Research Interests and Techniques

Neuronal Plasticity in the Auditory System

The Royal National Institute for Deaf People (RNID) estimates that 12.6 million people are affected by noise-induced hearing loss in the UK. Understanding the neurological basis of  noise-induced hearing loss is relevant to human environmental exposure, and is important for a better understanding of deafness and tinnitus. Our aim is to identify drug targets for the treatment of these debilitating conditions. We are currently investigating plastic changes in gene expression, particularly those genes that encode ion channels, with a view to identifying proteins that regulate the activity or level of excitability of neurones in the auditory pathway.

Pain Perception and Analgesia

Primary sensory neurones that convey information about nociceptive stimuli (painful heat or mechanical stimuli) express a number of GPCRs, ion channels and enzymes, that are important for the transduction and/or propagation of information from the peripheral tissue to the spinal cord. Our experimental programme is aimed at identifying novel targets in primary sensory neurones that might be suitable for the development of analgesic drugs.
Prostanoid receptors are expressed in primary sensory neurones. Prostaglandins released following damage to peripheral tissues contribute to the allodynia and hyperalgesia by binding to these receptors and altering nociceptor theshold. We are currently investigating which prostanoid receptor subtypes are expressed in subsets of primary sensory neurones and are looking at whether the expression of these receptors is altered in models of experimental inflammation. Prostaglandin E2 play a a particularly important role in the regulation of heat-sensing ion channel (TRPV1) and we are working to elucidate the underlying mechanisms that lead to heat sensitisation.

Stroke

A stroke is caused by bleeding within the brain or because blood vessels in the brain become blocked by an embolism. The result is that oxygen delivery to the affected brain regions is reduced and neurones and gial cells can be affected or die.  Depending on the region of the brain involved, a stroke can have a range of neurological consequences including weakness and motor impairment. We are using our knowledge of prostaglandin receptors derived from the pain field to team up with Dr Claire Gibson from the Department of Psychology, to investigate the neuroprotective role of EP receptor subtypes in stroke using a range of in vitro and in vivo models. The aim is to identify EP receptor subtypes and ligands that have a neuroprotective profile.

Research Group

Present group members

Mr Alistair Fryatt

Ms Asha Akram

Recent Publications

Fryatt AG, Vial C, Mulheran M, Gunthorpe MJ & Grubb BD (2009) Voltage-Gated Sodium Channel. Expression in Rat Spiral Ganglion Neurons. Molecular and Cellular Neuroscience. 42, 399-407.

Grubb BD (2009) Activation of sensory neurones in the arthritic joint. In: Pain in Osteoarthritis; Felson DT & Schaible H-G (Eds) pp25-38. ISBN: 978-0-470-40388-4.

Eyre J, Ioannou K, Grubb BD, Saleem M, , Mathieson P, Christtensen EIC, Brunskill NJ and Topham P (2007) Statin-sensitive endocytosis of albumin by glomerular podocytes. Am J Physiol. - Renal Physiology. 292 (2), F674-F681.

Mayer S, Izydorczyk I, Reeh PW and Grubb BD (2007) Bradykinin-induced nociceptor sensitisation to heat depends on cox-1 and cox-2 in isolated rat skin. Pain 130, 14-24.

Mongan LC, Neville MJ, Chen MX, Collins S, Clayton NM, Tate SN and Grubb BD (2005) Small and Intermediate Conductance Calcium-Activated Potassium Channels in Rat Sensory Nervous System. Neuroscience 131, 161-175.

Stonehouse AH, Grubb BD, Pringle JH, Norman RI, Stanfield PR and Brammar WJ (2003) Nuclear Immunostaining in Rat Neuronal Cells Using Two Anti-Kir2.2 Ion Channel Polyclonal Antibodies. J. Mol. Neurosci. 20,189-194.

Oldfield, S, Grubb, BD and Donaldson, LF (2001) Identification of a prostaglandin E2 receptor splice variant and its expression in rat tissues. Prostaglandins and other Lipid Mediators 63(4) 165-173.

Donaldson LF, Humphrey PS, Oldfield S, Giblett S and Grubb BD (2001) Expression and regulation of prostaglandin E receptor subtype mRNAs in rat sensory ganglia and spinal cord in response to peripheral inflammation. Prostaglandins & Other Lipid Mediators 63: (3) 109-122.

Chopra B, Giblett S, Little JG, Donaldson LF, Tate S, Evans RJ and Grubb BD (1999) Cyclooxygenase-1 is a marker for a sub-population of putative nociceptive neurones in rat dorsal root ganglia. European Journal of Neuroscience.

Harris JB, Grubb BD, Maltin C and Dixon R (1999) The neurotoxicity of the venom phospholipases A2, notexin and taipoxin. Experimental Neurology.
Ebersberger A, Grubb BD, Willingale HL, Gardiner NJ, Nebe J and Schaible H-G (1999) The intraspinal release of prostaglandin E2 in a model of acute arthritis is accompanied by an upregulation of cyclooxygenase-2 in the spinal cord. Neurosci. 93, 775-781.

Grubb BD and Evans RJ (1999) Characterization of cultured dorsal root ganglion neuron P2X receptors. Eur. J. Neurosci. 11, 149-154.

Willingale HL, Gardiner NJ, McLymont N, Giblett S and Grubb BD. (1997) Prostanoids synthesised by cyclooxygenase isoforms in rat spinal cord contribute to the development of neuronal hyperexcitability. Br. J. Pharmacol. 122., 1593-1604.

Grubb BD, Riley RC, Hope PJ, Pubols L and Duggan AW (1996) The burst-like firing of spinal neurons in rats with peripheral inflammation is reduced by an antagonist of N-methyl-D-aspartate. Neurosci 74, 1077-1086.