Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia
Summary: Mechanical allodynia and hyperalgesia are intractable symptoms lacking effective clinical treatments in patients with neuropathic pain. However, whether and how mechanically responsive non-peptidergic nociceptors are involved remains elusive. Here, we showed that von Frey-evoked static allo...
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Elsevier
2023-05-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223008416 |
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author | Liangbiao Wang Xiaojing Su Jinjin Yan Qiaofeng Wu Xiang Xu Xinyue Wang Xiaoqing Liu Xiaoyuan Song Zhi Zhang Wei Hu Xinfeng Liu Yan Zhang |
author_facet | Liangbiao Wang Xiaojing Su Jinjin Yan Qiaofeng Wu Xiang Xu Xinyue Wang Xiaoqing Liu Xiaoyuan Song Zhi Zhang Wei Hu Xinfeng Liu Yan Zhang |
author_sort | Liangbiao Wang |
collection | DOAJ |
description | Summary: Mechanical allodynia and hyperalgesia are intractable symptoms lacking effective clinical treatments in patients with neuropathic pain. However, whether and how mechanically responsive non-peptidergic nociceptors are involved remains elusive. Here, we showed that von Frey-evoked static allodynia and aversion, along with mechanical hyperalgesia after spared nerve injury (SNI) were reduced by ablation of MrgprdCreERT2-marked neurons. Electrophysiological recordings revealed that SNI-opened Aβ-fiber inputs to laminae I-IIo and vIIi, as well as C-fiber inputs to vIIi, were all attenuated in Mrgprd-ablated mice. In addition, priming chemogenetic or optogenetic activation of Mrgprd+ neurons drove mechanical allodynia and aversion to low-threshold mechanical stimuli, along with mechanical hyperalgesia. Mechanistically, gated Aβ and C inputs to vIIi were opened, potentially via central sensitization by dampening potassium currents. Altogether, we uncovered the involvement of Mrgprd+ nociceptors in nerve injury-induced mechanical pain and dissected the underlying spinal mechanisms, thus providing insights into potential therapeutic targets for pain management. |
first_indexed | 2024-04-09T13:14:57Z |
format | Article |
id | doaj.art-b07edf3379a842cd8ff71a328a7bf995 |
institution | Directory Open Access Journal |
issn | 2589-0042 |
language | English |
last_indexed | 2024-04-09T13:14:57Z |
publishDate | 2023-05-01 |
publisher | Elsevier |
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series | iScience |
spelling | doaj.art-b07edf3379a842cd8ff71a328a7bf9952023-05-12T04:16:58ZengElsevieriScience2589-00422023-05-01265106764Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodyniaLiangbiao Wang0Xiaojing Su1Jinjin Yan2Qiaofeng Wu3Xiang Xu4Xinyue Wang5Xiaoqing Liu6Xiaoyuan Song7Zhi Zhang8Wei Hu9Xinfeng Liu10Yan Zhang11Department of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, ChinaDepartment of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, ChinaDepartment of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, ChinaDepartment of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, ChinaDepartment of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, ChinaDepartment of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, ChinaSchool of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, ChinaHefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, ChinaDepartment of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Corresponding authorDepartment of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Corresponding authorDepartment of Neurology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Corresponding authorSummary: Mechanical allodynia and hyperalgesia are intractable symptoms lacking effective clinical treatments in patients with neuropathic pain. However, whether and how mechanically responsive non-peptidergic nociceptors are involved remains elusive. Here, we showed that von Frey-evoked static allodynia and aversion, along with mechanical hyperalgesia after spared nerve injury (SNI) were reduced by ablation of MrgprdCreERT2-marked neurons. Electrophysiological recordings revealed that SNI-opened Aβ-fiber inputs to laminae I-IIo and vIIi, as well as C-fiber inputs to vIIi, were all attenuated in Mrgprd-ablated mice. In addition, priming chemogenetic or optogenetic activation of Mrgprd+ neurons drove mechanical allodynia and aversion to low-threshold mechanical stimuli, along with mechanical hyperalgesia. Mechanistically, gated Aβ and C inputs to vIIi were opened, potentially via central sensitization by dampening potassium currents. Altogether, we uncovered the involvement of Mrgprd+ nociceptors in nerve injury-induced mechanical pain and dissected the underlying spinal mechanisms, thus providing insights into potential therapeutic targets for pain management.http://www.sciencedirect.com/science/article/pii/S2589004223008416NeuroscienceCellular neuroscienceCell biology |
spellingShingle | Liangbiao Wang Xiaojing Su Jinjin Yan Qiaofeng Wu Xiang Xu Xinyue Wang Xiaoqing Liu Xiaoyuan Song Zhi Zhang Wei Hu Xinfeng Liu Yan Zhang Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia iScience Neuroscience Cellular neuroscience Cell biology |
title | Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia |
title_full | Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia |
title_fullStr | Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia |
title_full_unstemmed | Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia |
title_short | Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia |
title_sort | involvement of mrgprd expressing nociceptors recruited spinal mechanisms in nerve injury induced mechanical allodynia |
topic | Neuroscience Cellular neuroscience Cell biology |
url | http://www.sciencedirect.com/science/article/pii/S2589004223008416 |
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