Developing Brain Stimulation as a Treatment for Chronic Pain in Opiate Dependent

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: Same as current

Summary

Conditions

Chronic Pain
Lower Back Pain
Opiate Dependence

Type

Interventional

Phase

Early Phase 1

Design

Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: This randomized, double-blind, sham-controlled study will parametrically evaluate the longitudinal effects of 16 days of rTMS to the DLPFC (Aim 1) or the MPFC (Aim 2) on self-reported pain and the brain's response to pain. This will be done in a cohort of patients recruited from Medical University of South Carolina clinics and the outer community with chronic lower back pain that have been using prescription opiates for 3 or more months without adequate pain relief. Participants will be randomized to receive TMS to the DLPFC, MPFC, or sham (50% at each site), using a Latin square randomization. Resting state connectivity will be collected along with data from a standardized thermal pain paradigm wherein individuals are exposed to pain and instructed to try to "control' the pain. Quantitative Pain Testing will be collected 12 times. MRI data will be collected 3 times: before the 1st visit of TMS, before the 12th visit of TMS, and before the 16th visit of TMS.Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Data for this randomized, double-blind, sham-controlled study (behavioral assessments, functional MRI measurements) will be acquired by the members of the Dr. Hanlon's lab, including graduate students and research specialists. These individuals will also perform data under the guidance of the PI. Manuscript composition will be led by the PI, with the assistance of the research team.Primary Purpose: Treatment

Participation Requirements

Age: Between 18 years and 75 years
Gender: Both males and females

Description

The goal of this proposal is to evaluate two novel non-invasive brain stimulation strategies to mitigate pain and the brain's response to pain in CLBP patients. Transcranial Magnetic Stimulation (TMS), can induce long term potentiation (LTP-like) and long term depression (LTD-like) effects on brain activity in a frequency dependent manner. The investigators have previously demonstrated that LTP-like TMS to the dorsolateral prefrontal cortex (DLPFC, a node in the Executive Control Network (ECN)) can decrease perceived pain and corresponding Blood Oxygen Level Dependent (BOLD) signal in the "Pain Network'. The Pain Network is an expansion of the Salience Network (SN; insula, dorsal anterior cingulate) which includes the thalamus and somatosensory cortex. The analgesic effects of DLPFC TMS can be blocked by naloxone - suggesting that the analgesic effects of LTP-like DLPFC TMS are opiate mediated. Additionally, DLPFC TMS delivered postoperatively leads to less patient administered morphine use (PCA-pump) in the hospital and less opiate use in the outpatient setting. These data all suggest that LTP-like DLPFC TMS is a promising candidate for treating pain. An alternative strategy is to apply LTD-like stimulation to the medial prefrontal cortex (LTD-like mPFC rTMS. This strategy is based on the understanding of functional neural architecture, wherein the SN is modulated by two other core networks: the ECN and the default mode network (DMN). As stated above, it is possible to attenuate activity in the SN through LTP-like TMS to the DLPFC, a node in the ECN. It is also possible to attenuate the SN through LTD-like TMS to the ventral medial prefrontal cortex (a node in the DMN). The proposed study will be the first to employ a randomized, double-blind, sham-controlled design to parametrically evaluate the longitudinal effects of 16 days of rTMS to the DLPFC (Aim 1) or the MPFC (Aim 2) on self-reported pain and the brain's response to pain. This will be done in a cohort of patients recruited from the community as well as Medical University of South Carolina clinics with chronic lower back pain that may or may not be using prescription opiates for 3 or more months without adequate pain relief. Participants will be randomized to receive rTMS to the DLPFC (10Hz), MPFC (cTBS), or sham (50% at each site), using a Latin square randomization. Resting state connectivity will be collected along with data from a standardized thermal pain paradigm wherein individuals are exposed to pain and instructed to try to "control' the pain. MRI data will be collected 3 times: before the 1st day of TMS, after the 12th day of TMS, and before the 16th day of TMS (the last day administered).

Tracking Information

NCT #: NCT03681769
Collaborators: Not Provided
Investigators: Principal Investigator: Jeffrey Borckardt, PhD Medical University of South Carolina