The expression of TRPV1, ASIC-3, TDV8 encode ionic channels in RA and modulate the pain, likewise, the transcription factors in RA, such as TNFα, TGF-β1, IL-6, IL-10, IFN-γ, IL-1b, mTOR, p21, caspase 3, EDNRB, CGRP-CALCB, CGRP-CALCA, TAC1 are also directly involved in pain perception.
Asic3<sup>-/-</sup> mice were impaired in only muscle allodynia development but not other pain symptoms in the ICS model, so the ASIC3-dependent metabolomics changes could be useful for developing diagnostic biomarkers specific to chronic widespread muscle pain, the core symptom of FM.
Accordingly, a number of selective as well as nonselective ASIC3 inhibitors have shown potential in attenuating pain and inflammation in animal models of rheumatoid arthritis.
The ASIC3 subunit has been shown to be of particular importance in the peripheral nervous system with pharmacological and genetic manipulations demonstrating a role in pain.
Therefore, the comparison of the efficacy of ASIC3 inhibitors revealed the importance of ASIC3-sustained currents' inhibition for promotion of acidosis-related pain relief.
Acid-sensing ion channels (ASICs) ASIC3 expressed mainly in peripheral sensory neurons play an important role in pain perception and inflammation development.
TDAG8 likely participates in the initiation of RA pain, but all three genes, TDAG8, TRPV1, and ASIC3, are essential to establish hyperalgesic priming to regulate the chronic phase of RA pain.
We identified a small conopeptide of only four amino acids from the venom of <i>Conus textile</i> that strongly potentiated currents of ASIC3, which has a specific role in the pain pathway.
Peripheral ASIC3 channels are thus essential sensors of acidic pain and integrators of molecular signals produced during inflammation where they contribute to primary hyperalgesia.