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. 2016 May 5;11(5):e0154553.
doi: 10.1371/journal.pone.0154553. eCollection 2016.

Sensitization of the Nociceptive System in Complex Regional Pain Syndrome

Maren Reimer  1 , Torge Rempe  1 , Carolina Diedrichs  1 , Ralf Baron  1 , Janne Gierthmühlen  1
Affiliations

Sensitization of the Nociceptive System in Complex Regional Pain Syndrome

Maren Reimer et al. PLoS One. .

Abstract

Background: Complex regional pain syndrome type I (CRPS-I) is characterized by sensory, motor and autonomic abnormalities without electrophysiological evidence of a nerve lesion.

Objective: Aims were to investigate how sensory, autonomic and motor function change in the course of the disease.

Methods: 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).

Results: 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.

Conclusions: 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.

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Conflict of interest statement

Competing Interests: Torge Rempe and Carolina Diedrichs report no conflicts of interests. Maren Reimer received travel grants from Astellas, Grünenthal and Pfizer and research support from Mundipharma. Janne Gierthmühlen received honoraria as a speaker from Pfizer and travel grants from Pfizer and Grünenthal and is a consultant for Glenmark pharma. Ralf Baron reports current grant/Research Support by Pfizer, Genzyme, Grünenthal, Mundipharma. Member of the IMI "Europain" collaboration and industry members of this are: Astra Zeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal, Eli Lilly and Boehringer Ingelheim, German Federal Ministry of Education and Research (BMBF): German Research Network on Neuropathic Pain, NoPain system biology, German Research Foundation (DFG). He received honoraria as a speaker from Pfizer, Genzyme, Grünenthal, Mundipharma, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Desitin, Teva Pharma, Bayer-Schering, MSD and is a consultant for Pfizer, Genzyme, Grünenthal, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, Lilly, Boehringer Ingelheim, Astellas, Novartis, Bristol-Myers Squibb, Biogenidec, AstraZeneca, Merck, Abbvie, Daiichi Sankyo and Glenmark Pharmaceuticals. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. There are no conflicts of interests relevant to this article.

Figures

Fig 1
Fig 1. QST Profiles patients with ongoing and intermittent pain.
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.
Fig 2
Fig 2. QST profiles of affected and unaffected extremity upon first visit.
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.
Fig 3
Fig 3. QST profiles of the affected extremity upon first visit and follow-up examination.
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.
Fig 4
Fig 4. QST profiles of the unaffected (contralateral) extremity upon first visit and follow-up examination.
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.
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