Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1–induced mechanisms
Open accessAbstract
Significance: Complex regional pain syndrome (CRPS) is a poorly understood painful condition, which typically arises after distal limb trauma; 20% of patients may develop lifelong severe incessant pain with few therapeutic options. In this study, we show that immunoglobulin G autoantibodies from patients with severe, persistent CRPS, on transfer to hind paw-injured mice, elicit important features of the clinical condition and profound glial activation in pain-related brain regions. Blockade of the proinflammatory cytokine interleukin-1 (IL-1) both prevents and reverses these changes. Our findings suggest that antibody-mediated autoimmunity contributes to the development of severe CRPS after injury and that blockade of IL-1 actions may be an attractive therapeutic prospect. Investigation of autoantibody contribution to other unexplained chronic pain syndromes seems warranted.
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Blockade of IL-1 reverses glial activation and allodynia in naïve mice receiving adoptive transfer of purified IgG isolated from CRPS model mice.
“Zsuzsanna Helyes et al. found that blockade of IL-1 successfully reversed profound glial activation and allodynia in naïve mice receiving adoptive transfer of purified IgG isolated from CRPS model mice”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [135]
IL-1 plays a key role in NPP development.
“indicating that IL-1 also plays a key role in NPP development (135).”
From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [135]
Cites
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · see citing works
Fate Mapping Reveals Origins and Dynamics of Monocytes and Tissue Macrophages under Homeostasis
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“Since IL-1– mediated actions are involved in the cross-talk between neurons, microglia, and astrocytes in promoting neuroinflammation (35, 36), we assessed glial IL-1β and IL-1α production in the spinal cord and found that microglial IL-1β production was increased on day 7 in the CRPS IgG-treated group.”
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Passive transfer of fibromyalgia symptoms from patients to mice
Goebel, A., Krock, E., Gentry, C., Israel, M. R., Jurczak, A., Urbina, C. M., Sandor, K., Vastani, N., Maurer, M., Cuhadar, U., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci144201 · Cited by 278 · see citing works
Self-citationNociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization
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- Authors
- Helyes, Z., Tékus, V., Szentes, N., Pohóczky, K., Botz, B., Kiss, T., Kemény, Á., Környei, Z., Tóth, K., Lénárt, N., Ábrahám, H., Pinteaux, E., Francis, S., Sensi, S., Dénes, Á., & Goebel, A.
- Affiliations
- University of Pecs (HU)
- HUN-REN Institute of Experimental Medicine (HU)
- University of Manchester (GB)
- University of Sheffield (GB)
- University of Liverpool (GB)
- Department of Translational Medicine, University of Liverpool, Liverpool L9 7AL, United Kingdom;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-06-10
- Volume
- 116
- Issue
- 26
- Pages
- 13067-13076
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6600930
- OpenAlex
- W2953088960
- Cited by
- 122
- References
- 5
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 21 · 2023: 14 · 2022: 18 · 2021: 21 · 2020: 13 · 2019: 3
- FWCI
- 19.55
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-07-08)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Funders
- Pain Relief Foundation (PRF 2015 BG-017 and 2015 ISG-001)
- National Brain Research Program (2017-1.2.1-NKP-2017-00002)
- GINOP (GINOP-2.3.2-15-2016-00050)
- EFOP (3.6.2-17-2017-00008)
- TAMOP (TÁMOP 4.2.4. A/2-11-1-2012-0001)
- Hungarian Brain Research Program (KTIA_13_NAP-A-I/)
- ERC (ERC-CoG 724994)
- British Heart Foundation (PG/13/55/30365)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- complex regional pain syndrome, autoantibodies, interleukin-1, antibody-mediated autoimmunity, glial activation, chronic pain, inflammatory cytokines, interleukin-1 blockade, pain-related brain regions, mouse model
- MeSH terms
- Adult, Animals, Autoantibodies, Disease Models, Animal, Female, Humans, Immunoglobulin G, Male, Mice, Inbred C57BL, Middle Aged, Pain Measurement, Microglia, Mice, Knockout, Complex Regional Pain Syndromes, Lower Extremity, Mice, Receptors, Interleukin-1 Type I, Interleukin-1alpha, Interleukin-1beta, Interleukin 1 Receptor Antagonist Protein, Spinal Cord Dorsal Horn
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