Expression and action of cyclic GMP-dependent protein kinase Iα in inflammatory hyperalgesia in rat spinal cord

Y. X. Tao, A. Hassan, E. Haddad, R. A. Johns

Research output: Contribution to journalArticlepeer-review

Abstract

Several lines of evidence have shown a role for the nitric oxide/cyclic guanosine monophosphate signaling pathway in the development of spinal hyperalgesia. However, the roles of effectors for cyclic guanosine monophosphate are not fully understood in the processing of pain in the spinal cord. The present study showed that cyclic guanosine monophosphate-dependent protein kinase Iα but not Iβ was localized in the neuronal bodies and processes, and was distributed primarily in the superficial laminae of the spinal cord. Intrathecal administration of a selective inhibitor of cyclic guanosine monophosphate-dependent protein kinase Iα, Rp-8-[(4-chlorophenyl)thio]-cGMPS triethylamine, produced a significant antinociception demonstrated by the decrease in the number of flinches and shakes in the formalin test. This was accompanied by a marked reduction in formalin-induced c-fos expression in the spinal dorsal horn. Moreover, cyclic guanosine monophosphate-dependent protein kinase Iα protein expression was dramatically increased in the lumbar spinal cord 96h after injection of formalin into a hindpaw, which occurred mainly in the superficial laminae on the ipsilateral side of a formalin-injected hindpaw. This up-regulation of cyclic guanosine monophosphate-dependent protein kinase Iα expression was completely blocked not only by a neuronal nitric oxide synthase inhibitor, 7-nitroindazole, and a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, but also by an N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (MK-801).The present results indicate that noxious stimulation not only initially activates but also later up-regulates cyclic guanosine monophosphate-dependent protein kinase Iα expression in the superficial laminae via an N-methyl-D-aspartate-nitric oxide-cyclic guanosine monophosphate signaling pathway, suggesting that cyclic guanosine monophosphate-dependent protein kinase Iα may play an important role in the central mechanism of formalin-induced inflammatory hyperalgesia in the spinal cord. Copyright (C) 1999 IBRO.

Original languageEnglish (US)
Pages (from-to)525-533
Number of pages9
JournalNeuroscience
Volume95
Issue number2
DOIs
StatePublished - Dec 1 1999

Keywords

  • Hyperalgesia
  • N-methyl-D-aspartate
  • Nitric oxide synthase
  • PKG Iα
  • Soluble guanylate cyclase
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

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