Effects of the co-administration of various indicated inhibitors on chronic morphine-induced CGRP up-regulation in the spinal cord dorsal horn. A) Western blot analysis revealed an increase in CGRP level following a daily intrathecal delivery of morphine (M, 15 μg/day) for 7 days, an effect prevented by a co-treatment with a MEK inhibitor, PD98059 (PD, 10 μg); a p38 inhibitor, SB203580 (SB, 10 μg); or a CaMKII inhibitor, KN93 (KN, 15 nmol). Data are expressed as mean ± SEM of 4 animals. *p < 0.01 vs saline (NS) group. #p < 0.05 vs morphine group. ##p < 0.01 vs morphine group. B and C) The immunohistochemical analysis showed that a 7-day treatment with morphine (15 μg/day) increased CGRP levels (Bc, d and Cc, d) when compared with the saline group (Ba, b and Ca, b), an effect inhibited by the co-administrationof PD (10 μg, Be, f), SB (10 μg, Bg, h) or KN (15 nmol, Ce, f). Scale bar, 200 μm (Ba-h, Ca-f).