Protocol for a pilot and feasibility randomized-controlled trial of four weeks of oral γ-aminobutyric acid (GABA) intake and its effect on pain and sleep in middle-to-older aged adults.

Approximately 1.71 billion people globally live with musculoskeletal pain conditions, including low back pain, knee pain, and neck pain Cieza et al. (2020). In the US, an estimated 20.4% of U.S. adult had chronic pain and 8.0% of U.S. adults had high-impact chronic pain, with higher prevalence associated with advancing age Dahlhamer et al. (2018). On the other hand, between 50 and 70 million US adults have a sleep disorder (American Sleep Association). Although the link between sleep and pain is widely established, the neurobiological mechanisms underlying this relationship have yet to be fully elucidated, specifically within an aged population. As currently available sleep and chronic pain therapies are only partially effective, novel treatment approaches are urgently needed. Given the potential mechanistic role of γ-aminobutyric acid (GABA) in both conditions, and the availability of GABA supplements over the counter, the present proposal will determine the feasibility and acceptability of oral GABA administration in middle-to-older aged adults with chronic pain and sleep disorders as well as characterize the potential neurobiological mechanisms involved in both conditions. Results from the present investigation using a parallel, double-blinded, placebo-controlled study will provide novel preliminary information needed for future translational pain and sleep research.

Experimental Pain Phenotype Profiles in Community-dwelling Older Adults.

OBJECTIVES: Pain sensitivity and the brain structure are critical in modulating pain and may contribute to the maintenance of pain in older adults. However, a paucity of evidence exists investigating the link between pain sensitivity and brain morphometry in older adults. The purpose of the study was to identify pain sensitivity profiles in healthy, community-dwelling older adults using a multimodal quantitative sensory testing protocol and to differentiate profiles based on brain morphometry. MATERIALS AND METHODS: This study was a secondary analysis of the Neuromodulatory Examination of Pain and Mobility Across the Lifespan (NEPAL) study. Participants completed demographic and psychological questionnaires, quantitative sensory testing, and a neuroimaging session. A Principal Component Analysis with Varimax rotation followed by hierarchical cluster analysis identified 4 pain sensitivity clusters (the "pain clusters"). RESULTS: Sixty-two older adults ranging from 60 to 94 years old without a specific pain condition (mean [SD] age=71.44 [6.69] y, 66.1% female) were analyzed. Four pain clusters were identified characterized by (1) thermal pain insensitivity; (2) high pinprick pain ratings and pressure pain insensitivity; (3) high thermal pain ratings and high temporal summation; and (4) thermal pain sensitivity, low thermal pain ratings, and low mechanical temporal summation. Sex differences were observed between pain clusters. Pain clusters 2 and 4 were distinguished by differences in the brain cortical volume in the parieto-occipital region. DISCUSSION: While sufficient evidence exists demonstrating pain sensitivity profiles in younger individuals and in those with chronic pain conditions, the finding that subgroups of experimental pain sensitivity also exist in healthy older adults is novel. Identifying these factors in older adults may help differentiate the underlying mechanisms contributing to pain and aging.

Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial.

RATIONALE: Most studies evaluating the safety and tolerability of intranasal oxytocin (OT) have not reported consistent adverse events (AEs), but they have largely focused on young men and single-dose administration. Thus, it is unclear whether these findings translate to older individuals and with longer administration periods. OBJECTIVE: Extending previous work, this study investigated the safety and tolerability of chronic intranasal OT in generally healthy older men. METHODS: Data were from a randomized, placebo (P)-controlled, double-blind clinical trial evaluating the effects of 4 weeks of self-administered intranasal OT (24 IU twice daily) in older adults with no major physical or cognitive impairments. Heart rate, blood pressure, urine osmolality, and serum metabolic biomarkers were obtained before and at the end of the intervention. AEs were collected during the first 3 weeks and 1 week after cessation of treatment. RESULTS: Of 103 participants recruited, 95 were randomized and received the intervention (OT = 49, P = 46). OT had no significant impact on cardiovascular, urine, or serum measures. The AEs reported for both treatments were generally mild and few in number, though one participant assigned to OT and two assigned to P dropped out due to AEs. Relative to P, OT did not significantly increase the likelihood of reporting AEs, nor the number or severity of AEs reported. CONCLUSION: Chronic intranasal OT appears safe and well-tolerated in generally healthy older men. These findings provide support for continued human research on potential benefits of chronic OT in older adult populations.

Age Differences in Multimodal Quantitative Sensory Testing and Associations With Brain Volume.

BACKGROUND AND OBJECTIVES: Somatosensory function is critical for successful aging. Prior studies have shown declines in somatosensory function with age; however, this may be affected by testing site, modality, and biobehavioral factors. While somatosensory function declines are associated with peripheral nervous system degradation, little is known regarding correlates with the central nervous system and brain structure in particular. The objectives of this study were to examine age-related declines in somatosensory function using innocuous and noxious stimuli, across 2 anatomical testing sites, with considerations for affect and cognitive function, and associations between somatosensory function and brain structure in older adults. RESEARCH DESIGN AND METHODS: A cross-sectional analysis included 84 "younger" (n = 22, age range: 19-24 years) and "older" (n = 62, age range: 60-94 years) healthy adults who participated in the Neuromodulatory Examination of Pain and Mobility Across the Lifespan study. Participants were assessed on measures of somatosensory function (quantitative sensory testing), at 2 sites (metatarsal and thenar) using standardized procedures, and completed cognitive and psychological function measures and structural magnetic resonance imaging. RESULTS: Significant age × test site interaction effects were observed for warmth detection (p = .018, η p 2 = 0.10) and heat pain thresholds (p = .014, η p 2 = 0.12). Main age effects were observed for mechanical, vibratory, cold, and warmth detection thresholds (ps < .05), with older adults displaying a loss of sensory function. Significant associations between somatosensory function and brain gray matter structure emerged in the right occipital region, the right temporal region, and the left pericallosum. DISCUSSION AND IMPLICATIONS: Our findings indicate healthy older adults display alterations in sensory responses to innocuous and noxious stimuli compared to younger adults and, furthermore, these alterations are uniquely affected by anatomical site. These findings suggest a nonuniform decline in somatosensation in older adults, which may represent peripheral and central nervous system alterations part of aging processes.