Overview on pathophysiology and newer approaches to treatment of peripheral neur

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CNS Drugs. 2007;21 Suppl 1:3-12; discussion 45-6.

Overview on pathophysiology and newer approaches to treatment of

peripheral neuropathies.

Vanotti A, Osio M, Mailland E, Nascimbene C, Capiluppi E, ni C.

U.O. Neurologia, Ospedale Luigi Sacco, Milan, Italy.

Peripheral neuropathies are extremely heterogeneous nosological

entities. One of the most common symptoms is pain, the underlying

mechanisms of which are numerous and complex. Inflammation,

reparative processes, and anatomical and gene expression alterations

lead to chronic pain, the persistence of which is sustained by

peripheral and central sensitisation mechanisms. Treatment of

peripheral neuropathies is targeted to its symptomatic and

aetiological features.

For pain relief, several types of drugs may be used, notably

antidepressants (e.g. tricyclic antidepressants, selective serotonin

reuptake inhibitors, and both serotonin and noradrenaline

[norepinephrine] reuptake inhibitors), antiepileptic drugs (e.g.

carbamazepine, phenytoin, lamotrigine, valproic acid, gabapentin,

topiramate and pregabalin), NSAIDs and opioid analgesics.

Aetiological therapy is aimed at modifying the pathophysiological

mechanisms underlying the neuropathy, some of which are common in

different neuropathic conditions. Certain drugs are known to exert

more than one action on different pathophysiological mechanisms.

This is the case with acetyl-L-carnitine (ALC), which can be

considered both a symptomatic therapy that can be used in any kind

of painful neuropathy, and an aetiological therapy, at least in

diabetic neuropathy and neuropathies induced by nucleoside reverse

transcriptase inhibitors and cancer chemotherapeutic agents. ALC

acts via several mechanisms, inducing regeneration of injured nerve

fibres, reducing oxidative stress, supporting DNA synthesis in

mitochondria, and enhancing nerve growth factor concentrations in

neurons.