Acetyl-L-Carnitine in Neuropathic Pain
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Acetyl-L-carnitine (ALC) has gained clinical interest for its analgesic effect in different forms of neuropathies associated with chronic pain, such as diabetic and HIV-related peripheral neuropathies. The antinociceptive effect of ALC has been confirmed in several experimental models of neuropathic pain, including streptozotocin- and chemotherapy-induced neuropathy, and the sciatic nerve chronic constriction injury model. In these models, prophylactic administration of ALC has proven to be effective in preventing the development of neuropathic pain. In addition, ALC is known to produce a strong antinociceptive effect when given after neuropathic pain has been established. ALC can also improve the function of peripheral nerves by increasing nerve conduction velocity, reducing sensory neuronal loss, and promoting nerve regeneration.
Analgesia requires repeated administrations of ALC, suggesting that the drug regulates neuroplasticity across the pain neuraxis. Recent evidence indicates that ALC regulates processes that go beyond its classical role in energy metabolism. These processes involve the activation of muscarinic cholinergic receptors in the forebrain, and an increased expression of type-2 metabotropic glutamate (mGlu2) receptors in dorsal root ganglia neurons. Induction of mGlu2 receptors is mediated by acetylation mechanisms that involve transcription factors of the nuclear factor (NF)-κB family.
Experiments on the regulation of mGlu2 receptor expression by ALC were supported by the McDonnell Center for Molecular and Cellular Neurobiology and by the National Institutes of Health.
Conflict of interest: S. Chiechio currently has a fellowship from Sigma-Tau, which produces and sells carnitine. Nevertheless, the author did not receive any financial support or benefit for writing this paper. The authors have no other potential conflicts of interest that are directly relevant to this review.
- 24.Chiechio S, Copani A, De Petris L, et al. Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. Molecular Pain 2006; 2: 20PubMedCrossRefGoogle Scholar
- 49.Varney MA, Gereau RW. Metabotropic glutamate receptor involvement in models of acute and persistent pain: prospects for the development of novel analgesics. Curr Drug Targets 2002; 1(3): 283–96Google Scholar