Chronic pain was associated with differences in CSF biomarkers when compared with those without chronic pain in a large study.

An association between chronic pain and cognitive decline has not been well established. In this study, researchers analysed data from the Alzheimer’s disease (AD) Neuroimaging Initiative to assess whether chronic pain was associated with cerebrospinal fluid (CSF) biomarkers for neurodegeneration and neuroinflammation. Based on the amyloid, tau, neurodegeneration (ATN) classification scheme and using CSF amyloid-beta 1-42, phosphorylated-tau 181 and total tau levels, participants were either on the AD continuum (amyloid-positive with or without neurodegeneration biomarkers), had suspected non-AD pathophysiology (SNAP; amyloid-negative with neurodegenerative-positive biomarkers) or lacked both amyloid and neurodegeneration biomarkers. CSF-soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was identified as a marker for neuroinflammation and microglial activation. Other inflammatory CSF proteins, such as tumour necrosis factor-alpha, were analysed. Cognitive assessments included tests of memory and executive function. Covariates included age, sex, education, apolipoprotein E4 status, depression, analgesic use and number of chronic conditions.

Among 995 participants (mean age, 73 years; 56% male), 61% reported chronic pain at baseline. In cross-sectional analyses, suspected non-AD pathophysiology participants with chronic pain had higher CSF total tau and sTREM2 levels than those without chronic pain. Chronic pain was associated with CSF tumour necrosis factor-alpha levels, regardless of ATN status. In longitudinal analyses, among participants without amyloid or neurodegeneration markers, those with chronic pain had increasing CSF phosphorylated-tau 181 levels over 12 to 24 months, while those without chronic pain had decreasing CSF amyloid-beta 1-42 levels. No ATN group had significant longitudinal decline in cognitive function.

Comment: These findings suggest that chronic pain may be associated with neuroinflammation, microglial activation and neurodegeneration, especially in those with suspected non-AD pathophysiology. Why longitudinal analyses showed increasing CSF phosphorylated-tau181 levels in those with chronic pain, but decreasing CSF amyloid-beta 1-42 levels in those without chronic pain, among the amyloid-negative and neuro- degeneration-negative group requires further study.

Jennifer Rose V. Molano, MD, Associate Professor, Department of Neurology and Rehabilitation Medicine, The University of Cincinnati, Ohio, USA.

Sadlon A, et al. Association of chronic pain with biomarkers of neurodegeneration, microglial activation, and inflammation in cerebrospinal fluid and impaired cognitive function. Ann Neurol 2024; 95: 195-206.

This summary is taken from the following Journal Watch title: Neurology.