4 YEAR PhD IN NEUROSCIENCE
Department of Neuroscience, Physiology & Pharmacology
The Developmental Biology of Spinal Cord and Cortical Pain Processing
The early postnatal weeks are a critical time for developing pain pathways when nociceptive circuits are shaped, endogenous pain control systems are activated and pain behaviour is organised. During this period, repeated peripheral tissue damage, such as arises in neonatal intensive care or surgery, alters the physiological balance of sensory input and can change the course of pain development. In the adult CNS, endogenous control systems gate the transmission of nociceptive information to the brain and increase or decrease pain according to the needs of the individual. We are investigating the functional developmental of these control systems and how they are permanently affected by neonatal tissue damage. We use electrophysiological analysis of nociceptive synapses and circuits in neonatal and adult spinal cord and cortex, supported by molecular, cellular and behavioural analysis to investigate the postnatal development and plasticity of (i) spinal inhibitory interneuronal circuits, (ii) descending brainstem-spinal controls and (iii) spinal neuronal-glial immune interactions (iv) early cortical pain activity. These studies form an important translational link between our laboratory and our clinical research.
Sample PhD Project:
This project will focus upon the changing temporal and spatial pattern of afferent evoked inhibitory control in spinal nociceptive circuits over the postnatal period and how this is altered by early pain experience using in vivo extracellular recording and in vitro whole cell patch recording of dorsal horn cells. Neurosteroids, a relatively new class of neuroactive compounds that have come into prominence in the past two decades, have been reported to play a role in the maturation of inhibitory signalling in the spinal cord. Absence or reduced concentrations of neurosteroids, during development have been associated with neurodevelopmental, psychiatric, and behavioural disorders. We will explore the effect of early pain and injury upon neurosteroid levels in the immature dorsal horn and how such alterations can influence the organization of inhibitory circuits.
Bremner LR, Fitzgerald M. (2008) Postnatal tuning of cutaneous inhibitory receptive fields in the rat. J Physiol. 586:1529-37.
Li J, Walker SM, Fitzgerald M, Baccei ML (2009) Activity-dependent modulation of glutamatergic signaling in the developing rat dorsal horn by early tissue injury. J Neurophysiol. 102:2208-19.
Walker SM, Tochiki KK, Fitzgerald M. (2009) Hindpaw incision in early life increases the hyperalgesic response to repeat surgical injury: Critical period and dependence on initial afferent activity. Pain. 147:99-106.