Deletion of the neuropeptide Y Y1 receptor affects pain sensitivity, neuropeptide transport and expression, and dorsal root ganglion neuron numbers

Détails

ID Serval
serval:BIB_4F5B654976A0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Deletion of the neuropeptide Y Y1 receptor affects pain sensitivity, neuropeptide transport and expression, and dorsal root ganglion neuron numbers
Périodique
Neuroscience
Auteur(s)
Shi  T. J., Li  J., Dahlstrom  A., Theodorsson  E., Ceccatelli  S., Decosterd  I., Pedrazzini  T., Hokfelt  T.
ISSN
0306-4522 (Print)
Statut éditorial
Publié
Date de publication
06/2006
Volume
140
Numéro
1
Pages
293-304
Notes
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Jun 19
Résumé
Neuropeptide Y has been implicated in pain modulation and is substantially up-regulated in dorsal root ganglia after peripheral nerve injury. To identify the role of neuropeptide Y after axotomy, we investigated the behavioral and neurochemical phenotype of neuropeptide Y Y1 receptor knockout mice with focus on dorsal root ganglion neurons and spinal cord. Using a specific antibody Y1 receptor immunoreactivity was found in dorsal root ganglia and in dorsal horn neurons of wild-type, but not knockout mice. The Y1 receptor knockout mice exhibited a pronounced mechanical hypersensitivity. After sciatic nerve axotomy, the deletion of Y1 receptor protected knockout mice from the axotomy-induced loss of dorsal root ganglion neurons seen in wild-type mice. Lower levels of calcitonin gene-related peptide and substance P were identified by immunohistochemistry in dorsal root ganglia and dorsal horn of knockout mice, and the axotomy-induced down-regulation of both calcitonin gene-related peptide and substance P was accentuated in Y1 receptor knockout. However, the transcript levels for calcitonin gene-related peptide and substance P were significantly higher in knockout than in wild-type dorsal root ganglia ipsilateral to the axotomy, while more calcitonin gene-related peptide- and substance P-like immunoreactivity accumulated proximal and distal to a crush of the sciatic nerve. These results indicate that the deletion of the Y1 receptor causes increased release and compensatory increased synthesis of calcitonin gene-related peptide and substance P in dorsal root ganglion neurons. Together, these findings suggest that, after peripheral nerve injury, neuropeptide Y, via its Y1 receptor receptor, plays a key role in cell survival as well as in transport and synthesis of the excitatory dorsal horn messengers calcitonin gene-related peptide and substance P and thus may contribute to pain hypersensitivity.
Mots-clé
Animals Axotomy/methods Behavior, Animal Biological Transport/genetics Calcitonin Gene-Related Peptide/genetics/metabolism Cell Count/methods Functional Laterality Ganglia, Spinal/*cytology Gene Expression/*genetics Immunohistochemistry/methods In Situ Hybridization/methods Male Mice Mice, Inbred C57BL Mice, Knockout Neurons/drug effects/*metabolism Neuropeptides/*metabolism Pain Measurement/methods Pain Threshold/drug effects/*physiology Posterior Horn Cells/metabolism Receptors, Neuropeptide Y/*deficiency Substance P/genetics/metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 8:45
Dernière modification de la notice
20/08/2019 14:05
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