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      The Cerebral Localization of Pain: Anatomical and Functional Considerations for Targeted Electrical Therapies

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          Abstract

          Millions of people in the United States are affected by chronic pain, and the financial cost of pain treatment is weighing on the healthcare system. In some cases, current pharmacological treatments may do more harm than good, as with the United States opioid crisis. Direct electrical stimulation of the brain is one potential non-pharmacological treatment with a long history of investigation. Yet brain stimulation has been far less successful than peripheral or spinal cord stimulation, perhaps because of our limited understanding of the neural circuits involved in pain perception. In this paper, we review the history of using electrical stimulation of the brain to treat pain, as well as contemporary studies identifying the structures involved in pain networks, such as the thalamus, insula, and anterior cingulate. We propose that the thermal grill illusion, an experimental pain model, can facilitate further investigation of these structures. Pairing this model with intracranial recording will provide insight toward disentangling the neural correlates from the described anatomic areas. Finally, the possibility of altering pain perception with brain stimulation in these regions could be highly informative for the development of novel brain stimulation therapies for chronic pain.

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          Most cited references98

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          Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain.

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            Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.

            The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain (CBP) patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. CBP patients were divided into neuropathic, exhibiting pain because of sciatic nerve damage, and non-neuropathic groups. Pain-related characteristics were correlated to morphometric measures. Neocortical gray matter volume was compared after skull normalization. Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10-20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm3 loss of gray matter for every year of chronic pain. Regional gray matter density in 17 CBP patients was compared with matched controls using voxel-based morphometry and nonparametric statistics. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic CBP. Our results imply that CBP is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.
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              Broadband shifts in local field potential power spectra are correlated with single-neuron spiking in humans.

              A fundamental question in neuroscience concerns the relation between the spiking of individual neurons and the aggregate electrical activity of neuronal ensembles as seen in local field potentials (LFPs). Because LFPs reflect both spiking activity and subthreshold events, this question is not simply one of data aggregation. Recording from 20 neurosurgical patients, we directly examined the relation between LFPs and neuronal spiking. Examining 2030 neurons in widespread brain regions, we found that firing rates were positively correlated with broadband (2-150 Hz) shifts in the LFP power spectrum. In contrast, narrowband oscillations correlated both positively and negatively with firing rates at different recording sites. Broadband power shifts were a more reliable predictor of neuronal spiking than narrowband power shifts. These findings suggest that broadband LFP power provides valuable information concerning neuronal activity beyond that contained in narrowband oscillations.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                22 June 2020
                June 2020
                : 9
                : 6
                : 1945
                Affiliations
                Department of Neurosurgery, University of Utah, Salt Lake City, UT 84106, USA; rose.caston@ 123456hsc.utah.edu (R.M.C.); e.h.smith@ 123456utah.edu (E.H.S.); tyler.davis@ 123456hsc.utah.edu (T.S.D.)
                Author notes
                Author information
                https://orcid.org/0000-0001-5375-869X
                https://orcid.org/0000-0003-4323-4643
                https://orcid.org/0000-0002-8843-5468
                Article
                jcm-09-01945
                10.3390/jcm9061945
                7355617
                32580436
                6326c93d-be53-49f4-bc47-233c7c865d39
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 13 May 2020
                : 18 June 2020
                Categories
                Review

                deep brain stimulation,closed loop,sensing,electrophysiology,neurophysiology,pain,thermal grill,imaging

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