Pain perception in Parkinson's disease: A systematic review and meta-analysis of experimental studies.
While hyperalgesia (increased pain sensitivity) has been suggested to contribute to the increased prevalence of clinical pain in Parkinson's disease (PD), experimental research is equivocal and mechanisms are poorly understood. We conducted a meta-analysis of studies comparing PD patients to healthy controls (HCs) in their response to experimental pain stimuli. Articles were acquired through systematic searches of major databases from inception until 10/2016. Twenty-six studies met inclusion criteria, comprising 1292 participants (PD=739, HCs=553). Random effects meta-analysis of standardized mean differences (SMD) revealed lower pain threshold (indicating hyperalgesia) in PD patients during unmedicated OFF states (SMD=0.51) which was attenuated during dopamine-medicated ON states (SMD=0.23), but unaffected by age, PD duration or PD severity. Analysis of 6 studies employing suprathreshold stimulation paradigms indicated greater pain in PD patients, just failing to reach significance (SMD=0.30, p=0.06). These findings (a) support the existence of hyperalgesia in PD, which could contribute to the onset/intensity of clinical pain, and (b) implicate dopamine deficiency as a potential underlying mechanism, which may present opportunities for the development of novel analgesic strategies.
Faculty of Education and Health, University of Greenwich, London SE9 2UG, UK. Electronic address: t.thompson@gre.ac.uk.
Trevor
T
Thompson
Acaster Consulting, London SE3 7HU, UK.
Katy
K
Gallop
epartment of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY 11004, USA; Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY 11549, USA.
Christoph U
CU
Correll
Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Andre F
AF
Carvalho
Institute for Clinical Research and Education in Medicine, I.R.E.M., Padova, Italy.
Nicola
N
Veronese
Department of Primary Care and Public Health Sciences, King's College London, London SE1 3QD, UK.
Ellen
E
Wright
Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK; Health Service and Population Research Department, King's College London, London SE5 8AF, UK.
Brendon
B
Stubbs
D004298:Dopamine / Q000172:deficiency*; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism; D058748:Pain Perception / Q000502:physiology*; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism / Q000503:physiopathology
D004298:Dopamine
Dopamine; Meta-analysis; Pain; Parkinson’s disease; Systematic review