Parkinson disease: A systemic review of pain sensitivities and its association with clinical pain and response to dopaminergic stimulation.

Patients with Parkinson disease (PD) experience hyperalgesia on evoked pain sensitivity testing, although the relationship of this with persistent pain in PD is less certain. Studies examining this have generated contradictory findings. Further, the role of dopaminergic deficiency as an underlying substrate for hyperalgesia is controversial. We report the results of meta-analyses of the PD pain sensitivity literature in an attempt to answer these questions. We identified 429 records, of which ten articles compared pain sensitivity between PD patients that experienced clinical pain (PDP) to those who did not (PDNP), and twenty studies that examined the effect of dopaminergic medications on pain sensitivity in PD patients. PDP patients experienced a moderate increase in pain sensitivity, had more severe disease, required higher dosages of medication, and were more likely to be female when compared to those PDNP patients. PD patients also had reduced pain sensitivity when tested on dopaminergic medications compared to when they were not on medications. Overall, the results of this systematic review and meta-analysis supports the hypothesis that hyperalgesia contributes to clinical pain in PD, and that the underlying mechanism may be dopaminergically driven.

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

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.