L-Acetylcarnitine Mitigates Chronic Inflammatory and Neuropathic Pain

by | Apr 23, 2018 | 2017, Amino Acids, Carnitine

Written by Angeline A. De Leon, Staff Writer. In a mouse models of chronic inflammatory and neuropathic pain, L-acetylcarnitine provided a long-lasting analgesic effect that persisted up to 37 days after treatment withdrawal, suggesting a potential to reduce relapse in patients suffering from chronic pain.

L-acetylcarnitine (LAC) is an amino acid known for its role in supporting cellular energy production. Widely distributed throughout the tissue and nervous system of mammals, ALC assists in the conversion of fatty acids in mitochondria to adenosine triphosphate (ATP), the molecular currency of cellular energy. ALC, noted for its ability to cross the blood-brain barrier, is also involved in the management of oxidative damage and neuroinflammation and has been shown to modulate the activity of various neurotransmitter systems as well as the expression of nerve growth factor NGF (involved in the development and maintenance of nerve cells) 1,2. Clinical studies suggest that ALC is critical not only to the maintenance of optimal neurological health, but may also be used as an effective treatment for chronic pain conditions involving inflammation or dysfunctional nerves, such as neuropathic pain and fibromyalgia 3. Experimental models of neuropathy have linked chronic administration of LAC with enhanced expression of type-2 metabotropic glutamate receptors (mGlu2, involved in suppression of neuronal excitability) in regions of the nervous system involved in pain transmission 4,5. LAC’s upregulation of mGlu2 expression, resulting in reduced glutamate release from primary sensory fibers 6, represents the primary mechanism through which this amino acid produces analgesic effects against clinical conditions such as chemotherapy-induced neuropathy, diabetic neuropathy, and HIV-associated sensory neuropathy 7-9. Based on current findings, researchers at Sapienza University in Rome, Italy used an animal model of inflammatory and neuropathic pain to evaluate whether LAC treatment could produce a persisting analgesic effect, based on treatment-induced changes in mGlu2 receptor activity in the spinal cord 10.

A two-part experiment was carried out using adult male mice (20-25 g) purchased from Calco, Italy. In the first part of the study, chronic inflammatory pain was induced in a group of 36 mice through injection of 20 µl of heat-killed mycobacteria in a mineral oil solution. Animals then underwent a treatment regimen in which they received an injection of saline (control), LAC (100 mg/kg), a conventional antibiotic medication for nerve pain (pregabalin, amitryptiline, or ceftriaxone), or an alternating combination of the three treatments administered over a varying schedule of up to seven days. Depending on their grouping, mice were assessed for pain threshold at baseline, following the last injection, and/or at seven and 14 days following drug withdrawal. Animals were then sacrificed for measurements of mGlu2/3 receptor protein in the spinal cord. In the second part of the study, neuropathic pain was induced using controlled cortical impact of the sciatic nerve (producing traumatic brain injury) in a group of about 40 mice. Mice were then divided into five groups and were treated daily with saline, LAC, pregabalin, amitryptiline, or tramadol (narcotic) for 14 days. Pain threshold was assessed at baseline, at the end of treatment, and again at seven and 37 days following drug withdrawal. mGlu2/3 receptor protein levels were also measured.

Results showed that treatment with LAS daily for one week was sufficient to produce analgesia in a mouse model of chronic inflammatory pain (F(5,25) = 11.13, p < 0.05) and that this effect persisted for at least 14 days after drug withdrawal (F(8,24) = 4.975, p < 0.01). Western blot analysis showed that after one week of treatment, LAC also enhanced mGlu2/3 receptor protein levels in the spinal cord and this effect persisted 14 days following drug withdrawal (F(3,23) = 5.884, p < 0.05). Two weeks of daily LAC treatment also significantly reduced pain thresholds in mice with chronic sciatic nerve injury, more so than any other drug. Effects persisted 37 days after drug withdrawal (F(14,89) = 8.984, p < 0.05), and mGlu2/3 receptor protein levels in the spinal cord were found to be elevated, relative to those of mice treated with saline (t = -3.89, p < 0.05).

Findings suggest that through persistent up-regulation of mGlu2 receptors, which are critically involved in regulating pain threshold, LAC is capable of inducing long-lasting analgesia in a mouse model of inflammatory and neuropathic pain. Thus, based on these encouraging results, researchers suggest clinical studies with LAC in patients suffering from chronic inflammatory or neuropathic pain in which the relapse rate at different time intervals after drug withdrawal is included as a primary endpoint.

Source: Notartomaso S, Mascio G, Bernabucci M, et al. Analgesia induced by the epigenetic drug, L-acetylcarnitine, outlasts the end of treatment in mouse models of chronic inflammatory and neuropathic pain. Molecular Pain. 2017; 13: 1-12. DOI: 10.1177/1744806917697009.

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Posted April 23, 2018.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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