The neuroaxis of pain: Peripheral transduction to central integration

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Acute pain is an unpleasant but vital and protective somatosensory experience, common to everyday life. A number of factors are known to influence the experience of pain, which contributes to a high degree of person-to-person variability. Biologically, pain critically depends on anatomical substrates and physiological processes that: i) transduce a noxious stimulus into neural signals in the periphery, ii) conduct neural impulses in thinly myelinated and unmyelinated afferents, and iii) integrate signals at various points along the neuroaxis (i.e., spinal cord to brain). Collectively, these are termed "nociception". A hallmark of nociception is a capacity to amplify pain in the absence of increasing noxious stimulation intensity. The process of amplifying pain occurs peripherally and centrally, at the level of the nociceptors and in the dorsal horn of the spinal cord, through processes of sensitization. To date, knowledge regarding the sensitization of pain have been primary generated in animal models. Moving these investigations into humans involves detailed neurophysiological and anatomical studies, which require specialized training, equipment, and skills. The overarching, long-term objective of my research is to reveal discrete neuroanatomical substrates and neurophysiological processes involved in nociception. This will be achieved by way of exploring how noxious stimuli are transduced in the periphery, conducted in peripheral afferents, integrated in the spinal cord, and processed in the brain of healthy participants. In the next 5 years, my proposed NSERC Discovery platform will primarily focus on the theme of pain amplification. Short-term objectives will: 1.Characterize the functional role of peripheral receptors in the sensitization of pain 2. Understand the relationship between sensitization of pain and extrasynaptic glutamate receptors 3. Examine the effect of pain on resting glutamate dynamics in the brain My NSERC Discovery Grant proposal integrates a variety of quantitative methods to assess pain, coupled with pharmacological approaches to manipulate processes involved in sensitization. Key collaborations include other NSERC funded researchers at UBC, including Drs. Blouin and Laule, as well as colleagues at the University of Zurich (e.g., Drs. Schweinhardt and Hubli). HQP from undergraduates to Postdoctoral Fellows will train in a research intensive environment, supported by 3 priority UBC research centres (i.e., ICORD, DMCBH, and the UBC MRI Research Centre), in a lab that is fully equipped to conduct the proposed experiments. Furthermore, they will develop skills in experimental models of pain, magnetic resonance spectroscopy, electroencephalography, and quantitative sensory testing, and be positioned to succeed in academics and industry.