P2Y6 promoted pruning of FSTL1 nerves by cutaneous macrophages to reset pain threshold and cardiac function.

ABSTRACT: Hyperactivation of cutaneous macrophages promotes the development of chronic pain. Stimulation of nociceptive regions promotes neuroplasticity, which affects pain perception and related physiological responses. However, the specific mechanisms by which cutaneous macrophages sense and elicit nociceptive responses are unknown. Here, we exacerbated the reduction of systemic pain threshold after chronic heart failure (CHF) by silencing follistatin-like 1 (FSTL1), especially the abnormal cutaneous nociceptive sensation at PC6 acupoint, the site associated with cardiac involvement pain. The upregulation of P2Y6 and interleukin-27 expression is intimately linked to the activation of skin macrophages. Hyperactivation of P2Y6 receptor (P2Y6R) may be associated with MHC II M1⁺ macrophage

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12454787 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature