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Cysteine-Rich Protein 2, a Novel Downstream Effector of cGMP/cGMP-Dependent Protein Kinase I-Mediated Persistent Inflammatory Pain
- Source :
- The Journal of Neuroscience. 28:1320-1330
- Publication Year :
- 2008
- Publisher :
- Society for Neuroscience, 2008.
-
Abstract
- The cGMP/cGMP-dependent protein kinase I (cGKI) signaling pathway plays an important role in spinal nociceptive processing. However, downstream targets of cGKI in this context have not been identified to date. Using a yeast two-hybrid screen, we isolated cysteine-rich protein 2 (CRP2) as a novel cGKI interactor in the spinal cord. CRP2 is expressed in laminas I and II of the mouse spinal cord and is colocalized with cGKI, calcitonin gene-related peptide, and isolectin B4. Moreover, the majority of CRP2 mRNA-positive dorsal root ganglion (DRG) neurons express cGKI and peripherin. CRP2 is phosphorylated in a cGMP-dependent manner, and its expression increases in the spinal cord and in DRGs after noxious stimulation of a hindpaw. To elucidate the functional role of CRP2 in nociception, we analyzed mice with a targeted deletion of CRP2. CRP2-deficient (CRP2−/−) mice demonstrate normal behavioral responses to acute nociception and after axonal injury of the sciatic nerve, but increased nociceptive behavior in models of inflammatory hyperalgesia compared with wild-type mice. Intrathecal administration of cGMP analogs increases the nociceptive behavior in wild-type but not in CRP2−/−mice, indicating that the presence of CRP2 is important for cGMP-mediated nociception. These data suggest 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.
- Subjects :
- Muscle Proteins
Pain
Mice
Dorsal root ganglion
Ganglia, Spinal
Cyclic GMP-Dependent Protein Kinases
Noxious stimulus
Animals
Medicine
Protein kinase A
Cyclic GMP
Cyclic GMP-Dependent Protein Kinase Type I
Mice, Knockout
business.industry
General Neuroscience
Nuclear Proteins
Peripheral Nervous System Diseases
Peripherin
Articles
LIM Domain Proteins
Spinal cord
Rats
Cell biology
Nociception
medicine.anatomical_structure
Spinal Cord
Anesthesia
Chronic Disease
Hyperalgesia
Sciatic nerve
Inflammation Mediators
medicine.symptom
business
Signal Transduction
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....88e200543a57ccc0eb5c29378c0938cd