Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway
Background: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL) on TCIP. Methods: Spon...
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doaj-4da1f276b79646ad95414515c6b089872020-11-24T22:15:21ZengMDPI AGMolecules1420-30492017-06-0122693710.3390/molecules22060937molecules22060937Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 PathwayYahui Hu0Nandani Darshika Kodithuwakku1Lin Zhou2Chengyuan Li3Dan Han4Weirong Fang5Jihua Liu6Yunman Li7State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, ChinaInstitute of Indigenous Medicine, University of Colombo, Rajagiriya 11600, Sri LankaState Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, ChinaBackground: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL) on TCIP. Methods: Spontaneous pain, paw withdrawal threshold and latency were assessed using TCIP mouse model. Immunofluorescence was used to identify the reactions of glia. RT-PCR and western blot or ELISA were used to determine mRNA or protein expression of tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), CC chemokine ligand 2 (CCL2) and chemotactic cytokine receptor 2 (CCR2) in vivo and in vitro. Results: l-CDL significantly attenuated TCIP hypersensitivity, accompanying with downregulation of TNF-α and IL-1β expression levels and declined astrocytes and microglial activation. It also significantly decreased the expression of the mRNA and protein level for CCL2 and CCR2. Further, l-CDL could suppress TNF-α-induced astrocytes activation and IL-1β expression through downregulating the CCL2/CCR2. Besides, CCL2-induced BV-microglia activation and inflammatory factors secretion were suppressed by l-CDL via CCR2. Conclusions: Suppression of CCL2/CCR2 by l-CDL may contribute to alleviate TCIP, offering an alternative medication for TCIP.http://www.mdpi.com/1420-3049/22/6/937microgliaastrocytestumor compression-induced pain (TCIP)CCL2CCR2inflammatory cytokineslevo-corydalmine (l-CDL) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yahui Hu Nandani Darshika Kodithuwakku Lin Zhou Chengyuan Li Dan Han Weirong Fang Jihua Liu Yunman Li |
spellingShingle |
Yahui Hu Nandani Darshika Kodithuwakku Lin Zhou Chengyuan Li Dan Han Weirong Fang Jihua Liu Yunman Li Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway Molecules microglia astrocytes tumor compression-induced pain (TCIP) CCL2 CCR2 inflammatory cytokines levo-corydalmine (l-CDL) |
author_facet |
Yahui Hu Nandani Darshika Kodithuwakku Lin Zhou Chengyuan Li Dan Han Weirong Fang Jihua Liu Yunman Li |
author_sort |
Yahui Hu |
title |
Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway |
title_short |
Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway |
title_full |
Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway |
title_fullStr |
Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway |
title_full_unstemmed |
Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway |
title_sort |
levo-corydalmine alleviates neuropathic cancer pain induced by tumor compression via the ccl2/ccr2 pathway |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2017-06-01 |
description |
Background: Tumor compression-induced pain (TCIP) is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL) on TCIP. Methods: Spontaneous pain, paw withdrawal threshold and latency were assessed using TCIP mouse model. Immunofluorescence was used to identify the reactions of glia. RT-PCR and western blot or ELISA were used to determine mRNA or protein expression of tumor necrosis factor-α (TNF-α), interlukin-1β (IL-1β), CC chemokine ligand 2 (CCL2) and chemotactic cytokine receptor 2 (CCR2) in vivo and in vitro. Results: l-CDL significantly attenuated TCIP hypersensitivity, accompanying with downregulation of TNF-α and IL-1β expression levels and declined astrocytes and microglial activation. It also significantly decreased the expression of the mRNA and protein level for CCL2 and CCR2. Further, l-CDL could suppress TNF-α-induced astrocytes activation and IL-1β expression through downregulating the CCL2/CCR2. Besides, CCL2-induced BV-microglia activation and inflammatory factors secretion were suppressed by l-CDL via CCR2. Conclusions: Suppression of CCL2/CCR2 by l-CDL may contribute to alleviate TCIP, offering an alternative medication for TCIP. |
topic |
microglia astrocytes tumor compression-induced pain (TCIP) CCL2 CCR2 inflammatory cytokines levo-corydalmine (l-CDL) |
url |
http://www.mdpi.com/1420-3049/22/6/937 |
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