Shikonin alleviates bone cancer pain through suppression of spinal IGF2-associated p38 MAPK signaling

Intrathecal Shikonin alleviates bone cancer pain in MADB106 tumor-bearing rats, producing dose- and time-dependent antinociception with an ED50 of 29.80 g/kg.

• Why it matters: Bone cancer pain often responds incompletely to current drugs, and the spinal mechanisms driving hypersensitivity and pain-related anxiety remain unclear.
• What they did: Rats received intrathecal Shikonin and were tested with mechanical/thermal assays plus gait and anxiety-like behavior tests; spinal dorsal horn transcriptomics and IGF2/p38 signaling readouts used Western blot, qPCR, and ELISA.
• The result: Shikonin reduced spinal IGF2 expression and p38 phosphorylation and lowered IL 6, IL 1{beta};, and TNF ;, while IGF2 siRNA phenocopied Shikonin and p38 inhibition reproduced key behaviors without additive effects.

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