Chronic low back pain (CLBP) poses a major public health burden, affecting 31% of the general population and 54% of older adults. Among individuals with CLBP, multisite pain increases the risk for persistent pain and can lead to physical and mental impairments. Despite this, multisite pain research is limited and little is known about its relationship with health-related quality of life (HRQoL). This study describes the effect of multisite pain on HRQoL and the association between multisite pain and falls in older adults with CLBP. We conducted a secondary analysis using the Back Pain Outcomes using Longitudinal Data (BOLD) registry. BOLD consists of 5,239 participants, ≥65 years, from three health systems, with new primary care visits for back pain. We identified 899 participants with CLBP (>2/10 pain intensity, 6 months after new visit) and assessed comorbid pain at 6 pain sites, including widespread pain. Outcomes of HRQoL (EQ-5D, scored 0-1) and falls prevalence in the past 3 weeks were evaluated 6 and 18 months after participants met the chronic pain criteria. We used linear and logistic regression models to test the relationship between number and type of pain sites with outcomes, adjusting for demographics and health characteristics. Widespread pain (b=-0.035; CI: -0.058, -0.012) and pelvic/groin pain (b=-0.027; CI: -0.050, -0.004) sites were associated with lower HRQoL. For each additional pain site, HRQoL scores decreased an average of 0.013 points (95% CI: -0.020, -0.007) and odds of a fall increased 30% (OR, 1.30; CI: 1.12, 1.51) with nearly all falls occurring in those with >1 pain site (>95%). Number of pain sites had stronger associations with decreasing HRQoL than individual pain sites. Multisite pain increased the risk for falls. Clinicians and researchers should assess multisite pain as a potential risk factor for low HRQoL and falls in older adults with CLBP.

Many children with Autism Spectrum Disorder (ASD) suffer from decreased gut motility that manifests as debilitating chronic constipation, leading to an unhealthy aversion to food. We hypothesized that the same neurological defects that cause the hallmark cognitive impairments in ASD also negatively impact the enteric nervous system controlling gut peristalsis. Within the autism spectrum, we chose to study one particular condition called Phelan-McDermid Syndrome (PMDS), because every patient with the diagnostic chromosome 22 micro-deletion has a dramatic decrease in gut motility. Evidence suggests that the gene-of-interest in the deleted region is SHANK3 because mice with SHANK3 haploinsufficiency show decreased postsynaptic density of neurotransmitter receptors. The overriding goal of this project is to develop novel drug treatments for patients with PMDS and ASD. Finding new compounds that can increase (or bypass) postsynaptic receptor density could alleviate these patients’ gut motility problems. However, models to study the enteric nervous system either involve invasive biopsy procedures to remove enteric tissue from patients or the use of animal models that fail to replicate the pathology observed in humans. Therefore, the objective of this study is to create a human disease-in-a-dish model of enteric nervous system dysfunction by generating stem cells from PMDS patients and differentiating them into enteric neurons (ENs). We predict that molecular characterization of SHANK3-deleted enteric neurons will identify aberrant signaling pathways suitable for therapeutic intervention. Preliminary experiments from our laboratory have demonstrated the feasibility of differentiating patient-derived induced pluripotent stem cells (iPSCs) into neural crest (NC) cells, which are necessary precursors to making enteric neurons. NC plus smooth muscle co-culture experiments will then be used to drive fluorescently labeled normal and SHANK3-deficient NC cells to enteric neurons, thus enabling phenotypic characterization of the disease phenotype in vitro.

Spinal cord injury (SCI) is a debilitating disease with few treatment options available for recovering motor function. Based on past studies using electrical stimulation of the spinal cord, we believe that long-term optogenetic spinal stimulation (OSS) may improve motor function after an SCI. We are investigating this therapeutic potential using a rat model of SCI with an implantable LED to deliver optogenetic stimulation in vivo. However, activation of the LED produces heat that could damage the surrounding tissue. I have modified these LED implants by incorporating a thermistor that tracks temperature changes during optical stimulation. Using this device, I determined how the modulation of stimulation parameters affects heat production at the site of the implant and have identified several safe parameter sets. These results will inform the parameter choices used in future studies on OSS. An optimized OSS methodology has the potential to improve the lives of those with an SCI by enhancing their capability for volitional movement.

Older adults are at high risk for fall-related injuries that contribute to decreased quality of life and higher health care costs. Risk for falling is especially high during everyday activities involving turns and transitional movements. However, little is known about movement strategies that older adults use when turning. Therefore, the purpose of this research is to identify turning strategies in older adults. In this study, we examined movement strategies used for 180 degree turns during a clinical test of functional mobility, the Timed Up and Go. The Timed Up and Go test measures the time it takes to stand up from a chair, walk, turn around, walk back to the chair, and sit down. Thirty-one older adults (means age 85.6 years) were studied using Qualisys Motion Capture laboratory-based quantitative motion analysis (eight-camera system) and APDM portable body-worn sensors (inertial sensor system). Five distinct turning patterns were identified through frame-by-frame observational analysis of the Qualisys output. Quantitative methods were then applied to characterize parameters of turning in older adults, including turn duration (seconds), turn angle (degrees), and peak turning velocity (meters/second). Finally, we explored relationships between turning patterns and predictive tests of functional mobility and falls in older adults. These measures will be vital in identifying early signs of fall risk in older adults. As a result of this research, we can classify and quantify turning strategies using innovative technology. The results of this research have clinical implications, for healthcare practitioners, to identify people who are at risk for falls and construct therapeutic activities to prevent fall-related injuries.