Clinical Neurology and Neurosurgery 115 (2013) 2313– 2317
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery
jou rn al h om epage: www.elsev ier .com/ locate /c l ineuro
eview
ain in Parkinson’s disease: Analysis and literature review
bdul Qayyum Ranaa,∗, Ashish Kabirb, Margaret Jesudasana, Ishraq Siddiquia,umaiya Khondkerb
Parkinson’s Clinic of Eastern Toronto & Movement Disorders Centre, 404-2863 Ellesmere Road, Toronto, Ontario M1E 5E9, CanadaAll Saints University School of Medicine, Roseau, Dominica
r t i c l e i n f o
rticle history:eceived 4 January 2013eceived in revised form 9 August 2013ccepted 20 August 2013vailable online 8 September 2013
eywords:on Motor symptomsarkinsonismainystonia
a b s t r a c t
Pain is a common problem faced by Parkinson’s disease (PD) patients. Despite its impact and disablingeffects pain is still frequently overlooked. In this study we analyze a representative sample of peerreviewed literature for the prevalence and types of pain in PD, the impact and significance of pain inthe quality of life of the PD patient and the challenges inherent in the diagnosis and management of painin PD patients.
We compared and analyzed the findings of articles indexed in the PubMed database which looked atsymptoms reported by large cohorts of PD patients. These articles all reported the incidence, nature andquality of pain in these patients and described the effects of pain on quality of life and generally werecross-sectional, retrospective or case–control studies, though a major pharmacoepidemiological designstudy was also analyzed.
Results of our analysis showed that the pain was prevalent in 59.77% of PD patients. Five differenttypes of pain were reported by PD patients – dystonia, muskuloskeletal pain, nerve/nerve root pain,primary/central pain and according to some, akathisia. Patients who reported pain symptoms were alsosignificantly more likely to report associated depression and a decreased quality of life. Many PD patients
also reported poor management of pain and lower analgesic use than would be expected. We furtherdiscuss some of the possible approaches toward the development of a treatment algorithm regarding themanagement of pain in PD. We conclude that pain in is an under-recognized and under treated symptomin PD patients. Effective management of pain in PD patients would significantly improve their quality oflife. Our analysis is in line with current thinking that identifies PD is much more of a multisystem diseasewith non-motor symptoms than previously thought.
Parkinson’s disease (PD) is a neurodegenerative disorder of the
postural instability, PD is now recognized as a multi-system diseasewhich may present with various non-motor symptoms. These non-motor symptoms are often reported by patients during a prodromal
entral nervous system resulting from the death of dopamine con-aining cells in the substantia nigra. Classically characterized by
otor symptoms – specifically resting tremor, rigidity, akinesia and
phase prior to the diagnosis of PD [1].Pain, a commonly reported non-motor symptom of PD, is preva-
lent in a large proportion of patients, however, the neurophysiologyof pain in PD is not well understood. There is abundant indirectevidence of abnormal somatosensory processing in the basal gan-
glia that involves the substantia nigra, caudate, putamen, globuspallidus, thalamus, and their interconnections [2]. A study doneusing electrical stimulation and EMG recording found that heat
ain threshold is decreased in PD patients and spinal nociceptions measured by NFR (nociception flexion reflex) threshold is alsoltered in PD patients [3].
Four different types of pain have been described in PD patients:1) musculoskeletal (due to PD rigidity/skeletal deformity), (2)adicular-neuropathic pain (due to root lesion, focal or peripheraleuropathy), (3) dystonic pain (often due to the effects of medica-ions) and (4) central or primary pain (considered a disease specificymptom in PD [2,4]). Patients may also report akathisia (a feelingf restlessness) but this sensation is not considered a pain symp-om in our study as it may be experienced as a feeling of discomfortithout pain in many cases.
This study analyses published, peer reviewed literature on therevalence and quality of pain in PD. Recent work by Toda andarada [5] and Ha and Jankovic [6], and Bonnet et al. [7]. demon-
trate increasing awareness in the movement disorders communityf the scale of the problem of effectively addressing non-motorymptoms in PD, and our analysis focuses on pain as a common,ignificant symptom seen in a majority of PD patients. This analysiss, to the best of our knowledge, unique in focusing on the preva-ence of pain reported across such a large number of PD patients.arly identification of pain in these patients may lead to signifi-antly improved quality of life and management of the patient’sisease.
