Aberrant microRNA expression in patients with painful peripheral neuropathies

Changes in the neuro-immune balance play a major role in the induction and maintenance of neuropathic pain. We recently reported pathophysiologically relevant alterations in skin and sural nerve cytokine expression in peripheral neuropathies of different etiologies. Immune processes and cytokine expression are under tight control of microRNAs (miRNAs). To identify potential master switches in the neuro-immune balance, we aimed at characterizing inflammation-regulating miRNA profiles in patients with peripheral neuropathies. In an unselected patient cohort with polyneuropathies of different etiologies seen at our neuromuscular center between 2014 and 2015, we determined the systemic and local relative expression of miR-21-5p, miR-146a, and miR-155. In white blood cells we found higher miR-21 (p<0.001) and miR-146a (p<0.001) expression and lower miR-155 (p<0.001) expression when compared to healthy controls. In sural nerve, miR-21 (p<0.02) was increased in painful compared to painless neuropathies. In painful neuropathies, skin biopsies from the lower leg had reduced miR-146a (p<0.001) and miR-155 (p<0.001) expression compared to the thigh. Thus, peripheral neuropathies are associated with aberrant miRNA expression in white blood cells, sural nerve, and skin. These miRNA patterns may help to identify factors that determine the painfulness of peripheral neuropathies and lead to druggable targets.