Professor Stuart Bevan
Our studies are focused on sensory transduction in neuronal and non-neuronal cells, the transduction and transmission of noxious and innocuous stimuli in peripheral sensory nerves and mechanisms of pain and analgesia. These investigations are carried out using a combination of in vitro and in vivo approaches.
Transient receptor potential (TRP) channels
Much of our current research involves studies on TRP Channels. TRP channels have diverse roles in sensory transduction and cellular regulation. We have a specific interest in TRP channels expressed by peripheral sensory neurons and interacting cells such as keratinocytes as well as non-neuronal cells in the gastro-intestinal tract. Several of these channels are important sensors of thermal stimuli. For example, TRPV1 is activated by noxious high temperature (>42°C), TRPM8 by cool temperatures (<~28°C) and TRPV3 by warm temperatures (>32°C). TRPA1 can also be activated by noxious cold temperatures. TRPV1 and TRPA1 are expressed by sensory nerves that respond to noxious stimuli and these two channels are also sensitive to pungent chemicals such as capsaicin found in chilli peppers (TRPV1) and allyl isothiocyanate found in mustard and wasabi (TRPA1).
Our interest is to determine the roles of TRP channels and other ion channels and receptors in normal physiology and in disease states. The activities of channels and receptors are studied using electrophysiological measurements from native cells (such as sensory neurons) and cells heterologously expressing molecules of interest.
The ion channel TRPM8 is the physiological receptor for cold temperature, menthol and other agents that evoke a cooling sensation. The figure shows that a rapid cooling of the ambient solution evokes a large TRPM8 mediated current (control). Increasing concentrations of a TRPM8 antagonist blocks the cold activated current.
The behaviour of single cells to various stimuli is also investigated in microfluorimetry or multiwell plate assays using ion sensitive dyes to monitor changes in intracellular ion concentrations.
We also use RT-PCR and immunocytochemical approaches to reveal mechanisms that control the expression of key transduction molecules both in vitro and in vivo. Using these approaches we have identified some of the key endogenous mechanisms that activate and regulate TRP channels in sensory neurons.Our in vitro studies are complemented by behavioural experiments in animal models. Here we study the importance of different molecules and mediators by using pharmacological interventions and RNA interference as well as genetically modified mice.
- Gentry C, Stoakley N, Andersson DA, Bevan S. (2010) The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity. Mol Pain 6:4.
- Andersson DA, Gentry C, Moss S, Bevan S. (2009) Clioquinol and pyrithione activate TRPA1 by increasing intracellular Zn2+. Proc Natl Acad Sci U S A. 106:8374-9.
- Andersson DA, Gentry C, Moss S, Bevan S. (2008) Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 28:2485-94.
- Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Högestätt ED, Zygmunt PM. (2008) Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol. 53:391-9.
- Andersson DA, Nash M, Bevan S. (2007) Modulation of the cold-activated channel TRPM8 by lysophospholipids and polyunsaturated fatty acids. J Neurosci. 27:3347-55.
- Clark AK, Yip PK, Grist J, Gentry C, Staniland AA, Marchand F, Dehvari M, Wotherspoon G, Winter J, Ullah J, Bevan S, Malcangio M. (2007) Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc Natl Acad Sci U S A. 104:10655-60.
- Barclay J, Clark AK, Ganju P, Gentry C, Patel S, Wotherspoon G, Buxton F, Song C, Ullah J, Winter J, Fox A, Bevan S, Malcangio M. (2007) Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain. 130:225-34.
- David A. Andersson, KCL/London Law Trust Medal Fellow
- Clive Gentry/Research Fellow
- Chancie Knights/PhD Student
- Jack Bircher/PhD Student
- Talisia Quallo/PhD Student