Neural Plasticity and Inflammatory Pain
We are exploring both the signals that activate and regulate the excitability of neurons in response to infection and inflammation and the nature and direction of the reciprocal interactions of the nervous and immune systems. We propose that pathogens can directly activate neurons and that inflammatory mediators through generating posttranslational changes on ion channels, can sensitize neurons. Among the specific questions we are asking are: which immune mediators produced by immune cells during inflammation are responsible for altering ion channel function. We are also defining the sequential recruitment and activation of different immune cells in pathogen- and sterile tissue injury- based models of inflammation and their temporal association with the inflammatory pain phenotype, testing the effect of immune cell depletion on peripheral inflammatory pain, as well as measuring immune-derived factors produced during peripheral inflammation that can act on cognate receptors expressed by nociceptor neurons to alter their function.
We also will explore what the effect is on immune mediated reactions of ablating specific neurons or pharmacologically silencing them.
Increasingly our data point to a major functional integration of the two systems, both are designed to detect danger, process information, store information as memories and initiate defensive/protective effector functions.