Prof Sue Fleetwood-Walker
We are interested in Neuronal Molecular Mechanisms of Pain and Analgesia.
- Recipient of Royal College of Anaesthetists Patrick Wall Medal for Pain Research
- 2004 - present: Professor, School of Biomedical Sciences, University of Edinburgh
- 1995 - 2004: SHEFC Academic staff, Preclinical Veterinary Sciences, Edinburgh
- 1984 - 1994: Wellcome Lecturer and Fellow, Preclinical Veterinary Sciences, Edinburgh
- 1979 - 1984: Postdoctoral Fellowships with Prof John Coote and Prof Ainslie Iggo FRS
- 1979: PhD in Neurophysiology, Department of Physiology, University of Birmingham
- 1976: BSc in Physiology, University of Birmingham
Our work centres on the receptors, intracellular signals and protein:protein interactions that underpin hypersensitive chronic pain states. These are highly resistant to reversal by current analgesic treatments, especially where patients have suffered damage to nerves and remain a major unmet therapeutic need. We seek new selective targets for more effective analgesic intervention with minimal side effects.
We use a range of molecular, biochemical, anatomical, pharmacological and behavioural techniques to address this in animal models that utilise genetic modification to help answer key questions. Our development of new techniques to assess transmission/responsiveness in ex-vivo synaptic preparations has made a major contribution to progress in this area.
Collaborations with Dr Rory Mitchell are central to the receptor and signalling investigations, which focus on roles of metabotropic and ionotropic glutamate receptors and their partner proteins.
We discovered a novel endogenous analgesic system mediated by the TRPM8 ion channel and are currently working on the underlying peripheral and central mechanisms, clinical evaluation (in collaboration with Marie Fallon and Lesley Colvin), and a related drug-discovery programme.
- Merck KGaA
- Dr Marta Mikolajczak (Postdoctoral Fellow)
- Professor Chi-Wei Cheung and Dr Liting Sun (The University of Hong Kong, China), Professor Bert Joosten (University of Maastricht, The Netherlands). Neurostimulation and analgesia.
- Dr Christian Kirsten (Cancer Center, Kristiansand, Norway) and Dr Martin Michaelis (Preclinical Drug Discovery and Development, Merck KGaA, Darmstadt, Germany). The role of growth factor receptors in pain.
The University of Edinburgh:
- Dr Rory Mitchell (CBDS). Mechanisms of pain and analgesia. Drug discovery – novel analgesics for neuropathic pain.
- Dr Don Mahad (Centre for Clinical Brain Sciences) and Dr Graham Campbell (CDBS). Role of Role of mitochondria function in pain/fatigue models of multiple sclerosis.
- Professor Philippa Saunders (Centre for Inflammation Research), Professor Andrew Horne and Dr Erin Greaves (MRC Centre for Reproductive Health). Endometriosis pain.
- Professor Juri Rappsilber (The Wellcome Trust Centre for Cell Biology). Molecular changes underlying lasting stress-induced neuronal hyper-responsiveness in pain pathways.
- Professor Marie Fallon (Cancer Research UK Edinburgh Centre) and Professor Ted Hupp (MRC Institute of Genetics & Molecular Medicine). New analgesic agents for control of cancer-induced chronic pain.
- Professor Stuart Ralston, Dr Simon Roberts (Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine) and Dr Anna Törnqvist (Gothenburg University, Sweden). Molecular mediators and analgesia in osteoarthritis.
- Dr Dylan Clements (R(D)SVS/Roslin Institute). Mechanisms of osteoarthritis in dogs.
Sun, L, Tai, L, Qiu Q, Mitchell R, Fleetwood-Walker SM, Joosten EA, Cheung CW. (2017) Endocannabinoid activation of CB1 receptors contributes to long-lasting reversal of neuropathic pain by repetitive spinal cord stimulation. Eur J Pain 21(5): 804-814.
Greaves E, Horne AW, Jerina H, Mikolajczak M, Hilferty L, Mitchell R, Fleetwood-Walker SM, Saunders PT. (2017) EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis. Scientific Reports 7: 44169.
Vinuela-Fernandez I, Sun L, Jerina H, Curtis J, Allchorne A, Gooding H, Rosie R, Holland P, Tas B, Mitchell R, Fleetwood-Walker SM. (2014) The TRPM8 channel forms a complex with the 5-HT1B receptor and phospholipase D that amplifies its reversal of pain hypersensitivity. Neuropharmacology 79:136-151.
Sun L, Gooding HL, Brunton PJ, Russell JA, Mitchell R, Fleetwood-Walker SM. (2013) Phospholipase D-mediated hypersensitivity at central synapses is associated with abnormal behaviours and pain sensitivity in rats exposed to prenatal stress. Int J Biochem Cell Biol. 45(11):2706-12.
Barclay Z, Dickson L, Robertson DN, Johnson MS, Holland PJ, Rosie R, Sun L, Fleetwood-Walker SM, Lutz EM, Mitchell R. (2011) 5-HT2A receptor signaling through phospholipase D1 associated with its C-terminal tail. Biochemical Journal 436: 651-60.
Arbuckle MI, Komiyama NH, Delaney A, Coba M, Garry EM, Rosie R, Allchorne AJ, Forsyth LH, Bence M, Carlisle HJ, O'Dell TJ, Mitchell R, Fleetwood-Walker SM, Grant SG. (2010) The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment. EMBO Reports 11(6):473-8.
Proudfoot, CJW; Garry, EM; Cottrell, DF; Rosie, R; Anderson, H; Robertson, DC; Fleetwood-Walker, SM & Mitchell, R. (2006) Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Current Biology 16: 1591-1605.
Garry, EM; Moss, A; O’Neill, F; Blakemore, J; Bowen, J; Husi, H; Mitchell, R; Grant, SGN & Fleetwood-Walker, SM. (2003) Lack of neuropathic pain behaviour and disruption of spinal NMDA receptor/CaM kinase II interaction in PSD-95 mutant mice. Current Biology 13 (4): 321-328.
Court, FA; Sherman, DL; Pratt, T; Garry, EM; Ribchester, RR; Cottrell, DF; Fleetwood-Walker, SM & Brophy, PJ. (2004) Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature 431: 191-194.
Gillespie, CS; Sherman, DL; Fleetwood-Walker, SM; Cottrell, DF; Tait, S; Garry, EM; Wallace, CJ; Ure, J; Griffiths, IR; Smith, A & Brophy, PJ. (2000) Peripheral demyelination and neuropathic pain behaviour in periaxin-deficient mice. Neuron 26: 523-531.