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

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.

Anti-ulcerogenic effect of KFP-H008 against ethanol-induced gastric ulcerviap38 MAPK/NF-κB pathway

“…Dishes were rinsed with PBS and incubated with goat antirabbit IgG/FITC and goat anti-rabbit IgG/Cy3, respectively for 2 h at room temperature, and the nuclei was stained with DAPI. 16 The stained dishes were examined with laser scanning confocal microscope (Carl Zeiss, Oberkochen, Germany) and images were assessed by Image J 1.50i (National Institutes of Health, USA).…”

Selective blockade of spinal D2DR by levo-corydalmine attenuates morphine tolerance via suppressing PI3K/Akt-MAPK signaling in a MOR-dependent manner

“…In the current study, the natural compound l -CDL, which exerted a potent analgesic effect on alleviating bone cancer pain, significantly attenuated morphine tolerance by antagonizing spinal D2DR at nonnarcotic analgesic doses, and we further explored its underlying mechanism. Both intragastric and intrathecal administration of l- CDL were reported to attenuate chronic pain, 19 , 46 , 47 and l- CDL (p.o.) did not affect the motor function of rats 19 at analgesic doses in our previous study.…”

Levo-corydalmine attenuates microglia activation and neuropathic pain by suppressing ASK1-p38 MAPK/NF-κB signaling pathways in rat spinal cord

“…l -CDL is an alkaloid from the traditional Chinese Medicine, Corydalis yanhusuo W. T. Wang, and is also the main metabolite of l -tetrahydropalmatine ( l- THP), which possesses analgesic effects and has been used as an analgesic and sedative medicine for more than 40 years in China. In our previous report, we discovered that l- CDL reduced cancer-induced and vincristine-induced neuropathic pain and chronic bone cancer pain in the spinal cord 14–16. Additionally, previous studies have demonstrated that l -CDL inhibited the activation of spinal neurons, astrocytes, and microglia in patients with neuropathic cancer pain and vincristine-induced neuropathic pain.…”