Neuroscience Letters 555 (2013) 203–208 Contents lists available at ScienceDirect Neuroscience Letters jou rn al hom epage: www.elsevier.com/locate/neulet Enhanced temporal pain processing in multiple system atrophy Armando Perrotta a,∗ , Monica Bolla b , Mariano Serrao c , Marco Paparatti c , Cristina Tassorelli b,d , Francesco Pierelli a , Giorgio Sandrini b,d a IRCCS Mediterranean Neurological Institute Neuromed, Pozzilli, Italy b IRCCS National Neurological Institute C. Mondino Foundation, Pavia, Italy c Department of Medical and Surgical Science and Biotechnology, Sapienza University of Rome, Rome, Italy d Department of Public Health and Neuroscience, University of Pavia, Pavia, Italy h i g h l i g h t s • Multiple system atrophy subjects showed a facilitated temporal processing of pain. • MSA and PD showed a comparable level of facilitation in temporal pain processing. • Striatonigral neurodegeneration could favor a facilitated temporal pain processing. a r t i c l e i n f o Article history: Received 8 July 2013 Received in revised form 26 August 2013 Accepted 14 September 2013 Keywords: Multiple system atrophy Pain Temporal summation Nociceptive withdrawal reflex a b s t r a c t Pain processing has been poorly studied in multiple system atrophy (MSA), notwithstanding these subjects complaint pain very frequently. We hypothesized that, as observed in other basal ganglia neurodegenerative disorders involving the striatonigral projections, also in MSA with predominant parkinsonian signs could be detected an abnormal pain processing. We used the temporal summation threshold (TST) of the nociceptive withdrawal reflex (NWR) and the related pain sensation to evaluate the temporal pain processing at spinal level in eleven MSA subjects and compared them with fifteen Parkin- son’s disease (PD) subjects, in both during “on” and “off” treatment with l-Dopa, and fifteen healthy subjects. MSA showed a significant reduction in NWR TST as well as facilitation in other pain responses when compared to healthy subjects; no differences were detected between “on” and “off” condition; no differences were detected between MSA and PD subjects in term of neurophysiological and pharmaco- logical responses. We demonstrated a facilitated temporal processing of pain in MSA subjects paralleling findings from PD. We hypothesize that the abnormal pain processing detected in both MSA and PD, could represent a consequence of the striatonigral neurodegeneration which in turn make these subjects more prone to develop pain conditions. © 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Multiple system atrophy (MSA) is a progressive neurodegen- erative disorder, characterized by variable combination of parkin- sonism, autonomic failure, cerebellar ataxia and corticospinal symptoms, as consequence of degeneration of striatonigral, olivo- ponto-cerebellar and spinal structures [11,12,28]. Very little is known about pain elaboration in MSA, notwithstanding epidemi- ological studies have revealed that MSA patients complaint pain symptoms very frequently [4,27]. Pain symptoms have been rec- ognized and largely described in basal ganglia disorders, such as ∗ Corresponding author at: INM Neuromed, IRCCS, via Atinense, 18, 86077 Pozzilli, Isernia, Italy. Tel.: +39 0865 929471; fax: +39 0865 929530. E-mail addresses: arm.perrotta@gmail.com, armando.perrotta@neuromed.it (A. Perrotta). Parkinson’s disease (PD) [2,5] and it has been hypothesized that the neurodegeneration of the basal ganglia could act in favor of this phenomenon [3]. In particular, in animal models have been demon- strated that basal ganglia exert a balancing role on pain processing at spinal level, via descending inhibitory and facilitatory projec- tions, confirming that abnormalities in their activity could have a direct or indirect consequence on pain perception [21,22]. It is conceivable that in MSA with predominant parkinsonian signs, the basal ganglia neurodegeneration, leading to a dysfunction of the striatal dopaminergic projection, could give rise, per se, to an abnormal pain processing which, in turn, could predispose these subjects to a clinical pain syndromes. A useful tool to evaluate the pain processing and the related influence of the supraspinal descending control pathways, is the study of the wind-up phenomenon in animals and of the temporal summation of pain in humans, consisting both in a temporary frequency-dependent facilitation of the responses of sensory 0304-3940/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neulet.2013.09.035