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Autoantibodies produce pain in complex regional pain syndrome by sensitizing nociceptors

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Cuhadar, Ulku, Gentry, Clive, Vastani, Nisha, Sensi, Serena, Bevan, Stuart, Goebel, Andreas, Andersson, David A.·2019·Pain
DOI 10.1097/j.pain.0000000000001662
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Abstract

Complex regional pain syndrome (CRPS) is a posttraumatic pain condition with an incompletely understood pathophysiological basis. Here, we have examined the cellular basis of pain in CRPS using behavioral and electrophysiological methods in mice treated with IgG from CRPS patients, in combination with a paw incision. Mice were subjected to a hind paw skin–muscle incision alone, or in combination with administration of IgG purified from either healthy control subjects or patients with persistent CRPS. Nociceptive function was examined behaviorally in vivo, and electrophysiologically in vitro using skin–nerve preparations to study the major classes of mechanosensitive single units. Administration of IgG from CRPS patients exacerbated and prolonged the postsurgical hypersensitivity to noxious mechanical, cold, and heat stimulation, but did not influence tactile sensitivity after a paw incision. Studies of IgG preparations pooled from patient cohorts (n = 26-27) show that pathological autoantibodies are present in the wider population of patients with persistent CRPS, and that patients with more severe pain have higher effective autoantibody titres than patients with moderate pain intensity. Electrophysiological investigation of skin–nerve preparations from mice treated with CRPS IgG from a single patient identified both a significantly increased evoked impulse activity in A and C nociceptors, and an increased spontaneous impulse rate in the intact saphenous nerve. Our results show that painful hypersensitivity in persistent CRPS is maintained by autoantibodies, which act by sensitizing A and C nociceptors.

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Metadata

Authors
Cuhadar, U., Gentry, C., Vastani, N., Sensi, S., Bevan, S., Goebel, A., & Andersson, D. A.
Affiliations
  • King's College London (GB)
  • University of Liverpool (GB)
  • Pain Research Institute, University of Liverpool, Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
Corresponding author
Andersson, David A.
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-07-22
Volume
160
Issue
12
Pages
2855-2865
ISSN
  • 0304-3959 (ISSN-L)
  • 1872-6623
DOI
10.1097/j.pain.0000000000001662
OpenAlex
W2964089773
Cited by
74
References
1
Citations by year
2026: 8 · 2025: 17 · 2024: 5 · 2023: 8 · 2022: 14 · 2021: 14 · 2020: 8
FWCI
6.19
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, other-oa)
  • Research Portal (King's College London) (submittedVersion)
Funders
  • Pain Relief Foundation
  • Versus Arthritis (21544)
  • Medical Research Council (MR/L010747/1)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords
complex regional pain syndrome, autoantibodies, nociceptor sensitization, post-traumatic pain, mechanical allodynia, saphenous nerve, pain pathophysiology
MeSH terms
Animals, Autoantibodies, Disease Models, Animal, Humans, Hyperalgesia, Immunoglobulin G, Nociceptors, Pain Measurement, Skin, Pain Threshold, Complex Regional Pain Syndromes, Mice

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Cuhadar, U., Gentry, C., Vastani, N., Sensi, S., Bevan, S., Goebel, A., & Andersson, D. A. (2019). Autoantibodies produce pain in complex regional pain syndrome by sensitizing nociceptors. Pain. https://doi.org/10.1097/j.pain.0000000000001662