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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\u2010<jats:sc>L\u2010C<\/jats:sc>arnitine (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\u2010pressure 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\u2010linked inhibitor of apoptosis protein\u2013related protective effect of ALCAR on the apoptosis induced by ligation of the sciatic nerve. Taken together, these data highlight the relevance of nicotinic modulation in neuropathy treatment. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21815","type":"journal-article","created":{"date-parts":[[2008,8,15]],"date-time":"2008-08-15T17:07:38Z","timestamp":1218820058000},"page":"200-207","source":"Crossref","is-referenced-by-count":43,"title":["Neuroprotective effects of acetyl\u2010<scp>L<\/scp>\u2010carnitine on neuropathic pain and apoptosis: A role for the nicotinic receptor"],"prefix":"10.1002","volume":"87","author":[{"given":"Lorenzo","family":"Di Cesare Mannelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Ghelardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menotti","family":"Calvani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Nicolai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Mosconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Toscano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Pacini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Bartolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,8,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2005.01.010"},{"key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.279.5347.77","article-title":"Broad spectrum, non\u2010opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors","volume":"279","author":"Bannon AW","year":"1998","journal-title":"Science"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90209-6"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00667-5"},{"key":"e_1_2_5_6_1","first-page":"297","article-title":"The role of carnitine in intracellular metabolism","volume":"28","author":"Bremer J","year":"1990","journal-title":"J Clin Chem Clin Biochem"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bse0330043"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm070018l"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-006-5700-3"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.5.989"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03033901"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509313103"},{"key":"e_1_2_5_13_1","first-page":"418","article-title":"Visceral pain","volume":"55","author":"Davis L","year":"1932","journal-title":"Surg Gynecol Obstet"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05722.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.1989.11739863"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.03.016"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(02)00225-3"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-002-1100-2"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90826-4"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01302-4"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.08.010"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03750.x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008035200"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00138-3"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb10310.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705653"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0736-5748(92)90021-Q"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2006.04.003"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00982-5"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03290-0"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1085-9489.2006.00066.x"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000805"},{"key":"e_1_2_5_33_1","first-page":"5756","article-title":"Paclitaxel and cisplatin\u2010induced neurotoxicity. 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