. Method
The PubMed medical database was queried for articles pub-ished between 2004 and 2011 that reported the prevalence ofain in patients diagnosed with Parkinson’s disease. Articles werexcluded if they were in a language other than English, if the dis-ase studied was not specifically PD, if pain was not discussed as aymptom in these patients, or if the sample size was smaller than0. We then reviewed the prevalence of the type of pain reported byhese patients according to the four major types noted above (mus-uloskeletal, radicular/neuropathic, dystonia or central/primaryain.) Finally, we reviewed recent articles which looked at the man-gement of pain in PD using pharmacologic and non-pharmacologicherapy based on the type of pain experienced by the patient.
. Results
The articles we studied were published between 2004 and 2011nd covered PD patients in a wide ranging geographic area (Table 1).hree of the papers studied were from Italy [8–10], two fromorway [4,11] two from France [12,13], two from Brazil [14,15],
wo from Germany [16,17], two from the UK [1,18], two from theSA [19,20] and one each from Australia [21], Turkey [22], andouth Korea [23]. The total number of cases studied in the arti-les was 15,636 of which 7503 were males and 8126 were females.ean age ranged between 53.2 and 77. Average prevalence rate
f pain was 58.36% through all the papers with a range between1% and 83% depending on the population studied. The Nebe et al.aper which only looked at PD patients with pain symptoms (100%revalence) was not included in the calculation for prevalence. Ninef the articles described the types and location of pain (Table 2).ight articles described the distribution of musculoskeletal pain.our articles focused mainly on shoulder pain. Most of the patientsad musculoskeletal pain (48%) followed by dystonic pain (26%),europathic pain (13%), nonlocalized/central pain (8%). One arti-le studied akathisia and found it to present in 27% of patients.
he articles presented in Tables 1 and 2 are mainly Case control,ross sectional, Prospective or Retrospective studies, however, thearone et al. multicenter survey and the Brefel-Courbon et al. majorpidemiological work also help to provide a more accurate picture
eurosurgery 115 (2013) 2313– 2317
of the prevalence of pain in PD patients. In addition, five of theabove noted articles explored analgesic use in PD patients and wereview these as well as more recent literature on pain managementin these patients using pharmacological and non-pharmacologicalmethods.
4. Discussion
Parkinson’s disease is now widely recognized as a complex dis-order with clinical features encompassing motor, non-motor andneuro-psychiatric symptoms. Tables 1 and 2 summarize the find-ings of the individual authors regarding the demographics andtypes of pain in PD. In its totality, this sample of papers representsa very large PD patient cohort and draws general conclusions basedon the aggregate research of a number of authors. We discuss someof these findings below.
O’Sullivan et al. found that pain was the most frequent nonmotor symptom reported by Parkinson’s disease patients, seen in53% of PD patients who first presented with non motor symptoms– though their chart review showed an overall pain prevalence of15% in all PD patients. Other non-motor symptoms included urinarysymptoms, depression, anxiety, cognitive impairment, functionallimitation or dementia, and lethargy. When patients were askedabout non motor symptoms at PD onset, joint/muscular pain, anx-iety, fatigue and depression were the ones that were recalled withmost frequency.
Pain symptoms may not be identified if patients do not reportthem or if providers do not carefully include questions about painsymptoms as part of a complete patient history. A survey of 444PD sufferers and 326 caregivers found that 36% feel their physicianappears to have little or no understanding of what it like to livewith PD [21]. Toda et al. found that the reasons for the inadequatemanagement of pain in PD patients included the following – (1)pain is not visible therefore difficult for physicians to immediatelyidentify, (2) patients don’t often mention pain, (3) even if patientscomplain of pain, physicians do not often respond to or prioritize it,(4) physicians are more adept at managing acute pain than chronicpain and therefore treat chronic pain like acute pain, and (5) painwithout sufficient objective signs is often regarded as psychogenicpain [5].
