Neuroprotective effects of acetyl-L-carnitine on neuropathic pain and apoptosis:

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J Neurosci Res. 2008 Aug 15.

Neuroprotective effects of acetyl-L-carnitine on neuropathic pain and

apoptosis: A role for the nicotinic receptor.

Di Cesare Mannelli L, Ghelardini C, Calvani M, Nicolai R, Mosconi L,

Toscano A, Pacini A, Bartolini A.

University of Florence, Department of Preclinical and Clinical

Pharmacology, Florence, Italy.

Several pathologies related to nervous tissue alterations are

characterized by a chronic pain syndrome defined by persistent or

paroxysmal pain independent or dependent on a stimulus.

Pathophysiological mechanisms related to neuropathic disease are

associated with mitochondrial dysfunctions that lead to an activation

of the apoptotic cascade.

In a model of peripheral neuropathy obtained by the loose ligation of

the rat sciatic nerve, acetyl-L-Carnitine (ALCAR; 100 mg/kg

intraperitoneally [i.p.] twice daily for 14 days) was able to reduce

hyperalgesia and apoptosis.

In the present study, different mechanisms for the analgesic and the

antineuropathic effect of ALCAR are described. The muscarinic blocker

atropine (5 mg/kg i.p.) injected simultaneously with ALCAR did not

antagonize the ALCAR antihyperalgesic effect on the paw-pressure test

but significantly reduced the analgesic effect of ALCAR.

Conversely, the antineuropathic effect of ALCAR was prevented by

cotreatment with the nicotinic antagonist mecamylamine (2 mg/kg i.p.

twice daily for 14 days). A pharmacological silencing of the

nicotinic receptors significantly reduced the X-linked inhibitor of

apoptosis protein-related protective effect of ALCAR on the apoptosis

induced by ligation of the sciatic nerve.

Taken together, these data highlight the relevance of nicotinic

modulation in neuropathy treatment.

Definition of nicotinic: relating to, resembling, producing, or mediating the

effects that are produced by acetylcholine liberated by nerve fibers at

autonomic ganglia and at the neuromuscular junctions of voluntary muscle and

that are mimicked by nicotine which increases activity in small doses and

inhibits it in larger doses