Neuropathic Pain

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Focused Ultrasound Therapy

Focused ultrasound is a noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with neuropathic pain. This novel technology focuses beams of ultrasonic energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue.

How it Works
Where the beams converge, focused ultrasound produces several therapeutic effects that are being evaluated. One mechanism is the production of precise ablation (thermal destruction of tissue) enabling the destruction of the neuropathic pain without surgery. While there are several potential treatment targets, the central lateral thalamus has been the target of initial studies. Another mechanism of action is to use neuromodulation to decrease the response to the stimuli, which reduces the sensation of pain.

Advantages
The primary options for treatment of neuropathic pain include medication and invasive surgery (e.g. deep brain stimulation, radiofrequency lesioning).

Focused ultrasound is non-invasive, so it does not carry added concerns like surgical wound healing or infection. It can reach the desired target without damaging surrounding tissue, and it can be repeated, if necessary.

Clinical Trials

University of Utah 
A clinical trial is using low intensity focused ultrasound to do deep brain stimulation to help patients with chronic pain. 

Virginia Polytechnic Institute and State University
A clinical trial is investigating the treatment of patients with chronic pain with low intensity focused ultrasound. Patients can be added to this trial by invitation only.

A clinical trial is treating patients with chronic pain. Patients can be added to this trial by invitation only.

University of Virginia
There is also a clinical trial at UVA is treating patients with severe opioid resistant pain from head or neck cancer with focused ultrasound.

Another clinical trial at UVA is treating patients with chronic pain with neuromodulation from focused ultrasound and other devices.

University of Maryland
study for patients with trigeminal neuralgia has begun at the University of Maryland.

Italy
There is a clinical trial in Milan, Italy, for the treatment of neuropathic pain.

See a full list of neuropathic pain clinical trials >

Treatment Sites

See a list of treatment sites >
See a list of clinical trials sites >
See a list of laboratory research sites >

Regulatory Approval and Reimbursement

Regulatory approvals in Europe, Korea, Middle East and Russia for the treatment of neuropathic pain have been achieved.  

Notable Papers

Badran BW, Peng X. Transcranial focused ultrasound (tFUS): a promising noninvasive deep brain stimulation approach for pain. Neuropsychopharmacology. 2023 Aug 10. doi: 10.1038/s41386-023-01699-w. PMID: 37563280 

Gallay MN, Magara AE, Moser D, Kowalski M, Kaeser M, Jeanmonod D. Magnetic resonance-guided focused ultrasound central lateral thalamotomy against chronic and therapy-resistant neuropathic pain: retrospective long-term follow-up analysis of 63 interventions. J Neurosurg. 2023 Feb 24:1-10. doi: 10.3171/2023.1.JNS222879.

Anderson TA, Pacharinsak C, Vilches-Moure J, Kantarci H, Zuchero JB, Butts-Pauly K, Yeomans D. Focused ultrasound-induced inhibition of peripheral nerve fibers in an animal model of acute pain. Reg Anesth Pain Med. 2023 Feb 23:rapm-2022-104060. doi: 10.1136/rapm-2022-104060.

Magara AE, Gallay MN, Moser D, Jeanmonod D. Complete resolution of chronic cluster headache following central lateral thalamotomy using incisionless MRI-guided focused ultrasound with 6 years of follow-up: illustrative case. J Neurosurg Case Lessons. 2022 Nov 28;4(22):CASE22259. doi: 10.3171/CASE22259. Print 2022 Nov 28.   

Nachtigal A, Cozakov R, Grinfeld A, Haddad M, Eisenberg E. Feasibility of Magnetic Resonance-Guided High-Intensity-Focused Ultrasound (MRgHIFU) Ablation of Stump Neuromas for the Relief of Chronic Postamputation Neuropathic Pain. J Ultrasound Med. 2022 Dec;41(12):3119-3124. doi: 10.1002/jum.16026. Epub 2022 May 28.

