Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway.
Molecules, 2017/6/06;22(6)
Hu Y[1], Kodithuwakku ND[2], Zhou L[3], Li C[4], Han D[5], Fang W[6], Liu J[7], Li Y[8]
Affiliations
PMID: 28587280DOI: 10.3390/molecules22060937
Impact factor: 4.927
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.
Keywords: CCL2; CCR2; astrocytes; inflammatory cytokines; levo-corydalmine (l-CDL); microglia; tumor compression-induced pain (TCIP)
MeSH terms
Animals; Astrocytes; Berberine; Cancer Pain; Chemokine CCL2; Cytokines; Disease Models, Animal; Heterografts; Inflammation Mediators; Male; Mice; Molecular Structure; Neuralgia; Neuroglia; Receptors, CCR2; Signal Transduction; Spinal Cord
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