PAIN IN PARKINSON'S DISEASE

Abstract

Background: Pain is a very common symptom in Parkinson's disease (PD). The underlying mechanism of pain in PD is poorly understood. Compared to PD, the characteristics of pain in other parkinsonian disorders such as Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have not been studied. Musculoskeletal factors have been implicated in the generation of pain in PD. However, studies in PD have shown impaired central processing of nociceptive inputs. Recently, small fibre neuropathy has also been found to be common in PD with significantly reduced C-fibres density compared to controls. A subclass of C-fibres known as C tactile afferents (CT) mediate the pleasant sensation associated with gentle skin stroking (affective touch). CT afferents have recently been shown to have pain-inhibiting properties. These findings may implicate central sensitisation in pain generation in PD. Objectives: 1) To better understand the mechanisms of pain in PD and study the characteristics of pain in MSA and PSP compared to PD. 2) To quantify small fibre neuropathy in PD and explore its relation to pain utilising a novel diagnostic technique: corneal confocal microscopy (CCM). 3) To assess the perception of affective touch in PD and its relationship to pain. Methods: Four studies were conducted: Study 1: A cross sectional study of pain characteristics in PD, MSA and PSP. Study 2: A descriptive study of pain characteristics in a large cohort of early PD (disease duration < 3 years, n=1763). Study 3: A cross sectional study to quantify small fibre density in PD (n=26) compared to control subjects (n=26) using CCM and skin biopsies. Nerve density was correlated with non-motor symptoms in PD including pain. Study 4: A study to assess the CT-mediated perception of affective touch in PD and correlate it with clinical symptoms such as pain. Results: Study 1: Pain prevalence and intensity was significantly higher in MSA and PD compared to PSP, p < 0.05. Female sex and motor fluctuations but not motor severity were predictors for pain intensity in PD. Study 2: Pain was common in early PD (84.2%). Only a minority of PD patients (19.7%) reported that their pain improved with Levodopa therapy of their motor symptoms. Study 3: PD patients had significantly reduced small fiber nerve density on both CCM and skin biopsies compared to controls. Denervation correlated with autonomic symptoms but not with pain intensity. Study 4: Perception of pleasantness followed a linear relationship with nerve density and was abnormally enhanced in PD compared to control and correlated with pain at a very slow stroking velocity. Conclusions: Pain is common in early PD, does not respond to levodopa treatment and correlates with motor complications but not motor severity favouring central sensitisation. Pain is significantly less common in PSP compared to PD and MSA. Small fibre neuropathy does not appear to be an important cause of pain in PD but small fibre nerve density correlates with affective touch perception, which is enhanced in PD despite peripheral denervation. Corneal confocal microscopy identifies corneal denervation in PD offering a novel non-invasive way of assessing PD pathology.

Date of Award	1 Aug 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Monty Silverdale (Supervisor) & Rayaz Malik (Supervisor)