The management of pain symptoms using analgesics wasreported by fewer patients with PD-pain than non-PD-painand, than patients with other disorders exhibiting chronic pain[4,12,16,18]. Pain estimated by analgesic drug prescription is moreprevalent in PD patients than in the general population [13]. Inour review, five studies were identified that had reported analgesicusage for pain management and of those patients, 52% were treated,much lower than the prevalence of pain routinely reported by mostresearchers examining PD patient cohorts.
A majority of the studies we reviewed did not find significantdifferences in these results with reference to sex, geographic dis-tribution or age. However Bieske et al. and Barone et al. foundthat pain, fatigue, and psychiatric complaints were more commonlyreported in women.
The literature identifies four major types of pain, as stated above.Muskuloskeletal pain, determined by rigidity/skeletal deformityand radicular or neuropathic pain are differentiated by whether ornot the pain is described as radiating [4]. Dystonic pain (often asso-ciated with medication use) and central neuropathic pain are mostoften associated with PD. Therefore, the management of pain in PDpatients should seek to alleviate the increased dystonic and cen-
tral pain by optimizing dopaminergic therapy. Pain associated withdystonia may be related to involuntary muscular contraction andmay be best managed with options like botulinum toxin whereasneuropathic pain may be related to a central dopaminergic deficit
A.Q. Rana et al. / Clinical Neurology and Neurosurgery 115 (2013) 2313– 2317 2315
Table 1Demographic information in a sample set of articles reporting on pain in PD between 2004 and 2011.
Author No of Pts. Males Females Age range Mean age Prevalence Type of study Country Year
AG Bieske et al. 176 104 72 35–90 69 83% Cross sectional study Norway 2009M Tinazzi et al. 117 50 67 69.4 ± 8.1 40% Case control Italy 2006L Negre-pages et al. 450 254 196 68 ± 9.7 68.8 ± 9.7 61.8% Cross sectional survey France 2008G Defazio et al. 402 254 148 67.4 ± 9.1 69.90% Double blind case control Italy 2008GH Letro et al. 50 30 20 62 ± 11 66% Prospective study Brazil 2009MA Lee et al. 123 59 64 51–89 74.3 62.60% Cross sectional survey UK 2006S Mott et al. 442 257 185 40–89 69 64% PD patient and caregiver
surveyAustralia 2004
U Ehrt et al. 227 111 116 72.8 67% Cross sectional Cohortstudy
Norway 2009
HA Hanagasi et al. 96 54 42 25–84 62 ± 11 64.90% Prospective study Turkey 2011D Broetz PT et al. 101 58 43 40–89 68 74% Controlled study Germany 2007EG da Silva et al. 50 34 16 31–74 53.2 ± 10.3 56% Prospective study Brazil 2008MB Madden et al. 25 12 13 65.3 ± 12.3 80% Cross sectional case and
retrospective studyUSA 2010
A Nebe et al. 15 11 4 71 ± 6.48 100%a Retrospective analysis Germany 2009C Brefel-Courbon et al. 11,466 5096 6370 35–103 77 82% Pharmacoepidemiological
designFrance 2009
JH Roh et al. 82 28 54 40–81 66.4 ± 8.7 34% Cross-sectional study Korea 2009P Barone et al. 1072 647 425 68.2 ± 9.1 60.90% Multicenter cross sectional
surveyItaly 2009
W Stamey et al. 309 170 132 64 ± 9.6 35% Retrospective analysis USA 2008SS O’Sullivan et al. 433 274 159 60.9 ± 10.4 15% Retrospective analysis UK 2008
a Only included patients who had both pain and PD. Not included in average.
nd may benefit from therapeutic options targeted at this pathology12]. In addition, anti-inflammatory medication may help reduceocal irritation and opiates may help modulate pain pathways [27].
