Korean J Pain.  2013 Oct;26(4):356-360. 10.3344/kjp.2013.26.4.356.

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

• Jung KT
• Lee HY
• Yoon MH
• Lim KJ

• KMID: 2074043
• DOI: http://doi.org/10.3344/kjp.2013.26.4.356

Abstract

BACKGROUND
Nerve 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.
METHODS
Neuropathic 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.
RESULTS
The paw withdrawal thresholds were significantly increased in the rats of group 2 compared to the other groups (P < 0.05).
CONCLUSIONS
Ulinastatin, 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.

Keyword

neuropathic pain; rats; urinary trypsin inhibitor

MeSH Terms

Animals
Glycoproteins
Humans
Hypersensitivity
Ligation
Male
Nervous System
Neuralgia
Neuroprotective Agents
Rats
Rats, Sprague-Dawley
Spinal Nerves
Trypsin
Veins
Glycoproteins
Neuroprotective Agents
Trypsin

Figure

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  Fig. 1 Schematic diagram of study design. UTI: urinary trypsin inhibitor.

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  Fig. 2 Withdrawal thresholds of paw in rats were observed for 3 days from 5th day after spinal nerve ligation. The withdrawal thresholds were significantly increased in the rats of group 2 than those of group 1 (P < 0.05). *P < 0.05 compared with the group 1. Group 1, Sham group; Group 2, UTI 50,000 U/kg administration from the day of SNL for 3 days before neuropathic pain has evoked; Group 3-15 min, withdrawal thresholds were assessed 15 minutes after UTI injection, UTI 50,000 U/kg administration was started from the 5th day after SNL, which is after neuropathic pain has evoked; Group 3-30 min, withdrawal thresholds were assessed 30 minutes after UTI injection, UTI 50,000 U/kg administration was started from the 5th day after SNL, which is after neuropathic pain has evoked; Day 5, 5th day after spinal nerve ligation; Day 6, 6th day after spinal nerve ligation; Day 7, 7th day after spinal nerve ligation. Values are mean ± SD of withdrawal threshold.

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  Fig. 3 Percentage of maximal possible effect (%MPE) according to the groups. Group 2 showed the largest MPE at the 5th day after SNL. Group 2, UTI 50,000 U/kg administration from the day of SNL for 3 days before neuropathic pain has evoked; Group 3-15 min, withdrawal thresholds were assessed 15 minutes after UTI injection, UTI 50,000 U/kg administration was started from the 5th day after SNL, which is after neuropathic pain has evoked; Group 3-30 min, withdrawal thresholds were assessed 30 minutes after UTI injection, UTI 50,000 U/kg administration was started from the 5th day after SNL, which is after neuropathic pain has evoked; Day 5, 5th day after spinal nerve ligation; Day 6, 6th day after spinal nerve ligation; Day 7, 7th day after spinal nerve ligation. Values are mean ± SD of withdrawal threshold.

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