Activation of cGMP-dependent protein kinase I alpha is required for N-methyl-D-aspartate- or nitric oxide-produced spinal thermal hyperalgesia

The effect of a selective cyclic guanocine 3',5'-monophosphate (cGMP)-depen dent protein kinase I alpha inhibitor, Rp-8-[(4-chlorophenyl)thio]-cGMPS tr iethylamine (Rp-8-p-CPT-CGMPS), on either N-methyl-D-aspartate (NMDA)- or N -ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)ethanamine (NOC-12, a nitric oxide (NO) donor)-produced thermal hyperalgesia was examined in the rat. I ntrathecal administration of NMDA (15 pg/10 mu l) or NOC-12 (10, 20 and 30 mu g/10 yl) produced a marked curtailment of the tail-flick latency. Maxima l NMDA- or NOC-12-produced facilitation of the tail-flick reflex was signif icantly and dose-dependently blocked by intrathecal pretreatment with Rp-8- p-CPT-CGMPS (7.5, 15 and 30 mu g/10 mu l). Rp-8-p-CPT-CGMPS given alone did not markedly alter baseline tail-flick latency. These results suggest that the activation of cGMP-dependent protein kinase lot is required for NMDA- or NO-produced facilitation of thermal hyperalgesia at the spinal cord leve l. (C) 2000 Elsevier Science B.V. All rights reserved.