Impact of Nervous System Hyperalgesia on Pain, Disability, and Quality of Life in Patients With Knee Osteoarthritis: A Controlled Analysis MARTA IMAMURA, 1 SATIKO TOMIKAWA IMAMURA, 1 HELENA H. S. KAZIYAMA, 1 ROSA ALVES TARGINO, 1 WU TU HSING, 1 LUIZ PAULO MARQUES DE SOUZA, 1 MARTIN MENDONC ¸ A CUTAIT, 1 FELIPE FREGNI, 2 AND GILBERTO LUIS CAMANHO 1 Objective. Refractory, disabling pain associated with knee osteoarthritis (OA) is usually treated with total knee replace- ment. However, pain in these patients might be associated with central nervous sensitization rather than peripheral inflammation and injury. We evaluated the presence of hyperalgesia in patients scheduled for a total knee replacement due to knee osteoarthritis with refractory pain, and we assessed the impact of pressure pain threshold measurements (PPT) on pain, disability, and quality of life of these patients. Methods. Sixty-two female patients were compared with 22 age-matched healthy controls without reported pain for the last year. PPT was measured at the lower extremities subcutaneous dermatomes, over the vastus medialis, adductor longus, rectus femoris, vastus lateralis, tibialis anterior, peroneus longus, iliacus, quadratus lumborum and popliteus muscles and at the supraspinous ligaments from L1–L5, over the L5–S1 and S1–S2 sacral areas and at the pes anserinus bursae and patellar tendon. Results. Patients with knee OA had significantly lower PPT over all evaluated structures versus healthy control subjects (P < 0.001). Lower PPT values were correlated with higher pain intensity, higher disability scores, and with poorer quality of life, except for the role-emotional and general health status. Combined PPT values over the patellar tendon, at the S2 subcutaneous dermatome and at the adductor longus muscle were the best predictors for visual analog scale and Western Ontario and McMaster Universities Osteoarthritis Index pain scores. Conclusion. Patients with pain due to osteoarthritis who were scheduled for total knee replacement showed hyperalgesia of nervous system origin that negatively impacted pain, knee functional capacity, and most aspects of quality of life. INTRODUCTION Osteoarthritis (OA) is the most common form of arthritis, and is a major cause of pain and disability in the elderly (1), affecting millions of people in the US (2,3). OA is the fourth most frequently predicted cause of health problems worldwide in women (4). However, because OA has no cure, therapeutic goals are focused on maximizing func- tion and quality of life while controlling pain and mini- mizing the potentially harmful side effects of medications and therapies (2,3). Contemporary pain management has shifted from symptom control to management based on the pathophysiologic mechanisms of pain (5). Control of pain in patients with OA remains challenging, and patients with severe OA of the knee who have failed to respond to an extended course of conservative therapeutic modalities are usually scheduled for total knee replacement (1–3). We are now beginning to have a better understanding of the concepts of peripheral and central sensitization as they relate to knee OA pain (1). Recently, it has been recognized that constant and intense nociceptive sensory information, generated by painful and inflamed deep somatic struc- tures, produces significant neurochemical and metabolic changes, as well as neurologic reorganization within spi- nal cord segments (6,7). These changes include an in- creased excitability of dorsal horn neurons, which in turn produces pain hypersensitivity in a segmental distribution 1 Marta Imamura, MD, PhD, Satiko Tomikawa Imamura, MD, PhD, Helena H. S. Kaziyama, MD, Rosa Alves Targino, MD, PhD, Wu Tu Hsing, MD, PhD, Luiz Paulo Marques de Souza, MS, Martin Mendonc ¸a Cutait, PA, Gilberto Luis Ca- manho, MD, PhD: University of Sao Paulo School of Medi- cine, Sao Paulo, Brazil; 2 Felipe Fregni, MD, PhD: Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Med- ical Center, Harvard Medical School, Boston, Massachu- setts. Address correspondence to Marta Imamura, MD, PhD, Division of Physical Medicine and Rehabilitation, Institute of Orthopedics and Traumatology, University of Sao Paulo School of Medicine, Rua Dr. Ovidio Pires de Campos, 333 3rd Floor, B-317, Cerqueira Cesar, Sao Paulo, Brazil 05403- 010. E-mail: marta@imf.org.br. Submitted for publication February 1, 2008; accepted in revised form July 16, 2008. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 59, No. 10, October 15, 2008, pp 1424 –1431 DOI 10.1002/art.24120 © 2008, American College of Rheumatology SPECIAL ARTICLE: DISABILITY AND REHABILITATION IN THE RHEUMATIC DISEASES 1424