Association Between C-reactive Protein and Chronic Pain in US Adults: A Nationwide Cross-sectional Study

Overview

Journal PLoS One

Date 2025 Feb 7

PMID 39919114

Authors

Chunsheng Huang

Qizhen Tong

Qiaoling Tong

Affiliations

Soon will be listed here.

Abstract

Background: Chronic pain has emerged as a significant global public health concern. Hence, it is imperative to acquire a more comprehensive comprehension of these characteristics in the adult population of the United States in order to facilitate the development of effective interventions. The objective of this study is to ascertain the prevalence of chronic pain among people in the United States and investigate its association with C-reactive protein (CRP) levels.

Methods: The present study employed a cross-sectional design and utilized data from three cycles of the National Health and Nutrition Examination Survey (NHANES). The study aimed to investigate the relationship between chronic pain status, CRP levels, and potential confounding factors. The study incorporated individuals who successfully fulfilled chronic questionnaires and had CRP assays. Weighted univariate and multivariate logistic regression analyses were performed to examine the correlation between chronic pain and CRP levels. To explore the non-linear relationship, weighted restricted cubic spline (RCS) with three knots coupled with a weighted logistic regression model to assess the dose-response relationship between CRP (continuous variables) and chronic pain.

Results: A total of 10,680 (Weighted 250,814,660.8) adult participants with complete information were included in the analysis and 2612 (Weighted 67978784.88, 27.1%) subjects met the definition of chronic pain. Compared with participants without chronic pain, those with chronic pain had a higher CRP level (P < 0.001). The results of the multivariable adjusted logistic regression model suggested that the highest CRP quartile (CRP > 0.52 mg/dL) was associated with a 32% increase in the risk of chronic pain compared with the lowest CRP quartile (CRP ≤ 0.09 mg/dL). The RCS result showed that the OR of chronic pain and CRP displayed a linear relationship (P = 0.027, Non-linear P = 0.541).

Conclusions: The study found a significant correlation between CRP levels and the presence of chronic pain among people in the United States. Individuals exhibiting elevated levels of CRP demonstrated a heightened propensity for experiencing chronic pain in comparison to individuals with lower CRP levels. Additional investigation is necessary to explore the presence of a causal association between the two variables, as well as the potential underlying mechanisms.

References

Fiore N, Debs S, Hayes J, Duffy S, Moalem-Taylor G . Pain-resolving immune mechanisms in neuropathic pain. Nat Rev Neurol. 2023; 19(4):199-220. DOI: 10.1038/s41582-023-00777-3. View

Scholz J, Finnerup N, Attal N, Aziz Q, Baron R, Bennett M . The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain. 2018; 160(1):53-59. PMC: 6310153. DOI: 10.1097/j.pain.0000000000001365. View

Pope J, Choy E . C-reactive protein and implications in rheumatoid arthritis and associated comorbidities. Semin Arthritis Rheum. 2021; 51(1):219-229. DOI: 10.1016/j.semarthrit.2020.11.005. View

Voon P, Karamouzian M, Kerr T . Chronic pain and opioid misuse: a review of reviews. Subst Abuse Treat Prev Policy. 2017; 12(1):36. PMC: 5558770. DOI: 10.1186/s13011-017-0120-7. View

Jiang W, Zhang L, Tan X, Yu P, Dong M . Inflammation and histone modification in chronic pain. Front Immunol. 2023; 13:1087648. PMC: 9880030. DOI: 10.3389/fimmu.2022.1087648. View

Adam F, Jouet P, Sabate J, Perrot S, Franchisseur C, Attal N . Thermal grill illusion of pain in patients with chronic pain: a clinical marker of central sensitization?. Pain. 2022; 164(3):638-644. DOI: 10.1097/j.pain.0000000000002749. View

Lee Y, Lu B, Bathon J, Haythornthwaite J, Smith M, Page G . Pain sensitivity and pain reactivity in osteoarthritis. Arthritis Care Res (Hoboken). 2010; 63(3):320-7. PMC: 3030930. DOI: 10.1002/acr.20373. View

Fitzcharles M, Cohen S, Clauw D, Littlejohn G, Usui C, Hauser W . Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet. 2021; 397(10289):2098-2110. DOI: 10.1016/S0140-6736(21)00392-5. View

Karimi R, Mallah N, Nedjat S, Beasley M, Takkouche B . Association between alcohol consumption and chronic pain: a systematic review and meta-analysis. Br J Anaesth. 2022; 129(3):355-365. DOI: 10.1016/j.bja.2022.03.010. View

10.

Kumar A, Dhaliwal N, Dhaliwal J, Dharavath R, Chopra K . Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis in rats. Pharmacol Rep. 2020; 72(1):104-114. DOI: 10.1007/s43440-019-00022-z. View

11.

Klyne D, Barbe M, Hodges P . Systemic inflammatory profiles and their relationships with demographic, behavioural and clinical features in acute low back pain. Brain Behav Immun. 2016; 60:84-92. DOI: 10.1016/j.bbi.2016.10.003. View

12.

Guo R, Chen L, Xing C, Liu T . Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. Br J Anaesth. 2019; 123(5):637-654. DOI: 10.1016/j.bja.2019.07.026. View

13.

Salaffi F, Giacobazzi G, Di Carlo M . Chronic Pain in Inflammatory Arthritis: Mechanisms, Metrology, and Emerging Targets-A Focus on the JAK-STAT Pathway. Pain Res Manag. 2018; 2018:8564215. PMC: 5829432. DOI: 10.1155/2018/8564215. View

14.

Puthucheary Z, Tadie J, Patel J . C-reactive protein in immunometabolism: spared from 'paying the piper'. Intensive Care Med. 2021; 48(1):103-105. DOI: 10.1007/s00134-021-06586-w. View

15.

Bruehl S . Complex regional pain syndrome. BMJ. 2015; 351:h2730. DOI: 10.1136/bmj.h2730. View

16.

Porter B, St Marie B, Milavetz G, Herr K . Cannabidiol (CBD) Use by Older Adults for Acute and Chronic Pain. J Gerontol Nurs. 2021; 47(7):6-15. PMC: 8344100. DOI: 10.3928/00989134-20210610-02. View

17.

Qi X, Cui K, Zhang Y, Wang L, Tong J, Sun W . A nociceptive neuronal ensemble in the dorsomedial prefrontal cortex underlies pain chronicity. Cell Rep. 2022; 41(11):111833. DOI: 10.1016/j.celrep.2022.111833. View

18.

Ahluwalia N, Dwyer J, Terry A, Moshfegh A, Johnson C . Update on NHANES Dietary Data: Focus on Collection, Release, Analytical Considerations, and Uses to Inform Public Policy. Adv Nutr. 2016; 7(1):121-34. PMC: 4717880. DOI: 10.3945/an.115.009258. View

19.

Patten D, Schultz B, Berlau D . The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders. Pharmacotherapy. 2018; 38(3):382-389. DOI: 10.1002/phar.2086. View

20.

Parisien M, Lima L, Dagostino C, El-Hachem N, Drury G, Grant A . Acute inflammatory response via neutrophil activation protects against the development of chronic pain. Sci Transl Med. 2022; 14(644):eabj9954. PMC: 10317000. DOI: 10.1126/scitranslmed.abj9954. View