Autoantibodies produce pain in Complex Regional Pain Syndrome by sensitizing nociceptors.

Cuhadar, Ulku, Gentry, Clive, Vastani, Nisha, Sensi, Serena, Bevan, Stuart, Goebel, Andreas and Andersson, David
(2019) Autoantibodies produce pain in Complex Regional Pain Syndrome by sensitizing nociceptors. Pain.

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Complex regional pain syndrome (CRPS) is a post-traumatic 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 (HC) 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 post-surgical hypersensitivity to noxious mechanical, cold and heat stimulation, but did not influence tactile sensitivity following 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.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 01 Aug 2019 10:53
Last Modified: 11 Sep 2019 23:11
DOI: 10.1097/j.pain.0000000000001662
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