Minocycline attenuates gulf war illness-related pain sensitization and preserves descending control of nociception in mice

Gulf War Illness (GWI) is a chronic multisymptom condition characterized by widespread pain. In a murine model of GWI-related chemicals exposure for one month, the efficiency of endogenous pain control systems, latent pain sensitization and anxiety state were examined. Circulating cytokines were quantified with multiplex assay and ELISAs.

Effects of minocycline treatment were evaluated in GWI mice. We observed robust periorbital sensitization after exposure to the bright light stress (BLS headache model), increased hindpaw allodynia in osteoarthritis and musculoskeletal pain models in GWI mice. Minocycline reduced or eliminated the GWI chemical-related excess sensitization and loss of descending control of nociception (DCN), suggesting the drug preserves a key component of endogenous pain modulation.

GWI-related chemical exposure caused a mild anxiety-like state not prevented by minocycline. Multiplexed analysis of plasma cytokines revealed no significant differences 3 months after completion of chemical administration between control mice and other treatment groups. However, a more sensitive ELISA demonstrated elevation of circulating MCP-1 in GWI chemical-treated mice, which was blocked by co-treatment with minocycline.

Our findings suggest that the widespread pain-related complaints characteristic of GWI may be due to loss of DCN. Minocycline, potentially through its anti-neuroinflammatory activity, prevents damage to endogenous pain control systems. This work was supported by a grant from the Dept. of Veterans Affairs I01BX006217 to J.D.C. and T.T.H.

Anesthesiology Service, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave (112-A), VA Palo Alto HCS, 3801 Miranda Ave, Palo Alto, CA, 94304, USA Peyman Sahbaie, Xiaoyou Shi & J. David Clark Palo Alto Veterans Institute for Research, 3801 Miranda Ave, Palo Alto, CA, 94304, USA Department of Anesthesia, Perioperative and Pain Medicine, School of Medicine, Stanford University, Stanford, CA, 94305, USA Shahin Sanaei Esfahani, Peyman Sahbaie, Xiaoyou Shi, Nazanin Mahinparvar & J. David Clark Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, 94305, USA The authors declare no competing interests.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.