Based entirely on rodent studies, there is growing acceptance that dorsal spinal cord glia (microglia & astrocytes) contribute to the creation & maintenance of enhanced pain, including pathological pain. Glial activation occurs in every rodent model of enhanced pain examined to date, & disruption of glial activation or glial proinflammatory cytokines blocks rodent enhanced pain responses. It has been proposed, based on such studies, that disruption of glial function should ameliorate human chronic pain. Whether it is valid to extrapolate these rodent glia data to humans has never been tested. It is critical to know whether there are, or are not, parallels between rodent & human dorsal spinal cord glial responses. This is not simply of theoretical importance, but of impending practical importance as well, as there is growing interest in the pharmaceutical/biotech sector in clinical approaches that target gila. Whether or not this is an approach to be encouraged depends on whether human glial responses mirror those of rodents. The purpose of the present small grant proposal is to provide an initial investigation of whether rodent data concerning glia involvement in pain reflect the human condition. Examining spinal cord glial activation & glial products in humans requires postmortem donor tissues. While this presents some constraints, these can be minimized by restricting analyses to tissues collected <4 hr of death. Sun Health Research Institute (SHRI) will provide chronic pain & control donor tissues for this project. Selected donors will provide brain, spinal cord, CSF, & plasma for protein, mRNA & immunohistochemical analyses of glial activation & glial products. SHRI will also assess the feasibility of using their donor population for a future prospective study of glial activation in chronic pain. The results from these studies will provide the first insights into whether glia are, or are not, activated in human chronic pain states. Either answer has major implications for the development of drug therapies for the control of clinical pain. ? ?
