Ickowicz Diana E, Golovanevski Ludmila, Haze Amir, Domb Abraham J, Weiniger Carolyn F
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel.
J Pharm Sci. 2014 Jan;103(1):185-90. doi: 10.1002/jps.23770. Epub 2013 Nov 20.
Local anesthetics play an important role in postoperative pain management in orthopedic joint procedures. The aim of this study was to determine the effect of an intraoperative extra-articular injection of poly(DL-lactic acid co castor oil 3:7), p(DLLA:CO) 3:7 loaded with 15% bupivacaine, for postoperative analgesia following knee arthroplasty. Prolonged release local anesthetic formulation was synthesized by mixing p(DLLA:CO) 3:7 with bupivacaine base. Under anesthesia, the knee joint of Sprague-Dawley rats was exposed, a hole drilled in the femoral trochlea. 0.2 mL of either 15% polymer-bupivacaine formulation or plain bupivacaine (control) was injected locally and compared with a nonsurgery control group. Mechanical hyperalgesia was determined by counting the vocalizations and leg withdrawal after joint squeezing. Behavioral assessments over a day postoperative period revealed a reduction in rearing and ambulation in an open-field apparatus in animals of both experimental groups compared with the nonsurgery control. The vocalizations during the hyperalgesia test increased compared with the control at 24 h. At 48 h, 3.667 ± 0.5138, p = 0.0076 vocalizations were recorded for the plain bupivacaine group versus 1.417 ± 0.5138, p < 0.0001 in the 15% polymer-bupivacaine formulation. Bupivacaine encapsulated in p(DLLA:CO) 3:7 extended the duration of the analgesia compared with plain drug in rats and could represent effective postoperative analgesic in orthopedic joint procedures.
局部麻醉剂在骨科关节手术的术后疼痛管理中发挥着重要作用。本研究的目的是确定术中在关节外注射含15%布比卡因的聚(DL-乳酸共蓖麻油3:7)[p(DLLA:CO) 3:7]对膝关节置换术后镇痛的效果。通过将p(DLLA:CO) 3:7与布比卡因碱混合合成长效局部麻醉剂制剂。在麻醉状态下,暴露Sprague-Dawley大鼠的膝关节,在股骨滑车钻一个孔。局部注射0.2 mL的15%聚合物-布比卡因制剂或普通布比卡因(对照组),并与非手术对照组进行比较。通过计数关节挤压后的发声次数和腿部回缩情况来确定机械性痛觉过敏。术后一天的行为评估显示,与非手术对照组相比,两个实验组动物在旷场装置中的竖毛和走动次数减少。痛觉过敏测试期间的发声次数在24小时时与对照组相比增加。在48小时时,普通布比卡因组记录到3.667±0.5138次发声,p = 0.0076,而15%聚合物-布比卡因制剂组为1.417±0.5138次发声,p < 0.0001。与普通药物相比,包裹在p(DLLA:CO) 3:7中的布比卡因延长了大鼠的镇痛时间,可能是骨科关节手术有效的术后镇痛剂。