Background/Objective:Peripheral-nerve blocks (PNBs) using continuous-infusion of local anesthetics are used to provide perioperative analgesia. Yet little research exists to characterize the histopathological effects of continuous long-duration PNBs. Herein we test the hypothesis that continuous peri-neural bupivacaine infusion (3-day vs. 7-day infusion) contributes to histologic injury in a duration-dependent manner using an in vivo model of rat sciatic nerves. Methods:We placed indwelling catheters in 22 rats for infusion with low-dose (0.5mg/kg/hr) bupivacaine or normal saline proximal to the right sciatic nerves for 3 or 7 consecutive days. Hind-limb analgesia was measured using Von-Frey nociceptive testing. At infusion end, rats were sacrificed, bilateral nerves were sectioned and stained with hematoxylin and eosin and CD68 for evaluation of inflammatory response, and eriochrome to assess damage to myelin. Results:Animals receiving continuous infusion of bupivacaine maintained analgesia as demonstrated by significant decrease (50%on average) in nociceptive response in bupivacaine-infused limbs across time points. Both 7-day saline and bupivacaine-infused sciatic nerves showed significantly-increased inflammation by H&E staining compared to untreated native nerve controls (P = 0.0001, P < 0.0001). Extent of inflammation did not vary significantly based on infusate (7-day saline vs. 7-day bupivacaine P > 0.99) or duration (3-day bupivacaine vs 7-day bupivacaine P > 0.99). No significant change in sciatic nerve myelin was found in bupivacaine-infused animals compared to saline-infused controls, regardless of duration. Conclusions:Long-duration (7-day) bupivacaine infusion provided durable post-operative analgesia, yet contributed to equivalent neural inflammation as short duration (3-day) infusion of bupivacaine or saline with no evidence of demyelination.

中文翻译：

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延长神经周围布比卡因输注对大鼠坐骨神经（轴突和髓鞘）的影响

背景/目的：使用持续输注局部麻醉剂的外周神经阻滞（PNB）用于围手术期镇痛。然而，很少有研究来描述连续长期 PNB 的组织病理学影响。在这里，我们使用大鼠坐骨神经的体内模型检验了连续神经周围布比卡因输注（3 天与 7 天输注）以持续时间依赖性方式导致组织学损伤的假设。方法：我们在 22 只大鼠体内放置留置导管，连续 3 或 7 天在右侧坐骨神经附近输注低剂量（0.5mg/kg/hr）布比卡因或生理盐水。使用 Von-Frey 伤害性测试测量后肢镇痛。在输注结束时，处死大鼠，双侧神经被切片并用苏木精、伊红和 CD68 染色以评估炎症反应，并用 eriochrome 评估髓鞘损伤。结果：接受连续输注布比卡因的动物维持镇痛，如在不同时间点输注布比卡因的肢体的伤害性反应显着降低（平均 50%）。与未经处理的天然神经对照相比，7 天盐水和布比卡因注入的坐骨神经通过 H&E 染色显示炎症显着增加（P = 0.0001，P < 0.0001）。根据输液（7 天盐水 vs. 7 天布比卡因 P > 0.99）或持续时间（3 天布比卡因 vs 7 天布比卡因 P > 0.99），炎症程度没有显着差异。与注射盐水的对照组相比，注射布比卡因的动物的坐骨神经髓鞘没有显着变化，无论持续时间长短。结论：长时间（7 天）布比卡因输注提供了持久的术后镇痛，但与短时间（3 天）布比卡因或盐水输注导致的神经炎症相当，没有脱髓鞘迹象。