Letter to the Editor Impaired pain processing in patients with silent myocardial ischemia ☆ , ☆☆ Antonino Di Franco a , Gaetano A. Lanza a, ⁎, Massimiliano Valeriani b,c , Angelo Villano a , Giulio Russo a , Daniela Virdis d , Costanza Pazzaglia e , Filippo M. Sarullo f , Paolo M. Rossini d , Filippo Crea a , Catello Vollono d a Dpt. of Cardiovascular Sciences, Università Cattolica del Sacro Cuore, Largo F. Vito, 1, Rome, Italy b Neurology Division, Pediatric Hospital “Bambino Gesù” IRCCS, Rome, Italy c Center for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark d Dpt. of Geriatrics, Neuroscience & Orthopedics, Università Cattolica del Sacro Cuore, Largo F. Vito, 1, Rome, Italy e Don Carlo Gnocchi Onlus Foundation, Milan, Italy f Cardiovascular Rehabilitation Unit, Buccheri La Ferla Fatebenefratelli Hospital, Palermo, Italy article info Article history: Received 27 January 2015 Accepted 7 March 2015 Available online 10 March 2015 Keywords: Silent myocardial ischemia Coronary artery disease Nociceptive function Angina is the typical symptom of myocardial ischemia (MI). Howev- er, MI often occurs without any symptom (silent MI) and some patients with coronary artery disease (CAD) never experience chest pain during MI [1]. Various neural, psychologic, cognitive and humoral factors have been suggested to be involved in silent MI, but mechanisms remain con- troversial. In this study, we investigated the integrity of nociceptive pathways in silent MI patients, by assessing cortical laser evoked poten- tials (LEPs) in response to cutaneous CO 2 laser pulses, which specifically stimulate the thin myelinated (Aδ) and unmyelinated (C) pain fibers [2]. We studied 3 groups: 1) 11 non-diabetic patients who never experi- enced chest pain, but showed ST-segment depression ≥2 mm during exercise stress test (EST), ≥ 1 episodes of silent MI during 24-hour Holter monitoring, and obstructive CAD (≥ 70% stenosis in ≥ 1 major coronary arteries) at angiography (silent MI group); 2) 10 non-diabetic patients with stable angina, angina and ST-segment depression N 1 mm during ETT, and documented obstructive CAD (angina group); and 3) 14 apparently healthy subjects comparable in age and gender to patients (control group). The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by our institutional Ethics committee. Written informed consent to participate in the study was obtained from all subjects. LEP recordings were blindly performed by an expert neurologist, fol- lowing a protocol described in detail elsewhere [3]. Shortly, laser pulses were delivered by a CO 2 Neurolas system (Electronic Engineering, Flor- ence, Italy) on the chest skin and right hand dorsum of subjects. Chest skin stimuli are likely to be processed by the same dorsal horn neurons onto which cardiac nociceptive stimuli converge, whereas nociceptive pathways of the right hand are usually separated from cardiac stimuli [4]. Stimulus intensity was set at 2.5 × the sensory threshold (the lowest intensity required to elicit a distinct sensation). LEPs were recorded with two scalp electrodes placed along the midline in the frontal and the vertex regions and one electrode in the left temporal region. The reference electrode was placed at the nose and the ground on the forehead. Signals were amplified, filtered (0.3– 70 Hz), and stored for off-line analysis [5]. Three consecutive sequences of 30 stimuli were delivered to the chest and the right hand. In each site, the sequences were separated by a 5 min interval, and a 10 min interval elapsed after the stimulation site was changed. The sequence of the stimulation sites was randomly varied across subjects. Subjects were asked to score pain sensation in- duced by laser pulses during each sequence according to a 0–100 point visual analogic scale (VAS). Two LEP waves were identified and measured during laser stimula- tion: 1) the biphasic (negative–positive) complex N2–P2 from midline electrodes, whose amplitude was measured from the negative to the positive peak of the complex; 2) the N1/P1 potential from the temporal (N1) and frontal (P1) region, whose amplitude was measured off-line by referring the temporal lead to Fz. Continuous variables were compared by analysis of variance (ANOVA) or Kruskal–Wallis test, with multiple comparisons done by t test or Mann–Whitney test, with Bonferroni correction. Categorical vari- ables were compared by χ 2 test. LEP variables and VAS scores during the three sequences of laser pulses were compared by repeated measure International Journal of Cardiology 186 (2015) 204–206 ☆ All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ☆☆ Grant support: none. ⁎ Corresponding author at: Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Roma, Italy. E-mail address: g.a.lanza@rm.unicatt.it (G.A. Lanza). http://dx.doi.org/10.1016/j.ijcard.2015.03.097 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard