Figure 1.

Inhibition of TrkB signaling by 1NM-PP1 in TrkB^F616A mice prevents capsaicin-induced mechanical hyperalgesia and inhibits TrkB phosphorylation. A, Changes in mechanical threshold were measured 15, 30, and 60 min after injection of capsaicin (3.0 μg/10 μl, s.c.) into the left ankle. Capsaicin produced a rapid drop of mechanical threshold in wild-type mice (n = 5) but not in TrkB^F616A mice (n = 5) that drank water containing 1NM-PP1 (final concentration, 5.0 μm); ***p < 0.001. B, Paw-withdrawal latency to noxious heat did not differ between WT and TrkB^F616A mice. C, D, Western blots of lumbar spinal cords from four WT and four TrkB^F616A mice show that Trk phosphorylation after capsaicin treatment in the absence of 1NM-PP1 (C) in the drinking water did not differ. Total TrkB loaded for WT and mutant mice is equivalent. In contrast, in the presence of 1NM-PP1 (D), there is a significant decrease of Trk phosphorylation in the TrkB^F616A mice (for quantification, see Results).