Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ

Objective To explore the analgesic effect and underlying mechanisms of dexmedetomidine(DEX) with spared nerve injury(SNI) rat model. Methods Forty-eight SD rats were randomly divided into control group, SNI group, DEX group and DEX+GW9662 group, with 12 rats in each. From first day to 14th days afte...

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Main Author: ZHU Feng, ZHONG Yue, DENG Yijiang, LIU Wenzhi, BIAN Jiang
Format: Article
Language:zho
Published: Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. 2023-09-01
Series:Jichu yixue yu linchuang
Subjects:
Online Access:http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2023-43-9-1369.pdf
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author ZHU Feng, ZHONG Yue, DENG Yijiang, LIU Wenzhi, BIAN Jiang
author_facet ZHU Feng, ZHONG Yue, DENG Yijiang, LIU Wenzhi, BIAN Jiang
author_sort ZHU Feng, ZHONG Yue, DENG Yijiang, LIU Wenzhi, BIAN Jiang
collection DOAJ
description Objective To explore the analgesic effect and underlying mechanisms of dexmedetomidine(DEX) with spared nerve injury(SNI) rat model. Methods Forty-eight SD rats were randomly divided into control group, SNI group, DEX group and DEX+GW9662 group, with 12 rats in each. From first day to 14th days after SNI surgery, rats in DEX group were intra-thecally injected with 2 μg/kg (10 μL) of dexmedetomidine,rats in DEX group were intrathecally injected with 2 μg/kg of dexmedetomidine+300 μg of PPAR-γ inhibitor (GW9662), while rats in control and SNI groups were intrathecally injected with equal volume of solvent. At day 1 before operation, day 3, 7, 14 after operation, paw withdrawal threshold and thermal withdrawal latency were detected to evaluate the painintensity. At post-operative day 14,immunofluorescence staining was used to detect the expression of Iba-1 in spinal dorsal horn, Western blot was used to detect the expression of Iba-1 and PPAR-γ in ipsilateral spinal dorsal horn, ELISA was used to detect the levels of IFN-γ and IL-6 in ipsilateral spinal dorsal horn. Results On postoperative day 7 and 14, compared with control group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal horn were enhanced in SNI group(P<0.05). Compared with SNI group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal horn decreased in EDX group(P<0.05). Compared with DEX group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal increased in DEX+GW9662 group(P<0.05). Conclusions Dexmedetomidine obviously inhibits pain sensitization of SNI rats. The underlying analgesic mechanism may be related to the up-regulation of PPAR-γ in spinal dorsal horn.
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spelling doaj.art-0ec12fcbe40c448e837536c24f77a26a2024-01-04T07:33:35ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252023-09-014391369137410.16352/j.issn.1001-6325.2023.09.1369Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γZHU Feng, ZHONG Yue, DENG Yijiang, LIU Wenzhi, BIAN Jiang01. Department of Anesthesiology, Affiliated Hospital of Panzhihua University, Panzhihua, 617000; ;2. Department of Anesthesiology, Panzhihua Central Hospital, Panzhihua 617000, ChinaObjective To explore the analgesic effect and underlying mechanisms of dexmedetomidine(DEX) with spared nerve injury(SNI) rat model. Methods Forty-eight SD rats were randomly divided into control group, SNI group, DEX group and DEX+GW9662 group, with 12 rats in each. From first day to 14th days after SNI surgery, rats in DEX group were intra-thecally injected with 2 μg/kg (10 μL) of dexmedetomidine,rats in DEX group were intrathecally injected with 2 μg/kg of dexmedetomidine+300 μg of PPAR-γ inhibitor (GW9662), while rats in control and SNI groups were intrathecally injected with equal volume of solvent. At day 1 before operation, day 3, 7, 14 after operation, paw withdrawal threshold and thermal withdrawal latency were detected to evaluate the painintensity. At post-operative day 14,immunofluorescence staining was used to detect the expression of Iba-1 in spinal dorsal horn, Western blot was used to detect the expression of Iba-1 and PPAR-γ in ipsilateral spinal dorsal horn, ELISA was used to detect the levels of IFN-γ and IL-6 in ipsilateral spinal dorsal horn. Results On postoperative day 7 and 14, compared with control group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal horn were enhanced in SNI group(P<0.05). Compared with SNI group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal horn decreased in EDX group(P<0.05). Compared with DEX group, the pain intensity of ipsilateral hind paw and the expression of Iba-1, PPAR-γ, IL-6 and IFN-γ in ipsilateral spinal dorsal increased in DEX+GW9662 group(P<0.05). Conclusions Dexmedetomidine obviously inhibits pain sensitization of SNI rats. The underlying analgesic mechanism may be related to the up-regulation of PPAR-γ in spinal dorsal horn.http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2023-43-9-1369.pdfdexmedetomidine|neuropathic pain|microglia|peroxisome proliferator-activated receptor-γ(ppar-γ)
spellingShingle ZHU Feng, ZHONG Yue, DENG Yijiang, LIU Wenzhi, BIAN Jiang
Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ
Jichu yixue yu linchuang
dexmedetomidine|neuropathic pain|microglia|peroxisome proliferator-activated receptor-γ(ppar-γ)
title Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ
title_full Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ
title_fullStr Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ
title_full_unstemmed Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ
title_short Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ
title_sort dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of ppar γ
topic dexmedetomidine|neuropathic pain|microglia|peroxisome proliferator-activated receptor-γ(ppar-γ)
url http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2023-43-9-1369.pdf
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