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Acetyl-L-Carnitine in Neuropathic Pain

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Catania, Catania, Italy

    Santina Chiechio & Agata Copani

  2. IBB, CNR, Catania, Italy

    Agata Copani

  3. Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri, USA

    Robert W. Gereau IV

  4. Department of Human Physiology and Pharmacology, University of Rome ‘La Sapienza’, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Ferdinando Nicoletti

  5. Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy

    Ferdinando Nicoletti

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  1. Santina Chiechio
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  2. Agata Copani
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  3. Robert W. Gereau IV
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  4. Ferdinando Nicoletti
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Correspondence to Ferdinando Nicoletti.

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Chiechio, S., Copani, A., Gereau, R.W. et al. Acetyl-L-Carnitine in Neuropathic Pain. CNS Drugs 21 (Suppl 1), 31–38 (2007). https://doi.org/10.2165/00023210-200721001-00005

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