Both sensory and sympathetic neurons have a direct efferent role in regulating the inflammatory and immune response. The major thrust of the present proposal is to explore the neurochemical interactions between sensory neurons, sympathetic neurons and their common target tissue change the expression of their neurotransmitters and receptors in an inflammatory state. To explore these interactions we will use the carrageenan induced inflammation of the guinea pig distal colon as our model. We have chosen this model because it is a well established model of inflammation, we can quantify the level of inflammation, there is a substantial sensory and sympathetic innervation of the colon, and because the colon has proven to be an excellent tissue to monitor alterations in the expression of neurotransmitters and receptors in an inflammatory state. The neurotransmitters and receptors we will use to define this interaction will be calcitonin gene related peptide alpha & beta, substance K and substance P which are synthesized in dorsal root ganglion neurons and noradrenaline and neuropeptide Y which are synthesized by post-ganglionic sympathetic neurons. The techniques we will use include immunohistochemistry, in situ hybridization, northern blot analysis, quantitative receptor autoradiography and homogenate receptor binding. These studies should provide a new understanding of how the sensory and sympathetic neurons regulate their target tissues and each other in a model of inflammation. In addition these studies should provide an insight as to how pathophysiological neurotransmitter interactions between the DRG and sympathetic neurons may give rise to the chronic pain state of reflex sympathetic dystrophy.
Showing the most recent 10 out of 96 publications
