1. 2017;20;E807-E822Complex Regional Pain Syndrome Type I, a Debilitating and Poorly Understood Syndrome. Possible Role for Pulsed Electromagnetic Fields: A Narrative Review
   Narrative Review
   Stefania Pagani, BSc, Francesca Veronesi, PhD, Nicolo Nicoli Aldini, MD, and Milena Fini, MD.

BACKGROUND: Complex regional pain syndrome type I (CRPS-I), also called algodystrophy, is a complex syndrome characterized by limb pain, edema, allodynia, hyperalgesia and functional impairment of bone with a similar clinical picture of osteoporosis, including an increased release of various pro-inflammatory neuropeptides and cytokines.

Several treatments have been proposed for CRPS-I, but due to the poor outcome of conventional drugs and the invasiveness of some techniques, expectations are now directed towards new resources that could be more effective and less invasive.

OBJECTIVE: In the light of preclinical evidence, which underlined pulsed electromagnetic fields’ (PEMFs) properties on osteoblasts (OBs), osteoclasts (OCs), and pathologies with an inflammatory profile, the present review aims to investigate whether there is a rationale for the use of PEMFs, as a combined approach, in CRPS-I.

STUDY DESIGN: This review analyzed the 44 in vitro and in vivo studies published in the last decade that focused on 2 main aspects of CRPS-I: local osteoporosis (OP) and inflammation.

SETTING: Not applicable.

METHODS: This review includes in vitro and in vivo studies found with a PubMed and Web of Knowledge database search by 2 independent authors. The limits of the search were the publication date between January 1, 2006, and January 1, 2016, and English language. In detail, the search strategy was based on: 1) CRPS-I or algodystrophy; 2) OP, OCs, and OBs; and 3) inflammatory aspects.

RESULTS: The included studies looked at the relationship between PEMFs and OCs (2 in vitro studies), osteoporotic animal models (8 in vivo studies), OBs (20 in vitro studies), inflammatory cytokines, and reactive oxygen species. They also tried to define the molecular cell pathways involved (5 in vivo and 9 in vitro studies on inflammatory models). It was observed that PEMFs increased OC apoptosis, OB viability, bone protein and matrix calcification, antioxidant protein, and the levels of adenosine receptors, while it decreased the levels of pro-inflammatory cytokines.

LIMITATIONS: Data from clinical trials are scarce; moreover, experimental conditions and PEMF parameters are not standardized.

CONCLUSIONS: The present review underlined the rationale for the use of PEMFs in the complex contest of CRPS-I syndrome, in combination with conventional drugs.

Key words: Complex regional pain syndrome type I, algodystrophy, pulsed electromagnetic field stimulation, osteoporosis, inflammation, osteoclasts, osteoblasts, pain