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Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats

Mechanical allodynia (pain produced by innocuous stimuli such as touch) is the main symptom of neuropathic pain. Its underlying mechanism remains to be elucidated, but peripheral nerve injury (PNI)-induced malfunction of neuronal circuits in the central nervous system, including the spinal dorsal ho...

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Autores principales: Ishibashi, Tadayuki, Yoshikawa, Yu, Sueto, Daichi, Tashima, Ryoichi, Tozaki-Saitoh, Hidetoshi, Koga, Keisuke, Yamaura, Ken, Tsuda, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260077/
https://www.ncbi.nlm.nih.gov/pubmed/35813063
http://dx.doi.org/10.3389/fnmol.2022.911122
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author Ishibashi, Tadayuki
Yoshikawa, Yu
Sueto, Daichi
Tashima, Ryoichi
Tozaki-Saitoh, Hidetoshi
Koga, Keisuke
Yamaura, Ken
Tsuda, Makoto
author_facet Ishibashi, Tadayuki
Yoshikawa, Yu
Sueto, Daichi
Tashima, Ryoichi
Tozaki-Saitoh, Hidetoshi
Koga, Keisuke
Yamaura, Ken
Tsuda, Makoto
author_sort Ishibashi, Tadayuki
collection PubMed
description Mechanical allodynia (pain produced by innocuous stimuli such as touch) is the main symptom of neuropathic pain. Its underlying mechanism remains to be elucidated, but peripheral nerve injury (PNI)-induced malfunction of neuronal circuits in the central nervous system, including the spinal dorsal horn (SDH), is thought to be involved in touch-pain conversion. Here, we found that intra-SDH injection of adeno-associated viral vectors including a prodynorphin promoter (AAV-PdynP) captured a subset of neurons that were mainly located in the superficial laminae, including lamina I, and exhibited mostly inhibitory characteristics. Using transgenic rats that enable optogenetic stimulation of touch-sensing Aβ fibers, we found that the light-evoked paw withdrawal behavior and aversive responses after PNI were attenuated by selective ablation of AAV-PdynP-captured SDH neurons. Notably, the ablation had no effect on withdrawal behavior from von Frey filaments. Furthermore, Aβ fiber stimulation did not excite AAV-PdynP(+) SDH neurons under normal conditions, but after PNI, this induced excitation, possibly due to enhanced Aβ fiber-evoked excitatory synaptic inputs and elevated resting membrane potentials of these neurons. Moreover, the chemogenetic silencing of AAV-PdynP(+) neurons of PNI rats attenuated the Aβ fiber-evoked paw withdrawal behavior and c-FOS expression in superficial SDH neurons. Our findings suggest that PNI renders AAV-PdynP-captured neurons excitable to Aβ fiber stimulation, which selectively contributes to the conversion of Aβ fiber-mediated touch signal to nociceptive. Thus, reducing the excitability of AAV-PdynP-captured neurons may be a new option for the treatment of neuropathic allodynia.
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spelling pubmed-92600772022-07-08 Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats Ishibashi, Tadayuki Yoshikawa, Yu Sueto, Daichi Tashima, Ryoichi Tozaki-Saitoh, Hidetoshi Koga, Keisuke Yamaura, Ken Tsuda, Makoto Front Mol Neurosci Molecular Neuroscience Mechanical allodynia (pain produced by innocuous stimuli such as touch) is the main symptom of neuropathic pain. Its underlying mechanism remains to be elucidated, but peripheral nerve injury (PNI)-induced malfunction of neuronal circuits in the central nervous system, including the spinal dorsal horn (SDH), is thought to be involved in touch-pain conversion. Here, we found that intra-SDH injection of adeno-associated viral vectors including a prodynorphin promoter (AAV-PdynP) captured a subset of neurons that were mainly located in the superficial laminae, including lamina I, and exhibited mostly inhibitory characteristics. Using transgenic rats that enable optogenetic stimulation of touch-sensing Aβ fibers, we found that the light-evoked paw withdrawal behavior and aversive responses after PNI were attenuated by selective ablation of AAV-PdynP-captured SDH neurons. Notably, the ablation had no effect on withdrawal behavior from von Frey filaments. Furthermore, Aβ fiber stimulation did not excite AAV-PdynP(+) SDH neurons under normal conditions, but after PNI, this induced excitation, possibly due to enhanced Aβ fiber-evoked excitatory synaptic inputs and elevated resting membrane potentials of these neurons. Moreover, the chemogenetic silencing of AAV-PdynP(+) neurons of PNI rats attenuated the Aβ fiber-evoked paw withdrawal behavior and c-FOS expression in superficial SDH neurons. Our findings suggest that PNI renders AAV-PdynP-captured neurons excitable to Aβ fiber stimulation, which selectively contributes to the conversion of Aβ fiber-mediated touch signal to nociceptive. Thus, reducing the excitability of AAV-PdynP-captured neurons may be a new option for the treatment of neuropathic allodynia. Frontiers Media S.A. 2022-06-23 /pmc/articles/PMC9260077/ /pubmed/35813063 http://dx.doi.org/10.3389/fnmol.2022.911122 Text en Copyright © 2022 Ishibashi, Yoshikawa, Sueto, Tashima, Tozaki-Saitoh, Koga, Yamaura and Tsuda. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Ishibashi, Tadayuki
Yoshikawa, Yu
Sueto, Daichi
Tashima, Ryoichi
Tozaki-Saitoh, Hidetoshi
Koga, Keisuke
Yamaura, Ken
Tsuda, Makoto
Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats
title Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats
title_full Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats
title_fullStr Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats
title_full_unstemmed Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats
title_short Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats
title_sort selective involvement of a subset of spinal dorsal horn neurons operated by a prodynorphin promoter in aβ fiber-mediated neuropathic allodynia-like behavioral responses in rats
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260077/
https://www.ncbi.nlm.nih.gov/pubmed/35813063
http://dx.doi.org/10.3389/fnmol.2022.911122
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