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Molecules 2017, 22(6), 937; doi:10.3390/molecules22060937

Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway

1
State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China
2
Institute of Indigenous Medicine, University of Colombo, Rajagiriya 11600, Sri Lanka
3
State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Hala Gali-Muhtasib
Received: 14 April 2017 / Revised: 2 May 2017 / Accepted: 2 June 2017 / Published: 6 June 2017
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Abstract

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. View Full-Text
Keywords: microglia; astrocytes; tumor compression-induced pain (TCIP); CCL2; CCR2; inflammatory cytokines; levo-corydalmine (l-CDL) microglia; astrocytes; tumor compression-induced pain (TCIP); CCL2; CCR2; inflammatory cytokines; levo-corydalmine (l-CDL)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Hu, Y.; Kodithuwakku, N.D.; Zhou, L.; Li, C.; Han, D.; Fang, W.; Liu, J.; Li, Y. Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway. Molecules 2017, 22, 937.

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