Central mechanisms related to referred
muscle pain and temporal summation of muscular nociceptive activity are facilitated in
fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an
NMDA-antagonist (
ketamine) on these central mechanisms. FMS patients received either i.v. placebo or
ketamine (0.3 mg/kg,
Ketalar((R))50% decrease in
pain intensity at rest by active
drug on two consecutive VAS assessments). Fifteen out of 17
ketamine-responders were included in the second part of the study. Before and after
ketamine or placebo, experimental local and
referred pain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 ml, 5%) into the tibialis anterior (TA) muscle. The saline-induced
pain intensity was assessed on an electronic VAS, and the distribution of
pain drawn by the subject. In addition, the pain threshold (PT) to i.m. electrical stimulation was determined for single stimulus and five repeated (2 Hz, temporal summation) stimuli. The pressure PT of the TA muscle was determined, and the pressure PT and pressure
pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper trapezius). VAS scores of
pain at rest were progressively reduced during
ketamine infusion compared with placebo infusion.
Pain intensity (area under the 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
ketamine (-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) indicating a predominant effect on temporal summation. Mean pressure
pain tolerance 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). The 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 temporal summation in a sub-group of the
fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known.