Ionic channels and neuropathic pain: physiopathology and applications

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J Cell Physiol. 2008 Apr;215(1):8-14.

Ionic channels and neuropathic pain: physiopathology and applications.

Aurilio C, Pota V, Pace MC, Passavanti MB, Barbarisi M.

Department of Anaesthesiology Surgical and Emergency Science, Second

University of Studies of Naples, Naples, Italy.

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.