Brain Connectivity Changes With Spinal Cord Stimulation and Treatment of Chronic Pain: A Resting State NIRS/EEG Study

Brain Connectivity Changes With Spinal Cord Stimulation Treatment of Chronic Pain: A Resting State NIRS/EEG Study

This study aims to assess how use of spinal cord stimulation for the treatment of chronic pain impacts brain structure and function. The investigators will use a non-invasive neuroimaging technique called resting state Near Infrared Spectroscopy and Electroencephalography (rs-fNIRS/EEG). The investigators will enroll Veterans who are currently receiving care at the Medical Center and who are either long term users of SCS for the treatment of their chronic pain or being evaluated for use of SCS to treat their pain.

Study Overview

• Status: Recruiting
• Conditions: Neuropathic Pain

Detailed Description

Chronic pain is a complex neurological disease that adversely impacts function and quality of life. Brain structure and function are altered when an individual is in the chronic pain state. Furthermore, chronic pain is associated with disruptions in functional brain connectivity. Spinal cord stimulation (SCS) is a clinically available non-pharmacological therapy that is used in the management of chronic pain. Although SCS is effective for many, there are individuals who do not benefit. Therefore, in order to better understand brain mechanisms that underlie SCS treatment of chronic pain and to develop brain biomarkers of SCS efficacy, the investigators propose to evaluate functional brain changes in response to SCS. Finding a brain signature of pain relief in response to SCS would improve understanding of how SCS alleviates chronic pain and may help to identify those most likely to respond. The main objective of this study is to assess changes in brain connectivity in response to SCS in individuals with chronic neuropathic pain. The investigators will study two cohorts: Cohort 1 - naïve to SCS patients who are undergoing SCS trial period; Cohort 1 - long-term SCS users ( 6 months post implantation). The investigators aim to identify neurophysiological brain signatures of pain relief in these two populations using resting state Near Infrared Spectroscopy and Electroencephalography (rs-fNIRS/EEG). Study Design: The investigators will enroll Veterans with refractory chronic neuropathic pain who are currently receiving clinical care within the medical center. Cohort 1: Individuals with chronic neuropathic pain who are naïve to SCS and were selected for SCS trial period as part of their clinical care will participate in two study visits: before the beginning of the SCS trial and the end of the trial period. Data collection will be consistent across all data collection timepoints (T1 - T3) and include rs-fNIRS/EEG and clinical pain measures. Cohort 2: Participants with effective implanted SCS 6 months will participate in three study visits conducted 24-48 hours apart. Data will be collected during SCS use and following an SCS washout period. Data collection will be consistent across all data collection timepoints(T1-T4) and include rs-fNIRS/EEG and clinical pain measures. Both cohorts will receive paresthesia based SCS. AIM 1 is to characterize neurophysiological (rs-fNIRS/EEG) brain signature of pain relief during the SCS trial period for patients with chronic neuropathic pain who are naïve to SCS. AIM 2 is to characterize neurophysiological (rs-fNIRS/EEG) brain signature of pain relief in patients with chronic neuropathic pain who have utilized SCS for 6 months. Outcome Measures to address both aims include rs-functional connectivity (rs-fNIRS/EEG); and a composite clinical pain assessment that will include Numeric Pain Rating Scale (NPRS), Patient Reported Outcomes Measurement Information System-29 profile v2.1(PROMIS-29); EQ-5D-5L; Patient Global Impression of Change (PGIC); painDetect; and activity monitoring. Significance: Studying changes in brain connectivity in response to SCS will provide insight into the treatment mechanism of SCS. Use of neuroimaging methods such as rs-fNIRS/EEG that can be easily applied in the clinical setting to further refine patient selection for SCS may improve outcome in SCS therapy. This grant will provide preliminary data for future studies aimed at developing biomarkers of pain-relief with SCS treatment.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Cheryl Dudek; Phone Number: (216) 679-3800; Email: cheryl.dudek@va.gov
• Study Contact Backup: Name: Holly B Henry; Phone Number: 64657 (216) 791-3800; Email: holly.henry@va.gov

