The following is a summary of “Microglial P2Y12 Signalling Contributes to Cisplatin-induced Pain Hypersensitivity via IL-18-mediated Central Sensitization in the Spinal Cord,” published in the May 2023 issue of Pain by Chen et al.

It is essential to administer cisplatin and other chemotherapy medications when treating tumors. Despite this, cisplatin-induced hypersensitivity to pain remains a critical clinical issue, and the underlying molecular mechanisms remain unknown. In this study, researchers discovered that repeated cisplatin treatments significantly upregulated the expression of P2Y12 in the spinal cord. P2Y12 expression was predominant in microglia. 

The cisplatin-induced pain hypersensitivity was drastically reduced by pharmacological inhibition of P2Y12 expression. Moreover, inhibiting the P2Y12 signal suppressed the hyperactivity of microglia induced by cisplatin. In addition, the microglia Src family kinase/p38 pathway is necessary for P2Y12-mediated cisplatin-induced pain hypersensitivity via the production of the proinflammatory cytokine IL-18 in the spinal cord. The P2Y12/IL-18 signaling pathway inhibition reversed cisplatin-induced hypersensitivity to pain and activated the N-methyl-D-aspartate receptor and subsequent Ca²⁺– dependent signals. 

Their findings suggest that microglia P2Y12-SFK-p38 signaling contributes to cisplatin-induced pain hypersensitivity via IL-18-mediated central sensitization in the spine, and P2Y12 could be a potential intervention target for preventing chemotherapy-induced pain hypersensitivity. Their research revealed that P2Y12/IL-18 plays a crucial role in cisplatin-induced hypersensitivity to pain. This research suggests that P2Y12/IL-18 signaling may effectively treat chemotherapy-induced hypersensitivity to pain.

Source: sciencedirect.com/science/article/pii/S1526590023000135