Two members of the anoctamin family, a recently discovered group of membrane proteins, have unexpectedly been found to play important roles in nociception and pain.
Ano1 and Ano3, modulate the properties of nociceptive dorsal root ganglion (DRG) neurons, determining their sensitivity to painful stimuli.
Ano1 acts as a heat sensor in nociceptive neurons both in vitro and in vivo.
More and more evidence points to a link between heat and pain sensors. comment by Zyp Czyk
Members of the anoctamin family, at least one of which is a calcium-activated chloride channel (CaCC), may represent new therapeutic targets for pain.
movement of chloride, which can be inward or outward depending on the cell type, changes the cell’s resting membrane potential and thus alters its electrical excitability.
Further experiments revealed details of the acute pain mechanism. Bradykinin activation of the bradykinin receptor 2 (B2R) initiates inositol triphosphate (IP3) signaling, which in turns leads to the release of calcium stored in the endoplasmic reticulum into the cytoplasm. The resulting increase in cytoplasmic calcium activates CaCCs, making neurons more excitable. The increase in cytoplasmic calcium also inhibits M-type potassium channels, whose activity would otherwise have a dampening effect. These two events lead to membrane depolarization, increased excitability, and the rapid firing of increased numbers of action potentials, sending a signal of acute pain to the spinal cord and ultimately to the brain.
“The interactions between the proteins could dial pain sensations up or down,” Jan said, thus conferring great sensitivity and selectivity on the pain signaling system.
In animals and humans, nociceptive DRG neuronal cell bodies are located near the spinal cord, far from the action at the periphery.