Potential of animal models for advancing the understanding and treatment of pain in Parkinson’s disease

Abstract

Pain is a commonly occurring non-motor symptom of Parkinson's disease (PD). Treatment of pain in PD remains less than optimal and a better understanding of the underlying mechanisms would facilitate discovery of improved analgesics. Animal models of PD have already proven helpful for furthering the understanding and treatment of motor symptoms of PD, but could these models offer insight into pain in PD? This review addresses the current position regarding pain in preclinical models of PD, covering the face and predictive validity of existing models and their use so far in advancing understanding of the mechanisms contributing to pain in PD. While pain itself is not usually measured in animals, nociception in the form of thermal, mechanical or chemical nociceptive thresholds offers a useful readout, given reduced nociceptive thresholds are commonly seen in PD patients. Animal models of PD including the reserpine-treated rat and neurodegenerative models such as the MPTP-treated mouse and 6hydroxydopamine (6-OHDA)-treated rat each exhibit reduced nociceptive thresholds, supporting face validity of these models. Furthermore, some interventions known clinically to relieve pain in PD, such as dopaminergic therapies and deep brain stimulation of the subthalamic nucleus, restore nociceptive thresholds in one or more models, supporting their predictive validity. Mechanistic insight gained already includes involvement of central and spinal dopamine and opioid systems. Moving forward, these preclinical models should advance understanding of the cellular and molecular mechanisms underlying pain in PD and provide test beds for examining the efficacy of novel analgesics to better treat this debilitating non-motor symptom.

Pain in the neurodegenerating brain: insights into pharmacotherapy for Alzheimer disease and Parkinson disease

“…Identifying well-defined subtypes, and elucidating their concomitant underlying mechanisms, should facilitate the development of personalised treatment of pain in PwP. 24 , 143 …”

Roles for the Dorsal Striatum in Aversive Behavior

“…Various aversive stimuli such as noxious heat, cold, mechanical, and electrical stimuli alter the activity of the DS, and many studies report that alterations of DS function using lesions and microinjections affect pain perception (Chudler and Dong, 1995 ; Borsook et al, 2010 ). Interestingly, patients with Parkinson’s disease, a movement disorder mostly due to decreased dopamine release in the DS, often present with comorbid chronic pain (Buhidma et al, 2020 ). Chronic pain is also co-morbid with PTSD (Fishbain et al, 2017 ), and processing of aversive stimuli within the DS is important for pain-avoidance learning (Koyama et al, 2000 ).…”

Part of the Covid19 puzzle: Acute parkinsonism

“…The direct effect occurs with the development of virus tropism, replication and subsequent neuronal lysis for the basal ganglia. On the other way, microglia activation, release of proinflammatory factors and T cell response, hyperstokinemia with vascular damage and hypoxic brain are possible indirect pathophysiological mechanisms [ 4 ].…”

“…These findings are thought to be the direct consequences of the virus on the nervous system or para-infectious/post-infectious immune-mediated or neurological complications of the systemic effects of COVID-19 [ 3 ]. Neurological involvements and complications such as stroke, encephalitis, headache, seizure, impaired consciousness, hyposmia and hypogeusia, Guillain Barré syndrome (GBS) and Miller Fisher syndrome have been reported to date [ 4 ].…”