Cono RPRF-amide conotoxin is a peptide toxin originally isolated from the venom of the cone snail Conus textile. It strongly potentiates ASIC3 by directly binding to the channel, thus modulating the proton-activated current. Cono RPRF-amide belongs to the subgroup of cono-RFamides containing C-terminal sequence of four amino acids and a C-terminal Arg–Phe–NH₂ (RFa) motif. Research shows that injection of the cono-RFamide in mice muscle enhanced acid-induced muscle pain¹.

ASIC channels are proton-gated Na⁺ channels directly activated by extracellular protons. They are expressed throughout the CNS and the peripheral nervous system. They are responsible for synaptic transmission and detection of painful acidosis. ASICs play an important role in several physiological and pathological conditions including synaptic plasticity and learning, fear conditioning, and neurodegeneration associated with ischemic stroke^1,2.