High-Intensity Ultrasound Treatment for Vincristine-Induced Neuropathic Pain

Neurosurgery. 2018 Nov 1;83(5):1068-1075. doi: 10.1093/neuros/nyx488.

Abstract

Background: Vincristine is a commonly used chemotherapeutic agent that results in debilitating untreatable peripheral neuropathy.

Objective: To determine the effects of pulsed high-intensity focused ultrasound (HIFU) on sensory thresholds in a validated vincristine-induced neuropathy (VIN) rodent model.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Hyperalgesia / physiopathology
  • Male
  • Neuralgia / chemically induced
  • Neuralgia / physiopathology*
  • Pain Threshold / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Ultrasonography / methods*
  • Vincristine / toxicity

Substances

  • Vincristine