Tissue acidosis can directly induce pain sensation which is mediated by ion channels in peripheral sensory neurons. To date, several ion channel superfamilies are identified to be involved in the pain from tissue acidosis. (1) ASICs can be gated by proton and directly mediate the acidosis pain; (2) VR1 can be sensitized by acidosis as well as activated by pH＜6.0; (3) P2X2 receptor is up-modulated whereas P2X3 is down-modulated by acidosis; (4) TASK is one of the tandem pore and the inwardly rectifying K⁺ channel which can be closed by acidosis.