Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients

Central mechanisms related to referred muscle pain and temporal summation o f muscular nociceptive activity are facilitated in fibromyalgia syndrome (F MS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. p lacebo or ketamine (0.3 mg/kg, Ketalar(R)) given over 30 min on two separat e occasions. Habitual pain intensity was assessed on a visual analogue scal e (VAS). Initially, 29 FMS patients received ketamine or isotonic saline to determine which patients were ketamine responders (>50% decrease in pain i ntensity at rest by active drug on two consecutive VAS assessments). Fiftee n out of 17 ketamine-responders were included in the second part of the stu dy. Before and after ketamine or placebo, experimental local and referred p ain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 mi, 5%) into the tibialis anterior (TA) muscle. The saline-induced pain int ensity was assessed on an electronic VAS, and the distribution of pain draw n by the subject. In addition, the pain threshold (PT) to i.m, electrical s timulation was determined for single stimulus and five repeated (2 Hz, temp oral summation) stimuli. The pressure PT of the TA muscle was determined, a nd the pressure PT and pressure pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper tr apezius). VAS scores of pain at rest were progressively reduced during keta mine infusion compared with placebo infusion. Pain intensity (area under th e VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (-18.4 +/- 0.3% of pre-drug VAS area) compared with placebo (29.9 +/- 18.8%, P < 0.02). Local and referred pain areas were reduced by ketamin e (-12.0 +/- 14.6% of pre-drug pain areas) compared with placebo (126.3 +/- 83.2%, P < 0.03). Ketamine had no significant effect on the PT to single i .m. electrical stimulation. However, the span between the PT to single and repeated i.m. stimuli was significantly decreased by the ketamine (-42.3 +/ - 15.0% of pre-drug PT) compared with placebo (50.5 +/- 49.2%, P < 0.03) in dicating a predominant effect on temporal summation. Mean pressure pain tol erance from the three paired tenderpoints was increased by ketamine (16.6 /- 6.2% of pre-drug thresholds) compared with placebo (-2.3 +/- 4.9%, P < 0 .009). The pressure PT at the TA muscle was increased after ketamine (42.4 +/- 9.2% of pre-drug PT) compared with placebo (7.0 +/- 6.6%, P < 0.011). T he present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and tem poral summation in a sub-group of the fibromyalgia syndrome patients. Wheth er this is specific for FMS patients or a general phenomena in painful musc uloskeletal disorders is not known. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.