In addition, some authors [2,22] have discussed akathisia as aymptom of dopaminergic deficit in PD. While akathisia may be
erceived as painful by the patient, the feeling of restlessness asso-iated with it not seen as a primary pain type. While managementf these symptoms is key and pain associated with akathisia haseen reported in the literature [12], since not all authors classified
able 2D pain by type in a sample set of articles reporting on pain in PD between 2004 and 201
Author Location of musculoskeletal pain Type of pain
Muskulo-skeleta
AG Bieske et al. 70.00%
M Tinazzi et al. BPa (45%), shoulder (23%), limbs (27%),neck (2%)
47.00%
L Negre-pages et al. Limbs 88%, BP (12.6), head 8.7% 37.00%
G Defacazio et al. Neck (6.2%), shoulder (10.9%), limbs(27.6%), back (15.7%)
25.40%
GH Letro et al. Limbs 8 (16%), shoulder 7 (14%), BP 7(14%)
MA Lee et al. Neck (9.1%), BP (25.6%), limbs (57.3%) 67.00%
S Mott et al. BP (61%), limbs (80%), shoulders (23%),chest (6%)
U Ehrt et al.HA Hanagasi et al. Shoulder pain (2.8%) 44.40%
D Broetz et al. BP 74.00%
EG da Silva et al. 50.00%
MB Madden et al. Shoulder pain 80.00%A Nebe et al. Localized to lower back and/or
shoulder66.67%
C Brefel-Courbon et al.
JH Roh et al. BP (70%), limbs (28%), shoulders (21%),neck (10%)
P Barone et al. Limbs (37.9%), shoulder pain (19.1%)
W Stamey et al. Shoulder pain (11%) 11.00%SS O’Sullivan et al. Shoulder pain (3.2%) 4.80%
Average = 48%
a BP, cervical, thoracic, lumbar back.
(±18.68)
or included akathisia as a pain subtype, our review does not inves-tigate it further. Further studies are required in order to classify therole of this symptom in the possible presentation of PD.
The articles we have compared measured pain using a few dif-ferent scales and so the data may not be precisely comparable
between different authors work in a numerically quantifiable fash-ion. PD patients were assessed most commonly using the Brief PainInventory [4,12,18], however studies also employed the PDQ-39scale [10,12,14], the Medical Outcomes Study 36-Item Short form
1.
l Neuropathic Dystonia Non-localizedPD/central pain
Usage of analgesics
20% 40% 10% 38%8% 40% 4%
50%4.70% 11.40% 4.50%
8%
4.90% 26.40% 58.50%
11.10% 19.10% 12.70%38%10.70% 21.40% 1% 78.60%
33%1%
20.80%
Average = 13% Average = 26% Average = 8% Average = 52%
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6 (SF-36) [4,23] the Visual Analog Scale [8,17,18,22,23], and thecGill Pain Questionnaire short form [12,17]. In addition direct
uestions regarding the presence and nature of pain as part of thelinical interview of the patient were utilized. The UPDRS scale wasommonly used to describe the severity of motor symptoms in PDatients – a higher value implying additional motor complications.isease progression was reported using Hoehn and Yahr staging.
The Negre-Pages paper and other material [12] looked at painot in terms of the various kinds of pain but instead as a character-
stic of PD itself. Patients with PD often have various comorbiditiesnd it is important from a management perspective that PD asso-iated pain is treated correctly and separately from non PD painven if present in the same patient. This, and other studies, exam-ned patients in order to distinguish between pain caused solely byD and “non-PD” pain and determined that in many cases, PD pains quite prevalent and also under-managed. Further work on theseubjects and analysis on this matter follows, but the challenge facedy these and other investigators is to decide on the cause of pain
n, for example, a PD patient with co-existing osteorarthritis whoresents with radicular pain. On the other hand, picking a cohorthat is pain free except for PD pain would not be representativef the population in general and this artificial cohort would not beseful when attempting to assess the prevalence of PD pain or inhe management of specific pain types.
Once pain in PD patients has been correctly classified accordingo subtype and separated from pain associated with comorbid con-itions (most commonly osteoarthritis but also other conditionsuch as diabetes and rheumatological conditions) the managementf pain with various pharmacologic and non-pharmacologic thera-ies may be initiated. The patients who have pain associated withigidity due to parkinsonism may have damage to non-neural tis-ue due to muscle/joint stretching and subsequent inflammation25]. The use of NSAIDs, opiates, co-analgesics and antidepressantsnd/or medications which modulate Serotonin/Norepinephrineathways may provide effective relief. In addition, these patientsay benefit from non-pharmacological treatment such as stretch-
ng exercises, repetitive transcranial magnetic stimulation (rTMS)r cranial electrotherapy stimulation. rTMS therapy has been effec-ive in the management of dystonic pain [27]. Dystonic pain maylso present as frozen shoulder or as foot dystonia and analge-ia in these presentations may include botulinum toxin injectionn addition to optimizing dopaminergic therapy with l-Dopa orther agents [6,27]. In the latter presentation, there might be aore limited role for NSAIDs as the cause of the pain may not be
nflammatory, however, Deep Brain Stimulation of the subthalamicucleus has been proven to be effective in the management of theseymptoms [6].
Pain in PD may also be neuropathic in nature – arising from central basal ganglia dysfunction [2,13]. The involvement of theasal ganglia in pain processing has been established and a centralause of the increased pain sensitivity of PD patients due to theopaminergic deficit has been demonstrated. Evidence for this has
ncluded increased incidence of non-dystonic or musculoskeletalain and also the increased pain relief patient’s felt subsequent toevodopa therapy and the increased pain threshold seen during theN period [17].
While trials are underway for controlling pain with rTMSclinicaltrials.gov no.: NCT01275573), oxycodone/naloxone (clin-caltrials.gov no.: NCT01439100) and botulinum toxin for dystoniaclinicaltrials.gov no.: NCT00909883) an answer to the broaderuestion of developing a management algorithm for the overallpproach to addressing pain in PD patients remains elusive [26].
he articles reviewed here reported mean dosage and duration ofevodopa usage. The effect of dose and duration variation on painymptoms in particular have not been conclusively addressed in theiterature and therefore the creation of an evidence based approach
eurosurgery 115 (2013) 2313– 2317
to the formation of a treatment algorithm will require addition datawith randomized controlled trials (RCT) including both Levodopaitself (both regular as well as controlled release versions) as well asdopamine agonists and muscle relaxants. The role of incorporatingduloxetine like drugs to modulate non-dopaminergic pain path-ways into this algorithm as adjunctive treatment also needs to bestudied further as drugs like this may in addition address the oftencomorbid depression and improve overall health related quality oflife. Finally, specific indications for the use of NSAIDs and opiatesin PD patients need to be developed.
With the advent of the recognition of non-motor symptoms assignificant components of the presentation of PD and clinical trialslooking at specifically addressing PD pain (especially dystonic painusing subthalamic nucleus DBS vs. rTMS and central pain using l-Dopa and dopamine agonist therapy optimizaiton), the role of thesetherapies needs to also be incorporated into the algorithm definingthe approach to PD pain. Sophie and Ford’s [27] recent work is oneof the first papers to propose approaches to addressing the variousforms of pain in PD separately based on which of the four typesof PD pain the patient complains of. The results of ongoing andfuture randomized clinical trials as outlined above will help supportsuch approaches and lead to the creation of clear guidelines andthe possible incorporation of alternative treatment strategies anddosage regimens into these treatment algorithms.
The literature indicates a relationship in PD patients betweenpain and depression symptoms [2,7,11,15]. PD patients with painhad more severe depressive symptoms, indicated by higher meanscores on tests such as the Montgomery-Asberg Depression RatingScale [11], the Zung depression inventory [23], Hospital anxiety anddepression scale – D [12] and most commonly the Beck DepressionInventory [8,9,11,12,14,22,23]. Patients with pain also had moresevere motor symptoms, longer disease duration, and lower mini-mental status exam scores than those without pain [1,11,12,23].However, whether the severity of PD correlates with the severityof depression or, conversely, whether treating PD helps alleviatedepression is more controversial. Some of the articles we reviewedscreened the patients for depression but only corrected for depres-sion while quantifying pain [9]. However, a definitive correlationwas found by Ehrt et al. [11] and others. Authors did find, howeverthat even if PD severity and depression were not correlated, thequality of life was heavily influenced by depression and pain in PDpatients [23].
