Human Studies

Chronic pain is associated with brain atrophy with limited evidence on its impact in the older adult's brain. We aimed to determine the associations between chronic pain and a brain aging biomarker in persons aged 60 to 83 years old. Participants of the Neuromodulatory Examination of Pain and Mobility Across the Lifespan (NEPAL) study (N = 47) completed demographic, psychological, and pain assessments followed by a quantitative sensory testing battery and a T1-weighted magnetic resonance imaging. We estimated a brain-predicted age difference (brain-PAD) that has been previously reported to predict overall mortality risk (brain-PAD, calculated as brain-predicted age minus chronological age), using an established machine-learning model. Analyses of covariances and Pearson/Spearman correlations were used to determine associations of brain-PAD with pain, somatosensory function, and psychological function. Individuals with chronic pain (n = 33) had "older" brains for their age compared with those without (n = 14; F[1,41] = 4.9; P = 0.033). Greater average worst pain intensity was associated with an "older" brain (r = 0.464; P = 0.011). Among participants with chronic pain, those who reported having pain treatments during the past 3 months had "younger" brains compared with those who did not (F[1,27] = 12.3; P = 0.002). An "older" brain was significantly associated with decreased vibratory (r = 0.323; P = 0.033) and thermal (r = 0.345; P = 0.023) detection, deficient endogenous pain inhibition (F[1,25] = 4.6; P = 0.044), lower positive affect (r = -0.474; P = 0.005), a less agreeable (r = -0.439; P = 0.020), and less emotionally stable personality (r = -0.387; P = 0.042). Our findings suggest that chronic pain is associated with added "age-like" brain atrophy in relatively healthy, community-dwelling older individuals, and future studies are needed to determine the directionality of our findings. A brain aging biomarker may help identify people with chronic pain at a greater risk of functional decline and poorer health outcomes.

To investigate the validity of comparisons across patients with different musculoskeletal disorders and persons from the general population by evaluating differential item functioning (DIF) for the PROMIS physical function (PROMIS-PF), pain interference (PROMIS-PI), and pain behavior (PROMIS-PB) item banks.

To examine the rates and predictors of long-term opioid therapy in older cancer survivors.

Neuropathic pain encompasses a diverse array of clinical entities affecting 7-10% of the population, which is challenging to adequately treat. Several promising therapeutics derived from molecular discoveries in animal models of neuropathic pain have failed to translate following unsuccessful clinical trials suggesting the possibility of important cellular-level and molecular differences between animals and humans. Establishing the extent of potential differences between laboratory animals and humans, through direct study of human tissues and/or cells, is likely important in facilitating translation of preclinical discoveries to meaningful treatments. Patch-clamp electrophysiology and RNA-sequencing was performed on dorsal root ganglia taken from patients with variable presence of radicular/neuropathic pain. Findings establish that spontaneous action potential generation in dorsal root ganglion neurons is associated with radicular/neuropathic pain and radiographic nerve root compression. Transcriptome analysis suggests presence of sex-specific differences and reveals gene modules and signalling pathways in immune response and neuronal plasticity related to radicular/neuropathic pain that may suggest therapeutic avenues and that has the potential to predict neuropathic pain in future cohorts.

We hypothesized that patients with characteristics of centralized pain (fibromyalgia (FM)-like phenotype) would be less likely to respond to radiofrequency ablation (RFA), which may explain some of the failures of this peripherally directed therapy.