Department of Anesthesiology and.
Br J Anaesth. 2012 Dec;109(6):957-67. doi: 10.1093/bja/aes302. Epub 2012 Aug 23.
Single applications of sustained-release local anaesthetics may provide prolonged pain relief without requiring indwelling catheters, but have not yet been investigated for epidural postoperative pain management. We synthesized injectable sustained-release lidocaine particles (SRLPs) from biodegradable polymers and examined their effect in a rat model of postoperative pain.
Two types of polylactic acid particles, SRLP-10 and SRLP-25, containing 10% or 25% lidocaine, respectively, were generated and the lidocaine release was evaluated in vitro for 14 days. The SRLPs were then injected epidurally in the male Sprague-Dawley rats immediately before they received a hindpaw incision (the postoperative pain model), and hindpaw hypersensitivity was evaluated with the von Frey test. Motor paralysis and coordination were also assessed using a paralysis score and rota-rod test. Neurotoxicity and inflammation of the spinal cord, cauda equina, and tissue surrounding the injection site were histologically evaluated.
In vitro, SRLP-10 and SRLP-25 released lidocaine over 7 and 3 days, respectively. The in vivo injection of SRLP-10 (80 mg) produced anti-hypersensitivity with no evidence of motor paralysis for 7 days after the paw incision, and SRLP-25 (60 mg) inhibited postoperative hypersensitivity for 7 days. Temporary motor paralysis (15 min) was observed after the injection of SRLP-25 (even with 40 mg). Foreign body reactions were observed around the SRLP injection site at 1 and 4 weeks after injection. No histopathological changes were observed at 1 or 4 weeks.
The epidural injection of SRLPs produced prolonged anti-hypersensitivity in a rat model of postoperative pain with no major complications.
单次应用缓释局部麻醉剂可能提供持久的疼痛缓解,而无需留置导管,但尚未在硬膜外术后疼痛管理中进行研究。我们从可生物降解聚合物中合成了可注射缓释利多卡因颗粒(SRLP),并在大鼠术后疼痛模型中研究了其效果。
生成了两种类型的聚乳酸颗粒,SRLP-10 和 SRLP-25,分别含有 10%或 25%的利多卡因,并在体外评估了 14 天的利多卡因释放情况。然后,在雄性 Sprague-Dawley 大鼠接受后足切口(术后疼痛模型)之前,将 SRLP 硬膜外注射,并使用 von Frey 测试评估后足过敏。还使用瘫痪评分和旋转棒测试评估运动麻痹和协调。使用组织学评估脊髓、马尾和注射部位周围组织的神经毒性和炎症。
体外,SRLP-10 和 SRLP-25 分别在 7 天和 3 天内释放利多卡因。SRLP-10(80mg)的体内注射在足切口后 7 天内产生抗过敏作用,且无运动麻痹迹象,而 SRLP-25(60mg)抑制术后过敏反应持续 7 天。注射 SRLP-25 后(即使是 40mg)也观察到短暂的运动麻痹(15 分钟)。在 SRLP 注射部位周围观察到异物反应,分别在注射后 1 周和 4 周。在 1 周和 4 周时均未观察到组织病理学变化。
硬膜外注射 SRLP 在大鼠术后疼痛模型中产生了持久的抗过敏作用,没有出现重大并发症。