The postnatal development and plasticity of central pain circuits

Many infants undergo multiple painful procedures as a result of neonatal intensive care or surgery. Pain pathways in young infants appear to be extra sensitive because they lack pain control systems, where the brain dampens pain signals as they enter the spinal cord. We aim to understand more about the way these controls develop in babies and how the connections in the brain that signal and control pain are affected by their time in hospital intensive care.

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 have shown that these pain control systems do not mature until well after birth and before that time appear to operate differently from the adult. Here we plan to investigate the functional developmental of these control systems and determine how they influence the maturation of somatosensory and pain. We will test how neonatal tissue damage leads to life long alterations in these control systems and hence the ability of the CNS to modulate nociceptive circuits. We will 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 will form an important translational link between our laboratory and clinical research.