Pain sensitivity in Parkinson's disease: Systematic review and meta-analysis

Simon Sung, Nirosen Vijiaratnam, Daniela Wan Chi Chan, Michael Farrell, Andrew H. Evans

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Introduction: Pain is a common and disabling non-motor symptom of Idiopathic Parkinson's disease (PD) but its underlying pathophysiological mechanisms are not well understood. There is evidence to suggest that altered pain sensitivity may contribute to the experience of pain in PD patients, but clinical studies investigating this have yielded inconsistent results. Objectives: To examine whether pain thresholds are altered in PD patients compared to normal healthy controls (HC), via the use of systematic review and meta-analysis. Data sources: A systematic search of the MEDLINE and EMBASE library from 1966 to April 2015. Study selection: Studies that compared pain thresholds in PD patients versus HC were included in the systematic review. Additionally, data comparing PD patients off dopaminergic medications (PDMoff) to HC off medications (HCMoff) were pooled for meta-analysis by pain modality. Main outcomes: Heat pain threshold, cold pain threshold, electrical pain threshold, nociceptive withdrawal reflex threshold, pressure pain threshold, and pain ratings. Results: 22 studies were reviewed, comprising of 616 PD and 451 HC. In the comparison of PDMoff versus HCMoff, a large majority of trials (15/19) found reduced pain thresholds (increased pain sensitivity) in PD patients. Meta-analysis of these trials revealed significantly reduced pain thresholds, of moderate to large effect size, in PD patients across all pain modalities. Results were much more heterogenous when PD patients on medications were compared with HC off medications, with most trials reporting no significant difference in pain thresholds between groups. No significant differences were found in pain thresholds for trials that compared PD patients on medications and HC on medications. Conclusion: PD patients are more sensitive to noxious stimuli compared to HC when tested in the off medication state. This increase in pain sensitivity is observed across all modalities, but is not as apparent when PD patients are administered Levodopa, suggesting that dopamine deficient states may contribute to hyperalgesia. However, it remains to be seen whether or not increased pain sensitivity translates clinically into increased prevalence of pain. Similarly, it is unclear if dopaminergic medications influence pain sensitivity. Performing a meta-analysis on studies comparing pain thresholds in PD patients with and without pain, and on and off dopaminergic medications, may draw more definitive conclusions in this regard.

Original languageEnglish
Pages (from-to)17-27
Number of pages11
JournalParkinsonism and Related Disorders
Volume48
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Meta-analysis
  • Pain
  • Parkinson disease

Cite this

Sung, Simon ; Vijiaratnam, Nirosen ; Chan, Daniela Wan Chi ; Farrell, Michael ; Evans, Andrew H. / Pain sensitivity in Parkinson's disease : Systematic review and meta-analysis. In: Parkinsonism and Related Disorders. 2018 ; Vol. 48. pp. 17-27.
@article{d049dcbf715844aabdc7ed36e4b5a8f7,
title = "Pain sensitivity in Parkinson's disease: Systematic review and meta-analysis",
abstract = "Introduction: Pain is a common and disabling non-motor symptom of Idiopathic Parkinson's disease (PD) but its underlying pathophysiological mechanisms are not well understood. There is evidence to suggest that altered pain sensitivity may contribute to the experience of pain in PD patients, but clinical studies investigating this have yielded inconsistent results. Objectives: To examine whether pain thresholds are altered in PD patients compared to normal healthy controls (HC), via the use of systematic review and meta-analysis. Data sources: A systematic search of the MEDLINE and EMBASE library from 1966 to April 2015. Study selection: Studies that compared pain thresholds in PD patients versus HC were included in the systematic review. Additionally, data comparing PD patients off dopaminergic medications (PDMoff) to HC off medications (HCMoff) were pooled for meta-analysis by pain modality. Main outcomes: Heat pain threshold, cold pain threshold, electrical pain threshold, nociceptive withdrawal reflex threshold, pressure pain threshold, and pain ratings. Results: 22 studies were reviewed, comprising of 616 PD and 451 HC. In the comparison of PDMoff versus HCMoff, a large majority of trials (15/19) found reduced pain thresholds (increased pain sensitivity) in PD patients. Meta-analysis of these trials revealed significantly reduced pain thresholds, of moderate to large effect size, in PD patients across all pain modalities. Results were much more heterogenous when PD patients on medications were compared with HC off medications, with most trials reporting no significant difference in pain thresholds between groups. No significant differences were found in pain thresholds for trials that compared PD patients on medications and HC on medications. Conclusion: PD patients are more sensitive to noxious stimuli compared to HC when tested in the off medication state. This increase in pain sensitivity is observed across all modalities, but is not as apparent when PD patients are administered Levodopa, suggesting that dopamine deficient states may contribute to hyperalgesia. However, it remains to be seen whether or not increased pain sensitivity translates clinically into increased prevalence of pain. Similarly, it is unclear if dopaminergic medications influence pain sensitivity. Performing a meta-analysis on studies comparing pain thresholds in PD patients with and without pain, and on and off dopaminergic medications, may draw more definitive conclusions in this regard.",
keywords = "Meta-analysis, Pain, Parkinson disease",
author = "Simon Sung and Nirosen Vijiaratnam and Chan, {Daniela Wan Chi} and Michael Farrell and Evans, {Andrew H.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.parkreldis.2017.12.031",
language = "English",
volume = "48",
pages = "17--27",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier",

}

Pain sensitivity in Parkinson's disease : Systematic review and meta-analysis. / Sung, Simon; Vijiaratnam, Nirosen; Chan, Daniela Wan Chi; Farrell, Michael; Evans, Andrew H.

