Selective PKA inhibitors attenuate sustained morphine-mediated
sensitization 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 487 ± 48% basal (n = 5). Mor + Cap, sustained
morphine (1 μM) treatment augmented capsaicin-evoked CGRP release to 946
± 71% basal, which is a 94% increase relative to Cap alone (***,
p < 0.001 relative to Cap, one-way ANOVA; n = 5). Mor +
PKI + Cap, pretreatment (1 h) of the cells with 50 nM PKI followed by 24-h
coincubation with morphine (1 μM) attenuated the effect of sustained
morphine treatment on capsaicin (1 μM; 10 min)-evoked CGRP release by 67%
relative to Mor + Cap group (**, p < 0.01 relative to Mor + Cap,
one-way ANOVA; n = 5). PKI + Cap, treatment of the DRG neurons with
50 nM PKI followed by stimulation with 1 μM capsaicin had no effect on
capsaicin-evoked CGRP release [542 ± 61% basal, p > 0.05
relative to Cap (487 ± 48% basal), one-way ANOVA; n = 5]. Mor
+ H-89 + Cap, pretreatment (1 h) of the cells with H-89 (1 μM), followed by
24-h coincubation with the inhibitor in the presence of morphine (1 μM)
attenuated sustained morphine-mediated augmentation of capsaicin (1 μM; 10
min)-evoked CGRP release by 57% relative to Mor + Cap group (**, p
< 0.01, one-way ANOVA; n = 5). H-89 + Cap, treatment of the DRG
neurons with 1 μM H-89 alone caused no difference in basal CGRP release
relative to capsaicin alone [478 ± 53% basal, p > 0.05
relative to Cap (487 ± 48% 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.