves high resolution imaging with ultrahigh field (7 Tesla) MRI.
3) Probing the spinal circuits involved in pain processing in painful and non-painful neuropathy (diabetic neuropathy) using a non-invasive biomarker of spinal inhibitory function - H-reflex rate dependent depression (HRDD). This research incorporates translational studies in collaboration with colleagues at University of California, San Diego. We believe that abnormal HRDD is a biomarker of a spinally mediated pain mechanism - spinal disinhibition - and that identification of patients with abnormal HRDD may help guide mechanistically informed treatment of neuropathic pain.
Evaluation of sensory function following anterolateral cordotomy
Microneurography recording of A-beta and C-Fibres in awake human subjects
Investigation of nociceptive and touch sensation and brain networks in a unique pain-free patient with raised endocannabinoids
Defining the role of cortical area nociresponsive Brodmann Area 3a in processing C-fibre mediated pain in health and pathological states, including central post-stroke pain - funded by the Pain Relief Foundation and MRC
DEFINE-FMS - Diagnosing and determining the contribution of small fibre neuropathy to pain in fibromyalgia syndrome - funded by Versus Arthritis (PI Dr Uazman Alam University of Liverpool)
AN EYE FOR artificial intelligence for the diagnosis of PAINful diabetic peripheral neuropathy - funded by Proctor and Gamble (PI Dr Uazman Alam University of Liverpool)
REliability of HRDD as a biomarker in Painful diabetic nEuropathy - a vaLidation study (REPEL) - funded by The Pain Relief Foundation
Prof Hakan Olausson Linkoping University, Sweden
Dr Saad Nagi Linkoping University, Sweden
Prof Susan Francis Sir Peter Mansfield Imaging Centre University of Nottingham
Prof Oleg Favorov University North Carolina, Chapel Hill, US
Prof Francis McGlone
Prof David Mahns, University of Western Sydney, Australia
Prof Nigel Calcutt, University of California, San Diego
Prof Rayaz Malik, Weill Cornell Medical College, Qatar
Dr Devjit Srivastava, Raigmore Hospital, Inverness, Scotland
Dr Ken Valyear, Bangor University, Wales
Dr Manohar Sharma, The Walton Centre, Liverpool