Volume 7 Supplement 1

3rd International Conference on cGMP Generators, Effectors and Therapeutic Implications

Open Access

Cysteine-rich protein 2 is a downstream effector of cGMP-dependent protein kinase I in nociception

  • Achim Schmidtko1Email author,
  • Wei Gao1,
  • Matthias Sausbier2,
  • Inga Grundei1,
  • Ellen Niederberger1,
  • Klaus Scholich1,
  • Andrea Huber3, 4,
  • Hans-Dieter Allescher5,
  • Franz Hofmann3,
  • Peter Ruth2 and
  • Gerd Geisslinger1
BMC Pharmacology20077(Suppl 1):P52

DOI: 10.1186/1471-2210-7-S1-P52

Published: 25 July 2007

The experience of pain is mediated by a specialized sensory system, the nociceptive system. There is considerable evidence that the cGMP/cGMP kinase I (cGKI) signaling pathway modulates the nociceptive processing within the spinal cord. However, downstream targets of cGKI in this context have not been identified to date. In this study we investigated whether cysteine-rich protein 2 (CRP2) is a downstream effector of cGKI in the spinal cord and is involved in nociceptive processing. Immunohistochemistry of the mouse spinal cord revealed that CRP2 is expressed in superficial laminae of the dorsal horn. CRP2 is colocalized with cGKI and with markers of primary afferent C fibers. Importantly, the majority of CRP2 mRNA-positive dorsal root ganglion (DRG) neurons express cGKI and CRP2 is phosphorylated in a cGMP-dependent manner. To elucidate the functional role of CRP2 in nociception, we investigated the nociceptive behavior of CRP2-deficient (CRP2-/-) mice. Touch perception and acute thermal nociception were unaltered in CRP2-/- mice. However, CRP2-/- mice showed an increased nociceptive behavior in models of persistent pain as compared to wild type mice. Intrathecal administration of cGKI activating cGMP analogs increased the nociceptive behavior in wild type but not in CRP2-/- mice, indicating that the presence of CRP2 was essential for cGMP/cGKI-mediated nociception. These data indicate that CRP2 is a new downstream effector of cGKI-mediated spinal nociceptive processing and point to an inhibitory role of CRP2 in the generation of inflammatory pain.

Declarations

Acknowledgements

Our studies were supported by the Deutsche Forschungsgemeinschaft [SFB 553 (C6)].

Authors’ Affiliations

(1)
Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Johann Wolfgang Goethe-Universität
(2)
Pharmazeutisches Institut, Pharmakologie und Toxikologie
(3)
Institut für Pharmakologie und Toxikologie, Technische Universität
(4)
Implen GmbH
(5)
Zentrum für Innere Medizin, Klinikum Garmisch-Partenkirchen

Copyright

© Schmidtko et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.

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