PloS one, 2011-04, Vol.6 (4), p.e19270-e19270
2011
Details
- Autor(en) / Beteiligte
- Titel
- Nerve injury evoked loss of latexin expression in spinal cord neurons contributes to the development of neuropathic pain
- Ist Teil von
- PloS one, 2011-04, Vol.6 (4), p.e19270-e19270
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Nerve injury leads to sensitization mechanisms in the peripheral and central nervous system which involve transcriptional and post-transcriptional modifications in sensory nerves. To assess protein regulations in the spinal cord after injury of the sciatic nerve in the Spared Nerve Injury model (SNI) we performed a proteomic analysis using 2D-difference gel electrophoresis (DIGE) technology. Among approximately 2300 protein spots separated on each gel we detected 55 significantly regulated proteins after SNI whereof 41 were successfully identified by MALDI-TOF MS. Out of the proteins which were regulated in the DIGE analyses after SNI we focused on the carboxypeptidase A inhibitor latexin because protease dysfunctions contribute to the development of neuropathic pain. Latexin protein expression was reduced after SNI which could be confirmed by Western Blot analysis, quantitative RT-PCR and in-situ hybridisation. The decrease of latexin was associated with an increase of the activity of carboxypeptidase A indicating that the balance between latexin and carboxypeptidase A was impaired in the spinal cord after peripheral nerve injury due to a loss of latexin expression in spinal cord neurons. This may contribute to the development of cold allodynia because normalization of neuronal latexin expression in the spinal cord by AAV-mediated latexin transduction or administration of a small molecule carboxypeptidase A inhibitor significantly reduced acetone-evoked nociceptive behavior after SNI. Our results show the usefulness of proteomics as a screening tool to identify novel mechanisms of nerve injury evoked hypernociception and suggest that carboxypeptidase A inhibition might be useful to reduce cold allodynia.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0019270Titel-ID: cdi_plos_journals_1296874757
- Format
- –
- Schlagworte
- Acetone, Adenoviridae - genetics, Animals, Antigens - genetics, Antigens - metabolism, Biology, Blotting, Western, Carboxypeptidase A, Carboxypeptidases A - antagonists & inhibitors, Carboxypeptidases A - genetics, Carboxypeptidases A - metabolism, Care and treatment, Central nervous system, Cold spinning, Cold Temperature, Electrophoresis, Gel, Two-Dimensional, Gel electrophoresis, Hyperalgesia - metabolism, Hyperalgesia - physiopathology, Hypotheses, In Situ Hybridization, Inhibitors, Injuries, Injury analysis, Male, Medicine, Mice, Mice, Inbred C57BL, Narcotics, Nerves, Neuralgia - metabolism, Neuralgia - physiopathology, Neurons, Neurons - metabolism, Neuropathy, Neurosciences, Pain, Pain management, Pain perception, Peptides, Peripheral nerves, Peripheral neuropathy, Polymerase chain reaction, Post-transcription, Proteases, Proteins, Proteomics, Proteomics - methods, Rats, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Rodents, Sciatic nerve, Sciatic Nerve - injuries, Sciatic Nerve - physiopathology, Sciatic Neuropathy - physiopathology, Sensory neurons, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Spinal cord, Spinal Cord - cytology, Spinal Cord - metabolism, Spinal cord injuries, Spinal cord injury, Spots, Succinates - pharmacology, Sural Nerve - physiopathology, Surgery, Transcription, Two dimensional analysis, Two dimensional models