The relevance of real-world data for the evaluation of neuropathic pain treatments - Supplementary material

   Supplementary table 1. Results of EudraCT clinical trial registry search  Supplementary table 2. Results of ClinicalTrial.gov registry search </p

Sensitization of the Nociceptive System in Complex Regional Pain Syndrome

<div><p>Background</p><p>Complex regional pain syndrome type I (CRPS-I) is characterized by sensory, motor and autonomic abnormalities without electrophysiological evidence of a nerve lesion.</p><p>Objective</p><p>Aims were to investigate how sensory, autonomic and motor function change in the course of the disease.</p><p>Methods</p><p>19 CRPS-I patients (17 with acute, 2 with chronic CRPS, mean duration of disease 5.7±8.3, range 1–33 months) were examined with questionnaires (LANSS, NPS, MPI, Quick DASH, multiple choice list of descriptors for sensory, motor, autonomic symptoms), motor and autonomic tests as well as quantitative sensory testing according to the German Research Network on Neuropathic Pain at two visits (baseline and 36±10.6, range 16–53 months later).</p><p>Results</p><p>CRPS-I patients had an improvement of sudomotor and vasomotor function, but still a great impairment of sensory and motor function upon follow-up. Although pain and mechanical detection improved upon follow-up, thermal and mechanical pain sensitivity increased, including the contralateral side. Increase in mechanical pain sensitivity and loss of mechanical detection were associated with presence of ongoing pain.</p><p>Conclusions</p><p>The results demonstrate that patients with CRPS-I show a sensitization of the nociceptive system in the course of the disease, for which ongoing pain seems to be the most important trigger. They further suggest that measured loss of function in CRPS-I is due to pain-induced hypoesthesia rather than a minimal nerve lesion. In conclusion, this article gives evidence for a pronociceptive pain modulation profile developing in the course of CRPS and thus helps to assess underlying mechanisms of CRPS that contribute to the maintenance of patients’ pain and disability.</p></div

QST Profiles patients with ongoing and intermittent pain.

<p>When patients were grouped into those with ongoing or intermittent pain at follow-up examination, patients with ongoing pain showed higher mechanical pain sensitivity as well as a stronger loss for mechanical detection on the affected extremity. CDT: cold detection threshold; WDT: warm detection threshold; TSL: thermal sensory limen; CPT: cold pain threshold; HPT: heat pain threshold; PPT: pressure pain threshold; MPT: mechanical pain threshold, MPS: mechanical pain sensitivity; WUR: wind-up ratio; MDT: mechanical detection threshold; VDT: vibration detection threshold; PHS: paradoxical heat sensitivity; DMA: dynamic mechanical allodynia. * p < 0.05.</p

Absolute abnormal values upon QST at follow-up and their change compared to visit 1.

<p>Absolute abnormal values upon QST at follow-up and their change compared to visit 1.</p

QST profiles of the unaffected (contralateral) extremity upon first visit and follow-up examination.

<p>CDT: cold detection threshold; WDT: warm detection threshold; TSL: thermal sensory limen; CPT: cold pain threshold; HPT: heat pain threshold; PPT: pressure pain threshold; MPT: mechanical pain threshold, MPS: mechanical pain sensitivity; WUR: wind-up ratio; MDT: mechanical detection threshold; VDT: vibration detection threshold; PHS: paradoxical heat sensitivity; DMA: dynamic mechanical allodynia. ** p < 0.01, *** p < 0.001.</p

Characteristics of patients (n = 19).

<p>Characteristics of patients (n = 19).</p

Signs and symptoms including Budapest criteria at visit 1 and follow-up examination.

<p>Signs and symptoms including Budapest criteria at visit 1 and follow-up examination.</p

Frequencies of abnormal pathological values (including abnormal side-to-side differences) in CRPS-I.

<p>Frequencies of abnormal pathological values (including abnormal side-to-side differences) in CRPS-I.</p

Investigations at visit 1 and 2 (follow-up).

<p>Investigations at visit 1 and 2 (follow-up).</p

QST profiles of the affected extremity upon first visit and follow-up examination.

<p>CDT: cold detection threshold; WDT: warm detection threshold; TSL: thermal sensory limen; CPT: cold pain threshold; HPT: heat pain threshold; PPT: pressure pain threshold; MPT: mechanical pain threshold, MPS: mechanical pain sensitivity; WUR: wind-up ratio; MDT: mechanical detection threshold; VDT: vibration detection threshold; PHS: paradoxical heat sensitivity; DMA: dynamic mechanical allodynia. * p < 0.05, ** p < 0.01, *** p < 0.001.</p