Fig. 1.
Capsaicin treatment induces axonal degeneration in vivo. a Male ICR mice received daily hindpaw intradermal injections of capsaicin (CAP) or vehicle (control) solutions. Unmyelinated axons in the medial plantar nerves (red dashed box) and their nerve terminals in the dermis and epidermis (blue dashed box) were examined with protein gene product 9.5 (PGP9.5) immunohistochemistry and electron microscopy. DRG dorsal root ganglia. b Axonal pathologies in epidermal nerves after daily capsaicin injections. b 1 Epidermal nerve terminals were evenly distributed in controls (b 1 inset, arrowheads). Following 2 (b 2) and 3 (b 3) daily capsaicin injections, swelling of epidermal axons was significantly increased (b 4). Epidermal nerve density (b 5) was significantly reduced (b 6) after 7 daily capsaicin (CAP D7) injections (**P < 0.01 by Kruskal–Wallis test and Dunn’s multiple comparison test). D day. c Electron microscopic images demonstrate unmyelinated axonal degeneration in medial plantar nerves after 7 daily capsaicin injections. Compared to control nerves, which displayed normal axoplasm (c 1), unmyelinated axons treated with capsaicin displayed characteristics of degeneration including swollen mitochondria with reduced cristae (c 2, inset) and pale axoplasm (c 2, arrowhead). Degenerating axons were increased (c 3) and axonal density was decreased (c 4) in capsaicin-injected nerves (*P < 0.05, **P < 0.01 by Mann–Whitney test and unpaired t test). The numbers of subjects are shown in the bar graphs. Scale Bars b 1–b 3, b 5: 25 μm; b 1 –b 3, b 5 insets 10 μm; c 1 , c 2 500 nm; c 1 , c 2 insets 100 nm