Sensitisation of Nociceptors – What are Ion Channels Doing?

摘要

Nociceptors are peripheral sensory neurones which respond to painful (noxious) stimuli. The terminals ofnociceptors, which have a high threshold to stimulation in their native state, undergo a process known as sensitisation, orlowering of threshold, following injury or inflammation. Amongst sensory receptors, sensitisation is a property unique tonociceptors. A shift in the stimulus-response function of nociceptors renders them more sensitive, resulting in both areduction in the activation threshold, such that previously non-noxious stimuli are perceived as noxious (allodynia) andan increased response to suprathreshold stimuli (hyperalgesia). Sensitisation protects us from harm and is essential forsurvival, but it can be disabling in conditions of chronic inflammation. This review focuses on three stages insensitisation: 1) Inflammatory mediators, which are released from damaged resident cells and from others that invade inresponse to inflammation, and include bradykinin, prostaglandins, serotonin, low pH, ATP, neurotrophins, nitric oxideand cytokines; 2) Intracellular signalling molecules which are important in transmitting the actions of inflammatorymediators and include protein kinase A and C, Src kinase, mitogen-activated protein kinases and the membrane lipid PIP2;and 3) Ion channel targets of intracellular signalling which ultimately cause sensitisation and include the temperaturesensitivetransient receptor potential channels, acid-sensitive ion channels, purinoceptor-gated channels, and the voltagesensitivesodium, potassium, calcium and HCN channels.