Role of interleukin-17 in peripheral nerve in blood-nerve barrier injury in a rat model of neuropathic pain

Abstract

Objective To evaluate the role of interleukin-17 (IL-17) in the peripheral nerve in blood-nerve barrier injury in a rat model of neuropathic pain(NP). Methods Forty healthy adult male Sprague-Dawley rats, weighing 250-280 g, were divided into 4 groups (n=10 each) using a random number table method: sham operation group(Sham group), NP group, blank vector group (BV group) and IL-17 siRNA recombinant lentivirus group (siRNA group). The rats were anesthetized with chloral hydrate, and intrathecal catheters were implanted.NP was produced by chronic constriction injury (CCI) to the sciatic nerve.Normal saline 10 μl was intrathecally injected at day 3 after CCI in Sham and NP groups.Blank vector and IL-17 siRNA-GFP recombinant lentivirus 1×107 TU 10 μl were intrathecally injected, and then the tube was washed using normal saline 10 μl with the total volume of 20 μl once a day for 4 consecutive days.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured on day 1 before CCI and days 1, 7, 10, 11, 12, 13 and 14 after CCI.Animals were sacrificed after the last behavior testing, and a segment of injured sciatic nerve 7 mm in length and containing 3 ligatures were harvested for examination of the ultrastructure and for detection of the expression of IL-17, occludin and claudin-5 by Western blot. Results Compared with Sham group, the MWT was significantly decreased, TWL was shortened, the expression of IL-17 was up-regulated, and the expression of occludin and claudin-5 was down-regulated at each time point after CCI in the other groups (P<0.05 or 0.01). Compared with NP group or with BV group, the MWT was significantly increased, TWL was prolonged, the expression of IL-17 was down-regulated, the expression of occludin and claudin-5 was up-regulated (P<0.05), and the pathological changes of sciatic nerve were significantly attenuated in siRNA group. Conclusion The mechanism of blood-nerve barrier injury may be related to increased level of IL-17 in the peripheral nerve in a rat model of NP. Key words: Interleukin-17; Neuralgia; Blood-nerve barrier