Temporal summation of pain from mechanical stimulation of muscle tissue in normal controls and subjects with fibromyalgia syndrome Roland Staud a, * , Richard C. Cannon b , Andre P. Mauderli c , Michael E. Robinson d , Donald D. Price b,e , Charles J. Vierck Jr b a Department of Medicine, McKnight Brain Institute, University of Florida College of Medicine, 1600 SW Archer Rd, P.O. Box 100221, Gainesville, FL 32610-0221, USA b Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA c Department of Prosthodontics, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA d Department of Clinical Health and Psychology, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA e Department of Oral and Maxillofacial Surgery, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA Received 24 April 2002; accepted 16 September 2002 Abstract Individuals diagnosed with fibromyalgia syndrome (FMS) report chronic pain that is frequently worsened by physical activity and improved by rest. Palpation of muscle and tendinous structures suggests that nociceptors in deep tissues are abnormally sensitive in FMS, but methods of controlled mechanical stimulation of muscles are needed to better characterize the sensitivity of deep tissues. Accordingly, force-controlled mechanical stimulation was applied to the flexor digitorum muscle of the forearm in a series of brief contacts (15 stimuli, each of 1 s duration, at 3 or 5 s interstimulus intervals). Repetitive stimulation was utilized to determine whether temporal summation of deep muscular pain would occur for normal subjects and would be enhanced for FMS subjects. Moderate temporal summation of deep pain was observed for normal controls (NC), and temporal summation was greatly exaggerated for FMS subjects. Temporal summation for FMS subjects occurred at substantially lower forces and at a lower frequency of stimulation. Furthermore, painful after- sensations were greater in amplitude and more prolonged for FMS subjects. These observations complement a previous demonstration that temporal summation of pain and after-sensations elicited by thermal stimulation of the skin are moderately enhanced for FMS subjects. Abnormal input from muscle nociceptors appears to underlie production of central sensitization in FMS that generalizes to input from cutaneous nociceptors. q 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. Keywords: Fibromyalgia; Muscle pain; Chronic pain; Temporal summation 1. Introduction Widespread musculoskeletal pain is one of the key complaints by individuals who present with fibromyalgia syndrome (FMS). The pain is described as dull and aching and appears to be related to deep tissues. FMS pain seems to worsen with physical activity and improve with rest, and palpation of standard pressure points is an important diag- nostic tool for FMS (Wolfe et al., 1990). Despite extensive research, however, no muscle abnormalities have been demonstrated consistently that would explain FMS pain (Bengtsson et al., 1986; Jacobsen et al., 1992; Simms et al., 1994). Instead, increasing evidence implicates abnormal central pain processing as an important feature of FMS pain. Across multiple experimental stimulus modalities (e.g. heat, pressure, electrical stimulation) FMS patients show signs of hyperalgesia/allodynia (Granges and Littlejohn, 1993; Arroyo and Cohen, 1993; Lautenbacher et al., 1994; Vecchiet et al., 1994). Furthermore, when repeated heat taps are delivered to the thenar surface of the hand, temporal summation of second pain (wind-up) is enhanced, and the decay of nociceptive heat sensations is considerably prolonged in FMS subjects as compared to normal control subjects (NC) (Staud et al., 2001). Enhanced temporal summation (TS) of pain implicates central N-methyl-d- aspartate (NMDA) receptor mechanisms (Price et al., 1994; Vierck, et al., 1997), and administration of an NMDA antagonist (ketamine) reduces clinical pain and TS of pain for FMS patients (Graven-Nielsen et al., 2000). However, questions remain as to the source(s) of sensitiza- Pain 102 (2003) 87–95 0304-3959/02/$20.00 q 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. doi:10.1016/S0304-3959(02)00344-5 www.elsevier.com/locate/pain * Corresponding author. Tel.: 11-352-392-4681, fax: 11-352-392-8483. E-mail address: staudr@ufl.edu (R. Staud).