Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, New York.
Department of Neurosurgery, Albany Medical Center, Albany, New York.
Neurosurgery. 2018 Nov 1;83(5):1068-1075. doi: 10.1093/neuros/nyx488.
Vincristine is a commonly used chemotherapeutic agent that results in debilitating untreatable peripheral neuropathy.
To determine the effects of pulsed high-intensity focused ultrasound (HIFU) on sensory thresholds in a validated vincristine-induced neuropathy (VIN) rodent model.
VIN was induced and mechanical allodynia was confirmed by nociceptive testing. von Frey fibers and Randall-Sellito test were used as measures of innocuous and noxious mechanical thresholds, respectively, and the hot plate test for thermal thresholds. Tests were performed before VIN, after 2 wk of vincristine, at 24, 48, 72, and 120 h after HIFU applied to the left L5 dorsal root ganglia at 3 Watts for 3 min. Comparisons were made between a VIN cohort who underwent HIFU, a VIN cohort who underwent sham HIFU, and naïve rodents who underwent HIFU.
VIN HIFU rats had significantly increased mechanical thresholds at 24 h (P < .001), 48 h (P = .008), 72 h (P = .003), and 120 h (P = .03) after treatment, when compared to pre-HIFU thresholds. Furthermore, at 24 and 48 h following treatment, VIN HIFU rats had significantly higher innocuous and noxious mechanical thresholds and thermal thresholds than VIN sham HIFU rats (P < .001). Thresholds were not altered in naïve rodents who underwent HIFU. Histological data of L5 dorsal root ganglia of VIN HIFU rats suggest that transient cellular edema resolves by 48 h.
Our data suggest that HIFU increases mechanical and thermal thresholds in VIN rodents. Whether HIFU can preclude the development of reduced thresholds in the VIN model warrants further study.
长春新碱是一种常用的化疗药物,会导致无法治疗的进行性周围神经病变。
在已验证的长春新碱诱导的周围神经病(VIN)啮齿动物模型中,确定脉冲高强度聚焦超声(HIFU)对感觉阈值的影响。
通过疼痛测试诱导 VIN 并确认机械性感觉过敏。von Frey 纤维和 Randall-Sellito 测试分别用于测量无害和有害机械阈值,热板测试用于测量热阈值。在 VIN 之前、长春新碱后 2 周、HIFU 后 24、48、72 和 120 小时进行测试,将 3 瓦特的 HIFU 应用于左侧 L5 背根神经节 3 分钟。将接受 HIFU 的 VIN 队列、接受假 HIFU 的 VIN 队列和接受 HIFU 的天真啮齿动物进行比较。
与 HIFU 前阈值相比,VIN HIFU 大鼠在治疗后 24 小时(P <.001)、48 小时(P =.008)、72 小时(P =.003)和 120 小时(P =.03)时机械阈值显着增加。此外,在治疗后 24 和 48 小时,VIN HIFU 大鼠的无害和有害机械阈值以及热阈值显着高于 VIN 假 HIFU 大鼠(P <.001)。接受 HIFU 的天真啮齿动物的阈值没有改变。VIN HIFU 大鼠 L5 背根神经节的组织学数据表明,细胞水肿在 48 小时内得到缓解。
我们的数据表明,HIFU 增加了 VIN 啮齿动物的机械和热阈值。HIFU 是否可以防止 VIN 模型中阈值降低的发展值得进一步研究。