Pain perception in Parkinson’s disease : a systematic review and meta-analysis of experimental studies

Abstract

While hyperalgesia (increased pain sensitivity) has been suggested to contribute to the increased preva- lence 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 con- trols (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 unmedi- cated 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 stim- ulation 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 mecha- nism, which may present opportunities for the development of novel analgesic strategies.