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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lin, Chia-ching John Chen, Chien-ju Chen, Chih-cheng Chen, Wei-nan Lin, Yi-wen Zimmer, Andreas |
| Description | Author Affiliation: Lin CC ( Molecular Medicine Program, Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica, Section 2, Nankang, Taipei 115, Taiwan.); |
| Abstract | Release of substance P (SP) from nociceptive nerve fibers and activation of its receptor neurokinin 1 (NK1) are important effectors in the transmission of pain signals. Nonetheless, the role of SP in muscle pain remains unknown. Here we show that a single i.m. acid injection in mice lacking SP signaling by deletion of the tachykinin precursor 1 (Tac1) gene or coadministration of NK1 receptor antagonists produces long-lasting hyperalgesia rather than the transient hyperalgesia seen in control animals. The inhibitory effect of SP was found exclusively in neurons expressing acid-sensing ion channel 3, where SP enhances M-channel-like potassium currents through the NK1 receptor in a G protein-independent but tyrosine kinase-dependent manner. Furthermore, the SP signaling could alter action potential thresholds and modulate the expression of TTX-resistant sodium currents in medium-sized muscle nociceptors. Thus, i.m. SP mediates an unconventional NK1 receptor signal pathway to inhibit acid activation in muscle nociceptors, resulting in an unexpected antinociceptive effect against chronic mechanical hyperalgesia, here induced by repeated i.m. acid injection. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Analgesics Metabolism Chronic Pain Musculoskeletal Pain Receptors, Neurokinin-1 Substance P Acid Sensing Ion Channels Action Potentials Physiology Animals Chemically Induced Electrophysiology Ganglia, Spinal Gene Deletion Mice Mice, Inbred C57BL Neurokinin A Genetics Neurokinin-1 Receptor Antagonists Pain Measurement Patch-Clamp Techniques Protein Precursors Deficiency Sodium Channels Tachykinins Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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