Ionic channels and neuropathic pain: physiopathology and applications

Abstract

Neuropathic pain is defined by the International Association for Pain research as a pain associated to a primary lesion or a dysfunction of the central or peripheral system. Over the past few years the causes of the neuropathic pain were not known and there were not good treatments for it, now we have a better knowledge of the physiopathological aspects and there is a wider diffusion of the research for target aimed therapies. The physiologic genesis of nervous messages occurs exclusively in skin sensorial endings or in nerve tissues as a consequence of an adequate sensorial stimulus and depends on the quick variations of the electric potential difference at the endings of ionic membranes. These variations of even 500 V a second are possible because of the presence of ionic channels. In neuropathic pain impulses can be originated even from ectopic sites. Ectopic discharges originated in a peripheral neuropathic system have an important role in the early stage of neuropathic pain development in two different ways. First they give an excess of spontaneous and evoked electric impulses to the central nervous system, causing a primitive neuropathic pain signal; then the ectopic activity develops and maintains the central sensitisation process. All this amplifies the afferent signals deriving from residual efferents that go on innerving cutaneous areas damaged and partly disnerved, causing tactile allodynie. Sodium channels are the greatest responsible for electrogenesis, that is the basis of the action potential generation and its propagation. Action potential begins after a depolarization such that it could cause a membrane transitory modification, turning prevalently permeable to Na+ more than to K+ as during a release phase. Neuropathy generates a local accumulation of sodium channels, with a consequent increase of density. This remodel seems to be the basis of neuro hyperexecitably. Calcium channels have also an important role in cell working. Intracellular calcium increase contributes to depolarization processes, through kinase and determines the phosphorylation of membrane proteins that can make powerful the efficacy of the channels themselves. In the future new diagnostic opportunities of physiopathologist mechanism leading to neuropathic pain will allow treatments aimed at specific molecular changes of ionic channels.