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KMID : 0614520020120010067
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Journal of the Korean Pain Research Society
2002 Volume.12 No. 1 p.67 ~ p.75
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Inhibitory Action of Guanosine 3’,5’-cyclie Monophosphate (cGMP) on the Responses of Rat Dorsal Horn Neuron
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Kim Ji-Hun
Shin Hong-Kee
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Abstract
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Nitric oxide (NO)-cGMP signaling pathway has been reported to have dual effects on the transmission of nociceptive signals in the spinal cord: hyperalgesia and antinociception. The mechanism by which NO-cGMP pathway induces hyperalgesia is well documented, but the antinociceptive action is still unclear. In this experiment, the effect of iontophoretically applied cGMP on the dorsal horn cell responses were studied using electrophysiological technigue.
After recording the control responses of wide dynamic range (WDR) neurons to iontophoretic application of NMDA and to C fiber stimulation, effects of 8-bromo-cGMP (Br-cGMP) on the WDR cell responses were recorded. We also observed the effects of H-9 dihydrochloride, an inhibitor of cAMP- and cGMP-dependent kinase and PKG inhibitor on the modulatory actions of Br-cGMP. Br-cGMP induced 3 types of action on the WDR cell responses: excitation, inhibition and no change. In addition to the well-known excitatory action, Br-cGMP inhibited NMDA-induced responses in 53.9% of WDR cells. Effect of Br-cGMP on the responses of WDR cells to C-fiber stimulation was weaker than that on the NMDA-induced responses and more than half of WDR cell responses to C-fiber stimulation were not changed by Br-cGMP. H-9 and PKG inhibitor by themselves had excitatory action on the WDR cell responses and antagonized the excitatory and inhibitory effects of Br-cGMP. In the WDR cells on which Br-cGMP induced inhibitory action, Br-cGMP also suppressed morphine-induced excitatory action on the WDR cell responses to NMDA. This study demonstrates that cGMP is implicated in the suppression of WDR cell responses to noxious stimuli (antinociception) and morphine-induced analgesic action as well as the well-known excitatory action (pain).
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KEYWORD
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Nitric oxide, cGMP, Dorsal horn neuron, Protein kinase
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