Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors
<p>Abstract</p> <p>Background</p> <p>The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, howev...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2012-06-01
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| Series: | Molecular Pain |
| Subjects: | |
| Online Access: | http://www.molecularpain.com/content/8/1/42 |
| _version_ | 1811264311391158272 |
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| author | Ito Akitoshi Takeda Mineko Yoshimura Takeshi Komatsu Takayuki Ohno Takeshi Kuriyama Hiroshi Matsuda Akio Yoshimura Megumu |
| author_facet | Ito Akitoshi Takeda Mineko Yoshimura Takeshi Komatsu Takayuki Ohno Takeshi Kuriyama Hiroshi Matsuda Akio Yoshimura Megumu |
| author_sort | Ito Akitoshi |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats.</p> <p>Results</p> <p>Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI). Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX)-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG), which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of <sup>125</sup>I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions.</p> <p>Conclusions</p> <p>These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.</p> |
| first_indexed | 2024-04-12T20:02:04Z |
| format | Article |
| id | doaj.art-2ee59b5326bc457ca46b263b5218b318 |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-04-12T20:02:04Z |
| publishDate | 2012-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-2ee59b5326bc457ca46b263b5218b3182022-12-22T03:18:30ZengSAGE PublishingMolecular Pain1744-80692012-06-01814210.1186/1744-8069-8-42Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptorsIto AkitoshiTakeda MinekoYoshimura TakeshiKomatsu TakayukiOhno TakeshiKuriyama HiroshiMatsuda AkioYoshimura Megumu<p>Abstract</p> <p>Background</p> <p>The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats.</p> <p>Results</p> <p>Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI). Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX)-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG), which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of <sup>125</sup>I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions.</p> <p>Conclusions</p> <p>These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.</p>http://www.molecularpain.com/content/8/1/42ElcatoninCalcitoninPeripheral nerve excitabilityNeuropathic painCCI modelNa<sup>+</sup> channelAnalgesia |
| spellingShingle | Ito Akitoshi Takeda Mineko Yoshimura Takeshi Komatsu Takayuki Ohno Takeshi Kuriyama Hiroshi Matsuda Akio Yoshimura Megumu Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors Molecular Pain Elcatonin Calcitonin Peripheral nerve excitability Neuropathic pain CCI model Na<sup>+</sup> channel Analgesia |
| title | Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors |
| title_full | Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors |
| title_fullStr | Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors |
| title_full_unstemmed | Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors |
| title_short | Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors |
| title_sort | anti hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors |
| topic | Elcatonin Calcitonin Peripheral nerve excitability Neuropathic pain CCI model Na<sup>+</sup> channel Analgesia |
| url | http://www.molecularpain.com/content/8/1/42 |
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