Differential expression of a brain aging biomarker across discrete chronic pain disorders

Abstract

Chronic pain has widespread, detrimental effects on the human nervous system and its prevalence and burden increase with age. Machine learning techniques have been applied on brain images to produce statistical models of brain aging. Specifically, the Gaussian process regression is particularly effective at predicting chronological age from neuroimaging data which permits the calculation of a brain age gap estimate (brain-AGE). Pathological biological processes such as chronic pain can influence brain-AGE. Because chronic pain disorders can differ in etiology, severity, pain frequency, and sex-linked prevalence, we hypothesize that the expression of brain-AGE may be pain specific and differ between discrete chronic pain disorders. We built a machine learning model using T1-weighted anatomical MRI from 812 healthy controls to extract brain-AGE for 45 trigeminal neuralgia (TN), 52 osteoarthritis (OA), and 50 chronic low back pain (BP) subjects. False discovery rate corrected Welch t tests were conducted to detect significant differences in brain-AGE between each discrete pain cohort and age-matched and sexmatched controls. Trigeminal neuralgia and OA, but not BP subjects, have significantly larger brain-AGE. Across all 3 pain groups, we observed female-driven elevation in brain-AGE. Furthermore, in TN, a significantly larger brain-AGE is associated with response to Gamma Knife radiosurgery for TN pain and is inversely correlated with the age at diagnosis. As brain-AGE expression differs across distinct pain disorders with a pronounced sex effect for female subjects. Younger women with TN may therefore represent a vulnerable subpopulation requiring expedited chronic pain intervention. To this end, brain-AGE holds promise as an effective biomarker of pain treatment response.

Cross-Sectional Brain-Predicted Age Differences in Community-Dwelling Middle-Aged and Older Adults with High Impact Knee Pain

“…However, a recent study found that across three different pain conditions, individuals with osteoarthritis pain and trigeminal neuralgia showed significantly older appearing brains. 27 Despite these findings, there has been limited examination of the global brain aging patterns in persons with chronic pain. Given that brain aging as measured employing brain aging biomarkers has been associated with worse cognitive performance, increased likelihood for chronic disease (eg, cardiovascular diseases), and increased mortality, 17,[28][29][30] it is imperative to elucidate the relationship between chronic pain and brain aging to identify adults at greater risk for cognitive and physical function decline.…”

Thalamic neurometabolite alterations in chronic low back pain: a common phenomenon across musculoskeletal pain conditions?

“…Indeed, we speculate that this synergistic effect might be a substrate underlying accelerated brain aging, a phenomenon that has been proposed to occur in patients with cLBP and other chronic pain. 29,47,71 Future investigations should explicitly evaluate this intriguing question.…”

Managing Older Adults' Chronic Pain: Higher-Risk Interventions

“…The prevalence of chronic pain increases with age, affecting 28% of adults ages 65 to 84 years and 34% of those 85 and older, with high-impact chronic pain (chronic pain that regularly limits daily activities) affecting the latter more than any other age group 1. Chronic pain impairs older adults physically, mentally, and socially; diminishes general health, biopsychosocial functioning, and longevity; and accelerates brain aging 2, 3. Older adults are also more likely to transition from acute pain to chronic, disabling, treatment-resistant pain due to neuroimmune changes seen with aging 4.…”

“…1 Chronic pain impairs older adults physically, mentally, and socially; diminishes general health, biopsychosocial functioning, and longevity; and accelerates brain aging. 2,3 Older adults are also more likely to transition from acute pain to chronic, disabling, treatment-resistant pain due to neuroimmune changes seen with aging. 4 People with chronic pain face stigma and discrimination and are increasingly denied access to treatment.…”