Antimicrobial therapies for chronic pain (part 1): analgesic mechanisms

Eric J Wang; Jay Karri; Nuj Tontisirin; Steven P Cohen

doi:10.3344/kjp.23129

Antimicrobial therapies for chronic pain (part 1): analgesic mechanisms

Korean J Pain. 2023 Jul 1;36(3):281-298. doi: 10.3344/kjp.23129.

Authors

Eric J Wang¹, Jay Karri², Nuj Tontisirin³, Steven P Cohen^{1

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Affiliations

¹ Department of Anesthesiology and Critical Care Medicine, Division of Pain Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Departments of Orthopedic Surgery and Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA.
³ Department of Anesthesiology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
⁴ Department of Physical Medicine and Rehabilitation, Walter Reed National Military Medical Center, Bethesda, MD, USA.
⁵ Departments of Physical Medicine & Rehabilitation, Neurology, and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Departments of Physical Medicine & Rehabilitation and Anesthesiology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Abstract

There is increasing evidence that the relationship between chronic pain and infections is complex and intertwined. Bacterial and viral infections can cause pain through numerous mechanisms such as direct tissue damage and inflammation, the induction of excessive immunologic activity, and the development of peripheral or central sensitization. Treating infections might relieve pain by attenuating these processes, but a growing body of literature suggests that some antimicrobial therapies confer analgesic effects, including for nociceptive and neuropathic pain symptoms, and affective components of pain. The analgesic mechanisms of antimicrobials are indirect, but might be conceptualized into two broad categories: 1) the reduction of the infectious burden and associated pro-inflammatory processes; and 2) the inhibition of signaling processes (e.g., enzymatic and cytokine activity) necessary for nociception and maladaptive neuroplastic changes via off-target effects (unintended binding sites). For the former, there is evidence that symptoms of chronic low back pain (when associated with Modic type 1 changes), irritable bowel syndrome, inflammatory bowel disease, chronic pelvic pain, and functional dyspepsia might be improved after antibiotic treatment, though significant questions remain regarding specific regimens and dose, and which subpopulations are most likely to benefit. For the latter, there is evidence that several antimicrobial classes and medications exert analgesic effects independent of their reduction of infectious burden, and these include cephalosporins, ribavirin, chloroquine derivatives, rapalogues, minocycline, dapsone, and piscidin-1. This article aims to comprehensively review the existing literature for antimicrobial agents that have demonstrated analgesic efficacy in preclinical or clinical studies.

Keywords: Analgesia; Anti-Bacterial Agents; Anti-Infective Agents; Antiviral Agents; Central Nervous System Sensitization; Chronic Pain; Infections; Neuralgia; Nociceptive Pain; Pain Management.

Publication types

Review

Grants and funding

FUNDING Dr. Cohen’s effort was funded in part by a grant from MIRROR, Uniformed Services University of the Health Sciences, U.S. Department of Defense, grant # HU00011920011. The views expressed in this article are those of the authors and do not necessarily reflect the official policy of the U.S. Department of Defense or the U.S. Government.