3 research outputs found
Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain
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