Role of interleukin-1β in activation of NMDA receptors in spinal dorsal horns of rats with neuropathic pain

Abstract

Objective To evaluate the role of interleukin-1β (IL-1β) in activation of N-methyl-D-aspartate (NMDA) receptors in spinal dorsal horns of rats with neuropathic pain. Methods One hundred twenty-eight pathogen-free healthy adult male Sprague-Dawley rats, weighing 200-250 g, were divided into 4 groups (n=32 each) using a random number table: control group (group C), recombinant adenovirus vector group (group rAd), recombinant adenovirus vector shRNA group (group rAd/shRNA), and recombinant adenovirus vector shRNA plus recombinant adenovirus vector IL-1β group (group rAd/shRNA+ rAd/IL-1β), receiving intrathecally injected equal volume of 0.9% sodium chloride solution, recombinant adenovirus vector, recombinant adenovirus vector shRNA, and recombinant adenovirus vector shRNA plus recombinant adenovirus vector IL-1β 5 μl, respectively.Chronic compression of dorsal root ganglia was performed on 8th day after intrathecal injection.The thermal paw withdrawal latency (TWL) was measured at 1 day before intrathecal injection (T0) and at 1, 2, 3 and 5 weeks after intrathecal injection (T1-4). After measurement of the pain threshold at each time point, 8 rats selected randomly were anesthetized and sacrificed, and the lumbar enlargement segments of the spinal cord were harvested for determination of the expression of IL-1β and phosphorylated NMDA receptor NR1 subunits at serine 896 (pNR1S896) in spinal dorsal horns on the injured side by immunohistochemistry and Western blot. Results Compared with group C, the TWL was significantly prolonged, and the expression of IL-1β and pNR1S896 in spinal dorsal horns was significantly down-regulated at T2-4 in group rAd/shRNA (P 0.05). Compared with group rAd, the TWL was significantly prolonged, and the expression of IL-1β and pNR1S896 in spinal dorsal horns was significantly down-regulated at T2-4 in group rAd/shRNA (P 0.05). Compared with group rAd/shRNA, the TWL was significantly shortened, and the expression of IL-1β and pNR1S896 in spinal dorsal horns was significantly up-regulated at T2-4 in group rAd/shRNA+ rAd/IL-1β (P<0.05). Conclusion IL-1β is involved in the activation of NMDA receptors in spinal dorsal horns of rats with reuropathic pain. Key words: Interleukin-1beta; Neuralgia; Spinal cord; Receptors, N-methyl-D-aspartate