Effect of toad skin extracts on the pain behavior of cancer model mice and its peripheral mechanism of action

•TSE significantly relieved pain in cancer pain model mice and raised their pain threshold.•TSE seems to play a prominent role in promoting the activity of TILs (CD3 + and CD8 + T cells).•This immune-cell-derived peripheral analgesic pathway might have widespread potential for clinical use.

The changes in thermal and mechanical hyperalgesia in paw cancer pain model mice and the action mechanism of toad skin extracts (TSE) was investigated. Eighty female mice were subcutaneously injected with saline or inoculated with H22 hepatoma cells in the right hind paw and administration with saline, vehicle, morphine and TSE. The pain behavior was recorded before treatment and at 0.5, 1.0, 1.5, 3 and 6 h after initial administration, and thereafter on the 2nd, 4th, 6th, and 8th day after administration. On the last day, samples were collected after the euthanasia for the detection of β-END, CRF, IL-1β, POMC, μ-OR, CD3 +, CD8 + and CD4 + in sera and the tumor tissues. The results showed that TSE significantly increased the thresholds of thermal pain and mechanical pain, and upregulated the expressions of β-END, CRF, POMC, CD3 +, CD8 + and μ-OR, and downregulated the expression of CD4 +. These results indicate that TSE significantly relieved pain in cancer pain model mice and raised their pain threshold. In addition, TSE seems to play a prominent role in promoting the activity of tumor infiltrating lymphocytes (TILs, CD3 + and CD8 + T cells), and this immune-cell-derived peripheral analgesic pathway might have widespread potential for clinical use.

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