Acetyl- l -carnitine increases artemin level and prevents neurotrophic factor alterations during neuropathy

• Published in: Neuroscience Vol. 167; no. 4; pp. 1168 - 1174
• Main Authors: Vivoli, E, Di Cesare Mannelli, L, Salvicchi, A, Bartolini, A, Koverech, A, Nicolai, R, Benatti, P, Ghelardini, C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 02.06.2010
• Subjects: Acetyl-L-carnitine; Acetylcarnitine - pharmacology; Analgesics - pharmacology; Animals; Biological and medical sciences; Constriction, Pathologic - complications; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - metabolism; Male; Nerve Growth Factors - metabolism; Nerve Tissue Proteins - metabolism; Neurology; Neuroprotective Agents - pharmacology; Pain - etiology; Pain - metabolism; Pain Threshold; Periaqueductal Gray - metabolism; Peripheral Nervous System Diseases - etiology; Peripheral Nervous System Diseases - metabolism; Rats; Rats, Sprague-Dawley; Sciatic Nerve - injuries; Spinal Cord - metabolism; Vertebrates: nervous system and sense organs; pain; acetyl- l-carnitine; periaqueductal grey matter; artemin; dorsal root ganglia; CCI; chronic constriction injury; NGF; glial cell line-derived neurotrophic factor; GDNF; ARTN; nerve growth factor; PAG; neurorestoration; DRG; ALCAR; Neurotrophic factor; Pain; Glial cell line derived neurotrophic factor; Nerve growth factor
• ISSN: 0306-4522; 1873-7544; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.03.017

Abstract Damages to the nervous system are the primarily cause of neuropathy and chronic pain. Current pharmacological treatments for neuropathic pain are not able to prevent or revert morphological and molecular consequences of tissue injury. On the other hand, many neurotrophins, like nerve growth factor (NGF), paired off restorative effects with hyperalgesia. Interestingly, the glial cell line–derived neurotrophic factors GDNF and Artemin (ARTN) seem to support neuron survival and to normalize abnormal pain behaviour. In the present research protein levels of NGF, GDNF and ARTN were evaluated in a rat model of peripheral neuropathy, the chronic constriction injury (CCI). NGF was increased by CCI in the ipsilateral dorsal root ganglia (DRG), in the spinal cord and in the periaqueductal grey matter (PAG). On the contrary, ARTN was decreased bilaterally in DRG, spinal cord and PAG. GDNF levels decreased in ipsilateral DRG, whereas the constriction did not modify its expression in the central nervous system districts. Repeated treatments with the antihyperalgesic and neuroregenerative compound acetyl- l -carnitine (ALCAR; 100 mgkg−1 i.p. twice daily for 15 days) was able to prevent the increase of NGF levels. In conditions of pain relief ALCAR normalized peripheral and central alterations of GDNF and ARTN levels. Characteristically, sham animals that underwent the same ALCAR treatment, showed increased levels of ARTN both in the DRG and in the spinal cord. These data offer a new point of view on the mechanism of the antihyperalgesic as well as the neuroprotective effect of ALCAR.