Inhibition of the development of tolerance to morphine-induced analgesia by the co-administration of various inhibitors. Paw-withdrawal latency was tested 30 min after morphine injection on days 1 and 7 following a daily intrathecal delivery of saline (10 μl), morphine (M, 15 μg/10 μl) alone or in combination with KN93 (KN, 15 nmol/10 μl), a CaMKII inhibitor, PD98059 (PD, 10 μg/10 μl), an MEK (ERK upstream kinase) inhibitor or SB203580 (SB, 10 μg/10 μl), a p38 inhibitor for 7 days. KN, PD and SB were administered 30 min before morphine injection. Data are expressed as mean ± SEM of 7-8 animals. *p < 0.01 vs saline group on day 1. #p < 0.01 vs morphine group on day1. $p < 0.01 vs morphine group on day 7.