Translating basic research on sodium channels in human neuropathic pain.
A number of experimental studies in animals have suggested that voltage-gated sodium channels may play a crucial role in neuropathic pain. However, it is still difficult to translate the pathophysiological mechanisms identified in animal studies to the clinic and several questions regarding the role of sodium channels in neuropathic pain must therefore be addressed primarily in the clinical setting. Despite providing indirect information, pharmacologic challenge using sodium channel blockers, such as some antiepileptics, local anesthetics and derivatives, is the best way to investigate the role of sodium channels in the various clinical symptoms of neuropathies (eg, spontaneous pain, mechanical or thermal allodynia, and hyperalgesia). Randomized controlled trials have demonstrated the efficacy of these compounds for various neuropathic pain conditions. Recent psychophysical studies in which symptoms and signs are more accurately assessed indicate that these compounds act as antihyperalgesic agents rather than as simple analgesics. They also show that the sensitivity to these drugs is not affected by the aetiology of pain and the peripheral or central location of the nerve lesion. These data emphasize the role of peripheral and central sodium channels in neuropathic pain. Studies using more selective sodium channel blockers are required to gain further insight into the role of the various subtypes of sodium channel in these pain conditions.


CONCLUSIONS
Pharmacological challenge using sodium channel blockers is the best way to translate basic research on sodium channels in human neuropathic pain. To date, the role of sodium channels in neuropathic pain symptoms/signs is mostly documented for mechanical static and dynamic allodynia, and either peripheral or central sodium channels may be involved.
Attal
Nadine
N
Centre d'Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, AP-HP and Université Versailles-Saint-Quentin, France. nadine.attal@apr.ap-hop-paris.fr
Bouhassira
Didier
D
D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology; D010146:Pain / Q000209:etiology* / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000503:physiopathology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
D015222:Sodium Channels