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Synaptic circuitry of the spinal dorsal horn: unmasking the cellular basis of chronic pain


   School of Psychology and Neuroscience

  Dr D Hughes, Prof A Todd  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Project Outline:

Chronic (persistent) pain affects approximately 20% of the global population, however, one in three of these patients do not respond to any form of treatments that are currently available. Our failure to offer effective pain relief for a significant proportion of the population not only presents serious welfare problems, but also serves to highlight how little is known about the anatomical, physiological and pharmacological basis of sensory systems in health and disease. Chronic pain can arise from the skin, from joints or from internal organs and in these projects, we will aim to identify circuits in the spinal cord that contribute to the development and maintenance of these conditions. These projects will use a variety of molecular, cellular and systems level techniques to study somatosensory circuits in rodent models and determine how these change in pathological states.

Summary aim: 

To identify spinal circuits implicated in the development of chronic pain from the skin, from joints and from internal organs.

Techniques to be used: 

A variety of molecular, cellular and systems level techniques will be used, including

  • recovery surgical techniques
  • optogenetics, chemogenetics and targeted silencing
  • behavioural testing
  • general histological techniques and immunocytochemistry
  • confocal microscopy
  • transmission electron microscopy
  • image analysis using dedicated software (eg Neurolucida for confocal, Neurolucida Explorer, Meta Morph and Image J)

Apply Now


References

Hughes DI and Todd AJ. (2020). Inhibitory interneurons in the spinal dorsal horn. Special issue on Pain: Aligning New Approaches to Accelerate the Development of Analgesic Therapies. Neurotherapeutics 17: 874-885. (doi: 10.1007/s13311-020-00936-0)
Boyle KA, et al., (2019). Defining a spinal microcircuit that gates myelinated afferent input: implications for tactile allodynia. Cell Reports 28:526-540.e6. (doi: 10.1016/j.celrep.2019.06.040)
Abraira VE, et al., (2017). The cellular and synaptic architecture of the mechanosensory dorsal horn. Cell 168: 295-310.e19. (doi: 10.1016/j.cell.2016.12.010)
Smith KM, et al., (2015). Functional heterogeneity of calretinin-expressing neurons in the mouse superficial dorsal horn: implications for spinal pain processing. Journal of Physiology 593: 4319-4339. (doi: 10.1113/JP270855)
Hughes DI et al., (2012). Morphological, neurochemical and electrophysiological features of parvalbumin-expressing cells: a likely source of axo-axonic inputs in the mouse spinal dorsal horn. Journal of Physiology 590: 3927-3951. (doi: 10.1113/jphysiol.2012.235655)
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