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Additional Supporting Information may be found in the online version of this article.

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AR_21237_sm_suppinfoFig1.tif4867KSupplemental Fig. 1. Colocalization of the pan-neuronal markers βIII tubulin and PGP in the glabrous skin of the rat. Skin sections from control (A, C, E) and capsaicin-treated rats (B, D, F) of 1M (A, B), 3M (C, D), and 6M (E, F) were inmunostained for neural beta III tubulin (βTub) and for PGP. In both groups of rats all the PGP+ fibers colocalized with βTub + fibers (yellow fibers). However, some βTub+ fibers were not labeled for PGP (B2a, E1;green arrows). The lack or faint staining for PGP seem to be in the distal part of the axons because all nerve fibers seem double labeled in the nerve plexus at the level of lower dermis (B3c). Even in controls rats there were intraepidermal nerve fibers that showed faint immunoreactivity for PGP (C2, yellow arrowhead). We observed in both groups that anti-βTub stained the upper strata of the epidermis. Images at the third column represent merged images of the first two images in each row. Counterstaining with DAPI is shown in blue. Scale bar = 50 μm
AR_21237_sm_suppinfoFig2.tif1080KSupplemental Fig. 2. Dopamine-β-hydroxylase immunoreactive (DBH+) fibers in the upper dermis of capsaicin-treated rats. In the skin of control rats, DBH+ fibers were easily observed around the blood vessels (A) and the sweet glands at 1M (not shown) and 3M and 6M (not shown). At 1M and 3M, DBH+ fibers were not observed near the dermal-epidermal border. In capsaicin-treated rats, DBH+ fibers were rarely observed in the upper dermis at 1M (not shown). While at 3M, treated rats exhibited numerous DBH+ fibers near the dermal-epidermal border (B, arrows). Additionally, some DBH+ fibers were observed to penetrate the epidermis (B, arrowhead). At 6M, DBH+ fibers (arrows) were observed in both the control (C) and treated rats (D). However, in treated rats the DBH+ fibers were thicker, and more numerous and more uniformly distributed than in the control rats. Intraepidermal DBH+ fibers were also present at 6M in treated rats. At 6M many of the DBH+ fibers in the control rats displayed a transverse trajectory with respect to dermal-epidermal border rather than a parallel distribution as in the treated rats. Scale bar = 100 μm.

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