Taking a bite out of pain Snake venom can be both a curse and a cure when targeting acid sensing ion channels (ASICs) in the pain pathway

摘要

E vidence that a proton (H+ )-activated conductance mechanism may be involved in nociception was first reported back in 1981 when Krishtal and Pidoplichko discovered that lowering external pH induced a transient increase in membrane sodium conductance in neurons isolated from rat trigeminal ganglia. 1 These authors hypothesized that since the trigeminal nerve is one of the important carriers of the nociceptive impulse and that acidosis often accompanies painful inflammatory responses, it was possible that this mechanism played a role in nociception by proton-sensitive neurons. The importance of this discovery, however, went largely unnoticed for nearly two decades until 1997, when Waldmann et al. identified and cloned the first acidsensing ion channel (ASIC). 2 Waldmann et al. went on to describe and identify ASICs as being H+ -gated Na + channels related to the subgroup of the degenerin/epithelial Na + channel (DEG/ENaC) family of cation channels. They also showed that ASICs were highly expressed in small diameter sensory neurons located within dorsal root ganglia (DRG), further implicating these channels in nociception.