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-1702
      • Recruiting
      • Louis Stokes VA Medical Center, Cleveland, OH
      • Contact: Svetlana Pundik, MD; Phone Number: 3732 (216) 791-3800; Email: svetlana.pundik@va.gov
      • Contact: Jessica P McCabe, MPT DPT; Phone Number: 4691 216-791-3800; Email: Jessica.Mccabe@va.gov
      • Principal Investigator: Svetlana Pundik, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Veterans with chronic pain who are being treated as part of their clinical care with spinal cord stimulation

Description

Inclusion Criteria:

• 18 years of age and a US veteran
• Diagnosis of chronic neuropathic pain.
• Current patient at Cleveland VA Medical Center receiving care via Pain Medicine Center.
• Current user of tonic parasthesia-based SCS (pain relief 50% according to NPRS) or undergoing trial SCS period as part of clinical care.
• Able to provide informed consent.
• Medically and psychologically stable.

Exclusion Criteria:

• Metal in the skull or deformity of the skull
• Pregnancy or pregnancy planning during the study period.
• Unable to provide informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cohort 1-individuals who are naïve to SCS; Individuals with chronic neuropathic pain who are naïve to SCS and were selected for SCS trial period as part of their clinical care will participate in two study visits: before the beginning of the SCS trial and the end of the trial period. Data collection will be consistent across all data collection timepoints (T1 - T3) and include rs-fNIRS/EEG and clinical pain measures.
Cohort 2-individuals with effective implanted SCS 6 months; Cohort 2: Participants with effective implanted SCS 6 months will participate in three study visits conducted 24-48 hours apart. Data will be collected during SCS use and following an SCS washout period. Data collection will be consistent across all data collection timepoints(T1-T4) and include rs-fNIRS/EEG and clinical pain measures. Both cohorts will receive paresthesia based SCS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in resting state Functional Connectivity	Resting state functional connectivity will be evaluated with fNIRS and EEG. The investigators will model "response to SCS" with changes in resting state functional connectivity between five bilateral cortical regions. These regions are the medial prefrontal cortex (mPF), dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), primary sensory cortex (S1), and posterior parietal cortex (PPC). Brain connectivity will be evaluated with fNIRS and EEG. Prefrontal medial cortex and posterior temporoparietal regions are good proxy measures of DMN activity using fNIRS. 45-47 DMN nodes include additional deep brain structures but they are outside the field of view for most fNIRS instruments. The investigators will evaluate S1 for its role in pain processing, M1 for its contribution to pain sensation via thalamic inhibition, and DLPFC for its known role in cognitive and affective pain processing.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Change in Numeric Pain Rating Scale (NPRS)	NPRS measures pain intensity. Individuals select a number on a 0-10 scale that best describes the intensity of their current, best and worst pain levels; 0-10 scale, with 10 indicating maximum pain.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in EQ-5D-5L	EQ-5D-5L is a 5-domain health-related quality of life measure; -0.59-1.00 scale, with 1=best health state.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Change in Patients Global Impression of Change (PGIC)	Patient's Global Impression of Change (PGIC) is a 7-point scale to assess patient perception of change in response to treatment. 1=no change, and 7=a great deal better.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Change in PROMIS-29 Profile v2.1	PROMIS-29 Profile v2.1 is a questionnaire covering 7 domains including physical function, anxiety, depression, fatigue, sleep disturbance, participation in social roles/activities, and pain interference. Higher T-scores indicate more severity/worse health.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Change in PainDetect	PainDetect is a self-report measure that was developed to assess neuropathic pain in adults with low back pain; 0-38 points, with higher score more indicative of neuropathic pain.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Change in Actigraphy	Activity monitoring using a wrist-worn device (Actigraphy) will be utilized to monitor real-life activity and sleep patterns; calculating % time active versus sedentary.	Cohort 1-between 5 and 9 days; Cohort 2-between 3-6 days.

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Svetlana Pundik, MD, Louis Stokes VA Medical Center, Cleveland, OH

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): April 13, 2023

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: chronic pain; neuropathic pain; fNIRS; spinal cord stimulation; electroencephalography
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Pain; Neuralgia
• Other Study ID Numbers: F4389-P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No