A detailed clinical study of pain in 1957 participants with early/moderate Parkinson's disease

Monty A Silverdale, Christopher Kobylecki, Lewis Kass-Iliyya, Pablo Martinez-Martin, Michael Lawton, Sarah Cotterill, K Ray Chaudhuri, Huw Morris, Fahd Baig, Nigel Williams, Leon Hubbard, Michele T Hu, Donald G Grosset, UK Parkinson's Pain Study Collaboration, Monty A Silverdale, Christopher Kobylecki, Lewis Kass-Iliyya, Pablo Martinez-Martin, Michael Lawton, Sarah Cotterill, K Ray Chaudhuri, Huw Morris, Fahd Baig, Nigel Williams, Leon Hubbard, Michele T Hu, Donald G Grosset, UK Parkinson's Pain Study Collaboration

Abstract

Introduction: The causes of pain in early/moderate Parkinson's disease (PD) are not well understood. Although peripheral factors such as rigidity, reduced joint movements and poor posture may contribute towards the development of pain, central mechanisms including altered nociceptive processing may also be involved.

Methods: We performed a large clinical study to investigate potential factors contributing towards pain in early/moderate PD. We recruited 1957 PD participants who had detailed assessments of pain, motor and non-motor symptoms. The King's Parkinson's Pain scale was used to quantify different subtypes of pain.

Results: 85% of participants reported pain (42% with moderate to severe pain). Pain influenced quality of life more than motor symptoms in a multiple regression model. Factors predicting overall pain severity included affective symptoms, autonomic symptoms, motor complications, female gender and younger age, but not motor impairment or disease duration. There was negligible correlation between the severity of motor impairment and the severity of musculoskeletal or dystonic pain as well as between the severity of OFF period motor problems and the severity of OFF period pain or OFF period dystonic pain. Features of central sensitization, including allodynia and altered pain sensation were common in this population. The use of drugs targeting central pain was very low.

Conclusions: Pain in early/moderate PD cannot be explained by peripheral factors. Central causes may play a much more important role than previously considered. These results should lead to a major shift in the investigation and management of this common and disabling symptom.

Keywords: Central sensitization; Musculoskeletal; Nonmotor; Pain; Parkinson's disease.

Copyright © 2018. Published by Elsevier Ltd.

References

    1. Beiske A.G., Loge J.H., Ronningen A., Svensson E. Pain in Parkinson's disease: prevalence and characteristics. Pain. 2009;141:173–177.
    1. Nègre-Pagès L., Regragui W., Bouhassira D., Grandjean H., Rascol O., Group D.S. Chronic pain in Parkinson's disease: the cross-sectional French DoPaMiP survey. Mov. Disord. 2008;23:1361–1369.
    1. Politis M., Wu K., Molloy S., Bain P.G., Chaudhuri K.R., Piccini P. Parkinson's disease symptoms: the patient's perspective. Mov. Disord. 2010;25:1646–1651.
    1. Ford B. Pain in Parkinson's disease. Mov. Disord. 2010;25(Suppl 1):S98–S103.
    1. Wasner G., Deuschl G. Pains in Parkinson disease-many syndromes under one umbrella. Nat. Rev. Neurol. 2012;8:284–294.
    1. Brown C.A., El-Deredy W., Jones A.K.P. When the brain expects pain: common neural responses to pain anticipation are related to clinical pain and distress in fibromyalgia and osteoarthritis. Eur. J. Neurosci. 2014;39:663–672.
    1. Costigan M., Scholz J., Woolf C.J. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu. Rev. Neurosci. 2009;32:1–32.
    1. Hirsch E.C. Biochemistry of Parkinson's disease with special reference to the dopaminergic systems. Mol. Neurobiol. 1994;9:135–142.
    1. H. Braak, K. Del Tredici, U. Rüb, R.A.I. de Vos, E.N.H. Jansen Steur, E. Braak, Staging of brain pathology related to sporadic Parkinson's disease., Neurobiol. Aging. 24 (n.d.) 197–211. (accessed March 3, 2018).
    1. Grinberg L.T., Rueb U., di A.T., Alho L., Heinsen H. Brainstem pathology and non-motor symptoms in PD. J. Neurol. Sci. 2010;289:81–88.
    1. Millan M.J. Descending control of pain. Prog. Neurobiol. 2002;66:355–474.
    1. Peter C., Watson N., Gilron I., Pollock B.G., Lipman A.G., Smith M.T. Antidepressant analgesics. In: McMahon S., editor. Wall Melzack's Textb. Pain, Philadelphia. 2013.
    1. Defazio G., Tinazzi M., Berardelli A. How pain arises in Parkinson's disease? Eur. J. Neurol. 2013;20:1517–1523.
    1. Schestatsky P., Kumru H., Valls-Solé J., Valldeoriola F., Marti M.J., Tolosa E. Neurophysiologic study of central pain in patients with Parkinson disease. Neurology. 2007;69:2162–2169.
    1. Brefel-Courbon C., Payoux P., Thalamas C., Ory F., Quelven I., Chollet F. Effects of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study. Mov. Disord. 2005;20:1557–1563.
    1. Forkmann K., Grashorn W., Schmidt K., Fründt O., Buhmann C., Bingel U. Altered neural responses to heat pain in drug-naive patients with Parkinson disease. Pain. 2017;158:1408–1416.
    1. Chaudhuri K.R., Rizos A., Trenkwalder C., Rascol O., Pal S., Martino D. EUROPAR, the IPMDS Non Motor PD Study Group, King's Parkinson's disease pain scale, the first scale for pain in PD: an international validation. Mov. Disord. 2015
    1. Malek N., Swallow D.M.A., Grosset K.A., Lawton M.A., Marrinan S.L., Lehn A.C. PRoBaND, tracking Parkinson's: study design and baseline patient data. J. Park. Dis. 2015;5:947–959.
    1. Lawton M., Baig F., Rolinski M., Ruffman C., Nithi K., May M.T. Parkinson's disease subtypes in the Oxford Parkinson disease centre (OPDC) discovery cohort. J. Parkinson's Dis. 2015;5:269–279.
    1. Melzack R. The short-form McGill pain questionnaire. Pain. 1987;30:191–197.
    1. Breivik H., Collett B., Ventafridda V., Cohen R., Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur. J. Pain. 2006;10:287–333.
    1. Snaith R.P., Bridge G.W., Hamilton M. The Leeds scales for the self-assessment of anxiety and depression. Br. J. Psychiatr. 1976;128:156–165.
    1. Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain. 2001;92:147–157.
    1. Martinez-Martin P., Manuel Rojo-Abuin J., Rizos A., Rodriguez-Blazquez C., Trenkwalder C., Perkins L., Sauerbier A., Odin P., Antonini A., Chaudhuri K.R., KPPS E., The IPMDS Non Motor PD Study Group Distribution and impact on quality of life of the pain modalities assessed by the King's Parkinson's disease pain scale. NPJ.Park.dis. 2017;3:8.
    1. Bedson J., Croft P.R. The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature. BMC Muscoskel. Disord. 2008;9:1–11.
    1. Tinazzi M., Recchia S., Simonetto S., Tamburin S., Defazio G., Fiaschi A. Muscular pain in Parkinson's disease and nociceptive processing assessed with CO2 laser-evoked potentials. Mov. Disord. 2010;25:213–220.
    1. Gagliese L., Melzack R. Pain in older persons. In: McMahon S., Koltzenburg M., Tracey I., Turk D., editors. Wall Melzack's Textb. Pain. Elsevier; Philadelphia: 2013.
    1. Kass-Iliyya L., Javed S., Gosal D., Kobylecki C., Marshall A., Petropoulos I.N. Small fiber neuropathy in Parkinson's disease: a clinical, pathological and corneal confocal microscopy study. Park. Relat. Disord. 2015;21:1454–1460.
    1. Djaldetti R., Yust-Katz S., Kolianov V., Melamed E., Dabby R. The effect of duloxetine on primary pain symptoms in Parkinson disease. Clin. Neuropharmacol. 2007;30:201–205.
    1. Marques A., Chassin O., Morand D., Pereira B., Debilly B., Derost P. Central pain modulation after subthalamic nucleus stimulation: a crossover randomized trial. Neurology. 2013;81:633–640.
    1. Perez-Lloret S., Ciampi de Andrade D., Lyons K.E., Rodríguez-Blázquez C., Chaudhuri K.R., Deuschl G. Rating scales for pain in Parkinson's disease: Critique and recommendations. Mov. Disord.Clin. Pract. 2016;3:527–537.

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