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: 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.