Human Studies

Knowledge of efficacious dosing respective to exercise type and pain condition is extremely limited in the literature. This study aimed to determine the impact of dose of moderate intensity treadmill walking on experimentally-induced pain in healthy human participants. Forty females were divided into 4 groups: control (no exercise), low dose exercise (3×/wk), moderate dose exercise (5×/wk) or high dose exercise (10×/wk). Over a 7-day period, subjects performed treadmill walking during assigned exercise days. Both qualitative and quantitative measures of pain were measured at baseline, during the trial, and 24 hrs post-final intervention session via sensitivity thresholds to painful thermal and painful pressure stimulation. Significant effects of treatment were found post-intervention for constant pressure pain intensity (p = 0.0016) and pain unpleasantness ratings (p = 0.0014). Post-hoc tests revealed significant differences between control and moderate and control and high dose groups for constant pressure pain intensity (p = 0.0015), (p = 0.0094), respectively and constant pressure pain unpleasantness (p = 0.0040), (p = 0.0040), respectively. Moderate and high dose groups had the greatest reductions in ratings of pain, suggesting that our lowest dose of exercise was not sufficient to reduce pain and that the moderate dose of exercise may be a sufficient starting dose for exercise-based adjuvant pain therapy.

Long-term trials are key to understanding chronic symptoms such as pain and itch. However, challenges such as high attrition rates and poor recruitment are common when conducting research. The aim of this work is to explore these issues within a long-term randomized control trial using transcranial direct current stimulation to treat pain and itch. This parallel double blinded, placebo-controlled randomized trial was comprised of 15 transcranial direct current stimulation visits and 7 follow-up visits. Participants were over the age of 18, had a burn injury that occurred at least 3 weeks prior to enrollment, and reported having pain and/or itch that was moderate to severe in intensity. A total of 31 subjects were randomized into either an active or sham transcranial direct current stimulation groups. There were no significant differences between the groups in terms of age, race, education, baseline depression, or anxiety. The median dropout time was at visit 19 [visit 16 (SE=1.98) for the sham group and visit 19 (SE=1.98) for the active group]. Analysis showed no differences in the dropout rate between groups (χ2(1)=0.003, p=0.954). The dropout rate was 46.7% for the sham group and 43.8% for the active group. Overall, 45.2% of the subjects dropped out of the trial. Long-term clinical trials are an essential part of evaluating interventions for symptoms such as chronic pain and itch. However, as seen in this trial, long-term studies in the burn population often face recruitment and adherence challenges.

Musculoskeletal pain is a cause of disability in older individuals and is commonly associated with executive function deficits. In particular, verbal fluency deficits have been previously reported in older individuals with and without musculoskeletal pain, however, no studies have examined non-verbal fluency. The present study investigated non-verbal fluency performance in younger and older individuals and associations with clinical and experimental pain. The NEPAL study included older (n = 63) and younger (n = 28) individuals who completed demographic, and clinical pain assessments followed by a multi-modal QST battery. A subset of participants (older n = 39/63, younger n = 11/28) underwent a structural 3T MRI to extract cortical thickness and subcortical gray matter volumes. The Ruff Figural Fluency Test was administered to assess fluid/divergent thinking, ability to shift cognitive set, and planning strategies. Total Unique Designs drawn and Error Ratio assessed participants' ability to minimize repetition while maximizing unique productions. Adjusting for race and education, older participants with chronic pain had significantly lower Total Unique Designs (67.1 ± 20.3) compared to older adults without chronic pain (78.8 ± 15.9) and younger controls (93.8 ± 20.3, p < 0.001). Within the older sample, those with chronic pain had a significantly greater Error Ratio (0.22 ± 0.3) compared to those without chronic pain (0.09 ± 0.06) and younger controls (0.05 ± 0.05, p = 0.002). In older participants, greater Total Unique Design scores were significantly associated only with lower pressure pain sensitivity (r = 0.300, p = 0.031) while greater Error Ratio scores were significantly associated with greater thermal pain sensitivity (r = 0.304, p = 0.027). However, after accounting for sleep quality, clinical and experimental pain associations were eliminated. Across all participants, non-verbal fluency performance was associated with cortical thickness in frontal, parietal and temporal regions as well as several subcortical gray matter structures even after adjusting for multiple comparisons (p's < 0.001). Our findings suggest a pain-related deficit in non-verbal fluency beyond the established age-related decrements that may be dependent on sleep quality and was associated with specific patterns of gray matter structure.

Recent experimental research has suggested that spinal manipulative therapy (SMT) may reduce pain through modulation of the ascending pain signals and/or the central pain-regulating mechanisms. People with persistent neck pain (NP) have also been found to have disturbances in autonomic nervous system (ANS) regulation. A common way to study the ANS is to measure heart rate variability (HRV). It is not known whether deviations in HRV are related to changes in pain perception or to the treatment response to SMT. Commonly, an individual in pain will experience pain reduction when exposed to a second pain stimulus, a mechanism known as conditioned pain modulation (CPM). Patients with persistent pain have been found to have a reduced CPM reaction. It is not known whether this is predictive of treatment response to SMT. The aim of the study is to examine the effects of SMT on HRV and pain. Further, a secondary aim is to test whether a CPM test can be used to predict treatment response in a population of patients with recurrent and persistent NP.

The Improving the Wellbeing of people with Opioid Treated CHronic Pain (I-WOTCH) randomised controlled trial uses a multicomponent self-management intervention to help people taper their opioid use. This approach is not widely used and its efficacy is unknown. A process evaluation alongside the trial will help to assess how the intervention was delivered, looking at the dose of intervention received and the fidelity of the delivery. We will explore how the intervention may have brought about change through the experiences of the participants receiving and the staff delivering the intervention and whether there were contextual factors involved.