Pain in Parkinson Disease

Heather Baer, MD

Associate Professor

Departments of PMR and Neurology

University of Colorado Denver

October 2016

Learning Objectives •  Review the types of pain that can occur

in Parkinson Disease.

•  Learn about how pain may fluctuate with ON/OFF medication cycles.

•  Discuss approaches to pain control in PD.

Pain is common in PD

•  40-75% of individuals with PD report current pain when asked.

•  Dystonic or cramping pain may be the most common, particularly in young onset PD.

Pain Type Subcategory Central pain (Primary) Off-period pain

Beginning of dose pain Peak dose pain

End of dose pain

Musculoskeletal

Pain due to parkinsonian rigidity Pain due to rheumatologic or

musculoskeletal disorder or deformity

Neuritic-radicular pain

Pain due to roots lesion, focal or

peripheral neuropathy

Dystonic pain

Off-period painful dystonia Beginning of dose dystonia

Peak dose pain End of dose pain

Akathisia Off period akathisia Drug induced akathisia

Ford 2005

Primary/Central Pain

•  Direct consequence of PD.

•  Occurs in 10-30% of individuals.

•  No identifiable tissue damage. •  Symptoms:

•  burning, stabbing, aching, itching, or tingling sensations in undefined and peculiar body regions.

•  vague overall sensation of tension and discomfort.

Primary/Central Pain

•  May be more severe and/or frequent on the more affected side.

•  Possibly more severe in the �off� condition.

Secondary Pain •  Musculoskeletal

•  Radicular/neuritic

•  Dystonic

•  Akathisia

Musculoskeletal Pain

•  Contributing factors may include: •  Rigidity and decreased movement •  Postural abnormalities •  Abnormal mechanics •  Severe dyskinesias •  Disordered sleep •  Depression

•  Tends to decrease during �on� states and be worst during �off� states.

Shoulder Pain •  May be very early presentation of PD.

•  Rigidity and akinesia thought to contribute.

•  Commonly misdiagnosed as being only due to arthritis, bursitis or rotator cuff injury.

•  Can present as frozen shoulder.

Back Pain •  More common in PD than age-matched �healthy� controls.

•  Multiple contributors: •  spinal degenerative changes (common)

•  postural abnormalities

•  rigidity and dystonia

•  dyskinesias

•  Inactivity

•  depression

•  fall-related trauma

Back Pain

Complex relationship to camptocormia and PISA syndrome.

Neuritic & Radicular PAIN

•  Localized to the territory of a peripheral nerve or a spinal nerve root.

•  14% of pain experienced by patients with PD.

•  Postural abnormalities, drug-induced dyskinesias and rigidity may contribute.

Dystonic Pain •  Dystonia = sustained, forceful twisting muscular activity that leads to abnormal postures.

•  May precede diagnosis of PD, develop as a late symptom, or be induced by DRT and by DBS.

•  Dystonic spasms are often painful and may brief or last for hours. They may be paroxysmal, spontaneous or triggered by activity.

•  Off period dystonia often affects the feet.

•  Hand involvement is also common.

•  Left unaddressed, contractures may develop and lead to increased pain or disability.

AKATHISIA

•  A feeling of general internal restlessness (often necessitating movement for relief).

•  May be a presenting feature of PD or may emerge as an �off� symptom.

•  About 50% of individuals with akathisia may respond to DRT.

•  However, akathisia can also present as an adverse effect of levodopa.

Pain and Depression

•  Increased incidence of depression in the presence of pain.

•  Causal relationship not established.

•  Generally recommended to treat both.

PAIN MANAGEMENT

•  General principles: •  Optimize PD medical management to decrease

potential negative impact of rigidity, slowness, tremor and dyskinesias.

•  Identify underlying pain generators (e.g. lumbar disc) and address if possible.

