• Amber De Groote, VyvereThijs VandeTVResearch Group MOVANT, Department of Rehabilitation Sciences and Physiotherapy (REVAKI), University of Antwerp, Wilrijk, Belgium; Pain in Motion International Research Group, www.paininmotion.be, Belgium; Department of Radiology, Antwer, Wiebren Tjalma, BergheWim VandenWVLab Protein Chemistry, Proteomics & Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium., Samir Kumar-Singh, An De Groef, and Mira Meeus.
• Research Group MOVANT, Department of Rehabilitation Sciences and Physiotherapy (REVAKI), University of Antwerp, Wilrijk, Belgium; Pain in Motion International Research Group, www.paininmotion.be, Belgium.
• Pain Physician. 2024 Feb 1; 27 (2): E207E220E207-E220.

BackgroundChronic cancer-related pain remains underdiagnosed and undertreated, although it affects 40% of cancer survivors. Recent insights suggest that cytokine signaling between immune, neuro, and glial cells contributes to chronic pain.ObjectivesThis study systematically reviewed cytokine levels and their relation to chronic cancer-related pain and, additionally, investigated differences in cytokine levels between cancer survivors with and without chronic pain.Study DesignSystematic review.MethodsThis systematic review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). The study conducted a systematic literature search in the databases PubMed, Web of Science, and Embase for articles examining cytokine levels and pain experience at a time point of a minimum of 3 months post-cancer diagnosis. Pain experience was categorized into a total pain score, pain intensity, and pain interference. The risk of bias was assessed using the Newcastle Ottawa Scale.ResultsEight articles were included, investigating 6 cancer types and 30 cytokines. Moderate evidence was found for pro-inflammatory cytokine IL-6 to be correlated with pain intensity, of which higher levels are observed in cancer survivors experiencing chronic pain compared to pain-free survivors. Moderate evidence was found for TNF-alpha to be not correlated with any pain experience, which is similar for anti-inflammatory cytokines IL-8 and IL-10 with pain intensity. For the remaining 26 cytokines and pain outcomes, only limited evidence was found for an association or alteration.LimitationsThe number of included studies was small. Overall, studies showed a moderate risk of bias, except one indicated a high risk of bias.ConclusionMore standardized post-cancer treatment studies are warranted to confirm these results and explore associations and alterations of other cytokines. Nonetheless, moderate evidence suggests that elevated levels of IL-6, in contrast with TNF-alpha levels, are correlated with pain intensity in cancer survivors experiencing chronic pain compared to pain-free survivors.

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