Bao J, Byraju K, Patel VJ, Hellman A, Neubauer P, Burdette C, Rafferty E, Park YL, Trowbridge R, Shin DS, Pilitsis JG. The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury. Neurosci Lett. 2022 Sep 21;789:136882. doi: 10.1016/j.neulet.2022.136882.

Nüssel M, Zhao Y, Knorr C, Regensburger M, Stadlbauer A, Buchfelder M, Del Vecchio A, Kinfe T. Deep Brain Stimulation, Stereotactic Radiosurgery and High-Intensity Focused Ultrasound Targeting the Limbic Pain Matrix: A Comprehensive Review. Pain Ther. 2022 Jun;11(2):459-476. doi: 10.1007/s40122-022-00381-1. Epub 2022 Apr 26.

Liss A, Hellman A, Patel VJ, Maietta T, Byraju K, Trowbridge R, Acheta J, Panse D, Srikanthan A, Neubauer P, Burdette C, Ghoshal G, Williams E, Qian J, Pilitsis JG. Low Intensity Focused Ultrasound Increases Duration of Anti-Nociceptive Responses in Female Common Peroneal Nerve Injury Rats. Neuromodulation. 2022 Jun;25(4):504-510. doi: 10.1111/ner.13531.

Bao J, Tangney T, Pilitsis JG. Focused Ultrasound for Chronic Pain. Neurosurg Clin N Am. 2022 Jul;33(3):331-338. doi: 10.1016/j.nec.2022.02.010. Epub 2022 May 25.

Nachtigal A, Cozakov R, Grinfeld A, Haddad M, Eisenberg E. Feasibility of Magnetic Resonance-Guided High-Intensity-Focused Ultrasound (MRgHIFU) Ablation of Stump Neuromas for the Relief of Chronic Postamputation Neuropathic Pain. J Ultrasound Med. 2022 May 28. doi: 10.1002/jum.16026.

di Biase L, Falato E, Caminiti ML, Pecoraro PM, Narducci F, Di Lazzaro V. Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications. Neurol Res Int. 2021 Jun 29;2021:8438498. doi: 10.1155/2021/8438498. eCollection 2021.

Zhang T, Wang Z, Liang H, Wu Z, Li J, Ou-Yang J, Yang X, Peng YB, Zhu B. Transcranial Focused Ultrasound Stimulation of Periaqueductal Gray for Analgesia. IEEE Trans Biomed Eng. 2022 Mar 24;PP. doi: 10.1109/TBME.2022.3162073.

Hellman A, Clum A, Maietta T, Srikanthan A, Patel V, Panse D, Zimmerman O, Neubauer P, Nalwalk J, Williams E, Ghoshal G, Burdette C, Pilitsis JG. Effects of External Low Intensity Focused Ultrasound on Inflammatory Markers in Neuropathic Pain. Neurosci Lett. 2021 May 20:135977. doi: 10.1016/j.neulet.2021.135977.

Liao YH, Wang B, Chen MX, Liu Y, Ao LJ. LIFU Alleviates Neuropathic Pain by Improving the KCC2 Expression and Inhibiting the CaMKIV-KCC2 Pathway in the L4-L5 Section of the Spinal Cord. Neural Plast. 2021 Apr 13;2021:6659668. doi: 10.1155/2021/6659668. eCollection 2021.

Hellman A, Maietta T, Clum A, Byraju K, Raviv N, Staudt MD, Jeannotte E, Ghoshal G, Shin D, Neubauer P, Williams E, Heffter T, Burdette C, Qian J, Nalwalk J, Pilitsis JG. Pilot study on the effects of low intensity focused ultrasound in a swine model of neuropathic pain. J Neurosurg. 2021 Apr 16:1-8. doi: 10.3171/2020.9.JNS202962.

Badran BW, Caulfield KA, Stomberg-Firestein S, Summers PM, Dowdle LT, Savoca M, Li X, Austelle CW, Short EB, Borckardt JJ, Spivak N, Bystritsky A, George MS. Sonication of the anterior thalamus with MRI-Guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study. Brain Stimul. 2020 Oct 24;13(6):1805-1812. doi: 10.1016/j.brs.2020.10.007.

Pérez-Neri I, González-Aguilar A, Sandoval H, Pineda C, Ríos C. Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence. Curr Neuropharmacol. 2020 Jul 20. doi: 10.2174/1570159X18666200720175253.

Gallay M, Moser D, Jeanmonod D. MR-Guided Focused Ultrasound Central Lateral Thalamotomy for Trigeminal Neuralgia. Single Center Experience Frontiers in Neurology, V11 2020. DOI=10.3389/fneur.2020.00271

Ma Y, Hsu G, Zhang F. The applicability and efficacy of magnetic resonance-guided high intensity focused ultrasound system in the treatment of primary trigeminal neuralgia. Med Hypotheses. 2020 Mar 25;139:109688. doi: 10.1016/j.mehy.2020.109688.

Hellman A, Maietta T, Byraju K, Linda Park Y, Shao M, Liss A, Neubauer P, Burdette C, Ghoshal G, Qian J, Nalwalk J, Pilitsis JG. Low Intensity Focused Ultrasound Modulation of Vincristine Induced Neuropathy. Neuroscience. 2020 Feb 4;430:82-93. doi: 10.1016/j.neuroscience.2020.01.021.

Hellman A, Maietta T, Byraju K, Park YL, Liss A, Prabhala T, Neubauer P, Williams E, Burdette C, Shin DS, Ghoshal G, Nalwalk J, Agrawal A, Qian J, Pilitsis J. Effects of external low intensity focused ultrasound on electrophysiological changes in vivo in a rodent model of common peroneal nerve injury. Neuroscience. 2020 Jan 28;429:264-272. doi: 10.1016/j.neuroscience.2020.01.016.

Prabhala T, Hellman A, Walling I, Maietta T, Qian J, Burdette C, Neubauer P, Shao M, Stapleton A, Thibodeau J, Pilitsis JG. External focused ultrasound treatment for neuropathic pain induced by common peroneal nerve injury. Neurosci Lett. 2018 Sep 25;684:145-151. doi: 10.1016/j.neulet.2018.07.037. Epub 2018 Jul 26.

Youn Y, Hellman A, Walling I, Gee L, Qian J, Burdette C, Frith L, Pilitsis JG. High-Intensity Ultrasound Treatment for Vincristine-Induced Neuropathic Pain. Neurosurgery. 2018 Nov 1;83(5):1068-1075. doi: 10.1093/neuros/nyx488.

Ghanouni P, Pauly KB, Elias WJ, Henderson J, Sheehan J, Monteith S, Wintermark M. Transcranial MRI-Guided Focused Ultrasound: A Review of the Technologic and Neurologic Applications. AJR Am J Roentgenol. 2015 Jul;205(1):150-9. doi: 10.2214/AJR.14.13632.

Varma P, Stineman MG, Dillingham TR. Epidemiology of limb loss. Phys Med Rehabil Clin N Am. 2014 Feb;25(1):1-8

Bauer R, Martin E, Haegele-Link S, Kaegi G, von Specht M, Werner B. Noninvasive functional neurosurgery using transcranial MR imaging-guided focused ultrasound. Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S197-9.

Hsu E, Cohen SP. Postamputation pain: epidemiology, mechanisms, and treatment. J Pain Res. 2013;6:121-36.

Jeanmonod D, Werner B, Morel A, Michels L, Zadicario E, Schiff G, Martin E. Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg Focus. 2012 Jan;32(1):E1.

Martin E, Jeanmonod D, Morel A, Zadicario E, Werner B. High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol. 2009 Dec;66(6):858-61.

Click here for additional references from PubMed.

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International Approval
Clinical Trials