Deep brain stimulation of the ventral striatum/anterior limb of the internal capsule in thalamic pain syndrome: study protocol for a pilot randomized controlled trial

Trials

Andre Machado³  Donald A Malone²  Ela B Plow¹ 

[1] Department of Biomedical Engineering, Department of Physical Medicine and Rehabilitation and Center for Neurological Restoration, Cleveland Clinic, 9500 Euclid Avenue, ND20, Cleveland, OH 44195, USA;Department of Psychiatry & Psychology and Center for Behavioral Health/P57, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA;Center for Neurological Restoration, Department of Neurological Surgery/S31, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA

关键词: Brain stimulation;    Central pain;    Post-stroke pain;    Anterior limb of internal capsule;    Ventral striatum;    Deep brain stimulation (DBS);    Thalamic pain syndrome;    Stroke;    Neuropathic pain;    Chronic pain;   

Others  :  1093296
DOI  :  10.1186/1745-6215-14-241

 received in 2013-03-29, accepted in 2013-07-22,  发布年份 2013

【 摘 要 】

Background

Chronic neuropathic pain in thalamic pain syndrome remains intractable. Its poor response is ascribed to destruction of the integrated neuromatrix in experience of pain. Deep brain stimulation is a promising technique to modulate activity of implicated structures. However, traditional approaches targeting sensori-motor substrates have failed to affect disability. The offending lesion in thalamic pain syndrome that almost invariably destroys sensory pain pathways may render these classical approaches ineffective. Instead, we hypothesize that targeting structures representing emotion and affective behavior-ventral striatum/anterior limb of the internal capsule, may alleviate disability.

Methods/design

We present the design of our phase I randomized, double-blinded, sham-controlled, crossover trial that examines safety, feasibility and efficacy of our proposed approach. In our ongoing trial, we intend to enroll ten patients with thalamic pain syndrome. Following implantation, patients are randomized to receive active deep brain stimulation to the ventral striatum/anterior limb of the internal capsule or sham for 3 months, after which they are crossed over. The primary endpoint is Pain Disability Index. Other outcomes include visual analog scale, depression and anxiety inventories, quality of life, and functional neuroimaging.

Discussion

Designing trials of deep brain stimulation for pain is challenging owing to the ethical-scientific dilemma of introducing a control arm, complicated blinding, heterogeneous etiologies, patient expectations, and inadequate assessment of disability. The quality of evidence in the field is classified as level III (poor) because it mainly includes a multitude of uncontrolled case series reporting variable outcomes, with little regard for the placebo effect related to implantation. Without valid data on efficacy, use of deep brain stimulation for pain remains “off label”. We present our trial design to discuss feasibility of conducting sham-controlled phase I studies that may represent significant refinement for the field. Double-blinding would reduce influence of patient expectations and therapeutic confusion amongst investigators. With a cross-over approach, the dilemma regarding including a control group can be mitigated. Use of homogeneous etiology, measurement of disability, depression and quality of life, besides pain perception, all represent strategies to evaluate efficacy rigorously. Functional imaging would serve to define mechanisms underlying observed effects and may help optimize future targeting.

Trial registration

Clinicaltrials.gov NCT01072656

【 授权许可】

   
2013 Plow et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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