About the Project
Acute pain is the normal physiologic response to noxious chemical, thermal, or mechanical stimuli. With inflammation or nerve injury/degeneration (often accompanied by inflammation as well) pain persists beyond the duration of the stimulus and may last for months or years (e.g. arthritis). Despite of the severity of health problems caused by pain, scientists don’t really understand enough about how nerve cells collect ‘painful’ information from the periphery and communicate it to the brain. If they did, it would open the door to new methods for pain relief. This research project will be centered on the question of how we sense acute pain, how this sensation is altered in inflammation and how can we stop such pains. Particular attention will be given to the role of G protein-coupled receptors (GPCR) and neuronal ion channels in regulation of neuronal functions (such as excitability and vesicle release), an area where our lab has significant expertise (1-7). To tackle these intricate questions we are going to use an array of cutting-edge technological tools and approaches available through Leeds University and through our collaborators in USA and China. These tools will include electrical recordings from living nerve cells, fluorescent imaging and molecular biology. For example, we will use advanced optical techniques (including super-resolution microscopy) which allow unprecedented insight into cellular function. Ultimately the project is aimed to develop brand new ways to understand and treat pains which not only cause incredible discomfort, but cost the Health Services and society billions of pounds.
References
1. Liu B, Linley JE, Du X, Zhang X, Ooi L, Zhang H, Gamper N. (2010) The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl- channels. J Clin Invest. 120:1240-52.
2. Linley JE, Ooi L, Pettinger L, Kirton H, Boyle JP, Peers C, Gamper N. (2012) Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):E1578-86
3. Ooi L, Gigout S, Pettinger L, Gamper N. (2013) Triple cysteine module within M-type K+ channels mediates reciprocal channel modulation by nitric oxide and reactive oxygen species. J Neurosci. 33:6041-6
4. Pettinger L, Gigout S, Linley JE, Gamper N. (2013) Bradykinin controls pool size of sensory neurons expressing functional δ-opioid receptors. J Neurosci. 33:10762-71
5. Jin X, Shah S, Liu Y, Zhang H, Lees M, Fu Z, Lippiat JD, Beech DJ, Sivaprasadarao A, Baldwin SA, Zhang H, Gamper N. (2013) Activation of the Cl- channel ANO1 by localized calcium signals in nociceptive sensory neurons requires coupling with the IP3 receptor. Sci Signal. 6:ra7
6. Jin X, Shah S, Du X, Zhang H, Gamper N. (2016) Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals. J Physiol. 594:19-30.
7. Huang D, Huang S, Gao H, Liu Y, Qi J, Chen P, Wang C, Scragg JL, Vakurov A, Peers C, Du X, Zhang H, Gamper N. (2016) Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P. Antioxid Redox Signal. 25:233-51.
Continue with Facebook
