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已发表论文
疼痛与精神障碍双向因果关系的综合孟德尔随机化研究
Received 17 August 2025
Accepted for publication 17 January 2026
Published 21 February 2026 Volume 2026:19 561284
DOI https://doi.org/10.2147/JPR.S561284
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Jonathan Greenberg
Xiao Liang,1 Yuchao Fan2
1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Anesthesiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China
Correspondence: Yuchao Fan, Department of Anesthesiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email yuchaofan_pain@126.com
Background: Pain and mental disorders frequently co-occur, yet the direction and specificity of their relationship remain uncertain due to limitations of observational studies. Mendelian randomization (MR) provides an opportunity to clarify causal links between distinct pain phenotypes and psychiatric outcomes.
Methods: We performed a comprehensive bidirectional MR analysis to investigate causal relationships between multiple pain conditions and mental and personality disorders. Multivariable MR was applied to assess the independence of these associations while accounting for common comorbidities. Robustness was evaluated using complementary sensitivity analyses.
Results: Forward analyses showed that several pain phenotypes - including back pain, headaches, neck or shoulder pain, stomach or abdominal pain, migraine, and trigeminal neuralgia—were associated with increased risk of specific mental disorders. Reverse analyses indicated that mental disorders also predispose individuals to certain pain conditions. Most associations remained robust after multivariable adjustment, although some were attenuated by obesity or substance use.
Conclusion: These findings demonstrate structured, pain - type - specific bidirectional relationships between pain and mental disorders. Clinically, they support phenotype-informed screening and management strategies, including targeted assessment of depression and anxiety in patients with high-risk pain conditions and proactive evaluation of pain symptoms in patients with mental disorders, to facilitate earlier risk stratification and integrated care.
Keywords: pain, mental disorders, bidirectional mendelian randomization, multivariate mendelian randomization, causal effect
1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Anesthesiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China
Correspondence: Yuchao Fan, Department of Anesthesiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email yuchaofan_pain@126.com
Background: Pain and mental disorders frequently co-occur, yet the direction and specificity of their relationship remain uncertain due to limitations of observational studies. Mendelian randomization (MR) provides an opportunity to clarify causal links between distinct pain phenotypes and psychiatric outcomes.
Methods: We performed a comprehensive bidirectional MR analysis to investigate causal relationships between multiple pain conditions and mental and personality disorders. Multivariable MR was applied to assess the independence of these associations while accounting for common comorbidities. Robustness was evaluated using complementary sensitivity analyses.
Results: Forward analyses showed that several pain phenotypes - including back pain, headaches, neck or shoulder pain, stomach or abdominal pain, migraine, and trigeminal neuralgia—were associated with increased risk of specific mental disorders. Reverse analyses indicated that mental disorders also predispose individuals to certain pain conditions. Most associations remained robust after multivariable adjustment, although some were attenuated by obesity or substance use.
Conclusion: These findings demonstrate structured, pain - type - specific bidirectional relationships between pain and mental disorders. Clinically, they support phenotype-informed screening and management strategies, including targeted assessment of depression and anxiety in patients with high-risk pain conditions and proactive evaluation of pain symptoms in patients with mental disorders, to facilitate earlier risk stratification and integrated care.
Keywords: pain, mental disorders, bidirectional mendelian randomization, multivariate mendelian randomization, causal effect