Professor Fiona Boissonade BDS, PhD

Professor of Neuroscience

Tel:    0114 271 7850/7849
Fax:    0114 271 7863
Email:  f.boissonade@sheffield.ac.uk

School Administrative Roles

Course organiser for 3rd BDS course in Dental Neuroscience/Facial Pain
Co-ordinator for Final BDS written paper in Oral Surgery
Committees: Strategic Advisory Board, Teaching Committee, 3rd BDS Working Party, Chair 1st BDS Working Party, Board of Dental Studies

National Administrative Roles

Reviewer for National/International Organisations

• Grant Awarding Bodies: MRC (UK), BBSRC, MRC of Canada, Royal College of Surgeons of England
  
• Journals: Am J Physiol, Arch Oral Biol, Brain Res, Can J Physiol Pharmacol, Histochem J, J Dent Res, J Physiol, Pain, Eur J Pain

Research Interests

The overall aim of my research is to address the aetiology and treatment of pain from the oro–facial region. My work has investigated pain of inflammatory and neuropathic origin and has involved collaborative links with other members of our research group, national and international academic collaboration and links with a number of industrial partners.

The studies of inflammatory pain have focused on two main areas; studies of peripheral mechanisms using normal and inflamed tooth pulp, and studies of central mechanisms which have examined the expression of neurochemicals and the nuclear phosphoprotein Fos (the protein product of the c-fos gene) in the trigeminal nuclear complex.

Key Achievements:

• Identification of specific regions in the brainstem involved in the processing of nociceptive input from the trigeminal region.
• Demonstration that inflammation of the tooth pulp induces sensitisation, which enhances pain-induced expression of the immediate-early gene (IEG) c-fos (a key event relating to adaptive responses to injury).
• The development of a model which accurately predicts analgesic effects of a wide range of molecules. This model has been used for an extensive series of translational studies in collaboration with GlaxoSmithKline (GSK).
• he development of a novel trigeminal slice preparation which allows expression of intracellular molecular markers to be associated directly with activation of identified glutamatergic or peptidergic receptor classes.
• Demonstration that changes in expression of a wide range of regulators of neuronal activity are associated with the presence of inflammation in, but far fewer of these changes (eg. substance P (SP), vasoactive intestinal polypeptide (VIP), TRPV1 and PAR2) correlate with the presence of pain.
• The aims of my current projects in this field are to utilise a novel in-vitro trigeminal slice preparation alongside my established methods to investigate intracellular signalling cascades which are activated in trigeminal inflammatory pain. These projects are currently funded by GSK and a recently-awarded BBSRC/GSK Industrial Partnership Award.

In a series of interdisciplinary studies with colleagues in the Department of Oral and Maxillofacial Surgery in Sheffield; GlaxoSmithKline UK; and the Karolinska Institute in Sweden, I have carried out a number of investigations examining the aetiology of nerve injury-induced (neuropathic) oro–facial pain using both animal models and human tissues.

Key Achievements:

• Demonstration that a range of neuropeptides, specific sodium channels and neuronal nitric oxide synthase accumulate at sites of trigeminal nerve injury with a time course that matches the development of abnormal neuronal activity at this site. This suggests a role for these compounds in the development of this ectopic activity, which is thought to be important in the development of neuropathic pain.
  
• A series of electrophysiological studies have confirmed that some of these neuropeptides can increase abnormal activity at injury sites. These data may provide novel therapeutic targets.
• Observation of changes in expression of the above molecules in the cell bodies of injured axons which may be associated with the development of increased activity following injury. These changes differ from those reported following injury to spinal nerves. This suggests that mechanisms of neuropathic pain may be system specific: this is important in the development of therapies for this type of pain.
• Quantification of neuropeptides, immune cells, sodium channel subtypes and morphological changes in injured human nerves. This work has demonstrated that numerous changes occur in injured nerves, but very few of them correlate with clinical pain history. This important finding has implications for the development of new therapeutic strategies for neuropathic pain.
• We are currently carrying out a series of studies to investigate the effect of anti-scarring agents on peripheral nerve regeneration. The initial studies have had very promising results and we have recently secured further funding from Renovo to further investigate this exciting new area.

Recently Published Papers

• Rodd HD, Boissonade FM. Immunocytochemical investigation of immune cells within human primary and permanent tooth pulp. Int J Paediatr Dent 2006;16:2–9
• Davies SL, Loescher AR, Clayton NM, Bountra C, Robinson PP, Boissonade FM. Changes in sodium channel expression following trigeminal nerve injury. Exp Neurol 2006;202:207–216
• Atkins S, Smith KG, Loescher AR, Boissonade FM, O’Kane S, Ferguson MW, Robinson PP. Scarring impedes regeneration at sites of peripheral nerve repair. NeuroReport 2006;17:1245–1249
• Atkins S, Smith KG, Loescher AR, Boissonade FM, Ferguson MW, Robinson PP. The effect of antibodies to TGFβ1 and TGFβ2 at a site of sciatic nerve repair. J Peripher Nerv Syst 2006;11:286–293
• Biggs JE, Yates JM, Loescher AR, Clayton NM, Boissonade FM, Robinson PP. Changes in vanilloid receptor 1 (TRPV1) expression following lingual nerve injury. Eur J Pain 2007;11:192–201
• Biggs JE, Yates JM, Loescher AR, Clayton NM, Boissonade FM, Robinson PP. Vanilloid receptor 1 (TRPV1) expression in lingual nerve neuromas from patients with or without symptoms of burning pain. Brain Res 2007;1127:59–65
• Bird EV, Robinson PP, Boissonade FM. Nav1.7 sodium channel expression in human lingual nerve neuromas. Arch Oral Biol 2007;52:494–502
• Worsley MA, Davies SL, Clayton NM, Bountra C, Loescher AR, Robinson PP, Boissonade FM. The effect of inflammation on Fos expression in the ferret trigeminal nucleus. Eur J Oral Sci 2007;115:40–47
• Vora AR, Bodell SM, Loescher AR, Smith KG, Robinson PP, Boissonade FM. Inflammatory cell accumulation in traumatic neuromas of the human lingual nerve. Arch Oral Biol 2007;52:74–82
• Worsley MA, Clayton NM, Bountra C, Boissonade FM. The effects of ibuprofen and the neurokinin-1 receptor antagonist GR205171A on Fos expression in the ferret trigeminal nucleus following tooth pulp stimulation. Eur J Pain, in press [doi:10.1016/j.ejpain.2007.07.010]
• Rodd HD, Morgan CR, Day PF, Boissonade FM. Pulpal expression of TRPV1 in molar incisor hypomineralisation. Eur Arch Paediatr Dent. 2007;8:184-188
• Atkins S, Loescher AR, Boissonade FM, Smith KG, Occleston N, O’Kane S, Ferguson MW, Robinson PP. Interleukin-10 reduces scarring and enhances regeneration at a site of peripheral nerve repair. J Peripher N Syst. 2007;12:269-76

Current MPhil / PhD Students

Yvonne Fok, 2005- current
Katie Bowler, 2007-current
Laura Evans, 2007-current
David Ngeow, 2007-current
Jenny Blackburn, 2007-current