Three subtypes of amiloride sensitive proton channels, referred to as ASIC 1, ASIC2 and ASIC3, have been implicated in pain transmission . Specifically, ASIC1 and a splice variant of ASIC2, ASIC1b, are activated by low pH and are expressed in both sensory neurons and the central nervous system. The activation of these channels may be involved in pain transmission, since acid itself produces pain and low pH conditions are associated with chronic joint inflammation, skin ulceration and some tumors. The VR1 vanilloid receptor antagonist, capsazepine, may reduce proton-induced activation of sensory neurons while NPFF appears to increase the sensitivity of ASICs to protons.
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