Subgroups in Fibromyalgia

Mechanisms of Pain in Patients with the
Fibromyalgia Syndrome

Roland Staud, M.D., Division of Rheumatology and Clinical Immunology
University of Florida, Gainesville, FL 32610

Introduction: Fibromyalgia Syndrome (FMS) is characterized by chronic widespread pain associated with allodynia. Our experiments with FMS subjects have indicated abnormalities of second pain in these patients which are related to central N-methyl-D-aspartate (NMDA) receptor processing. Our basic hypothesis is that abnormal central pain processing of second pain in FMS subjects is one of the fundamental abnormalities in this syndrome. Second pain results from impulse conduction in peripheral C (unmyelinated) afferent axons and is particularly sensitive to inhibition by opioid compounds. Second pain also increases in intensity when stimuli are applied more often than once every three seconds and this summation has been hypothesized to result from a central NMDA receptor mechanism. First pain is related to stimulation of A-Delta (myelinated) nociceptors and has been utilized almost exclusively to evaluate pain sensitivity. In order to compare directly abnormal processing of A-Delta and C-Fiber input in FMS subjects, we have utilized forms of brief experimental pain stimuli that can reliably evoke perceptions of first and second pain when applied to the hand or foot of human subjects.

RESULTS: Ten FMS patients and ten healthy age and sex matched controls were studied. The FMS subjects rated their level of pain, fatigue, and stiffness up to 30 times higher than control subjects. The average number of tender points was 16 for FMS patients and 1 for healthy controls, respectively. The rating of 2nd pain by FMS patients and control subjects using trains of 10, 15, or 20 stimuli at the fast interstimulatory interval of 2 seconds exceeded pain threshold on their first stimulation, and wound up more than three times compared to normal controls. At the slow speed of stimulation of 5 second ISI, normal controls consistently stayed below pain threshold after 10 or 15 stimulations. In contrast, FMS patients reported again pain on first stimulation and showed increasing pain even after 10 and 15 stimulations. FMS patients also showed a 40% Wind-up at this low frequency ISI.

These results indicate that FMS patients show excessive summation of second pain at 2 second ISI thermal stimulation and abnormal wind-up at 5 second ISI. Abnormal central pain processing in patients with FMS can lead to central sensitization which may be an important mechanism of chronic pain in this frequent and often disabling syndrome.

FMS is a generalized muscular pain disorder which characteristically worsens with physical activity. Because exercise has been sown to activate endogenous opioid and noradrenergic pain inhibitory systems we hypothesized that these pain modulatory systems may be compromised in FMS patients. We therefore compared the effects of exercise on different forms of pain sensitivity for fibromyalgia patients and matched normal controls.

Methods: We tested wind-up in ten FMS subjects matched to controls after exercise at V02 max. All subjects exercised to maximal exertion on a treadmill using the BRUCE protocol. The perceived level of exertion was tested every 3 minutes. V02 max, MET, RER were measured. Wind-up was tested with a Peltier device using numerical ratings of late sensations of pain after brief (700 ms) contact of the preheated thermode with the palmar skin of either hand. The interval between stimuli (ISI) varied between 2 and 5 sec. After each exercise session, wind-up was tested daily over 4 days and daily VAS pain questionnaires were completed by all subjects. Compared to baseline, exercise increased the 1st response to heat stimulation in FMS subjects and prolonged its after-effect, whereas max response remained unchanged. VAS of pain after exercise also remained unchanged over the next 96 h. In contract, controls showed decrease in all parameters of wind-up.

Conclusion: We conclude that wind-up of FMS subjects after exercise is abnormal and reflects the lack of pain improvement seen in FMS subjects after physical exertion.

Presented at the National Fibromyalgia Research Association's Subgroups in Fibromyalgia Symposium, September 26-27, 1999, in Portland, Oregon.