•  Look for non-pharmacologic interventions. •  Skilled PT

•  Exercise classes/individual exercise program

•  Meditation/relaxation

•  Acupuncture

•  Massage

•  Other body therapies

•  Cognitive behavioral therapy

PAIN MANAGEMENT •  Modalities:

•  Ice/Heat

•  Ultrasound +/- steroid

•  TENs unit

•  Topical medications to limit systemic side effects:

•  NSAIDs (e.g. asprecreme, Voltaren gel)

•  Anesthetics (e.g. lidoderm patch, lidocaine creams/gels)

•  Counter irritants (e.g. salon pas, capsaicin)

•  CBD preparations

PAIN MANAGEMENT

•  Oral medications as tolerated: •  Adjust dopamine replacement therapy

(DRT).

•  Antidepressants (to address mood, neuropathic pain and/or sleep)

•  Anticonvulsants (to address mood, neuropathic pain and/or sleep)

•  Muscle relaxants (short term use)

•  Opiates (short term and low dose)

PAIN MANAGEMENT

• DBS: •  Chronic GPi DBS

•  Report of alleviation of pain and other unpleasant sensations

•  Chronic bilateral STN DBS (1yr) associated with:

•  84% reduction in pain fluctuations in 7 patients.

•  49% reduction in pain prevalence

•  Dystonic and musculoskeletal pain responded, not central or neuropathic pain.

•  significant improvements in akathisia

PAIN MANAGEMENT

•  Duopa (intestinal levodopa):

•  Open label studies suggest possible improvements in pain, discomfort and muscle cramps.

WHAT YOU CAN DO:

•  Try to identify location, quality, provoking and relieving factors.

•  Keep a pain diary to capture the relationship of the pain to the timing of medications .

• Also consider the relationship of the pain to any feelings of anxiety, stress or depression.

WHAT YOU CAN DO:

•  Identify activities that help you cope and remember them.

• Discuss pain with your medical providers

•  Consider adjustment of PD medications

•  Consider further evaluation for pain source

•  Stay active

References •  Ashour R, Jankovic J. Joint and skeletal muscle deformities in Parkinson�s disease, multiple system atrophy, and

progressive supranuclear palsy. Mov Disord 2006;21(11):1856-1863.

•  Azher SN, Jankovic J. Camptocormia: pathogenesis, classification, and response to therapy. Neurol444444 2005;65:355-359.

•  Antonini, A., Isaias, I. U., Canesi, M., Zibetti, M., Mancini, F., Manfredi, L., Dal Fante, M., Lopiano, L. and Pezzoli, G. (2007), Duodenal levodopa infusion for advanced Parkinson's disease: 12-month treatment outcome. Mov. Disord., 22: 1145–1149.

•  Berg D, Becker G, Reiners K. Reduction of dykinesia and induction of akinesia induced by morphine in two Parkinson patients with severe sciatica. J Neural Trans 1999;106(7-8):725-728.

•  Bloch F, Houeto JL, Tezenas du Montcel S, Bonneville F, Etchepare F, Welter ML, Rivaud-Pechoux S, Hahn-Barma V, Maisonobe T, Behar C, Lazennec JY, Kurys E, Arnulf I, Bonnet AM, Agid Y. Parkinson�s disease with camptocormia. J Neurol Neurosurg Psych 2006;77:1223-1228.

•  Braak H. Staging of brain pathology related to sporadic Parkinson�s disease. Neurobiol Aging 2003;24:197-211.

•  Broetz D, Eichner M, Gasser T, WellerM, Steinbach JP. Radicular and nonradicular back pain in Parkinson's disease: a controlled study. Mov Disord 2007;22(6):853-856.

•  Chudler EH, Dong WK. The role of the basal ganglia in nociception and pain. Pain 1995;60:3-38.

•  de Lau LM, Breteler MM. Epidemiology of Parkinson�s disease. Lancet Neurol 2006;5:525-535.

•  Djaldetti R, Mosberg-Galili R, Sroka H, Merims D, Melamed E. Camptocormia (bent spine) in patients with Parkinson�s disease – characterization and possible pathogenesis of an unusual phenomenon. Mov Disord 1999;14(3):443-447.

•  Ehrt U, Larsen JP, Aarsland D. Pain and its relationship to depression in Parkinson disease. Am J Geriatr Psychiatry 2009;17(4):269-75.

•  Fahn S. Nonmotor problems in Parkinson disease. Movement Disorders Course Aspen, CO 2007.

•  Ford B. Pain in Parkinson�s disease. Clin Neurosci 1998;52(2):63-72.

•  Ford B. Pain in Parkinson�s Disease. Parkinson�s Disease. (ed Ebadi MS, Pfeiffer R. CRC Press. 2005;chap 19:199-206.

•  Ford B. Pain in Parkinson�s Disease. Mov Disord 2010:25(Suppl 1):S98-S103.

•  Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson�s disease. Arch Neurol 1999;56:33-39.

•  Goetz CG, Tanner CM, Levy M, Wilson RS, Garron DC. Pain in Parkinson�s disease. Mov Disord 1986;1(1):45-49.

•  Grimes JD, Hassan MN, Trent G, Halle D, Armstrong GWD. Clinical and radiographic features of scoliosis in Parkinson�s disease. Adv. Neurol 1986;45:353-355.

•  Hagelberg N, Martikainen IK, Mansikka H, Hinnka S, Nagren K, Hietala J, Scheinin H, Pertovaara A. Dopamine D2 receptor binding in the human brain is associated with the response to painful stimulation and pain modulatory capacity. Pain 2002;99(1-2):273-279.

•  Hellmann MA, Djaldetti R, Israel Z, Melamed E. Effect of deep brain subthalamic stimulation on camptocormia and postural abnormalities in idiopathic Parkinson�s disease. Mov Disord 2006;21(11):2008-2010.

•  Ho B, Prakash R, Morgan JC, Sethi KD. A case of levodopa-repsonsive camptocormia associated with advanced Parkinson�s disease. Nat Clin Pract Neurol 207;3(9):526-530.

•  Honig, H., Antonini, A., Martinez-Martin, P., Forgacs, I., Faye, G. C., Fox, T., Fox, K., Mancini, F., Canesi, M., Odin, P. and Chaudhuri, K. R. (2009), Intrajejunal levodopa infusion in Parkinson's disease: A pilot multicenter study of effects on nonmotor symptoms and quality of life. Mov. Disord., 24: 1468–1474.

•  Jankovic J. Parkinson�s disease: clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 2007;79:368-376.

•  Kodama M, Kasahara T, Hyodo M, Aono K, Sugaya M, Koyama Y, Hanayama K, Masakado Y. effect of low frequency repetative transcranial magnetic stimulation combined with physical therapy on L-dopa-induced painful off-period in Parkinson’s disease. Am J Phys Med Rehabil 2011;90(2):150-155.

•  Lepoutre AC, Devos D, Blanchard-Dauphin A, Pardessus V, Maurage CA, Ferriby D, Hurtevent JF, Cotton A, Destee A, Defebvre L. A specific clinical pattern of camptocormia in Parkinson�s disease. J. Neurol. Neurosurg. Psychiatry 2006;77:1229-1234.

•  Lim SY, Farrell M, Gibson SJ, Helme RD, Lang AE, Evans AH. Do duskinesias and pain share a common pathophysiological mechanisms n Parkinson’s disease. Mov Disords 2008;23(12):1689-1695.

•  Micheli F, Cersosimo MG, Piedmonte F. Camptocormia in a patient with Parkinson disease: beneficial effects of pallidal deep brain stimulation. Case report. J Neurosurg 2005;103(6):1081-3.

•  Pacchetti C, Albani G, Martignoni E, Godi L, Alfonsi E, Nappi G. �Off� painful dystonia in Parkinson�s disease treated with botulinum toxin. Mov Disord 1995;10(3):333-336.

•  Papapetropoulos S, Singer C. Botulinum toxin in movement disorders. Sem in Neurol 2007;27(2):183-194.

•  Peek AC, Quinn N, Casey AT, Etherington G. Thoracolumbar spinal fixation for acmptocormia in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2009;80(11):1275-8.