In: Parkinsonism and Related Disorders, Vol. 48, 01.03.2018, p. 17-27.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Pain sensitivity in Parkinson's disease

T2 - Systematic review and meta-analysis

AU - Sung, Simon

AU - Vijiaratnam, Nirosen

AU - Chan, Daniela Wan Chi

AU - Farrell, Michael

AU - Evans, Andrew H.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Introduction: Pain is a common and disabling non-motor symptom of Idiopathic Parkinson's disease (PD) but its underlying pathophysiological mechanisms are not well understood. There is evidence to suggest that altered pain sensitivity may contribute to the experience of pain in PD patients, but clinical studies investigating this have yielded inconsistent results. Objectives: To examine whether pain thresholds are altered in PD patients compared to normal healthy controls (HC), via the use of systematic review and meta-analysis. Data sources: A systematic search of the MEDLINE and EMBASE library from 1966 to April 2015. Study selection: Studies that compared pain thresholds in PD patients versus HC were included in the systematic review. Additionally, data comparing PD patients off dopaminergic medications (PDMoff) to HC off medications (HCMoff) were pooled for meta-analysis by pain modality. Main outcomes: Heat pain threshold, cold pain threshold, electrical pain threshold, nociceptive withdrawal reflex threshold, pressure pain threshold, and pain ratings. Results: 22 studies were reviewed, comprising of 616 PD and 451 HC. In the comparison of PDMoff versus HCMoff, a large majority of trials (15/19) found reduced pain thresholds (increased pain sensitivity) in PD patients. Meta-analysis of these trials revealed significantly reduced pain thresholds, of moderate to large effect size, in PD patients across all pain modalities. Results were much more heterogenous when PD patients on medications were compared with HC off medications, with most trials reporting no significant difference in pain thresholds between groups. No significant differences were found in pain thresholds for trials that compared PD patients on medications and HC on medications. Conclusion: PD patients are more sensitive to noxious stimuli compared to HC when tested in the off medication state. This increase in pain sensitivity is observed across all modalities, but is not as apparent when PD patients are administered Levodopa, suggesting that dopamine deficient states may contribute to hyperalgesia. However, it remains to be seen whether or not increased pain sensitivity translates clinically into increased prevalence of pain. Similarly, it is unclear if dopaminergic medications influence pain sensitivity. Performing a meta-analysis on studies comparing pain thresholds in PD patients with and without pain, and on and off dopaminergic medications, may draw more definitive conclusions in this regard.

AB - Introduction: Pain is a common and disabling non-motor symptom of Idiopathic Parkinson's disease (PD) but its underlying pathophysiological mechanisms are not well understood. There is evidence to suggest that altered pain sensitivity may contribute to the experience of pain in PD patients, but clinical studies investigating this have yielded inconsistent results. Objectives: To examine whether pain thresholds are altered in PD patients compared to normal healthy controls (HC), via the use of systematic review and meta-analysis. Data sources: A systematic search of the MEDLINE and EMBASE library from 1966 to April 2015. Study selection: Studies that compared pain thresholds in PD patients versus HC were included in the systematic review. Additionally, data comparing PD patients off dopaminergic medications (PDMoff) to HC off medications (HCMoff) were pooled for meta-analysis by pain modality. Main outcomes: Heat pain threshold, cold pain threshold, electrical pain threshold, nociceptive withdrawal reflex threshold, pressure pain threshold, and pain ratings. Results: 22 studies were reviewed, comprising of 616 PD and 451 HC. In the comparison of PDMoff versus HCMoff, a large majority of trials (15/19) found reduced pain thresholds (increased pain sensitivity) in PD patients. Meta-analysis of these trials revealed significantly reduced pain thresholds, of moderate to large effect size, in PD patients across all pain modalities. Results were much more heterogenous when PD patients on medications were compared with HC off medications, with most trials reporting no significant difference in pain thresholds between groups. No significant differences were found in pain thresholds for trials that compared PD patients on medications and HC on medications. Conclusion: PD patients are more sensitive to noxious stimuli compared to HC when tested in the off medication state. This increase in pain sensitivity is observed across all modalities, but is not as apparent when PD patients are administered Levodopa, suggesting that dopamine deficient states may contribute to hyperalgesia. However, it remains to be seen whether or not increased pain sensitivity translates clinically into increased prevalence of pain. Similarly, it is unclear if dopaminergic medications influence pain sensitivity. Performing a meta-analysis on studies comparing pain thresholds in PD patients with and without pain, and on and off dopaminergic medications, may draw more definitive conclusions in this regard.

KW - Meta-analysis

KW - Pain

KW - Parkinson disease

UR - http://www.scopus.com/inward/record.url?scp=85041615966&partnerID=8YFLogxK

U2 - 10.1016/j.parkreldis.2017.12.031

DO - 10.1016/j.parkreldis.2017.12.031

M3 - Review Article

VL - 48

SP - 17

EP - 27

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

SN - 1353-8020

ER -