Facilitated Temporal Summation of Pain at Spinal Level in Parkinson’s Disease Armando Perrotta, MD, PhD, 1,2 * Giorgio Sandrini, MD, 1 Mariano Serrao, MD, PhD, 3,4 Simona Buscone, MD, 1 Cristina Tassorelli, MD, PhD, 1 Michele Tinazzi, MD, PhD, 5 Roberta Zangaglia, MD, PhD, 6 Claudio Pacchetti, MD, 6 Michelangelo Bartolo, MD, PhD, 1,2 Francesco Pierelli, MD, 2,3 and Emilia Martignoni, MD 7 1 Department of Neurology, IRCCS ‘‘C. Mondino Institute of Neurology’’ Foundation, University of Pavia, Pavia, Italy 2 IRCCS ‘‘Neuromed’’, University of Rome ‘‘Sapienza’’, Pozzilli, Isernia, Italy 3 Neurorehabilitation Unit, University of Rome ‘‘Sapienza’’ Polo Pontino-ICOT, Latina, Italy 4 Casa di Cura Policlinico Italia, Rome, Italy 5 Dipartimento di Scienze Neurologiche e della Visione, Sezione di Neurologia Riabilitativa, Universita ` di Verona, Italy 6 Parkinson Unit, IRCCS ‘‘C. Mondino Institute of Neurology’’ Foundation, University of Pavia, Pavia, Italy 7 Department of Clinical Medicine, University of Insubria, Varese, Neurorehabilitation Unit and Movement Disorders Unit, IRCCS Fondazione S. Maugeri, Tradate, Italy ABSTRACT: Background: Pain is one of the major nonmotor symp- toms of Parkinson’s disease. We hypothesized that Par- kinson’s disease patients could show an early diffuse abnormal processing of the nociceptive inputs also in the absence of clinical pain syndrome and that this could represent the physiopathological substrate to explain the high incidence of diffuse pain symptoms. Materials and methods: We used the temporal summa- tion threshold of the nociceptive withdrawal reflex and the related pain sensation to evaluate the facilitation in pain processing at spinal level. Fifteen (7 Women; 8 Men; mean age 63.0 6 9.1) Parkinson’s disease patients with- out clinical pain and 12 (6 Women, 6 Men; mean age 61.2 6 4.2) healthy subjects were recruited. Parkinson’s dis- ease group has been subdivided into two subgroups, 7 early-stage Parkinson’s disease patients with unilateral signs (Hoehn and Yahr stage 1) and 8 patients in a more advanced stage of the disease showing bilateral parkinso- nian signs (Hoehn and Yahr stages 2 and 2.5), both ‘‘on’’ and ‘‘off’’ treatments with levodopa. Results: A significant facilitation in temporal summa- tion of pain (reduced temporal summation threshold and increased painful sensation) was found in Parkin- son’s disease patients when compared with controls. This facilitation is more evident in Parkinson’s disease with bilateral signs and on the side more affected in Parkinson’s disease with unilateral signs. Levodopa administration failed to significantly modify the neuro- physiological abnormalities; however, a slight improve- ment has been detected. Conclusions: The increased gain in pain processing at spinal level in Parkinson’s disease patients could be a consequence of the degenerative phenomena involving supraspinal projections implicated in the modulation of pain processing and could make Parkinson’s disease patients more predisposed to develop a pain condition. V C 2010 Movement Disorder Society Key Words: Parkinson’s disease; pain; temporal sum- mation; nociceptive withdrawal reflex Pain is one of the major nonmotor symptoms of Par- kinson’s disease (PD). 1–4 It can be secondary to the motor component of the disease (musculoskeletal or dystonia associated) or, less frequently, of central ori- gin, occurring without a definite correlation with spe- cific motor signs or motor fluctuations and in the absence of objective sensory loss. 1–5 Despite a growing body of evidence implicating diffuse abnormal processing of nociceptive inputs at central (both cerebral and spinal) level in PD patients with or without clinical pain, 6–12 the pathophysiology underlying the high incidence of pain complaints in PD is not well understood. ------------------------------------------------------------ Additional Supporting Information may be found in the online version of this article. * Correspondence to: Armando Perrotta, Department of Neurology, IRCCS ‘‘C. Mondino Institute of Neurology’’ Foundation, Via Mondino 2, 27100 Pavia, Italy; armando.perrotta@mondino.it Relevant conflict of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 16 June 2010; Revised: 15 August 2010; Accepted: 3 September 2010 Published online 15 December 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/23458 RESEARCH ARTICLE 442 Movement Disorders, Vol. 26, No. 3, 2011