title: Effect of levetiracetam versus gabapentin on peripheral neuropathy and sciatic degeneration in streptozotocin-diabetic mice: Influence on spinal microglia and astrocytes.
abstract: Peripheral diabetic neuropathy develops in diabetic patients. The current study tested the antiallodynic and antihyperalgesic effects of the anticonvulsant drug, levetiracetam compared with the standard drug, gabapentin, in a model of streptozotocin-induced peripheral diabetic neuropathy. Male albino mice were injected intraperitoneally with streptozotocin (40mg/kg) for five consecutive days to induce type 1 diabetes mellitus. After development of peripheral diabetic neuropathy, mice were then treated orally with 10 doses of levetiracetam or gabapentin (or vehicle). The effect of multiple doses of levetiracetam on the histopathology of sciatic nerve and spinal cord was tested. Furthermore, the effect of levetiracetam on the spinal expression of microglia and astrocytes was examined in comparison with gabapentin. Results indicated that the highest dose of levetiracetam and all doses of gabapentin increased the withdrawal threshold in von Frey test. Furthermore, all doses of levetiracetam and gabapentin prolonged the reaction time exhibited by diabetic mice tested in hot plate test. Both drugs provided protection for the sciatic nerve and the spinal cord. In addition, levetiracetam (20 and 40mg/kg) decreased spinal immunostaining for CD11b (microglia marker) and glial fibrillary acidic protein (GFAP, astrocytes marker) however; the high dose of gabapentin (40mg/kg) reduced the spinal immunostaining for GFAP only. In conclusion, levetiracetam produced antiallodynic and antihyperalgesic effect in diabetic mice with favorable effects on sciatic nerve and spinal cord that were accompanied by downregulation of the spinal expression of microglia and astrocytes. Thus, levetiracetam may have promise in alleviating neuropathic pain in diabetic patients.
authors.affiliation: Medical Center, Port-Said University, Port-Said, Egypt.
authors.forename: Heba M
authors.initials: HM
authors.lastname: Reda
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. Electronic address: Sawsan_zaytoon@pharm.suez.edu.eg.
authors.forename: Sawsan A
authors.initials: SA
authors.lastname: Zaitone
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Yasser M
authors.initials: YM
authors.lastname: Moustafa
mesh_terms: D000588:Amines / Q000627:therapeutic use*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D000077206:Gabapentin; D000077287:Levetiracetam; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D018697:Nootropic Agents / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D000077287:Levetiracetam; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D010889:Piracetam
keywords: Gabapentin; Hot plate test; Levetiracetam; Peripheral diabetic neuropathy; Spinal glia; Von Frey test