title: 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 U pre received ulinastatin (50,000 U/kg) intravenously for three days immediately following SNL, and group U post received ulinastatin (50,000 U/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 U pre compared with the rats from groups N and U post until the 7th post-SNL day (P<0.05). The levels of IL-6 also were significantly decreased in the rats from group U pre compared with the rats from group N and U post 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.
authors: The Division of Natural Medical Sciences, College of Health Science, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759, South Korea. Electronic address: seonh@chosun.ac.kr.
authors: Seon Hee
authors: SH
authors: Oh
authors: Department of Anesthesiology and Pain Medicine, Chosun University Hospital, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, South Korea. Electronic address: lsopp@naver.com.
authors: Hyung Jin
authors: HJ
authors: So
authors: Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, Chosun University Hostpital, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, South Korea. Electronic address: lhy109@chosun.ac.kr.
authors: Hyun Young
authors: HY
authors: Lee
authors: Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, Chosun University Hostpital, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, South Korea. Electronic address: kjlim@chosun.ac.kr.
authors: Kyung Joon
authors: KJ
authors: Lim
authors: Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University, 42 Jebongro, Donggu, Gwangju 501-757, South Korea. Electronic address: mhyoon@chonnam.ac.kr.
authors: Myung Ha
authors: MH
authors: Yoon
authors: Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, Chosun University Hostpital, 365 Pilmun-daero, Dong-gu, Gwangju 501-717, South Korea. Electronic address: mdmole@chosun.ac.kr.
authors: Ki Tae
authors: KT
authors: Jung
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000293:injuries*; D014110:Touch; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D006023:Glycoproteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; C028665:urinastatin
keywords: Interleukin-1β; Interleukin-6; Neuropathic pain; Rat; Tumor necrosis factor alpha (TNF-α); Urinary trypsin inhibitor