Relationship between VEGF and ERK signaling pathway in spinal dorsal horns of rats with neuropathic pain

Abstract

Objective To evaluate the relationship between vascular endothelial growth factor (VEGF) and extracellular signal-regulated kinase (ERK) signaling pathway in spinal dorsal horns of rats with neuropathic pain.Methods Twenty male Sprague-Dawley rats,aged 2 months,weighing 160-320 g,were randomly divided into 4 groups (n =5 each):sham operation group (group S); chronic constrictive injury (CCI) group; normal saline group (NS group); VEGF antibody group.Neuropathic pain was induced by CCI.The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The left sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.In group S,the left sciatic nerve was only exposed but not ligated.In VEGF antibody group,VEGF antibody 0.3μg/15 μl was injected intrathecally every 2 days for 4 times starting from 2 h after CCI,while the equal volume of normal saline was injected in NS group.Paw withdrawal threshold to von Frey filament stimulation (PWMT) and paw withdrawal latency to nociceptive thermal stimulation (PWTL) were measured at 1 day before CCI (T1),and 1,3,5 and 7 days after CCI (T2-5).The rats were sacrificed after PWMT and PWTL were measured and the L4-6 segments of the spinal cord were removed for determination of phosphorylated ERK (p-ERK) expression in spinal dorsal horns by immunohistochemistry and Western blot.Results Compared with group S,PWMT and PWTL were significantly decreased at T2-5,and the p-ERK expression in spinal dorsal horns was up-regulated in CCI and VEGF antibody groups (P ＜ 0.05).Compared with CCI group,PWMT and PWTL were significantly increased at T3-5,and the p-ERK expression in spinal dorsal horns was down-regualted in VEGF antibody group (P ＜ 0.05).Conclusion VEGF in the spinal dorsal horn is involved in the development and maintenance of neuropathic pain in rats through activating ERK signaling pathway. Key words: Vascular endothelial growth factors; Extracellular signal-regulated MAP kinases; Neuralgia ; Spinal cord