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Brain Stimulation in the Treatment of Chronic Neuropathic and Non-Cancerous Pain

  • Ela B. Plow
    Affiliations
    Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio

    Department of Physical Medicine and Rehabilitation, Neurological Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
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  • Alvaro Pascual-Leone
    Affiliations
    Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

    Instituto Guttmann de Neurorrehabilitación, Universidad Autónoma de Barcelona, Badalona, España
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  • Andre Machado
    Correspondence
    Address reprint requests to Andre Machado, MD, PhD, Director, Center for Neurological Restoration, Assistant Professor of Surgery, Department of Neurosurgery, Cleveland Clinic, 9500 Euclid Ave, S-31, Cleveland, OH 44195.
    Affiliations
    Center for Neurological Restoration, Department of Neurosurgery, Neurological Institute, The Cleveland Clinic Foundation, Cleveland, Ohio

    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
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      Abstract

      Chronic neuropathic pain is one of the most prevalent and debilitating disorders. Conventional medical management, however, remains frustrating for both patients and clinicians owing to poor specificity of pharmacotherapy, delayed onset of analgesia and extensive side effects. Neuromodulation presents as a promising alternative, or at least an adjunct, as it is more specific in inducing analgesia without associated risks of pharmacotherapy. Here, we discuss common clinical and investigational methods of neuromodulation. Compared to clinical spinal cord stimulation (SCS), investigational techniques of cerebral neuromodulation, both invasive (deep brain stimulation [DBS] and motor cortical stimulation [MCS]) and noninvasive (repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]), may be more advantageous. By adaptively targeting the multidimensional experience of pain, subtended by integrative pain circuitry in the brain, including somatosensory and thalamocortical, limbic and cognitive, cerebral methods may modulate the sensory-discriminative, affective-emotional and evaluative-cognitive spheres of the pain neuromatrix. Despite promise, the current state of results alludes to the possibility that cerebral neuromodulation has thus far not been effective in producing analgesia as intended in patients with chronic pain disorders. These techniques, thus, remain investigational and off-label. We discuss issues implicated in inadequate efficacy, variability of responsiveness, and poor retention of benefit, while recommending design and conceptual refinements for future trials of cerebral neuromodulation in management of chronic neuropathic pain.

      Perspective

      This critical review focuses on factors contributing to poor therapeutic utility of invasive and noninvasive brain stimulation in the treatment of chronic neuropathic and pain of noncancerous origin. Through key clinical trial design and conceptual refinements, retention and consistency of response may be improved, potentially facilitating the widespread clinical applicability of such approaches.

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