Human Studies

Gerontological research reveals considerable interindividual variability in aging phenotypes, and emerging evidence suggests that high impact chronic pain may be associated with various accelerated biological aging processes. In particular, epigenetic aging is a robust predictor of health-span and disability compared to chronological age alone. The current study aimed to determine whether several epigenetic aging biomarkers were associated with high impact chronic pain in middle to older age adults (44-78 years old). Participants ( = 213) underwent a blood draw, demographic, psychosocial, pain and functional assessments. We estimated five epigenetic clocks and calculated the difference between epigenetic age and chronological age, which has been previously reported to predict overall mortality risk, as well as included additional derived variables of epigenetic age previously associated with pain. There were significant differences across Pain Impact groups in three out of the five epigenetic clocks examined (DNAmAge, DNAmPhenoAge and DNAmGrimAge), indicating that pain-related disability during the past 6 months was associated with markers of epigenetic aging. Only DNAmPhenoAge and DNAmGrimAge were associated with higher knee pain intensity during the past 48 h. Finally, pain catastrophizing, depressive symptomatology and more neuropathic pain symptoms were significantly associated with an older epigenome in only one of the five epigenetic clocks (i.e. DNAmGrimAge) after correcting for multiple comparisons (corrected 's < 0.05). Given the scant literature in relation to epigenetic aging and the complex experience of pain, additional research is needed to understand whether epigenetic aging may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.

Migraine and major depressive disorder (MDD) are both highly prevalent brain disorders and are often comorbid. However, the common and distinctive neural mechanisms underlying these disorders and the brain function alterations associated with their comorbidity are largely unknown. We aimed to explore the functional abnormalities of the brain associated with the co-occurrence of migraine and depression.

Chronic low back pain (CLBP) is a lifelong condition causing disability and distress. One aim of treatment is to enhance self-management. To date, self-management interventions have had limited effectiveness. A greater understanding of self-management for CLBP has the potential to improve future interventional trials. The purpose of this study was to identify the experience of CLBP self-management for patients attending outpatient physical therapy and assess how the experience of CLBP self-management changes over time.

Irritable bowel syndrome (IBS) is a common disorder characterized by chronic abdominal pain and changes in bowel movements. Visceral hypersensitivity is thought to be responsible for pain complaints in a subset of patients. In an IBS-like animal model, visceral hypersensitivity was triggered by intestinal fungi, and lower mycobiota α-diversity in IBS patients was accompanied by a shift toward increased presence of Candida albicans and Saccharomyces cerevisiae. Yet, this shift was observed in hypersensitive as well as normosensitive patients and diversity did not differ between IBS subgroups. The latter suggests that, when a patient changes from hyper- to normosensitivity, the relevance of intestinal fungi is not necessarily reflected in compositional mycobiota changes. We now confirmed this notion by performing ITS1 sequencing on an existing longitudinal set of fecal samples. Since ITS1 methodology does not recognize variations within species, we next focused on heterogeneity within cultured healthy volunteer and IBS-derived C. albicans strains. We observed inter- and intra-individual genomic variation and partial clustering of strains from hypersensitive patients. Phenotyping showed differences related to growth, yeast-to-hyphae morphogenesis and gene expression, specifically of the gene encoding fungal toxin candidalysin. Our investigations emphasize the need for strain-specific cause-and-effect studies within the realm of IBS research.

Placement of percutaneous spinal cord stimulator (SCS) implant has become a therapeutic option for various chronic pain conditions; however, early surgical explant still occurs. Unfortunately, evidence regarding the incidence of early surgical explant, and patient-specific factors and comorbidities associated with such, is limited and mixed. The objective of this retrospective analysis was to elucidate the incidence and predictors of percutaneous SCS explant within the first two years of device placement.

The study sought to evaluate the influence of anesthesia on chronic pain after total knee arthroplasty (TKA). : This was a single-center, randomized controlled study, with patients receiving a spinal anesthetic (SP) alone or a general anesthetic (GA) with femoral block, with follow-up at 3 and at 6 months. The primary outcome was the WOMAC score at 6 months. : 199 patients were enrolled. Group SP had better function (WOMAC: GA: 16.9 vs SP: 14.4, p = 0.015) and less pain (WOMAC pain: GA: 3.04 vs SP: 2.69, p = 0.02) at 3 months, but not at 6 months. Overall, 11% of patients had chronic postsurgical pain (CPSP), with Group GA having a higher incidence of CPSP at 6 months. Neuropathic pain increased during the follow-up and was more common in patients with CPSP. : An SP reduces pain and incidence of CPSP after TKA. Clinical Trial Registration: NCT04206046 (ClinicalTrials.gov).