How does inflammation affect axonal excitability to mechanical stimulation of neurones in the rat pain pathway?

摘要

The causes of peripheral neuropathy are varied, encompassing inflammation, nerve compression, laceration or entrapment and exposure to toxins. These are not mutually exclusive and the mechanisms behind such neuropathies are incompletely understood. However, numerous studies have shown that at sites of neural inflammation, or neuritis, a sensitivity to mechanical stimulation is induced in intact, through-conducting axons. Such changes in axonal excitability are of considerable clinical importance because they may explain the typical presentation - of radiating pain evoked by mechanical tension of affected nerves - by patients suffering from common chronically painful conditions. This pain is sometimes elicited by neurologists in the outpatient clinic and is called the Hoffmann-Tinel sign. Dilley & Bove in a recent paper in The Journal of Physiology investigate a possible mechanism for explaining such neuritic axonal mechanical sensitivity (AMS) in a rat model. The authors use an integrative approach, combining electrophysiological, immuno-histochemical and histological cellular methods to test their hypothesis that disruption of fast axonal transport by localized neuritis is sufficient to cause the accumulation, and subsequent membrane insertion, of mechanosensitive ion channels. This hypothesis builds on previous studies from other research groups that suggest that the rapid inflammatory mediator, histamine, disrupts axonal transport and that, at least in the monkey, the requisite components for mechanical sensitivity are transported by fast axonal transport.