Neuropathic Pain

Background

Clinical KeyNeuropathic pain is a broad term that encompasses symptoms resulting from lesions or dysfunction within the nervous system. This pain lingers beyond the expected healing period and is poorly responsive to traditional pain medications. It has an estimated prevalence of 8% of adults. The impact includes ongoing pain for patients, with direct costs due to treatments and physician visits coupled with indirect costs due to lost productivity. 

The most common causes include trauma, diabetes, stroke, multiple sclerosis, infections, toxins and cancer. Approximately 4 million people in the United States are affected by neuropathic pain each year.

Current Treatment

Neuropathic pain can be very difficult to treat with approximately 40 - 60% of patients achieving partial relief. Treatment options for neuropathic pain include medication, deep brain stimulation (DBS), and lesioning procedures. Neuromodulation has been a more recent adjunct to efforts to treat neuropathic pain.

Deep Brain Stimulation
During this procedure, an electrode is inserted into the relevant target in the brain via a burr hole in the skull. The electrode is connected to a neurostimulator (a small pacemaker-sized device) that is permanently implanted under the skin typically near the patient’s collar bone. The electrode delivers a low level electrical current to suppress the pain.

Lesioning
Lesioning for neuropathic pain is a surgical procedure involving the use of either stereotactic radiosurgery (gamma knife) or radiofrequency ablation to destroy a small volume of tissue in the brain. Most Deep Brain Stimulation and Lesioning procedures carry the risks of surgical procedures and some types of lesioning also includes the risks from ionizing radiation.

Neuromodulation
There has been widespread interest in neuromodulation, with spinal cord stimulation representing a very commonly used application. The concept is that stimulation results in down-regulation of the region, and diminished pain. High complication rates and loss of efficacy have been ongoing challenges for this technique. Non-invasive methods such as transcranial magnetic stimulation and direct current application have been also studied. Despite initial promise, these methods continue to lack clinical evidence, and therefore remain investigational.

Neuropathic pain in amputees
Some neuropathic pain results from neuromas that occur outside of the brain. An example of this is amputee stump pain, which is believed to be due to regenerative neuron sprouting and resultant neuromas. These neuromas produce increased ectopic afferent input resulting in severe pain that is resistant to medical treatments and leads to considerable disability for the patient. Current treatment is aimed at neuroma ablation, which can include neurolytic injections, radiofrequency treatments and even surgical resection. All of these procedures are invasive and have the associated risks of morbidity. 

Focused Ultrasound Treatment

Focused ultrasound can be used to non-invasively and accurately destroy a predefined volume of tissue in the patient’s brain, which could be an effective option for certain patients with neuropathic pain. This technique is very similar to the process used for essential tremor, which received FDA approval this year, and is currently in use for studies on Parkinson’s Disease and other conditions which are currently in progress. Focused ultrasound is performed while the patient is awake and involves no anesthesia, no incisions in the scalp, and no burr holes through the skull or insertion of electrodes into the brain. While there are several potential treatment targets, the central lateral thalamus was studied by Dr. Jeanmonod (Solothurn, Switzerland), and will be the target of an upcoming study in the United States. During focused ultrasound therapy, the treatment target is visualized in real time using MR imaging. This highly precise treatment uses focused beams of acoustic energy to heat and destroy target tissue without harming adjacent cells.

Focused ultrasound treatment of amputee stump pain is the focus of an upcoming clinical trial in Israel. The goal is to use the non-invasive treatment of focused ultrasound to ablate the painful neuromas which are visualized on MRI, and quantify the impact on the patient’s level of pain.

Clinical Trials

See here for a list of clinical trials

Treatment Sites

See here for a list of treatment sites

Regulatory Approval and Reimbursement

CE approval in Europe was awarded at the end of 2012 to the ExAblate Neuro device for the treatment of neuropathic pain.

At this stage, there is no reimbursement for the use of focused ultrasound to treat neuropathic pain.

Notable Papers

Ghanouni P1, Pauly KB2, Elias WJ3, Henderson J4, Sheehan J3, Monteith S5, Wintermark M6. 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.

Video courtesy of InSightec

     

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