title: Patterns of nerve injury and neuropathic pain in ischemic neuropathy after ligation-reperfusion of femoral artery in mice.
abstract: Ischemia is an important etiology of painful neuropathies. We generated a mouse system of ischemic neuropathy by ligation-reperfusion of the femoral artery to mimic neuropathic pain and nerve injury patterns observed clinically. Mice exhibited spontaneous neuropathic pain behaviors, which were most obvious after ischemia for 5 h. Mechanical and cold allodynia developed by post-operative day (POD) 7 and persisted through the experimental period up to POD 56. Neuropathic pain behaviors were alleviated with intraperitoneal gabapentin (50 and 100 mg/kg) in a dose-dependent manner. Large-fiber deficit assessed with nerve conduction studies was demonstrated by reduced amplitudes of the compound muscle action potential (CMAP) on POD 7 (48.4% of the control side, p < 0.001). Small-fiber impairment was demonstrated by decreased epidermal nerve density (END) on POD 7 (29.1% of the control side, p < 0.001). Reductions in CMAP amplitudes and ENDs persisted through POD 56. Our system replicated the clinical manifestations of ischemic neuropathy: (1) neuropathic pain with cold and mechanical allodynia and (2) nerve injury to both large and small fibers with pathologic and physiologic evidence. This system produced by a simple procedure provides an opportunity to investigate mechanisms and further treatments of ischemic neuropathy on genetically engineered mice.
authors.affiliation: Department of Neurology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jing-Er
authors.initials: JE
authors.lastname: Lee
authors.forename: Kuo-Chuan
authors.initials: KC
authors.lastname: Wang
authors.forename: Hou-Yu
authors.initials: HY
authors.lastname: Chiang
authors.forename: Jung-Hsien
authors.initials: JH
authors.lastname: Hsieh
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
mesh_terms: D000588:Amines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D000077206:Gabapentin; D008026:Ligation; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin