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360 TLR4 Plays An Important Role In Chronic Relapsing Pruritus Induced By Subcutaneous Capsaicin Injection In Neonatal Rats

      Despite the high prevalence of chronic dermatitis and the accompanied intractable itch, therapeutics that specifically target itching have low efficacy. Although toll-like receptors (TLRs) are suggested to contribute to immune activation and neural sensitization, their roles in chronic itch in the skin remain elusive. Here, we show that the RBL-2H3 mast cell line expresses TLR4 and that treatment with a TLR4 antagonist opposes the LPS-dependent increase in mRNA levels of Th2 and innate cytokines. The role of TLR4 activation in pruritus was studied in neonate rats in which chronic relapsing pruritus was induced by neuronal damage following subcutaneous capsaicin injections. Treatment with a TLR4 antagonist protected these rats from chronic itch with scratching behavior and chronic dermatitis. TLR4 antagonist treatment also restored the density of cutaneous nerve fibers and inhibited the histopathological changes that are associated with mast cell activation after capsaicin injection. Additionally, the expression of IL-1β, IL-4, IL-5, IL-10, and IL-13 mRNA in the lesional skin decreased after TLR4 antagonist treatment. Based on these data, we propose that the reduction in the itch was associated with TLR4 signaling in mast cells and nerve fibers.