The Journal of neuroscience, 2010-08, Vol.30 (32), p.10927-10938
2010
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Details
- Autor(en) / Beteiligte
- Titel
- Inhibition of inflammatory pain by activating B-type natriuretic peptide signal pathway in nociceptive sensory neurons
- Ist Teil von
- The Journal of neuroscience, 2010-08, Vol.30 (32), p.10927-10938
- Ort / Verlag
- United States: Society for Neuroscience
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- B-type natriuretic peptide (BNP) has been known to be secreted from cardiac myocytes and activate its receptor, natriuretic peptide receptor-A (NPR-A), to reduce ventricular fibrosis. However, the function of BNP/NPR-A pathway in the somatic sensory system has been unknown. In the present study, we report a novel function of BNP in pain modulation. Using microarray and immunoblot analyses, we found that BNP and NPR-A were expressed in the dorsal root ganglion (DRG) of rats and upregulated after intraplantar injection of complete Freund's adjuvant (CFA). Immunohistochemistry showed that BNP was expressed in calcitonin gene-related peptide (CGRP)-containing small neurons and IB4 (isolectin B4)-positive neurons, whereas NPR-A was present in CGRP-containing neurons. Application of BNP reduced the firing frequency of small DRG neurons in the presence of glutamate through opening large-conductance Ca2+-activated K+ channels (BKCa channels). Furthermore, intrathecal injection of BNP yielded inhibitory effects on formalin-induced flinching behavior and CFA-induced thermal hyperalgesia in rats. Blockade of BNP signaling by BNP antibodies or cGMP-dependent protein kinase (PKG) inhibitor KT5823 [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester] impaired the recovery from CFA-induced thermal hyperalgesia. Thus, BNP negatively regulates nociceptive transmission through presynaptic receptor NPR-A, and activation of the BNP/NPR-A/PKG/BKCa channel pathway in nociceptive afferent neurons could be a potential strategy for inflammatory pain therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0270-6474eISSN: 1529-2401DOI: 10.1523/jneurosci.0657-10.2010Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6634694
- Format
- –
- Schlagworte
- Analysis of Variance, Animals, Antibodies - pharmacology, Antibodies - therapeutic use, Biophysical Phenomena - drug effects, Biophysical Phenomena - physiology, Calcitonin Gene-Related Peptide - metabolism, Carbazoles - pharmacology, Carbazoles - therapeutic use, Disease Models, Animal, Dose-Response Relationship, Drug, Double-Blind Method, Enzyme Inhibitors - pharmacology, Enzyme Inhibitors - therapeutic use, Excitatory Postsynaptic Potentials - drug effects, Freund's Adjuvant, Ganglia, Spinal - pathology, Gene Expression Regulation - drug effects, Gene Expression Regulation - physiology, Glutamic Acid - pharmacology, Hyperalgesia - complications, Hyperalgesia - drug therapy, Inflammation - chemically induced, Inflammation - complications, Lectins - metabolism, Male, Membrane Potentials - drug effects, Membrane Potentials - physiology, Natriuretic Peptide, Brain - immunology, Natriuretic Peptide, Brain - metabolism, Pain - drug therapy, Pain - etiology, Pain - metabolism, Pain Measurement - methods, Patch-Clamp Techniques - methods, Peptides - pharmacology, Rats, Rats, Sprague-Dawley, Receptors, Atrial Natriuretic Factor - metabolism, Sensory Receptor Cells - drug effects, Sensory Receptor Cells - metabolism, Signal Transduction - drug effects, Signal Transduction - physiology, Time Factors