Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome

• Published in: Pain (Amsterdam) Vol. 120; no. 3; pp. 244 - 266
• Main Authors: Albrecht, Phillip J., Hines, Scott, Eisenberg, Elon, Pud, Dorit, Finlay, Deborah R., Connolly, M. Kari, Paré, Michel, Davar, Gudarz, Rice, Frank L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-02-2006; Lippincott Williams & Wilkins, Inc; Elsevier
• Subjects: Adult; Afferent Pathways - pathology; Axons - pathology; Biological and medical sciences; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Evidence-Based Medicine; Extremities - blood supply; Extremities - innervation; Extremities - pathology; Fundamental and applied biological sciences. Psychology; Humans; Illness and personality; Illness, stress and coping; Immunohistochemistry; Male; Medical sciences; Middle Aged; Nerve Fibers - pathology; Nervous system (semeiology, syndromes); Neurology; Neuropathic pain; Peripheral Nervous System Diseases - pathology; Peripheral Vascular Diseases - pathology; Psychology and medicine; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Reflex Sympathetic Dystrophy - pathology; RSD; Skin - blood supply; Skin - innervation; Skin - pathology; Immunohistochemistry; RSD; Neuropathic pain; Human; Nervous system diseases; Innervation; Axon; Reflex sympathetic dystrophy; Peripheral neuropathy; Protein; Complex regional pain syndrome; Diseases of the autonomic nervous system; Skin; Peripheral nerve disease; Sweat
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2005.10.035

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.