Del Rosso, et al: Pupillometry and substance P in SSc 1231 2002-556-1 From the Department of Medicine, Section of Rheumatology, Headache, and Nephrology, University of Florence; Drugs Information Center, Careggi Hospital, Florence; Department of Neurological Rehabilitation, Rehabilitation Institute of Montescano, Foundation “S. Maugeri,” IRCCS, Pavia; Department of Internal Medicine and Public Health, University of L’Aquila, L’Aquila; and Division of Rheumatology, University of Padua, Padua, Italy. A. Del Rosso, MD, PhD, Consultant in Rheumatology; L. Bertinotti, MD, Fellow in Rheumatology; U. Pietrini, MD, PhD, Consultant in Clinical Pharmacology; M. Fanciullacci, MD, Associate Professor of Clinical Pharmacology; S. Generini, MD, PhD, Fellow in Rheumatology; R. Sicuteri, MD, PhD; A. Pignone, MD, PhD, Associate Professor of Medicine; M. Matucci-Cerinic, MD, PhD, Professor of Medicine, Department of Medicine, University of Florence; A. Messori, MD, Consultant in Pharmacology, Drugs Information Center, Careggi Hospital; R. Casale, MD, PhD, Consultant in Neurology, Department of Neurological Rehabilitation, Rehabilitation Institute of Montescano; R. Giacomelli, MD, PhD, Associate Professor of Rheumatology, Department of Internal Medicine and Public Health, University of L’Aquila; F. Cozzi, MD, Assistant Professor of Rheumatology, Division of Rheumatology, University of Padua. Address reprint requests to Dr. M. Matucci Cerinic, Department of Medicine, Villa Monna Tessa, Section of Rheumatology, Headache, and Nephrology, Viale G. Pieraccini 18, 50139 Florence, Italy. E-mail: cerinic@unifi.it Submitted June 7, 2002; revision accepted November 5, 2002. Systemic sclerosis (SSc) is characterized by microvascular involvement and abnormal immune and fibroblast activa- tion, which results in fibrosis of skin and internal organs [heart, lungs, gastrointestinal (GI) tract, kidney] 1 . In SSc, peripheral nervous system (PNS) involvement is frequent, ranging from 16 to 35% of cases 2 , and impairing both the function of cranial (mainly trigeminal) and spinal nerves (motor and sensory polyneuropathies and median nerve neuropathy) 2,3 . Involvement of the autonomic nervous system (ANS) seems to be characterized by the increase of sympathetic nervous system activity and reduction of parasympathetic function 4 . ANS impairment is involved in the genesis of Raynaud’s phenomenon 2,5,6 , in R-R tract modifications 7-9 , and in GI motility dysfunction 10-12 . In SSc, ANS involvement has been investigated by different methods, such as sympathetic skin response 13 , R-R tract evaluation 7-9,14 , and esophageal manometry 14 . Recently, ANS function in SSc was also assessed by pupillometry 14,15 . This technique allows study of systems regulating the pupillary cycle (mainly but not exclusively tuned by ANS) and its modulation by stimuli of different origins (physical, chemical, and biological). In SSc, pupil- lometry has identified a pupillary autonomic neuropathy 14,15 that was correlated with esophageal dysfunction 14 . Substance P (SP) is present in small myelinated Aδ fibers and in small unmyelinated sensory C fibers 16 . Upon different stimuli, SP can be released by sensory terminals and exerts a direct and an indirect vasoactive (inducing vasodilatation and vasopermeabilization), proinflammatory, mitogenic, nociceptive and immune-modulating activity, Pupillocynetic Activity of Substance P in Systemic Sclerosis ANGELA DEL ROSSO, LUCA BERTINOTTI, UMBERTO PIETRINI, ANDREA MESSORI, MARCELLO FANCIULLACCI, ROBERTO CASALE, ROBERTO GIACOMELLI, SERGIO GENERINI, RICCARDO SICUTERI, ALBERTO PIGNONE, FRANCO COZZI, and MARCO MATUCCI-CERINIC ABSTRACT. Objective. In systemic sclerosis (SSc), dysfunctions of peripheral nervous system (PNS) have been observed. Substance P (SP) instillation in human eye induces a cholinergic-independent pupil myosis. Pupil basal diameters (PBD) and pupil responsiveness to SP, expressed as area under the curve (AUC), were studied by pupillometry to assess SP-ergic fiber state and function in SSc. Methods. Forty SSc patients [24 with limited (lSSc), 16 with diffuse (dSSc) disease] and 40 controls underwent pupillometric evaluation. After evaluation of PBD, SP 10 -3 M was instilled in one eye and placebo in the contralateral eye. Antinuclear (ANA), anticentromere (ACA), and anti-Scl-70 autoan- tibodies were correlated with PBD and AUC. Results. PBD was significantly lower in SSc patients versus controls (p < 0.001). PBD was minor in lSSc versus both dSSc and controls (p < 0.05), but no difference was found between dSSc and controls. In SSc, SP 10 -3 M induced greater myosis compared to controls (p < 0.001). SP 10 -3 M-induced myosis was higher in lSSc versus both dSSc and controls (p < 0.05). ACA significantly correlated with decreased values of PBD and AUC (p < 0.001). Conclusion. Our results show that PBD is reduced in patients with SSc and that SP induces a more intense myosis in SSc than controls. Moreover, in lSSc PBD is lower and SP increases the myosis in lSSc compared to dSSc and controls. This suggests a peculiar dysfunction of PNS in patients with the limited subset of SSc. (J Rheumatol 2003;30:1231–7) Key Indexing Terms: SYSTEMIC SCLEROSIS PUPILLOMETRY SUBSTANCE P PERIPHERAL NERVOUS SYSTEM Personal, non-commercial use only. The Journal of Rheumatology Copyright © 2003. All rights reserved. www.jrheum.org Downloaded on September 29, 2021 from