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.
Key words
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Article info
Publication history
Published online: April 09, 2012
Footnotes
Suport included grants from the National Institutes of Health, including New Innovator's Award DOD006469A (A.M.), 1K01HD069504 (E.B.P.) and National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758) (for support of A.P.-L.’s role).
Ela B. Plow has no conflicts of interest. Alvaro Pascual-Leone serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Allied Mind, Neosync, and Novavision, and is listed as inventor in issued patents and patent applications on the real-time integration of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) and magnetic resonance imaging (MRI). Andre Machado has the following conflicts of interest to disclose: Intelect Medical (advisory board, consultant, shareholder), ATI and Cardionomics (shareholder), and Monteris (consultant).
Identification
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© 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.
