title: Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy.
abstract: Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ-) induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ). At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy.
authors.affiliation: Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Newton
authors.affiliation: Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Guck
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Cotter
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors.forename: Norman E
authors.identifier: 0000-0003-3169-6277
authors.initials: NE
authors.lastname: Cameron
authors.affiliation: Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Natalie J
authors.identifier: 0000-0001-8287-1181
authors.initials: NJ
authors.lastname: Gardiner
mesh_terms: D000588:Amines / Q000494:pharmacology / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D000077206:Gabapentin; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin