Pain and Sensory Abnormalities in Parkinson’s Disease— An Age- and Gender-matched Controlled Pilot Study

US Neurology, 2015;11(1):27–33 DOI:


Background/aims: To test whether patients with Parkinson’s disease (PD) have an altered sensory perception in response to painful and nonpainful stimuli and if the PD medications can influence the responses. Methods: PD patients (12) and healthy subjects (12) were recruited. Sensory perception was examined in forearms, low back, and hands by light brush, pinprick, cold pressure test (CPT), and pressure algometry. Results: A significant difference was found in PD patients in response to brush (p<0.05) and pinprick (p<0.001). Lower back and forearms were found to be more sensitive. Tolerance time in CPT was shorter in PD patients (p=0.016). Pressure pain threshold (PPT) before (p=0.011) and after (p=0.050) the CPT showed a higher sensitivity in the patients regardless of the site. No association was found between the sensory perception and the medications. Conclusion: PD patients demonstrated an altered perception to touch and pain stimuli with a general increased in pain intensity and independent of the PD medications.

Keywords: Parkinson’s disease, sensory perception, sensory disturbance, cold pressor test, pressure pain threshold, quantitative sensory testing, Mini Mental State Examination, allodynia, hyperalgesia, basal ganglia
Disclosure: Maria Skallerup Andersen, MMed Sci, Ali Karshenas, MD, Flemming Winther Bach, MD, Dr Med Sci, and Parisa Gazerani, Pharm D, PhD, have no conflicts of interest to declare. No funding was received for the publication of this article.
Received: December 04, 2014 Accepted February 09, 2015
Correspondence: Parisa Gazerani, Pharm D, PhD, Associate Professor, Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7D3, 9220 Aalborg East, Denmark. E:

Compliance with Ethics: Parkinson’s disease patients (with pain and without pain) and healthy subjects were all screened and written informed consent was obtained from all participants before the conduction of the experiments. The medications taken by patients were also recorded. The Ethical Committee of the Region Nordjylland Denmark approved the study protocol (N-20130073). The experiments were performed in accordance with the guidelines of Good Clinical Practice (GCP) from the International Conference on Harmonization (ICH) and the Declaration of Helsinki of 2008 (59th WMA General Assembly, Seoul).

Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit.

Parkinson’s disease (PD) is the second most common neurodegenerative disorders worldwide1 and is a chronic and progressive condition,2,3 which affects 1 % of the older population (>60 years of age).4 Over the years, major research has been focused on the motor impairments in PD, which has contributed to the development of symptomatic treatments for these patients. Evidence also demonstrates that PD patients have sensory impairments and chronic pain, which reduce their quality of life dramatically. Approximately 43 % of PD patients suffer from pain in general. There is no cure yet available and the number of affected PD patients is increasing, which highlights an existing socioeconomic burden.1

PD is characterized as a primary neurodegenerative disorder5 due to a dysfunction that might occur in the basal ganglia network following degeneration of dopaminergic pigmented neurons in the substantia nigra pars compacta, which gives rise to a significantly reduced dopaminergic deficit in striatum, especially in the putamen part.4 Several studies suggest that an abnormal basal ganglia function in PD can modulate pain directly by increasing or reducing the spread of nociceptive signals or indirectly by changes in affective and cognitive processes related to pain perception.6,7 Over the past decade, it has been gradually revealed that sensory perception in PD patients has been altered8–10 and the putative dysfunction in the basal ganglia is thought to lead to pain and sensory impairment in these patients.

The impairment of the sensory system is a less-explored area in PD. There are only few studies available applying sensory tests in PD patients with conflicting results.11,12 One study showed that PD patients had a lower threshold in both the cold pressure test (CPT) and pressure pain threshold (PPT) test13 and another study showed increased hypersensitivity to cold pain threshold (CPT) in PD patients compared with healthy subjects.6 However, there is a still uncertainty about this alteration in sensory perception as some studies have not been able to demonstrate any significant change.10 It remains to be determined whether PD patients suffer from sensory disturbances in terms of hyposensitivity or hypersensitivity in response to application of a painful or nonpainful stimulus and to what extent. In addition, it is still not clear whether sensory impairment is different in PD patients who suffer from a longterm spontaneous chronic pain, who also often have a poor quality of life, in comparison with those who do not have pain on a daily basis for a long term. It is also not known whether different PD medications have a possible effect on the perception of pain and peripheral sensory input. The primary aim of this study was to investigate whether PD patients have an altered sensory perception that might lead to an increased pain perception in response to noxious and non-noxious stimuli. We also investigated whether different medications taken by the PD patients can have an effect on responsiveness to the applied sensory tests. We proposed that some alterations in pain and sensory perception will be detected in mechanical and thermal perception in PD patients compared with healthy subjects and that drugs that might affect the sensory alterations are most likely levodopa preparation and dopamine agonists.

Materials and Methods
Subjects and Study Design
Twelve PD patients (nine males, three females with the mean age ± standard deviation [SD], 68.67±5.5 years) were recruited through arrangements with the chief physician, Ali Karshenas, Department of Neurology, Aalborg University Hospital, Denmark. Patients were of Caucasian descent, either with PD-related pain or without pain.

Patients >60 years who had been diagnosed ≤5 years with no central or peripheral disorders were included. Patients with pain (except the pain related to PD—defined as pain experienced in PD patients due to no other reason than PD based on the European Parkinson’s Disease Association), on painkillers, psychical disorders such as schizophrenia and dementia, mental retardation, memory impairment, or a Mini Mental State Examination (MMSE) score <24 (see description below) and other disorders of the central nervous system (CNS) or polyneuropathy were excluded from the study. The patients did not take alcohol, caffeinated drinks, or smoke 24 hours before the experiments. In addition, 12 bestmatched healthy volunteers (eight males, four females with the mean age ± SD, 67.5±5.39 years) of Caucasian descent were included as controls. The healthy volunteers were recruited through public notices posted at Aalborg University Hospital, Denmark, and social media. Having pain or taking any painkillers were among the exclusion criteria for healthy volunteers. The experiments took place in the outpatient clinic, Department of Neurology, Aalborg University Hospital, Denmark, and the participants attended one session, which lasted for about 1 hour.

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Keywords: Parkinson’s disease, sensory perception, sensory disturbance, cold pressor test, pressure pain threshold, quantitative sensory testing, Mini Mental State Examination, allodynia, hyperalgesia, basal ganglia