Tumor Necrosis Factor and Interleukin Modulators for Pathologic Pain States: A Narrative Review

Alan D Kaye; Dominique M Perilloux; Alison M Hawkins; Grace C Wester; Amanda R Ragaland; Sage V Hebert; Julian Kim; Michael Heisler; Rucha A Kelkar; Azem A Chami; Sahar Shekoohi; Adam M Kaye

doi:10.1007/s40122-024-00603-8

Tumor Necrosis Factor and Interleukin Modulators for Pathologic Pain States: A Narrative Review

Pain Ther. 2024 Jun;13(3):481-493. doi: 10.1007/s40122-024-00603-8. Epub 2024 May 9.

Authors

Affiliations

¹ Department of Anesthesiology and Department of Pharmacology, Toxicology, and Neurosciences, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA. alan.kaye@lsuhs.edu.
² School of Medicine, Louisiana State University Health Sciences Center at Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA.
³ Department of Anesthesiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, 71103, USA.
⁴ School of Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC, 29425, USA.
⁵ Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA, 95211, USA.

Abstract

Chronic pain, a complex and debilitating condition, involves intricate interactions between central and peripheral inflammatory processes. Cytokines, specifically tumor necrosis factor (TNF) and interleukins (IL), are key mediators in the initiation and maintenance of chronic pain states. Sensory neurons expressing receptors for cytokines like TNF, IL-1, and IL-6 are implicated in peripheral sensitization, contributing to increased signaling of painful sensations. The potential of targeting TNF and IL for therapeutic intervention in chronic pain states is the focus of this review, with preclinical and clinical evidence supporting the use of TNF and IL modulators for pain management. The physiological and pathological roles of TNF in neuropathic pain is complex. Experimental evidence highlights the effectiveness of TNF modulation in mitigating pain symptoms in animal models and displays promising outcomes of clinical trials with TNF inhibitors, such as infliximab and etanercept. ILs, a diverse group of cytokines, including IL-1, IL-6, and IL-17, are discussed for their contributions to chronic pain through inflammation and peripheral sensitization. Specific IL modulators, such as secukinumab and tocilizumab, have shown potential in managing chronic neuropathic pain, as demonstrated in various studies and clinical trials. The pharmacokinetics, safety profiles, and challenges associated with TNF and IL modulators highlight the need for cautious medication monitoring in clinical practice. Comparative evaluations have revealed distinct efficacy and safety profiles among different cytokine modulators, emphasizing the need for personalized approaches based on the specific underlying causes of pain. Further research is necessary to elucidate the intricate mechanisms by which cytokines contribute to chronic pain, as well as to understand why they may affect pain differently in various contexts. Additionally, long-term safety profiles of cytokine modulators require more thorough investigation. This continued exploration holds the promise of enhancing our comprehension of cytokine modulation in chronic pain and shaping more potent therapeutic strategies for the future.

Keywords: Chronic pain; Cytokine modulation; Inflammation; Interleukin modulation; Peripheral sensitization; TNF inhibitors.

Publication types

Review