Urinary trypsin inhibitor attenuates the development of neuropathic pain following spinal nerve ligation

Abstract

Following nerve injury, inflammatory and algesic mediators are released. This neuroinflammatory outbreak causes neuronal damage and chronic neuropathic pain. Urinary trypsin inhibitor (ulinastatin, UTI), which has anti-inflammatory properties and neuroprotective effects, is used to lower the levels of inflammatory factors during surgery. This study evaluated the effect of ulinastatin in a rat model of spinal nerve ligation (SNL). Neuropathic pain was induced by L5 and L6 SNL in male Sprague–Dawley rats. Rats were divided into three groups: group N (control) received normal saline through the tail vein for three days immediately following SNL, group Upre received ulinastatin (50,000U/kg) intravenously for three days immediately following SNL, and group Upost received ulinastatin (50,000U/kg) intravenously for three days from the 3rd day following SNL. The paw withdrawal threshold was examined and the development of mechanical allodynia was confirmed with a behavioral test using a von Frey filament three days following SNL. On the 3rd, 5th, 7th, 14th, and 28th day following SNL, the paw withdrawal threshold was examined and the levels of inflammatory mediators (i.e., tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and interleukin-6 [IL-6]) were measured by ELISA. The paw withdrawal threshold was significantly increased in the rats from group Upre compared with the rats from groups N and Upost until the 7th post-SNL day (P<0.05). The levels of IL-6 also were significantly decreased in the rats from group Upre compared with the rats from group N and Upost until the 7th post-SNL day (P<0.05). Ulinastatin increased the paw withdrawal threshold following SNL when it was administered before the development of neuropathic pain, and may attenuate the development of neuropathic pain.