Pain is the dominant symptom in osteoarthritis (OA) and sensitization may contribute to the pain severity. This study investigated the role of sensitization in patients with painful knee OA by measuring (1) pressure pain thresholds (PPTs); (2) spreading sensitization; (3) temporal summation to repeated pressure pain stimulation; (4) pain responses after intramuscular hypertonic saline; and (5) pressure pain modulation by heterotopic descending noxious inhibitory control (DNIC). Forty-eight patients with different degrees of knee OA and twenty-four age- and sex-matched control subjects participated. The patients were separated into strong/severe (VAS>or=6) and mild/moderate pain (VAS<6) groups. PPTs were measured from the peripatellar region, tibialis anterior (TA) and extensor carpi radialis longus muscles before, during and after DNIC. Temporal summation to pressure was measured at the most painful site in the peripatellar region and over TA. Patients with severely painful OA pain have significantly lower PPT than controls. For all locations (knee, leg, and arm) significantly negative correlations between VAS and PPT were found (more pain, more sensitization). OA patients showed a significant facilitation of temporal summation from both the knee and TA and had significantly less DNIC as compared with controls. No correlations were found between standard radiological findings and clinical/experimental pain parameters. However, patients with lesions in the lateral tibiofemoral knee compartment had higher pain ratings compared with those with intercondylar and medial lesions. This study highlights the importance of central sensitization as an important manifestation in knee OA.

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.

Chronic low back pain (CLBP) is a major clinical problem with a substantial socio-economical impact. Today, diagnosis and therapy are insufficient, and knowledge concerning interaction between musculoskeletal pain and motor performance is lacking. Most studies in this field have been performed under static conditions which may not represent CLBP patients' daily-life routines. A standardized way to study the sensory-motor interaction under controlled motor performances is to induce experimental muscle pain by i.m. injection of hypertonic saline. The aim of the present controlled study was to analyze and compare electromyographic (EMG) activity of and coordination between lumbar muscles (8 paraspinal recordings) during gait in 10 patients with CLBP and in 10 volunteers exposed to experimental back muscle pain induced by bolus injection of 5% hypertonic saline. When the results are compared to sex- and age-matched controls, the CLBP patients showed significantly increased EMG activity in the swing phase; a phase where the lumbar muscles are normally silent. These changes correlated significantly to the intensity of the back pain. Similar EMG patterns were found in the experimental study together with a reduced peak EMG activity in the period during double stance where the back muscles are normally active. Generally, these changes were localized ipsilaterally to the site of pain induction. The clinical and experimental findings indicate that musculoskeletal pain modulates motor performance during gait probably via reflex pathways. Initially, these EMG changes may be interpreted as a functional adaptation to muscle pain, but the consequences of chronic altered muscle performance are not known. New possibilities to monitor and investigate altered motor performance may help to develop more rational therapies for CLBP patients.