High-Intensity Ultrasound Treatment for Vincristine-Induced Neuropathic Pain

Youn, Youngwon; Hellman, Abigail; Walling, Ian; Gee, Lucy; Jiang, Qian; Burdette, Clif; Frith, Lance; Pilitsis, Julie G.

doi:10.1093/neuros/nyx488

Cited by 14 publications

(9 citation statements)

References 33 publications

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“…In the past, spinal cord stimulation was induced by electrodes placed in the epidural space with pulse currents of different stimulation modalities, including high-frequency technology, bust stimulation, or other paradigms [ 40 – 43 ]. The electric field formed by electrical stimulation between the electrodes can transfer a specific amount of charge, thus altering the neuronal membrane potential, which is the basis of nerve recruitment [ 44 ]. The current study is the first to explore spinal cord neuromodulation with percutaneous LIFU stimulation.…”

Section: Discussionmentioning

confidence: 99%

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo

Liao

Chen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Although neurocircuits can be activated by focused ultrasound stimulation, it is unclear whether this is also true for spinal cord neurocircuits. In this study, we used low-intensity focused ultrasound (LIFU) to stimulate lumbar 4–lumbar 5 (L4–L5) segments of the spinal cord of normal Sprague Dawley rats with a clapper. The activation of the spinal cord neurocircuits enhanced soleus muscle contraction as measured by electromyography (EMG). Neuronal activation and injury were assessed by EMG, western blotting (WB), immunofluorescence, hematoxylin and eosin (H&E) staining, Nissl staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and the Basso–Beattie–Bresnahan locomotor rating scale. When the LIFU intensity was more than 0.5 MPa, LIFU stimulation induced soleus muscle contraction and increased the EMG amplitudes ( P < 0.05 ) and the number of c-fos- and GAD65-positive cells ( P < 0.05 ). When the LIFU intensity was 3.0 MPa, the LIFU stimulation led to spinal cord damage and decreased SEP amplitudes for electrophysiological assessment ( P < 0.05 ); this resulted in coagulation necrosis, structural destruction, neuronal loss in the dorsal horn by H&E and Nissl staining, and increased expression of GFAP, IL-1β, TNF-α, and caspase-3 by IHC, ELISA, and WB ( P < 0.05 ). These results show that LIFU can activate spinal cord neurocircuits and that LIFU stimulation with an irradiation intensity ≤1.5 MPa is a safe neurostimulation method for the spinal cord.

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Section: Discussionmentioning

confidence: 99%

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo

Liao

Chen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…HIFU’s effect on peripheral nerve conduction may primarily be a result of temperature elevation,17 but mechanical (nonthermal and noncavitational) effects, perhaps as a result of changes in ion-channel permeability, also occur 18. Investigators have postulated that HIFU may be used to manage some pain conditions,19 and animal studies suggest further potential for this purpose 20…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent effects of high intensity focused ultrasound on compound action potentials in an ex vivo rodent peripheral nerve model: comparison to local anesthetics

Anderson

Delgado

Sun

et al. 2022

Reg Anesth Pain Med

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BackgroundIn animal models, focused ultrasound can reversibly or permanently inhibit nerve conduction, suggesting a potential role in managing pain. We hypothesized focused ultrasound’s effects on action potential parameters may be similar to those of local anesthetics.MethodsIn an ex vivo rat sciatic nerve model, action potential amplitude, area under the curve, latency to 10% peak, latency to 100% peak, rate of rise, and half peak width changes were assessed after separately applying increasing focused ultrasound pressures or concentrations of bupivacaine and ropivacaine. Focused ultrasound’s effects on nerve structure were examined histologically.ResultsIncreasing focused ultrasound pressures decreased action potential amplitude, area under the curve, and rate of rise, increased latency to 10% peak, and did not change latency to 100% peak or half peak width. Increasing local anesthetic concentrations decreased action potential amplitude, area under the curve, and rate of rise and increased latency to 10% peak, latency to 100% peak, and half peak width. At the highest focused ultrasound pressures, nerve architecture was altered compared with controls.DiscussionWhile some action potential parameters were altered comparably by focused ultrasound and local anesthetics, there were small but notable differences. It is not evident if these differences may lead to differences in clinical pain effects when focused ultrasound is applied in vivo or if focused ultrasound pressures that result in clinically relevant changes damage nerve structures. Given the potential advantages of a non-invasive technique for managing pain conditions, further investigation may be warranted in an in vivo pain model.

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“…Some minor side-effects may occur with this therapy. Pulsed LIFUS (2.05 W/cm 2 ) applied to the dorsal root ganglion reduces vincristine-induced NP and hyperalgesia [ 111 ], but this effect is accompanied by transient edema (<48h) [ 111 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence

Pérez-Neri

González-Aguilar

Sandoval

et al. 2021

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Background: For more than seven decades, ultrasound has been used as an imaging and diagnostic tool. Today, new technologies - as focused ultrasound (FUS) neuromodulation - has revealed some innovative, potential applications. However, those applications have been barely studied to deal with neuropathic pain (NP), a cluster of chronic pain syndromes with a restricted response to conventional pharmaceuticals. Objective: To analyze the therapeutic potential of low-intensity (LIFUS) and high-intensity (HIFUS) FUS for managing NP. Methods: We performed a narrative review, including clinical and experimental ultrasound neuromodulation studies published in three main database repositories. Discussion: Evidence shows that FUS may influence several mechanisms relevant for neuropathic pain managing as modulation of ion channels, glutamatergic neurotransmission, cerebral blood flow, inflammation and neurotoxicity, neuronal morphology and survival, nerve regeneration, and remyelination. Some experimental models have shown that LIFUS may reduce allodynia after peripheral nerve damage. At the same time, a few clinical studies support its beneficial effect on reducing pain in nerve compression syndromes. In turn, Thalamic HIFUS ablation can reduce NP from several etiologies with minor side-effects, but some neurological sequelae might be permanent. HIFUS is also effective useful in lowering non-neuropathic pain in several disorders. Conclusion: Although an emerging set of studies brings new evidence on the therapeutic potential of both LIFUS and HIFUS for managing NP with minor side-effects, we need more controlled clinical trials to conclude about its safety and efficacy.

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High-Intensity Ultrasound Treatment for Vincristine-Induced Neuropathic Pain

Abstract: 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.

Cited by 14 publications

References 33 publications

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo

Dose-dependent effects of high intensity focused ultrasound on compound action potentials in an ex vivo rodent peripheral nerve model: comparison to local anesthetics

Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence

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