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Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury

Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to n...

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Autores principales: Petitjean, Hugues, Pawlowski, Sophie Anne, Fraine, Steven Li, Sharif, Behrang, Hamad, Doulia, Fatima, Tarheen, Berg, Jim, Brown, Claire M., Jan, Lily-Yeh, Ribeiro-da-Silva, Alfredo, Braz, Joao M., Basbaum, Allan I., Sharif-Naeini, Reza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038918/
https://www.ncbi.nlm.nih.gov/pubmed/26527000
http://dx.doi.org/10.1016/j.celrep.2015.09.080
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author Petitjean, Hugues
Pawlowski, Sophie Anne
Fraine, Steven Li
Sharif, Behrang
Hamad, Doulia
Fatima, Tarheen
Berg, Jim
Brown, Claire M.
Jan, Lily-Yeh
Ribeiro-da-Silva, Alfredo
Braz, Joao M.
Basbaum, Allan I.
Sharif-Naeini, Reza
author_facet Petitjean, Hugues
Pawlowski, Sophie Anne
Fraine, Steven Li
Sharif, Behrang
Hamad, Doulia
Fatima, Tarheen
Berg, Jim
Brown, Claire M.
Jan, Lily-Yeh
Ribeiro-da-Silva, Alfredo
Braz, Joao M.
Basbaum, Allan I.
Sharif-Naeini, Reza
author_sort Petitjean, Hugues
collection PubMed
description Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV inter-neuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury.
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spelling pubmed-60389182018-07-10 Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury Petitjean, Hugues Pawlowski, Sophie Anne Fraine, Steven Li Sharif, Behrang Hamad, Doulia Fatima, Tarheen Berg, Jim Brown, Claire M. Jan, Lily-Yeh Ribeiro-da-Silva, Alfredo Braz, Joao M. Basbaum, Allan I. Sharif-Naeini, Reza Cell Rep Article Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV inter-neuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury. 2015-10-29 2015-11-10 /pmc/articles/PMC6038918/ /pubmed/26527000 http://dx.doi.org/10.1016/j.celrep.2015.09.080 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Petitjean, Hugues
Pawlowski, Sophie Anne
Fraine, Steven Li
Sharif, Behrang
Hamad, Doulia
Fatima, Tarheen
Berg, Jim
Brown, Claire M.
Jan, Lily-Yeh
Ribeiro-da-Silva, Alfredo
Braz, Joao M.
Basbaum, Allan I.
Sharif-Naeini, Reza
Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
title Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
title_full Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
title_fullStr Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
title_full_unstemmed Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
title_short Dorsal Horn Parvalbumin Neurons Are Gate-Keepers of Touch-Evoked Pain after Nerve Injury
title_sort dorsal horn parvalbumin neurons are gate-keepers of touch-evoked pain after nerve injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038918/
https://www.ncbi.nlm.nih.gov/pubmed/26527000
http://dx.doi.org/10.1016/j.celrep.2015.09.080
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