Aim: Severe painful neuropathy often occurs in cancer patients receiving chemotherapy. Emerging evidence has demonstrated that microglia contribute to the occurrence and development of cancer-associated pain. This study aimed to investigate the mechanisms by which piperine influences cancer-associated pain induced by microglia activation.
Methods: The tumor cell implantation (TCI) model was adopted as the cancer-associated pain model in mice. Behavioral tests were done to confirm that model mice were sensitive to acute mechanical and thermal pain. Western blot (WB) and immunofluorescence (IF) were conducted to quantify expression level of microglia marker protein Iba1 in mice spinal cord tissues. The expression of miR-150-5p and CXCL12 in the mice spinal cord was evaluated by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) and fluorescence in situ hybridization (FISH). Primary microglia from mice were treated with lipopolysaccharide (LPS) to investigate neuroinflammation.
Results: The modeled mice showed high susceptibility to acute mechanical hyperalgesia and thermal hyperalgesia. The expression of microglia marker protein Iba1 in the model group was increased in vitro and in vivo. Treatment with piperine effectively relieved the cancer-associated pain in mice. The results of FISH and qRT-PCR showed that piperine significantly increased the expression of miR-150-5p and reduced the expression of CXCL12 in the spinal cord of mice. Furthermore, it inhibited the microglia-induced cancer-associated pain.
Conclusions: Piperine upregulates miR-150-50p levels, inhibits CXCL12 expression, and reduces microglia levels at the lesion site. Therefore, piperine may be a potential drug candidate for the treatment of cancer-associated pain.
Keywords: CXCL12; cancer pain; miR-150-5p; microglia; piperine.