The pre-emptive analgesic effect of cyclooxygenase-2 inhibitor SC-236 in rat model of acute postoperative pain

• Main Authors: Pei-Yu Ku, 古佩玉
• Other Authors: Jong-Kang Liu
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/98021441739418107094

碩士 === 國立中山大學 === 生物科學系研究所 === 99 === In clinical situations, most of the patients suffer from inflammation and acute postoperative pain after surgery. Postoperative pain has been emphasized as a very crucial issue in improving the quality of medical care in each medical center. Therefore, management of the postoperative pain is an effective approach to reduce the painful unpleasant feeling, complications, and death rate after surgery. Surgical trauma results in the induction of COX-2, leading to the release of prostaglandins, which sensitize peripheral nociceptors and increase the excitability of spinal neurons, producing pain hypersensitivity in the surrounding uninjured tissue.The purpose of this study is to test the preventive effect of COX-2 inhibitor SC-236 for post-operative pain by rat plantar incision model.Then, we explored whether SC-236 is more effective in reducing the hyperalgesia and inflammation response administered before incision than after incision. Furthermore, we used male Sprague-Dawley rats received plantar incision were used in this study, the rats received subcutaneous injection of SC-236 before or after plantar incision. Behavior teste of mechanical allodynia、thermal hyperalgesia and COX-2 expression level was determined at 4 h and 1, 2, and 3 days after surgery. Mechanical allodynia was measured by mechanical withdrawal threshold that was determined by stimulating with von Frey filaments stimulation. Thermal hyperalgesia was measured by thermal withdrawal thermal tested by radioactive thermal assay. Mechanical allodynia、thermal hyperalgesia and COX-2 expression level were measured at various time points by behavior teste、real-time polymerase chain reaction、western blot and immunohistochemistry. The data from pre-incisional injection of SC-236 was compared with that from post-incisional injection of SC-236.The results revealed pre-incisional injection of COX-2 inhibitor significantly inhibited thermal hyperalgesia but not mechanical allodynia then post-incisional injection of COX-2 inhibitor group. Skin of pre-incisional injection of SC-236 show significant decreased mRNA expression of COX-2 at 1 day and 2 day after incision evidenced by real-time polymerase chain reaction. Western blot and immunohistochemistry also show significant decreased protein expression of COX-2 at 4 hours and 1 day after incision. Therefore, pre-incisional administration of SC-236 could prevent the surgical wound induced thermal hyperalgesia and decrease mRNA and protein expression level of cutaneous COX-2 at 4 hours and one day after surgical incision compared to post-incisional administration of SC-236 .