Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome.
Complex regional pain syndromes (CRPS, type I and type II) are devastating conditions that can occur following soft tissue (CRPS type I) or nerve (CRPS type II) injury. CRPS type I, also known as reflex sympathetic dystrophy, presents in patients lacking a well-defined nerve lesion, and has been questioned as to whether or not it is a true neuropathic condition with an organic basis. As described here, glabrous and hairy skin samples from the amputated upper and lower extremity from two CRPS type I diagnosed patients were processed for double-label immunofluorescence using a battery of antibodies directed against neural-related proteins and mediators of nociceptive sensory function. In CRPS affected skin, several neuropathologic alterations were detected, including: (1) the presence of numerous abnormal thin caliber NF-positive/MBP-negative axons innervating hair follicles; (2) a decrease in epidermal, sweat gland, and vascular innervation; (3) a loss of CGRP expression on remaining innervation to vasculature and sweat glands; (4) an inappropriate expression of NPY on innervation to superficial arterioles and sweat glands; and (5) a loss of vascular endothelial integrity and extraordinary vascular hypertrophy. The results are evidence of widespread cutaneous neuropathologic changes. Importantly, in these CRPS type I patients, the myriad of clinical symptoms observed had detectable neuropathologic correlates.
Albrecht
Phillip J
PJ
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY, USA Medical School Program, Albany Medical College, Albany, NY, USA Pain Relief Unit, Rambam Medical Center, Haifa, Israel Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Faculty of Social Welfare and Health Studies, University of Haifa, Haifa, Israel Department of Dermatology, University of California, San Francisco, CA, USA Early Development, Medical Sciences, Amgen, Inc., Thousand Oaks, CA, USA.
Hines
Scott
S
Eisenberg
Elon
E
Pud
Dorit
D
Finlay
Deborah R
DR
Connolly
Kari M
KM
Paré
Michel
M
Davar
Gudarz
G
Rice
Frank L
FL
D000328:Adult; D000344:Afferent Pathways / Q000473:pathology*; D001369:Axons / Q000473:pathology; D019317:Evidence-Based Medicine; D005121:Extremities / Q000098:blood supply / Q000294:innervation / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology*; D016491:Peripheral Vascular Diseases / Q000473:pathology*; D012019:Reflex Sympathetic Dystrophy / Q000473:pathology*; D012867:Skin / Q000098:blood supply* / Q000294:innervation* / Q000473:pathology