Deep Brain Stimulation of the Subgenual Cingulate Cortex for the Treatment of Medically Refractory Chronic Low Back Pain

ABSTRACT
Chronic low back pain (CLBP) is one of the most ubiquitous and intractable problems in medicine and a
significant source of patient suffering and disability, leading to opioid misuse and addiction. Previous
neuromodulatory therapies for CLBP have focused primarily on spinal etiologies and intra-spinal mechanisms of
pain transmission. However, existing pharmacological and neuromodulatory therapies have not been successful
in treating CLBP. Potential gaps and opportunities include: (1) a need to better understand the brain networks
underlying CLBP, (2) development of DBS devices that can better target the specific brain networks underlying
CLBP in a safe and clinically testable manner, and (3) identification of neuroimaging biomarkers of response to
DBS for CLBP. Pain can be separated into sensory, cognitive and affect components. Growing neuroimaging
evidence shows that chronic pain is associated with widespread changes in brain circuits mediating these
components with particular pathological overrepresentation of the affective component. The current proposal
aims to address these critical gaps and the unmet therapeutic needs of CLBP patients by using a next-
generation DBS device with directional steering capability to engage networks known to mediate the
affective component of CLBP. We will use the Abbott Infinity™ DBS System, which offers segmented
electrodes capable of providing directional current steering technology. In addition, we will utilize patient-
specific probabilistic tractography to target the subgenual cingulate cortex (SCC) in order to engage the
major fiber pathways mediating the affective component of chronic pain. The SCC region demonstrates
structural connectivity to downstream brain structures also known to be involved in the affective component of
chronic pain, and DBS of the SCC has been previously shown to improve affect in patients with intractable
depression. The objective of this application is to propose an exploratory first-in-human clinical trial of SCC DBS
for the treatment of medically refractory CLBP which leverages our multidisciplinary expertise and technical skills.
Specifically, we propose the following aims in order to carry out this trial: (1) Assess the preliminary efficacy of
DBS of the SCC in the treatment of medically refractory CLBP; (2) Demonstrate the safety and feasibility of SCC
DBS for CLBP; and (3) Develop diffusion tensor imaging (DTI)-based blueprints of response to SCC DBS for
CLBP. The overall impact of this proof-of-concept pilot trial includes validation of the concept that suffering from
CLBP results from pathological activity in affective brain networks, that these networks can be accurately
engaged using a next-generation directional DBS device in a safe and feasible manner, and the discovery of
neuroimaging biomarkers of response to SCC DBS for CLBP.

Grant Number: 5UH3NS113661-04
NIH Institute/Center: NIH
Principal Investigator: AUSAF BARI