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Activation of cortical somatostatin interneurons prevents the development of neuropathic pain
Neuropathic pain involves long-lasting modifications of pain pathways that result in abnormal cortical activity. How cortical circuits are altered and contribute to the intense sensation associated with allodynia is unclear. Here we report a persistent elevation of layer V pyramidal neuron activity...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559271/ https://www.ncbi.nlm.nih.gov/pubmed/28671692 http://dx.doi.org/10.1038/nn.4595 |
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author | Cichon, Joseph Blanck, Thomas JJ Gan, Wen-Biao Yang, Guang |
author_facet | Cichon, Joseph Blanck, Thomas JJ Gan, Wen-Biao Yang, Guang |
author_sort | Cichon, Joseph |
collection | PubMed |
description | Neuropathic pain involves long-lasting modifications of pain pathways that result in abnormal cortical activity. How cortical circuits are altered and contribute to the intense sensation associated with allodynia is unclear. Here we report a persistent elevation of layer V pyramidal neuron activity in the somatosensory cortex of a mouse model of neuropathic pain. This enhanced pyramidal neuron activity was caused in part by increases of synaptic activity and NMDA-receptor-dependent calcium spikes in apical tuft dendrites. Furthermore, local inhibitory interneuron networks shifted their activity in favor of pyramidal neuron hyperactivity: somatostatin-expressing and parvalbumin-expressing inhibitory neurons reduced their activity, whereas vasoactive intestinal polypeptide–expressing interneurons increased their activity. Pharmacogenetic activation of somatostatin-expressing cells reduced pyramidal neuron hyperactivity and reversed mechanical allodynia. These findings reveal cortical circuit changes that arise during the development of neuropathic pain and identify the activation of specific cortical interneurons as therapeutic targets for chronic pain treatment. |
format | Online Article Text |
id | pubmed-5559271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-55592712017-12-26 Activation of cortical somatostatin interneurons prevents the development of neuropathic pain Cichon, Joseph Blanck, Thomas JJ Gan, Wen-Biao Yang, Guang Nat Neurosci Article Neuropathic pain involves long-lasting modifications of pain pathways that result in abnormal cortical activity. How cortical circuits are altered and contribute to the intense sensation associated with allodynia is unclear. Here we report a persistent elevation of layer V pyramidal neuron activity in the somatosensory cortex of a mouse model of neuropathic pain. This enhanced pyramidal neuron activity was caused in part by increases of synaptic activity and NMDA-receptor-dependent calcium spikes in apical tuft dendrites. Furthermore, local inhibitory interneuron networks shifted their activity in favor of pyramidal neuron hyperactivity: somatostatin-expressing and parvalbumin-expressing inhibitory neurons reduced their activity, whereas vasoactive intestinal polypeptide–expressing interneurons increased their activity. Pharmacogenetic activation of somatostatin-expressing cells reduced pyramidal neuron hyperactivity and reversed mechanical allodynia. These findings reveal cortical circuit changes that arise during the development of neuropathic pain and identify the activation of specific cortical interneurons as therapeutic targets for chronic pain treatment. 2017-06-26 2017-08 /pmc/articles/PMC5559271/ /pubmed/28671692 http://dx.doi.org/10.1038/nn.4595 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Cichon, Joseph Blanck, Thomas JJ Gan, Wen-Biao Yang, Guang Activation of cortical somatostatin interneurons prevents the development of neuropathic pain |
title | Activation of cortical somatostatin interneurons prevents the development of neuropathic pain |
title_full | Activation of cortical somatostatin interneurons prevents the development of neuropathic pain |
title_fullStr | Activation of cortical somatostatin interneurons prevents the development of neuropathic pain |
title_full_unstemmed | Activation of cortical somatostatin interneurons prevents the development of neuropathic pain |
title_short | Activation of cortical somatostatin interneurons prevents the development of neuropathic pain |
title_sort | activation of cortical somatostatin interneurons prevents the development of neuropathic pain |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559271/ https://www.ncbi.nlm.nih.gov/pubmed/28671692 http://dx.doi.org/10.1038/nn.4595 |
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