The Effect of Urinary Trypsin Inhibitor Against Neuropathic Pain in Rat Models

Abstract

BackgroundNerve injury sometimes leads to chronic neuropathic pain associated with neuroinflammation in the nervous system. In the case of chronic neuropathic pain, the inflammatory and algesic mediators become predominant and result in pain hypersensitivity following nervous system damage. It is well known that urinary trypsin inhibitor (ulinastatin, UTI) has an anti-inflammatory activity. Recently, the neuroprotective action of UTI on the nervous system after ischemic injury has been reported. Thus, we evaluated the neuroprotective effect of ulinastatin in a rat model of neuropathic pain.MethodsNeuropathic pain was induced with L5 spinal nerve ligation (SNL) in male Sprague-Dawley rats weighing 100-120 g. The rats were divided into 3 groups, with n = 8 in each group. The rats in the control group (group 1) were administered normal saline and those in group 2 were administered UTI (50,000 U/kg) intravenously through the tail vein for 3 days from the day of SNL. Rats in group 3 were administered UTI (50,000 U/kg) intravenously from the 5th day after SNL. The paw withdrawal threshold was measured using the von Frey test for 3 days starting from the 5th day after SNL.ResultsThe paw withdrawal thresholds were significantly increased in the rats of group 2 compared to the other groups (P < 0.05).ConclusionsUlinastatin, which was administered for 3 days after SNL, increased the paw withdrawal threshold and it could have a neuroprotective effect in the rat model of neuropathic pain.

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

“…First, only one dose of UTI (50,000 U/kg intravenously) was used in the present study. We used the dosage of UTI which was effective in the previous study which was conducted as a preliminary study [12]. However, another study on the effect of UTI on the inflammatory response demonstrated the inhibition of TNF-␣ production with a higher dosage [23].…”

“…The rats in group U pre were administered 50,000 U/kg of UTI (Ulistin ® , Hanlim Pharmaceutical Co. Ltd., Seoul, Korea) through the tail vein for three days immediately following the SNL procedure, before the development of neuropathic pain was confirmed. The rats in group U post were administered 50,000 U/kg of UTI through the tail vein for three days from the 3rd day following the SNL procedure, after the development of neuropathic pain was confirmed [12].…”

“…Moreover, ulinastatin is also effective in the protection of the nervous system after an injury [10,11]. A recent study has demonstrated the possibility of using ulinastatin to reduce pain in a rat model following spinal nerve ligation (SNL) [12].…”

Gabexate mesilate ameliorates the neuropathic pain in a rat model by inhibition of proinflammatory cytokines and nitric oxide pathway via suppression of nuclear factor-κB

“…In terms of neuroinflammation, serine protease inhibitor has inhibitory properties on the proinflammatory cytokines and has the effect of attenuating the development of neuropathic pain [2,14]. Gabexate mesilate is one of those serine protease inhibitors with properties of antiinflammation and TNF-α inhibition by the suppression of NF-κB and the NO pathway [13,15,17] which are closely related with an inflammatory response and the development of neuropathic pain after spinal nerve injury.…”

“…Its property of TNF-α inhibition via monocyte also provides effectiveness in the treatment of sepsis-associated disseminated intravascular coagulation [13]. Recent studies have shown that the inhibitory effects of serine protease inhibitor on the proinflammatory cytokines can attenuate the development of neuropathic pain [2,14]. Gabexate mesilate also showed a protective effect after spinal cord trauma by inhibition of the increase in the myeloperoxidase activity in an animal model [15].…”