rlying the altered nociceptive behaviors, have not been well investigated. It is unknown how global are the long term-effects produced by local inflammatory insult. Therefore, in this project: I. We will characterize the early postnatal sensitive period(s) of nociceptive circuitry to modulation by short-lasting inflammation; II. We will test the hypothesis that short-lasting early local inflammation is capable of inducing long-term alterations in morphological, biochemical and electrophysiological properties of the peripheral and spinal nociceptive circuitry serving the affected peripheral region (this specific aim will be performed in conjunction with Project 3, which focuses on the ability of early local inflammation to affect ion channels and electrophysiological properties in cells of the dorsal root ganglia); and III. Together with Projects 1 and 4, we will test the proposition that early local inflammatory insults may have a global long-term effect on nocifensive responses of the organism and that this global effect may be associated with alterations in the descending modulatory circuitry.

Lymphedema (LE) following treatment for breast cancer is the most common form of secondary LE in the industrialized world. It occurs in 20% to 87% of patients following treatment for breast cancer and results in significant disability. At the present time, the definitive phenotypic, genotypic and epigenotypic predictors that place patients at highest risk for the development of LE are not known. Therefore, the specific aims of this study, in a sample of patients following treatment for breast cancer, are to: determine genetic predictors of LE using a candidate gene approach and evaluate for epigenetic changes, as measured by DNA methylation and subsequent gene expression, in candidate genes associated with the diagnosis of LE. The secondary aims of this study are to: evaluate for latent classes of women with distinct phenotypic predictors of LE; and evaluate for differences in symptoms, functional status, and QOL outcome