Neuropathic and Neuroplastic Features of Brain Processing of Itch

231 words 31 Article: 4,304 words. 32 33 Articles in PresS. J Neurophysiol (June 18, 2014). doi:10.1152/jn.00827.2013 Copyright © 2014 by the American Physiological Society. 2 Abstract. Pruritus of End-Stage-Renal-Disease is a multifactorial symptom of complex etiology 34 not yet fully understood. In this study we have investigated the cerebral perfusion patterns at rest 35 in ESRD patients on hemodialysis, in comparison with healthy volunteers. We have also studied 36 the brain responses evoked by experimental itch induction in ESRD, after stimulating the two 37 distinct histamine and cowhage itch pathways, and compared them with the responses evoked in 38 healthy volunteers. In order to identify potential structural alterations in ESRD patients in 39 comparison with a group of age-matched healthy volunteers, we calculated the density of gray 40 matter for the entire brain using a voxel-based morphometric analysis. Our results indicated that 41 gray matter density was significantly reduced in ESRD patients in the frontal, parietal, temporal, 42 occipital cortices, as well as in the S1, precuneus and insula, while the brainstem, hippocampus, 43 amygdala, the rostral anterior cingulate cortex and nucleus accumbens displayed an increased 44 gray matter density. Functionally, we found a significantly higher brain perfusion at baseline 45 associated with ESRD pruritus in the anterior cingulate, insula, claustrum, hippocampus and 46 nucleus accumbens. The brain responses evoked by cowhage itch, which are mediated by PAR2 47 receptors, displayed significant differences in comparison with healthy individuals and were 48 correlated with perceived itch intensity in a dual, complex manner. The inverse correlations in 49 particular suggested that a negative feedback mechanism modulated itch intensity, when elicited 50 in a pre-existent chronic itch background. 51 52 53 54