Enhanced Erk activation in the ACC after tissue and nerve injury. A. Immunohistochemical staining for phosphorylation of Erk illustrated time course-dependent activation of Erk in layer II neurons of the contralateral ACC after unilateral hindpaw injection of formalin (5%, 50 μl, n = 4-5 rats for each time point). B. The P-Erk expression in the layer II ACC neurons and their main apical dendrites (arrows) was increased at 2 weeks after the amputation of the unilateral hindpaw third digit (n = 5), compared to sham animals (n = 3). C. Mechanical stimulation by brushing hindpaw of digit amputation induced P-Erk expression in more number of layer II ACC neurons and the more distinctive apical dendrites at 2 weeks after the amputation (n = 5), compared to that in rats with amputation alone. There was not P-Erk activation in the ACC in normal animals after the brushing (n = 3). Left and middle columns: low power of the coronal ACC sections. Scale bar = 50 μm; Right column: enlarged layer II regions corresponding to the small rectangle areas in the middle column, respectively. Scale bar = 25 μm (from Reference 22).