Study results evaluating pain thresholds in patients with Parkinson's disease (PD) vary widely. Thus, we designed our study to determine the effects of levodopa on the thresholds of pressure (PPT), heat (HPT) and cold pain (CPT) in PD patients with motor fluctuations (18 patients: 10 men, 8 women; age: 65 +/- 10 years; mean disease duration: 11.6 +/- 6 years), six of whom (33%) reported pain related to their disease. We compared these thresholds in patients in the ON and OFF states with those in 18 age- and sex-matched controls. Pain thresholds were assessed over: the frontal bones. C5-C6 zygapophyseal joints and second metacarpals (PPT); the dorsal aspect of the hand (HPT and CPT); and the tibialis anterior (TA) muscles. PD patients in the OFF state had lower PPT thresholds at all sites (P < 0.001) than healthy controls. Moreover, HPT and CPT thresholds were lower at all sites except over the TA muscle (P < 0.01). In the ON state, the PPT and CPT thresholds in PD patients were lower than in controls at all points, except over the TA (CPT) and the second metacarpals (PPT) P < 0.01. Pain thresholds were no different in PD patients in the ON or OFF state (P > 0.10), and the existence of pain did not influence the results. We detected mechanical and thermal pain hypersensitivity in PD patients in the OFF state, and levodopa administration did not increase these thresholds. Thus, while dopamine may modulate pain responses, other mechanisms are likely to be implicated in the modulation of these pain responses in PD patients. (C) 2012 Elsevier Ltd. All rights reserved.