Identifying Body Awareness-Related Brain Network Changes after Cognitive Multisensory Rehabilitation for Neuropathic Pain Relief in Adults with Spinal Cord Injury: Delayed Treatment arm Phase I Randomized Controlled Trial

Abstract

Background: Neuropathic pain after spinal cord injury (SCI) is notoriously hard to treat. Mechanisms of neuropathic pain are unclear, which makes finding effective treatments challenging. Prior studies have shown that adults with SCI have body awareness deficits. Recent imaging studies, including ours, point to the parietal operculum and insula as key areas for both pain perception and body awareness. Cognitive multisensory rehabilitation (CMR) is a physical therapy approach that helps improve body awareness for pain reduction and sensorimotor recovery. Based on our prior brain imaging work in CMR in stroke, we hypothesized that improving body awareness through restoring parietal operculum network connectivity leads to neuropathic pain relief and improved sensorimotor and daily life function in adults with SCI. Thus, the objectives of this study were to (1) determine baseline differences in resting-state and task-based functional magnetic resonance imaging (fMRI) brain function in adults with SCI compared to healthy controls and (2) identify changes in brain function and behavioral pain and pain-associated outcomes in adults with SCI after CMR. Methods: Healthy adults underwent a one-time MRI scan and completed questionnaires. We recruited community-dwelling adults with SCI-related neuropathic pain, with complete or incomplete SCI >3 months, and highest neuropathic pain intensity level of >3 on the Numeric Pain Rating Scale (NPRS). Participants with SCI were randomized into two groups, according to a delayed treatment arm phase I randomized controlled trial (RCT): Group A immediately received CMR intervention, 3x/week, 45 min/session, followed by a 6-week and 1-year follow-up. Group B started with a 6-week observation period, then 6 weeks of CMR, and a 1-year follow-up. Highest, average, and lowest neuropathic pain intensity levels were assessed weekly with the NPRS as primary outcome. Other primary outcomes (fMRI resting-state and functional tasks; sensory and motor function with the INSCI AIS exam), as well as secondary outcomes (mood, function, spasms, and other SCI secondary conditions), were assessed at baseline, after the first and second 6-week period. The INSCI AIS exam and questionnaires were repeated at the 1-year follow-up. Findings: Thirty-six healthy adults and 28 adults with SCI were recruited between September 2020 and August 2021, and 31 healthy adults and 26 adults with SCI were enrolled in the study. All 26 participants with SCI completed the intervention and pre-post assessments. There were no study-related adverse events. Participants were 52+/-15 years of age, and 1-56 years post-SCI. During the observation period, group B did not show any reductions in neuropathic pain and did not have any changes in sensation or motor function (INSCI ASIA exam). However, both groups experienced a significant reduction in neuropathic pain after the 6-week CMR intervention. Their highest level of neuropathic pain of 7.81+/-1.33 on the NPRS at baseline was reduced to 2.88+/-2.92 after 6 weeks of CMR. Their change scores were 4.92+/-2.92 (large effect size Cohen d=1.68) for highest neuropathic pain, 4.12+/-2.23 (d=1.85) for average neuropathic pain, and 2.31+/-2.07 (d=1.00) for lowest neuropathic pain. Nine participants out of 26 were pain-free after the intervention (34.62%). The results of the INSCI AIS testing also showed significant improvements in sensation, muscle strength, and function after 6 weeks of CMR. Their INSCI AIS exam increased by 8.81+/-5.37 points (d=1.64) for touch sensation, 7.50+/-4.89 points (d=1.53) for pin prick sensation, and 3.87+/-2.81 (d=1.38) for lower limb muscle strength. Functional improvements after the intervention included improvements in balance for 17 out of 18 participants with balance problems at baseline; improved transfers for all of them and a returned ability to stand upright with minimal assistance in 12 out of 20 participants who were unable to stand at baseline. Those improvements were maintained at the 1-year follow-up. With regard to brain imaging, we confirmed that the resting-state parietal operculum and insula networks had weaker connections in adults with SCI-related neuropathic pain (n=20) compared to healthy adults (n=28). After CMR, stronger resting-state parietal operculum network connectivity was found in adults with SCI. Also, at baseline, as expected, right toe sensory stimulation elicited less brain activation in adults with SCI (n=22) compared to healthy adults (n=26). However, after CMR, there was increased brain activation in relevant sensorimotor and parietal areas related to pain and mental body representations (i.e., body awareness and visuospatial body maps) during the toe stimulation fMRI task. These brain function improvements aligned with the AIS results of improved touch sensation, including in the feet. Interpretation: Adults with chronic SCI had significant neuropathic pain relief and functional improvements, attributed to the recovery of sensation and movement after CMR. The results indicate the preliminary efficacy of CMR for restoring function in adults with chronic SCI. CMR is easily implementable in current physical therapy practice. These encouraging impressive results pave the way for larger randomized clinical trials aimed at testing the efficacy of CMR to alleviate neuropathic pain in adults with SCI.

Identifying body awareness-related brain network changes after Spring Forest Qigong™ practice or P.Volve low-intensity exercise in adults with chronic low back pain: a feasibility Phase I Randomized Clinical Trial

“…Table 2 shows the demographic and clinical characteristics of adults with cLBP per intervention group (n=14 for the Qigong group, n=16 for the P.Volve exercise group), as well as the demographic and clinical characteristics of the healthy adults (n=28), scanned in a previous study. 53 We obtained excellent intervention adherence as all participants practiced Qigong or did lowintensity P.Volve exercises on average more than 2x/week. More specifically, all of the participants in the Qigong group practiced more than 3 times per week, on average 158.52 minutes per week (128% treatment adherence).…”

“…Table 2 shows the demographic and clinical characteristics of adults with cLBP per intervention group (n=14 for the Qigong group, n=16 for the P.Volve exercise group), as well as the demographic and clinical characteristics of the healthy adults (n=28), scanned in a previous study. 52…”

“…For the baseline comparison of brain imaging of adults with cLBP with healthy adults, we used brain imaging data from 28 healthy adults from a previous study. 52…”

“…We used 2 sample t-tests to analyze between-group differences in adults with cLBP compared to 28 healthy adults (scanned in a previous study 53 ) of baseline brain function at rest and during tasks. We used paired t-tests for the Qigong group and P.Volve group separately to identify estimates of within-group pre-post changes in task-based brain activation and resting-state connectivity (with Fisher's Z transformation).…”

Using remotely delivered Spring Forest Qigong™ to reduce neuropathic pain in adults with spinal cord injury: A non-randomized controlled trial

“…We conducted a preliminary power calculation for the given sample size based on estimates from another body awareness therapy (i.e., cognitive multisensory rehabilitation) in adults with SCI. 78 In this prior study, we saw a reduction in neuropathic pain intensity of at least 2.31±2.07 points for the highest, average, and lowest neuropathic pain in the prior week. Assuming the same standard deviation estimate, a total sample size of 18 participants will have over 98% power to detect the same pain reduction of 2.31 points on the numeric pain rating scale (standardized Cohen’s d =1.12) with a two-sided significance level of 0.05 using a paired t-test, and 80% power to detect a pain reduction of 1.46 points (Cohen’s d =0.72) in this study.…”