Mechanisms of neuropathic pain and their importance in Fabry disease

One of the most prominent features of Fabry disease is neuropathic pain. Neuropathic pain occurs after neuronal damage. In contrast to inflammatory or trauma-related pain, which normally helps to maintain or restore body functions, neuropathic pain tends to become chronic, and must therefore be considered a 'pathological' pain. Neuropathic pain has usually been classified according to the aetiology of nerve damage: traumatic, inflammatory, cancer-related or metabolic (e.g. Fabry disease). However, use of this classification often results in inadequate therapy for neuropathic pain. Recent research has revealed distinct mechanisms that are responsible for neuropathic pain. These mechanisms are independent of the aetiology of nerve damage. The most important mechanisms are accumulation and maldistribution of sodium channels on injured axons, pathological sympatho-afferent coupling, disinhibition of nociception and central or peripheral nociceptive sensitization.

Future research should focus on diagnostic tools to identify the predominant mechanisms in individual patients. These mechanism could be targeted specifically by drugs, or non-drug therapy, enabling more effective treatment of neuropathic pain.