Cuhadar U, Gentry C, Vastani N, et al. - The cellular basis of pain in complex regional pain syndrome (CRPS) was investigated via employing behavioral and electrophysiological methods in mice treated with IgG from CRPS patients, in combination with a paw incision. Researchers performed a hind paw skin–muscle incision alone in mice, or in combination with administration of IgG purified from either healthy control individuals or patients with persistent CRPS. The major classes of mechanosensitive single units were studied via examining nociceptive function behaviorally in vivo, and electrophysiologically in vitro using skin–nerve preparations. The postsurgical hypersensitivity to noxious mechanical, cold, and heat stimulation exacerbated and prolonged on the administration of IgG from CRPS patients, but tactile sensitivity after a paw incision remained uninfluenced. As per studies of IgG preparations pooled from patient cohorts (n = 26-27), patients with persistent CRPS widely show pathological autoantibodies, and 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. Results here support the maintenance of painful hypersensitivity in persistent CRPS by autoantibodies, which act by sensitizing A and C nociceptors.