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Activation of cGMP-PKG signaling pathway contributes to neuronal hyperexcitability and hyperalgesia after in vivo prolonged compression or in vitro acute dissociation of dorsal root ganglion in rats.
MedLine Citation:
PMID:  23090497     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Injury or inflammation affecting sensory neurons in the dorsal root ganglia (DRG) causes hyperexcitability of DRG neurons that can lead to spinal central sensitization and neuropathic pain. Recent studies have indicated that, following chronic compression of DRG (CCD) or acute dissociation of DRG (ADD) treatment, both hyperexcitability of neurons in intact DRG and behaviorally expressed hyperalgesia are maintained by activity in cGMP-PKG signaling pathway. Here, we provide evidence supporting the idea that CCD or ADD treatment activates cGMP-PKA signaling pathway in the DRG neurons. The results showed that CCD or ADD results in increase of levels of cGMP concentration and expression of PKG-I mRNA, as well as PKG-I protein in DRG. CCD or ADD treated-DRG neurons become hyperexcitable and exhibit increased responsiveness to the activators of cGMP-PKG pathway, 8-Br-cGMP and Sp-cGMP. Hyperexcitability of the injured neurons is inhibited by cGMP-PKG pathway inhibitors, ODQ and Rp-8-pCPT-cGMPS. In vivo delivery of Rp-8-pCPT-cGMPS into the compressed ganglion within the intervertebral foramen suppresses CCD-induced thermal hyperalgesia. These findings indicate that the in vivo CCD or in vitro ADD treatment can activate the cGMP-PKG signaling pathway, and that continuing activation of cGMP-PKG pathway is required to maintain DRG neuronal hyperexcitability and/or hyperalgesia after these two dissimilar forms of injury-related stress.
Authors:
Zhi-Jiang Huang; Hao-Chuan Li; Su Liu; Xue-Jun Song
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Sheng li xue bao : [Acta physiologica Sinica]     Volume:  64     ISSN:  0371-0874     ISO Abbreviation:  Sheng Li Xue Bao     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  20730130R     Medline TA:  Sheng Li Xue Bao     Country:  China    
Other Details:
Languages:  eng     Pagination:  563-76     Citation Subset:  IM    
Affiliation:
Department of Neurobiology, Parker Research Institute, Parker University, 2540 Walnut Hill Lane, Dallas, Texas 75229, USA. E-mail: song@parker.edu.
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