Andy Marshall

Senior Clinical Lecturer University of Liverpool

Honorary Consultant the Walton Centre

Contact: Andrew.marshall@liverpool.ac.uk 

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.

Ongoing studies

  • 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

External collaborators

  • 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

 

Relevant publications

Middleton SJ, Perini I, Themistocleous AC, Weir GA, McCann K, Barry AM, Marshall A, Lee M, Mayo LM, Bohic M, Baskozos G, Morrison I, Löken LS, McIntyre S, Nagi SS, Staud R, Sehlstedt I, Johnson RD, Wessberg J, Wood JN, Woods CG, Moqrich A, Olausson H, Bennett DL. Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice. Brain. 2022 Oct 21;145(10):3637-3653. doi: 10.1093/brain/awab482. PMID: 34957475; PMCID: PMC9586547

Nagi SS, Marshall AG, Makdani A, Jarocka E, Liljencrantz J, Ridderström M, Shaikh S, O'Neill F, Saade D, Donkervoort S, Foley AR, Minde J, Trulsson M, Cole J, Bönnemann CG, Chesler AT, Bushnell MC, McGlone F, Olausson H. An ultrafast system for signaling mechanical pain in human skin. Sci Adv. 2019 Jul 3;5(7):eaaw1297. doi: 10.1126/sciadv.aaw1297. PMID: 31281886; PMCID: PMC6609212.

Marshall AG, Lee-Kubli C, Azmi S, Zhang M, Ferdousi M, Mixcoatl-Zecuatl T, Petropoulos IN, Ponirakis G, Fineman MS, Fadavi H, Frizzi K, Tavakoli M, Jeziorska M, Jolivalt CG, Boulton AJM, Efron N, Calcutt NA, Malik RA. Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy. Diabetes. 2017 May;66(5):1380-1390. doi: 10.2337/db16-1181. Epub 2017 Feb 15. PMID: 28202580; PMCID: PMC5399611

Marshall A, Kalteniece A, Ferdousi M, Azmi S, Jude EB, Adamson C, D'Onofrio L, Dhage S, Soran H, Campbell J, Lee-Kubli CA, Hamdy S, Malik RA, Calcutt NA, Marshall AG. Spinal disinhibition: evidence for a hyperpathia phenotype in painful diabetic neuropathy. Brain Commun. 2023 Feb 28;5(2):fcad051. doi: 10.1093/braincomms/fcad051. PMID: 36938521; PMCID: PMC10016414

Panchuelo RMS, Eldeghaidy S, Marshall A, McGlone F, Francis ST, Favorov O. A nociresponsive specific area of human somatosensory cortex within BA3a: BA3c? Neuroimage. 2020 Nov 1;221:117187. doi: 10.1016/j.neuroimage.2020.117187. Epub 2020 Jul 22. PMID: 32711068; PMCID: PMC7762820.

Marshall AG, Sharma ML, Marley K, Olausson H, McGlone FP. Spinal signalling of C-fiber mediated pleasant touch in humans. Elife. 2019 Dec 24;8:e51642. doi: 10.7554/eLife.51642. PMID: 31872799; PMCID: PMC6964968.