•  Riley D, Lang AE, Blair RD, Birnbaum A, Reid B. Frozen shoulder and other shoulder disturbances in Parkinson�s disease. J Neurol Neurosurg Psych 1989;52:63-66.

•  Sakas DE, Panourias IG, Stavrinou LC, Boviatsis EJ, Themistocleous M, Stathis P, Tagaris G, Angelopoulos E, Gatzonis S. Restoration of erect posture in idiopathic camptocormia by electrical stimulation of the globus pallidus internus. J Neurosurg 2010;113(6):1246-50.

•  Sako W, Nishio M, Maruo T, Shimazu H, Matsuzaki K, Tamura T, Mure H, Ushio Y, Nagahiro S, Kaji R, Goto S. Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson’s disease. Mov Disord 2009;24(7):1076-9.

•  Shannon KM. Contemporary diagnosis and management of Parkinson�s disease. Handbooks in Heath Care Company 2007.

•  Slaoui T, Mas-Gerdelat A, Ory-Magne F, Rascol O, Brefel-Courbon C. Levodopa modifies pain thresholds in Parkinson�s disease patients. Rev Neurol (Paris) 2007;163(1):66-71.

•  Snider SR, Fahn S, Isgreen WP, Cote LJ. Primary sensory symptoms in parkinsonism. Neurology 1976;26:423.

•  Thani NB, Bala A, Kimber TE, Lind CR. High frequency pallidal stimulation for camptocormia in Parkinson’s disease. Neurosurg 2011: feb 4, E Pub.

•  Tinazzi M, Del Vesco C, Fincati E, Ottaviani S, Smania N, Moretto G, Fiaschi A, Martino D, Defazio G. Pain and motor complications in Parkinson�s disease. J Neurol. Neurosurg Psych 2006;77:822-825.

•  Tracey I, Becerra L, Chang I, Breiter H, Jenkins L, Borsook D, Gonzalez RG. Noxious hot and cold stimulation produce common patterns of brain activation in humans: a functional magnetic resonance imaging study. Neurosci Lett 2000;288(2):159-162.

•  Toth C, Breithaupt K, Ge S, Duan Y, Terris JM, Theissen A, Weibe S, Zochodne DW, Suchowersky O. Levodopa, methylmalonic asid, and neuropathy in idiopathic Parkinson disease. Ann Neurol 2010;68(1):28-36.

•  Toth C, Brown MS, Furtado S, Suchowersky O, Zochodne D. Neuropathy as a potential complication of levodopa use in Parkinsons disease. Mov Disord 2010;25(5):660-1.

•  Umemura A, Oka Y, Ohkita K, Yamawaki T, Tamada K. Effect of subthalamic deep brain stimulation on postrual abnormality in Parkinson disease. J Neurosurg 2010;112(6):1283-8.

•  Upadhaya CD, Starr PA, Mummanei PV. Spinal deformity and Parkinson disease: a treatment algorithm. Neurosurg Focus 2010;28(3):E5.

•  Wadia PM, Tan G, Munhoz RP, Fox SH, Lewis SJ, Lang AE. Surgical correction of kyphosis in patients with camptocormia due to Parkinson’s disease: a retrospective evaluation. J Neurol Neurosurg Psychiatry 2010. Epub.

•  Waseem S, Gwinn-Hary K. Pain in Parkinson�s disease: common yet seldom recognized symptom is treatable. Postgrad Med 2001;110(6):33-40.

•  Witjas T, Kaphan E, Regis J, Jouve E, Cherif AA, Peragut JC, Azulay JP. Effects of chronic subthalamic stimultation on nonmotor flkuctuations in Parkinson’s disease. Mov Disord 2007;22(12):1729-1734.

•  Yamada K, Goto S, Matsuzaki K, Tamura T, Murase N, Shimazu H, Nagahiro S, Kuratsu J, Kaji R. Alleviation of camptocormia by bilateral subthalamic nucleus stimulation in a patient with Parkinson�s disease. Parkinsonism Relate Disord 2006;12:372-375.