Pain in Parkinson's disease: Mechanism-based treatment strategies

Chronic pain, highly prevalent throughout the course of Parkinson's disease (PD), has been ranked as one of the top ten most bothersome symptoms people with Parkinson's (PwP) are experiencing. Yet, robust evidence-based treatment strategies are lacking. This unmet need is partly attributable to the multifaceted nature of PD-related pain, which results in part from a complex and poorly understood interplay involving a range of neurotransmitter pathways. Degeneration of nigrostriatal dopaminergic pathways and alterations of central nervous system extra-striatal dopaminergic, noradrenergic, serotoninergic, glutamatergic, opioidergic and endocannabinoid circuits may all promote a heightened experience of pain in PwP. Thus, the potential targets for mechanism-based pain-relieving strategies in PwP are several. These targets are discussed herein.An increasing number of clinical trials and experimental studies in animal models of PD are being designed with the aim of addressing the pathophysiological mechanism(s) underlying PD-related pain. Overall, recent research findings highlight the analgesic effects of dopaminergic and opioidergic medication for certain subtypes of pain in PwP, whereas proposing novel strategies that involve targeting other neurotransmitter pathways.The origin of pain in PwP remains under investigation. Although our understanding of the mechanisms underpinning persistent pain in PD has improved in recent years, this has not yet translated to clinical alleviation of this most troublesome nonmotor symptom. Patient stratification linked with evidence-based personalized pain-treatment plans for optimal analgesic relief will rely on advances in our understanding of the dopaminergic and nondopaminergic targets outlined in this review.