Neuroprotective effects of acetyl-L-carnitine on neuropathic pain and apoptosis: a role for the nicotinic receptor

Journal of Neuroscience Research
Lorenzo Di Cesare MannelliAlessandro Bartolini

Abstract

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 b...Continue Reading

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Citations

May 8, 2013·European Journal of Pharmacology·Lorenzo Di Cesare MannelliCarla Ghelardini
Oct 1, 2009·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Thierry Bordet, Rebecca M Pruss
Feb 18, 2014·Journal of Neural Transmission·Calvin WuGuenter W Gross
Feb 15, 2014·BioMed Research International·Daniele TomassoniSeyed Khosrow Tayebati
Aug 24, 2013·Expert Review of Neurotherapeutics·Marco OnofrjAstrid Thomas
Dec 27, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Xiaodan LiSulan Luo
May 5, 2010·Journal of Neurochemistry·Samir P PatelAlexander G Rabchevsky
Nov 15, 2013·Neuropharmacology·Lorenzo Di Cesare MannelliCarla Ghelardini
Oct 8, 2016·Scientific Reports·Lorenzo Di Cesare MannelliCarla Ghelardini
Jan 26, 2018·Basic & Clinical Pharmacology & Toxicology·Geir BjørklundRoman Lysiuk
Jan 9, 2020·Psychopharmacology·Nazlı Turan YücelÜmide Demir Özkay
May 5, 2017·Neural Regeneration Research·Lorenzo Di Cesare Mannelli, Carla Ghelardini
Jul 28, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Laura MicheliLorenzo Di Cesare Mannelli
Sep 10, 2021·Pain Practice : the Official Journal of World Institute of Pain·Nicoletta MarchesiMassimo Allegri

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis