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Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I.

Authors: Tegeder, I  Del Turco, D  Schmidtko, A  Sausbier, M  Feil, R  Hofmann, F  Deller, T  Ruth, P  Geisslinger, G 
Citation: Tegeder I, etal., Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3253-7. Epub 2004 Feb 18.
Pubmed: (View Article at PubMed) PMID:14973199
DOI: Full-text: DOI:10.1073/pnas.0304076101

cGMP-dependent protein kinase I (PKG-I) has been suggested to contribute to the facilitation of nociceptive transmission in the spinal cord presumably by acting as a downstream target of nitric oxide. However, PKG-I activators caused conflicting effects on nociceptive behavior. In the present study we used PKG-I(-/-) mice to further assess the role of PKG-I in nociception. PKG-I deficiency was associated with reduced nociceptive behavior in the formalin assay and zymosan-induced paw inflammation. However, acute thermal nociception in the hot-plate test was unaltered. After spinal delivery of the PKG inhibitor, Rp-8-Br-cGMPS, nociceptive behavior of PKG-I(+/+) mice was indistinguishable from that of PKG-I(-/-) mice. On the other hand, the PKG activator, 8-Br-cGMP (250 nmol intrathecally) caused mechanical allodynia only in PKG-I(+/+) mice, indicating that the presence of PKG-I was essential for this effect. Immunofluorescence studies of the spinal cord revealed additional morphological differences. In the dorsal horn of 3- to 4-week-old PKG-I(-/-) mice laminae I-III were smaller and contained fewer neurons than controls. Furthermore, the density of substance P-positive neurons and fibers was significantly reduced. The paucity of substance P in laminae I-III may contribute to the reduction of nociception in PKG-I(-/-) mice and suggests a role of PKG-I in substance P synthesis.

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RGD Object Information
RGD ID: 7775058
Created: 2013-12-31
Species: All species
Last Modified: 2013-12-31
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.