The selective Raf-1 inhibitor GW5074 attenuates sustained morphine-mediated
augmentation of capsaicin-evoked CGRP release from neonatal rat DRG neurons.
Cap, capsaicin (1 μM) treatment (10 min) of neonatal rat DRG neurons evokes
CGRP release to 514 ± 33% basal (n = 5). Mor + Cap, sustained
morphine (1 μM) treatment augmented capsaicin-evoked CGRP release by 92%
(989 ± 62% basal, ***, p < 0.001 relative to Cap, one-way
ANOVA; n = 5). Mor + GW + Cap, pretreatment (1 h) of the cells with
GW5074 (10 μM), followed by 24-h coincubation in the presence of morphine
(1 μM), attenuated capsaicin (1 μM; 10 min)-evoked CGRP release to 691
± 47% basal, which is a 67% reduction of CGRP release to that of Mor +
Cap group (**, p < 0.01, one-way ANOVA; n = 5). GW + Cap,
treatment of the DRG neurons with GW5074 (10 μM) alone had no effect on
capsaicin-evoked CGRP release [498 ± 53% basal, p > 0.05 to
Cap (514 ± 33% basal), one-way ANOVA; n = 5]. The results
(mean ± S.E.M.) are expressed as the percentage of basal CGRP release
from unstimulated DRG neurons.