Health related quality of life (HRQoL) has become an importantissue in medical care and treatment. HRQoL takes into consider-ation the patient’s subjective experience of physical and mentalhealth, functions of daily living, participation in social networks.Pain was the leading factor influencing the physical HRQoL ofpatients with early stage PD followed by the Hoehn and Yahr stage[23]. Accordingly, the measures of mental health, pain levels and PDstage as detailed above were the major determinants of HRQoL andaddressing non-motor symptoms and developing evidence basedmanagement algorithms in these patients becomes a high priority.
A 2002 Global Parkinson’s disease survey showed that patients’disease severity accounted for only 17.3% of their stated qual-ity of life while psychosocial factors accounted for approximately60% [24]. Though PD patients did not expect a complete recoveryof functioning following treatment, patients reported, on averageacross all domains tested, a 50.32% reduction in their symptomsfrom their current state of disability, ranging from 40.63% (pain) to58.23% (walking difficulties) Since these are values well beyond the20–30% reduction in motor symptoms deemed clinically meaning-ful [24] the argument for early intervention in the management of
PD pain becomes very strong. In other words, non-motor symp-toms, especially pain, is seen by PD patients as a significantdetriment with respect to their disease and addressing this can altertheir perception of prognosis and disease severity.
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A.Q. Rana et al. / Clinical Neurology
When PD patients present with non-motor symptoms, diagnosiss typically delayed by a median interval of 1.6 years compared to
year when the presenting symptom is a motor one [1]. Therefore,isease features such as pain can be especially important prognosticnd diagnostic symptoms that need to be considered in the pro-ess of therapy initiation. Acutely treating pain symptoms withoutroper evaluation can result in painful, dangerous and unnecessar-
ly invasive pain management procedures [16]. On the other hand,arly, effective diagnosis of PD and its associated non motor symp-oms, especially pain can significantly lessen the disease burden ofarkinson’s disease and improve patient quality of life.
. Conclusions
Detection of non-motor symptoms in PD can be difficult, how-ver early diagnosis of these symptoms is crucial as this canave a substantial impact on the health-related quality of lifef PD patients, often more so than motor symptoms. Guidelinesroviding screening and management recommendations for painymptoms in PD patients would help address this issue our workas attempted to crystallize. Our recommendation then is that wehould routinely screen PD patients for the presence of non-motorymptoms, especially pain. Symptomatic and effective chronicanagement of pain should be initiated as early and as precisely as
ossible. In the PD patient population, many authors have pointedut that a study that excludes patients with other comorbiditiesay incorrectly imply a decreased prevalence of pain due to PD
4,12,17]. The goal then must be to separate PD pain from non PDain, and different types of PD pain from each other, especially inatients that may present with multiple types so as to ensure thathe whole patient is managed appropriately. Further research onon-motor symptoms will allow the formalizing of diagnostic andherapeutic recommendations associated with pain in PD patients.
eferences
[1] O’Sullivan SS, Williams DR, Gallagher DA, Massey LA, Silveira-Moriyama L, LeesAJ. Nonmotor symptoms as presenting complaints in Parkinson’s disease: aclinicopathological study. Mov Disord 2008;23:101–6.
[2] Ford B. Pain in Parkinson’s disease. Mov Disord 2010;25:S98–103.
Pain sensitivity and clinical progression in Parkinson’s disease. Mov Disord2011;26:2220–5.
[4] Beiske AG, Loge JH, Ronningen A, Svensson E. Pain in Parkinson’s disease: preva-lence and characteristics. Pain 2009;141:173–7.
[
[
eurosurgery 115 (2013) 2313– 2317 2317
[5] Toda K, Harada T. Prevalence, classification, and etiology of pain in Parkinson’sdisease: association between Parkinson’s disease and fibromyalgia or chronicwidespread pain. Tohoku J Exp Med 2010;222:1–5.
