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TRPV1 Channel Inhibition: Research published in Molecular Immunology (2023) identified a second direct analgesic mechanism ARA-290 specifically inhibits TRPV1 (Transient Receptor Potential Vanilloid 1) channel activity in peripheral nociceptors, increasing the pain threshold and relieving mechanical hypersensitivity independent of its anti-inflammatory IRR actions

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Specifically, treatment with nicotinamide significantly reduced the levels of key pro-inflammatory cytokines, including TNF-, IL-1, and IL-6, alongside a marked suppression of TGF-1, a central mediator of fibrogenesis (Figure 4A) (Sani et al., 2025)