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. 2023 Oct 1;137(4):896-905.
doi: 10.1213/ANE.0000000000006514. Epub 2023 May 12.

Chronic Pain, Analgesics, and Cognitive Status: A Comprehensive Mendelian Randomization Study

Xingzhi Guo  1   2   3 , Chen Hou  1   2 , Peng Tang  1   2 , Rui Li  1   2   3
Affiliations

Chronic Pain, Analgesics, and Cognitive Status: A Comprehensive Mendelian Randomization Study

Xingzhi Guo et al. Anesth Analg. .

Abstract

Background: Observational studies have suggested an intricate relationship among chronic pain (CP), use of analgesics, and cognitive status, but it remains unclear whether these associations are of a causal nature.

Methods: To investigate the causal relationship among them, summary statistics of 9 types of CP (headache, hip, neck/shoulder, stomach/abdominal, back, knee, facial, general, and multisite CP), analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, salicylic acid and derivatives, and anilides), and cognitive status (cognitive function, Alzheimer's disease [AD], vascular dementia, Lewy body dementia [LBD], and dementia) were included in this Mendelian randomization (MR) study. As both CP and analgesic use were associated with cognitive status and vice versa, we performed a bidirectional MR analysis between CP or analgesics and dementia using strong genetic instruments ( P < .001) identified from genome-wide association studies (GWAS). The inverse-variance weighted method was applied to calculate estimates. The MR estimated odds ratio (OR) was interpreted as odds of outcome per unit increase in the exposure. The Benjamini-Hochberg method was applied to adjust the P value for multiple testing, and P < .05 means statistically significant.

Results: Multisite CP (MCP) was associated with worse cognitive function (OR [95% confidence interval], 0.69 [0.53-0.89], P = .043), but no significant reverse effect of cognitive status on CP was found. There were no significant associations observed between analgesics and cognitive status. Unexpectedly, patients with AD and LBD had significantly lower exposure to anilides (AD: OR = 0.97 [0.94-0.99], P = .034; LBD: OR = 0.97 [0.96-0.99], P = .012) and NSAIDs (AD: OR = 0.96 [0.93-0.98], P = .012; LBD: OR = 0.98 [0.96-0.99], P = .034).

Conclusions: Our findings indicate that an elevated number of CP sites predict future cognitive decline. Patients with dementia had lower exposure to anilides and NSAIDs, suggesting that they might not be adequately medicated for pain.

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Conflict of interest statement

The authors declare no conflicts of interest.

Comment in

References

    1. Yong RJ, Mullins PM, Bhattacharyya N. Prevalence of chronic pain among adults in the United States. Pain. 2022;163:e328–e332.
    1. Cravello L, Di Santo S, Varrassi G, et al. Chronic pain in the elderly with cognitive decline: a narrative review. Pain Ther. 2019;8:53–65.
    1. van Kooten J, Binnekade TT, van der Wouden JC, et al. A review of pain prevalence in Alzheimer’s, vascular, frontotemporal and Lewy body dementias. Dement Geriatr Cogn Disord. 2016;41:220–232.
    1. Cao S, Fisher DW, Yu T, Dong H. The link between chronic pain and Alzheimer’s disease. J Neuroinflammation. 2019;16:204.
    1. Callaghan BC, Reynolds E, Banerjee M, Kerber KA, Skolarus LE, Burke JF. Longitudinal pattern of pain medication utilization in peripheral neuropathy patients. Pain. 2019;160:592–599.