Abstract | STUDY DESIGN: A prospective, randomized experimental research. OBJECTIVE: SUMMARY OF BACKGROUND DATA: METHODS: The rat model of bone cancer pain was produced by intramedullary injection of rat breast cancer cells (Walker 256) into right tibia. Thermal hyperalgesia and mechanical allodynia were measured before and after administration of inhibitor of cGMP-cGKs pathway (Rp-8-pCPT-cGMPS). Immunofluorescence and reverse transcription-polymerase chain reaction were used to reflect expression of cGKI in DRG neurons, whereas the concentration of cGMP in DRG was tested using enzyme-linked immunosorbent assay method. Whole-cell patch clamp was used to record the hyperexcitability of small neurons in DRG with or without cGKs inhibitor after tumor cell implantation (TCI). RESULTS: TCI treatment significantly increased the concentration of cGMP in DRG and activity of cGKs in DRG and the spinal cord. TCI treatment also induced upregulation of cGKI messenger ribonucleic acid and protein in DRG, as well as enhanced hyperexcitability in DRG neurons. Spinal administration of Rp-8-pCPT-cGMPS, cGMP-cGKs inhibitor, significantly suppressed TCI-induced activation of cGMP-cGKI signaling, and hyperexcitability of DRG neurons. Meanwhile, in vivo intrathecal delivery of the Rp-8-pCPT-cGMPS significantly prevented and suppressed TCI-induced hyperalgesia and allodynia. CONCLUSION: From these results, we confirm that TCI treatment activates cGMP-cGKI signaling pathway and continuing activation of this pathway in DRG is required for hyperalgesia and/or hyperalgesia and allodynia after TCI treatment. LEVEL OF EVIDENCE: N/A.
|
Authors | Su Liu, Mao-yin Zhang, Li-ping Chen, Yue-peng Liu, Gong-jian Liu |
Journal | Spine
(Spine (Phila Pa 1976))
Vol. 39
Issue 19
Pg. 1533-41
(Sep 01 2014)
ISSN: 1528-1159 [Electronic] United States |
PMID | 24921837
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate
- Neoplasm Proteins
- Protein Kinase Inhibitors
- RNA, Messenger
- RNA, Neoplasm
- Thionucleotides
- Cyclic GMP-Dependent Protein Kinase Type I
- Cyclic GMP
|
Topics |
- Animals
- Bone Neoplasms
(physiopathology, secondary)
- Carcinoma 256, Walker
(physiopathology, secondary)
- Cyclic GMP
(analogs & derivatives, pharmacology, physiology)
- Cyclic GMP-Dependent Protein Kinase Type I
(antagonists & inhibitors, biosynthesis, genetics, physiology)
- Enzyme Induction
- Female
- Ganglia, Spinal
(physiopathology)
- Hot Temperature
- Hyperalgesia
(etiology, physiopathology)
- Neoplasm Proteins
(antagonists & inhibitors, biosynthesis, genetics, physiology)
- Pain Threshold
- Patch-Clamp Techniques
- Protein Kinase Inhibitors
(pharmacology)
- RNA, Messenger
(biosynthesis, genetics)
- RNA, Neoplasm
(biosynthesis, genetics)
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Sensory Receptor Cells
(physiology)
- Thionucleotides
(pharmacology)
- Tibia
(innervation)
- Touch
|