Effects of caloric restriction on neuropathic pain, peripheral nerve degeneration and inflammation in normometabolic and autophagy defective prediabetic Ambra1 mice

• DOI: 10.1371/journal.pone.0208596
• Publication Date: 2018-12-10T19:30:28Z
• Authors: Roberto Coccurello; Francesca Nazio; Claudia Rossi; Federica De Angelis; Valentina Vacca; Giacomo Giacovazzo; Patrizia Procacci; Valerio Magnaghi; Domenico Ciavardelli; Sara Marinelli
• Keywords: Male; 0301 basic medicine; Heterozygote; 571; Science; Mice, Transgenic; AMP-Activated Protein Kinases; Prediabetic State; Mice; 03 medical and health sciences; Carnitine; Autophagy; Animals; Amino Acids; Adaptor Proteins, Signal Transducing; Caloric Restriction; neuropathic pain; Inflammation; Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA; Diabetes; Q; R; Autophagic cell death Sciatic nerves Energy metabolism Glucose metabolism Blood Insulin Neuropathic pain Diabetes mellitus; 3. Good health; Glucose; Nerve Degeneration; Medicine; Cytokines; Neuralgia; Schwann Cells; Insulin Resistance; Energy Metabolism; Research Article

There is a growing interest on the role of autophagy in diabetes pathophysiology, where development neuropathy one most frequent comorbidities. We have previously demonstrated that neuropathic pain after nerve damage exacerbated autophagy-defective heterozygous Ambra1 mice. Here, we show existence prediabetic state mice, characterized by hyperglycemia, intolerance to glucose and insulin resistance. Thus, further investigate hypothesis prediabetes may account for exacerbation allodynia chronic counteracting deficit relieve condition. took advantage from caloric restriction (CR) able exert double action: powerful increase control metabolic status. found CR ameliorates throughout anti-inflammatory mechanisms both WT animals subjected injury. Moreover, discovered lesion represents, per se, stressor reinstates homeostasis, resistance, incomplete fatty acid oxidation energy metabolism. As inducer, promotes anticipates Schwann cell via AMP-activated protein kinase (AMPK) facilitates remyelination peripheral nerve. In summary, provide new evidence metabolism identify depletion dietary therapeutic approach fight against pain.