1787 Furlan, et al: Cardiovascular neural control and FM Abnormalities of Cardiovascular Neural Control and Reduced Orthostatic Tolerance in Patients with Primary Fibromyalgia RAFFAELLO FURLAN, SIMONA COLOMBO, FRANCESCA PEREGO, FABIOLAATZENI, ALESSANDRO DIANA, FRANCA BARBIC, ALBERTO PORTA, FABIO PACE, ALBERTO MALLIANI, and PIERCARLO SARZI-PUTTINI ABSTRACT. Objective. Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain. Symptoms of orthostatic intolerance may also be present, suggesting underlying abnormalities of cardiovascular neural regulation. We tested the hypothesis that FM is characterized by sympathetic overactivity and alterations in cardiovascular autonomic response to gravitational stimulus. Methods. Sixteen patients with primary FM and 16 healthy controls underwent electrocardiography examination, finger blood pressure, respiration, and muscle sympathetic nerve activity (MSNA) recordings at rest and during stepwise tilt test, up to 75°. The autonomic profile was assessed by MSNA, plasma catecholamine, and spectral indices of cardiac sympathetic (LF RR in normalized units, NU) and vagal (HF RR both in absolute and NU) modulation and of sympathetic vasomotor control (LF SAP ) computed by spectrum analysis of RR and systolic arterial pressure (SAP) variabil- ity. Arterial baroreflex function was evaluated by the SAP/RR spontaneous-sequences technique, the index α, and the gain of MSNA/diastolic pressure relationship during stepwise tilt test. Results. At rest, patients showed higher values of heart rate, MSNA, LF RR NU, LF/HF, LF SAP , and reduced HF RR than controls. During tilt test, lack of increase of MSNA, less decrease of HF RR , and excessive rate (44%) of syncope were found in patients, suggesting reduced capability to enhance the sympathetic activity to vessels and withdraw the vagal modulation to sino-atrial node. Baroreflex function was similar in both groups. Conclusion. Patients with FM have an overall enhancement of cardiovascular sympathetic activity while recumbent. Lack of increased sympathetic discharge to vessels and decreased cardiac vagal activity characterize their autonomic profile during tilt test, and might account for the excessive rate of syncope. (J Rheumatol 2005;32:1787–93) Key Indexing Terms: FIBROMYALGIA SYNCOPE SYMPATHETIC NERVOUS SYSTEM TILT TEST BARORECEPTORS From the Department of Internal Medicine II, Department of Gastroenterology, and Department of Rheumatology, Ospedale L. Sacco, Università degli Studi di Milano, Milano; Department of Cardiology, Ospedale Salvini, Rho; and Medicina del Lavoro, Ospedale Novara, Novara, Italy. Supported in part by Italian Space Agency (ASI) grant ASII/R/135/2001 to Dr. Malliani. R. Furlan, MD; F. Perego, MD; A. Diana, MD; A. Porta, MS, PhD; A. Malliani, MD, Department of Internal Medicine II, Ospedale L. Sacco; S. Colombo, MD, Department of Cardiology, Ospedale Salvini; F. Atzeni, MD; P. Sarzi-Puttini, MD, Department of Rheumatology, Ospedale L. Sacco; F. Barbic, MD, Medicina del Lavoro, Ospedale Novara; F. Pace, MD, Department of Gastroenterology, Ospedale L. Sacco. Address reprint requests to Dr. R. Furlan, Unità Sincopi e Disturbi della Postura, Medicina Interna II, Ospedale L. Sacco, Università di Milano, Via G.B. Grassi 74, 20157 Milano, Italy. E-mail: raffaellof@fisiopat.sacco.unimi.it Accepted for publication April 11, 2005. Fibromyalgia (FM) is a chronic disabling syndrome affect- ing 2%–6% of the general population 1 , with higher preva- lence in women. It is characterized by diffuse tenderness and musculoskeletal pain and discomfort on palpation of specific sites known as tender points 2,3 . The mechanisms underlying pain in this syndrome are not fully understood. A potential role of an exaggerated neu- ral sympathetic activation in generating and sustaining chronic pain has been postulated 4,5 on the basis of similari- ties of FM with other chronic pain syndromes, such as reflex sympathetic dystrophy 6 and causalgia 7 , in which there is evidence of sympathetic overactivity. Nonrheumatic disabling symptoms such as palpitations and dizziness on standing, occasional orthostatic hypoten- sion, and syncope 8 are also present in primary FM 3 . These symptoms suggest a potential abnormality of cardiovascular autonomic regulation, and point to a remarkable comorbidi- ty with other dysfunctions of orthostatic cardiovascular neu- ral homeostasis 9 , including chronic orthostatic intolerance 10 and neurally mediated syncope 11,12 . Attempts to quantify possible abnormalities of cardio- vascular autonomic regulation in FM have furnished only partial and to some extent contradictory results. For instance, using the microneurographic technique, Elam and colleagues 13 found no differences in muscle sympathetic nerve activity (MSNA) of these patients compared with Personal non-commercial use only. The Journal of Rheumatology Copyright © 2005. All rights reserved. www.jrheum.org Downloaded on September 19, 2021 from