Immunological contributions to Age-dependent variations in response to cutaneous inflammation and the programming of later life pain

This project focuses on age-dependent alterations in inflammatory responses from birth to adulthood. Neonatal responses to pain are immature and significantly different to those seen in adults. Early life represents a period of intense activity-dependent remodelling of the nervous system. This has a particularly acute effect with regards to pain processing. Neonatal responses to pain are exaggerated, uncoordinated and often inappropriate. Pain thresholds are lower, yet, despite clinical reluctance to acknowledge this until recently, pain is appreciated at a conscious level. Pain in early life is capable of altering pain responses throughout the rest of an individuals life. Neonatal surgical injury or inflammation has been shown in both animal models and in clinical populations to alter pain thresholds through the life-course and result in enhanced responses to further injury in adulthood. Inflammatory pain is the most common form of pathological pain conditions and neonates are just as vulnerable to them as adults. However the response of neonates to inflammatory stimuli is different between adults and neonates. Experimental inflammogens such as carrageenan which evoke tissue swelling and painful hypersensitivity in adults provoke tissue swelling in the absence of pain in neonates but has the capability to "programme" the developing nervous system to future events.
Using a combination of in vivo, ex vivo and in vitro approaches this project will seek to characterise the differences between adults and neonates in terms of responses to inflammogens as well as identifying key molecular mechanisms that are responsible for this. We will be investigating the types of cells recruited to sites of inflammation in different ages of rats (from postnatal day 1 until adulthood), we will investigate the phenotype and transcriptome of these cells to try and identify key molecular pathways which are regulated in an age-dependent manner that may explain the differences in acute inflammatory responses as well as processes that can provoke long-term changes in neuronal behaviour.