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

General

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.
RGD ID:	7775058
Pubmed:	PMID:14973199 (View Abstract at PubMed)
PMCID:	PMC365776 (View Article at PubMed Central)
DOI:	DOI:10.1073/pnas.0304076101 (Journal Full-text)
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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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Hyperalgesia	treatment	ISO	Prkg1 (Mus musculus)	7775058; 7775058		RGD
Hyperalgesia	treatment	IMP		7775058		RGD

Objects Annotated

Genes (Rattus norvegicus)

Prkg1 (protein kinase cGMP-dependent 1)

Genes (Mus musculus)

Prkg1 (protein kinase, cGMP-dependent, type I)

Genes (Homo sapiens)

PRKG1 (protein kinase cGMP-dependent 1)

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