Fig. 5. Activated p38 mitogen-activated protein kinase (MAPK), but not extracellular signal–regulated kinase (ERK), mediates nerve growth factor (NGF)–dependent enhanced antinociceptive effects of the peripheral full opioid agonist fentanyl or partial opioid agonist buprenorphine. Paw pressure threshold (PPT) values are given as mean ± SD of the percentage of maximum possible effect (% MPE) according to the following formula: (PPTpostinjection− PPTbasal)/(250cut-off− PPTbasal). (A, B ) Fentanyl-induced, dose-dependent increases in PPT after intraplantar NGF (close d diamonds ) were shifted to the right after intrathecal p38-MAPK inhibitor SB203580 (A ), but not after intrathecal ERK-1/2 inhibitor PD98059 (B ). Buprenorphine-induced, dose-dependent increase in PPT after intraplantar NGF was abolished after intrathecal p38-MAPK inhibitor SB203580 (C ), but not after ERK-1/2 inhibitor PD98059 (D ). *P < 0.05 versus NGF plus p38-MAPK inhibitor SB203580 (two-way ANOVA, Newman-Keuls test).