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When applied to cryogenic wounds in rats, these formulations accelerated skin and hair follicle regeneration and reduced expression of inflammatory markers (IL-1β, IL-6, TNF-α) and pain-associated markers, including COX-2 (which drives prostaglandin-mediated nociceptor sensitization) [143,144], YKL-40 (associated with inflammation-induced pain signaling) [145], and substance P (a neuropeptide that transmits nociceptive signals) [146], while enhancing expression of angiogenic and remodeling markers (VEGF, TGF-β, FGF, PDGF, MMP-9, EGF) [142]
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