Postsurgical acute pain hinders children’s recovery from major surgery. Due to enhanced recovery after surgery (ERAS) approaches, patients are now discharged from the hospital sooner, and are managing more of their postsurgical recovery and pain at home. It is estimated that 80% of children undergoing major surgery experience moderate to severe pain two weeks post-surgery. Around 20% go on to develop chronic pain, which affects their long-term health related quality of life. There is currently no method for identifying patients prior to discharge who are at risk for poor acute recovery. This study aimed to determine if a patient’s functional ability as measured by the validated Youth Acute Pain Functional Ability Questionnaire (YAPFAQ) during hospitalization can predict pain and recovery at two-weeks post-surgery. We also aimed to compare the predictive ability of YAPFAQ to hospital pain intensity numerical rating score (PI-NRS) self-report. Adolescents undergoing major musculoskeletal surgery (N=119) completed YAPFAQ daily for up to three days following surgery, and questionnaires assessing health-related quality of life and pain intensity at two-week follow-up. Regression analyses showed that mean YAPFAQ score were significantly associated with both pain intensity and health-related quality of life at two-weeks post-surgery. In comparison, PI-NRS was significantly associated with pain intensity at two weeks, but not with health-related quality of life. The rate of improvement of both YAPFAQ and pain intensity score were not associated with two-week outcomes. YAPFAQ should be considered as a possible tool to alert providers of pediatric patients at risk for poor recovery at home following musculoskeletal surgery.

Knee osteoarthritis (OA) is a chronic condition that causes pain and disability in older adults. Currently, there are no curative treatments that reverse knee OA. However, exercise has been demonstrated to slow the progression of knee OA, reduce pain, and improve physical functioning. The mechanisms through which exercise improves pain in this population are unclear. Prior research in healthy adults suggests that physical activity, including acute bouts of exercise, is associated with improvements in central pain processing. We wanted to explore the relationships of free-living physical activity with somatosensory function and the acute effects of walking exercise in older adults with knee OA. Physical activity was measured with a thigh-mounted accelerometer worn for 1 week. Participants underwent pain pressure threshold (PPT) testing (algometer placed 2cm proximal to the superior edge of the patella) before and immediately after walking for 6-minutes at a fast pace. Participants (N=46) had a mean age of 73.5 (SD=6.3) years, 80.4% were women, and 17.4% self-identified as racial/ethnic minority. Mean pre-exercise PPT was significantly higher in men (6.6±1.9kg) than in women (4.7±2.0kg, P=0.01). There were no relationships between accelerometer measured physical activity and PPT in men or women (p>0.05 for all comparisons). For example, the correlation between average daily step count and pre-exercise PPT was -0.08 in women. When comparing PPT before versus after walking 6 minutes, women exhibited exercise-induced hypoalgesia (pre-post within person mean difference=-0.35kg, P=0.01), but this effect was not observed in men (mean difference=0.23kg, P=0.65). Preliminary results suggest that moderate-to-vigorous walking exercise can induce hypoalgesia in older women with knee OA, but free-living walking and other measures of physical activity were not associated with PPT. In the future, we plan to enroll additional participants and examine changes in PPT and other measures of somatosensory function after a multicomponent exercise intervention.

Gastrointestinal helminth infections are among the most common infections worldwide affecting about 1.5 billion people. Previous work shows that during infection with Trichuris muris, a mouse model of human whipworm in the large intestine, basophils, rare innate immune cells, accumulate at the site of infection and upregulate the expression of Notch receptors, part of a signaling pathway that regulates gene expression. Due to this discovery, we are investigating the importance of Notch receptor expression in basophils for the anti-helminth immune response and parasite clearance during infection. With single-cell RNA sequencing (scRNAseq) we are able to analyze the expression of individual cells to better understand immune cell response to infection. To investigate how Notch signaling in basophils impacts CD4 T cell function during infection, we performed scRNAseq on CD4 T cells from the intestine of naive and T. muris infected wild-type mice and mice without Notch signaling specifically in basophils. Using this approach, for the first time, we have characterized the gene expression profile of CD4 T cells at the site of infection, allowing us to identify different CD4 T cell subpopulations and their differential gene expression. This will provide insight into how T. muris infection impacts CD4 T cell gene expression and function, and the importance of Notch signaling in basophils for promoting T cell function during infection. Ongoing work is addressing how CD4 T cells and basophils interact in the large intestine, how the highly regulated environment impacts the development of the CD4 T cell response and the T cell receptor repertoire in T. muris infection, and the importance of basophil Notch signaling for this process. A better understanding of the response to helminth infection and manipulation of Notch signaling-dependent cellular responses can lead to the discovery of novel treatments for helminth infection and allergic diseases.