[6] Ha AD, Jankovic J. Pain in Parkinson’s disease. Mov Disord 2012;27(4):485–91.[7] Bonnet AM, Jutras MF, Czernecki V, Corvol JC, Vidailhet M. Nonmotor symp-
toms in Parkinson’s disease in 2012: relevant clinical aspects. Parkinsons Dis2012:198316. Pubmed id: 22888466.
[8] Tinazzi M, Del Vesco C, Fincati E, Ottaviani S, Smania N, Moretto G, et al. Painand motor complications in Parkinson’s disease. J Neurol Neurosurg Psychiatry2006;77:822–5.
[9] Defazio G, Berardelli A, Fabbrini G, Martino D, Fincati E, Fiaschi A, et al. Pain as anonmotor symptom of Parkinson disease: evidence from a case–control study.Arch Neurol 2008;65:1191–4.
10] Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello T, et al.The priamo study: a multicenter assessment of nonmotor symptoms and theirimpact on quality of life in Parkinson’s disease. Mov Disorders 2009;24:1641–9.
11] Ehrt U, Larsen JP, Aarsland D. Pain and its relationship to depression in Parkin-son’s disease. Am J Ger Psych 2009;17:269–75.
12] Negre-Pages L, Regragui W, Bouhassira D, Grandjean H, Rascol O. Chronic painin Parkinson’s disease: the cross-sectional French DoPaMiP survey. Mov Disord2008;23:1361–9.
13] Brefel-Courbon C, Grolleau S, Thalamas C, Bourrel R, Allaria-Lapierre V, Loι R,et al. Comparison of chronic analgesic drugs prevalence in Parkinson’s disease,other chronic diseases and the general population. Pain 2009;141:14–8.
15] Silva EGD, Viana MA, Quagliato EMAB. Pain in Parkinson’s disease: analysis of 50cases in a clinic of movement disorders. Arq Neuropsiquiatr 2008;66(1):26–9.
16] Broetz D, Eichner M, Gasser T, Weller M, Steinbach JP. Radicular and non-radicular back pain in Parkinson’s disease: a controlled study. Mov Disord2007;22:853–6.
17] Nebe A, Ebersbach G. Pain intensity on and off levodopa in patients with Parkin-son’s disease. Mov Disord 2009;24:1233–7.
18] Lee MA, Walker RW, Hildreth TJ, Prentice WM. A survey of pain in idiopathicParkinson’s disease. J Pain Symptom Manage 2006;32(5):462–9.
19] Madden MB, Hall DA. Shoulder pain in Parkinson’s disease: a case–controlstudy. Mov Disord 2010;25:1105–6.
20] Stamey W, Davidson A, Jankovic J. Shoulder pain: a presenting symptom ofParkinson’s disease. J Clin Rheum 2008;14:253–4.
21] Mott S, Kenrick M, Dixon M, Bird G. Living with Parkinson’s disease – the carer’sperspective. Int J Therapy Rehab 2005;12(4):159–64.
22] Hanagasi HA, Akat S, Gurvit H, Yazici J, Emre M. Pain is common in Parkinson’sdisease. Clin Neuro Neurosurg 2011;113:11–3.
23] Roh JH, Kim BJ, Jang JH, Seo W-K, Lee S-H, Kim JH, et al. The relationship of painand health-related quality of life in Korean patients with Parkinson’s disease.Acta Neurol Scand 2009;119:397–403.
24] Nisenzon AA, Robinson ME, Bowers D, Banou E, Malaty I, Okun MS. Measure-ment of patient-centered outcomes in Parkinson’s disease: what do patientsreally want from their treatment? Parkinsonism Relat Disord 2011;17:89–94.
25] Perez-Lloret S, Rey MV, Dellapina E, Pellaprat J, Brefel-Courbon C, Rascol O.Emerging analgesic drugs for Parkinson’s disease. Expert Opin Emerg Drugs
2012;17(2):157–71.
26] Truini A, Frontoni M, Cruccu G. Parkinson’s disease related pain: a review ofrecent findings. J Neurol 2013;260:330–4.
27] Sophie M, Ford B. Management of pain in Parkinson’s disease. CNS Drugs2012;26:937–48.
