Dopaminergic-Driven Hyperalgesia Contributes to Parkinson Disease Pain

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Investigators sought to determine the role hyperalgesia plays in the development of chronic pain in patients with Parkinson disease and whether dopamine may be the underlying mechanism.
Investigators sought to determine the role hyperalgesia plays in the development of chronic pain in patients with Parkinson disease and whether dopamine may be the underlying mechanism.

A recent meta-analysis study in the Journal of the Neurological Sciences found that dopamine may be involved in the underlying mechanism that contributes to hyperalgesia and associated clinical pain in Parkinson disease.

This study investigated pain sensitivity in patients with Parkinson disease and the role hyperalgesia plays in the development of chronic pain. The researchers performed a meta-analysis of the literature using case control studies of participants who experienced clinical persistent pain (PDPP) and participants who did not (PDNP). The meta-analysis on PDPP vs PDNP identified 429 studies of interest, of which 32 "dealt with pain sensitivity testing," 10 "examined pain sensitivities in [Parkinson disease] participants with pain and without pain," and 3 "had the primary aim of comparing of pain sensitivities between PDP[P] and PDNP." 

The Newcastle-Ottawa Scale, used to assess study quality, showed that "[o]verall, study quality scores were reasonable." The clinical characteristics showed participants with pain (n=199) and participants without (n=166). Significant differences were detected in Parkinson disease severity, dosage of dopaminergic medication, and sex ratios. The authors noted variability in the methodologies and outcome measures of the previously published studies. The investigators noted that "[m]ost of the studies (6/10) did not find any significant differences in the pain sensitivities between groups." In the meta-analysis of PDPP vs PDNP, the authors noted no significant difference between medications and demographics.

The meta-analysis of Med ON vs Med OFF showed the study quality (according to being low or of unknown risk for bias) as follows: low risk (7/20 studies), unknown risk (10/20 studies), and high risk (3/10 studies). The clinical characteristics showed 409 participants with Parkinson disease across 19 studies who underwent testing for pain sensitivity in Med ON/OFF states. These participants had a combined mean age of 63.2±8.1 years, an average disease duration of 7.4±4.9 years and took 426±376 mg levodopa daily. Acute dopaminergic medication challenge was used to examine pain sensitivities in 85% of the studies. Many studies reported pain threshold outcomes. Significant differences were detected in Med OFF and Med ON outcomes. In the meta-analysis of Med ON and Med OFF, the authors noted varying results.

This study identified the following as study limitations: first, the association and not causation between hyperplasia and clinical pain in Parkinson disease; second, lack of clarity on the association between Med OFF state and both dopaminergic and nondopaminergic mechanisms, and third, that the "presence of hyperalgesia in the Med OFF state and in the PDP[P] participant group cannot be taken as proof of central sensitization to pain."

Taken together, the authors noted the significant clinical implications this meta-analysis has on the approach of managing pain in Parkinson disease and the administration of dopamine treatment.

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Reference

Sung S, Vijiaratnam N, Chan DWC, Farrell M, Evans AH. Parkinson disease: a systemic review of pain sensitivities and its association with clinical pain and response to dopaminergic stimulationJ Neurol Sci. 2018;395:172-206.

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