Hypertonic saline effectively excites muscle nociceptors. Muscle hyperalgesia was assessed in osteoarthritis (OA) by intramuscular infusion of 0.5 ml hypertonic saline (6%) into the tibialis anterior muscle in humans. Patients (n=14) with OA in the lower extremities were compared with an equal number of age- and sex-matched healthy controls. Ten of the 14 OA patients had pain in the knee joint as the most common presenting complaint. Visual analogue scale (VAS) pain intensity and assessment of pain areas were recorded before infusion and immediately, 2, 5, 10 and 20 min after infusion, and then every 10 min, until the pain vanished. The mean pain offset time in OA patients (11.3+/-7.9 min) was larger as compared with the control subjects (6.04+/-2.1 min) (P=0.025). OA patients had increased pain intensity VAS after the infusion in the right leg compared with controls (P<0.05). Referred and radiating pain areas at 2 min post-infusion increased in OA patients and not in controls as compared with the local pain areas (P<0.05). It is concluded that muscle hyperalgesia and extended pain areas might be due to central sensitization caused by painful osteoarthritis.