Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease

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OBJECTIVE

Chronic pain is a major distressing symptom of Parkinson's disease (PD) that is often undertreated. Subthalamic nucleus (STN) deep brain stimulation (DBS) delivers high-frequency stimulation (HFS) to patients with PD and has been effective in pain relief in a subset of these patients. However, up to 74% of patients develop new pain concerns while receiving STN DBS. Here the authors explore whether altering the frequency of STN DBS changes pain perception as measured through quantitative sensory testing (QST).

METHODS

Using QST, the authors measured thermal and mechanical detection and pain thresholds in 19 patients undergoing DBS via HFS, low-frequency stimulation (LFS), and off conditions in a randomized order. Testing was performed in the region of the body with the most pain and in the lower back in patients without chronic pain.

RESULTS

In the patients with chronic pain, LFS significantly reduced heat detection thresholds as compared with thresholds following HFS (p = 0.029) and in the off state (p = 0.010). Moreover, LFS resulted in increased detection thresholds for mechanical pressure (p = 0.020) and vibration (p = 0.040) compared with these thresholds following HFS. Neither LFS nor HFS led to changes in other mechanical thresholds. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick compared with thresholds following HFS (p = 0.032).

CONCLUSIONS

Recent literature has suggested that STN LFS can be useful in treating nonmotor symptoms of PD. Here the authors demonstrated that LFS modulates thermal and mechanical detection to a greater extent than HFS. Low-frequency stimulation is an innovative means of modulating chronic pain in PD patients receiving STN DBS. The authors suggest that STN LFS may be a future option to consider when treating Parkinson's patients in whom pain remains the predominant complaint.

ABBREVIATIONSDBS = deep brain stimulation; HFS = high-frequency stimulation; LFS = low-frequency stimulation; PD = Parkinson disease; QST = quantitative sensory testing; STN = subthalamic nucleus.

OBJECTIVE

Chronic pain is a major distressing symptom of Parkinson's disease (PD) that is often undertreated. Subthalamic nucleus (STN) deep brain stimulation (DBS) delivers high-frequency stimulation (HFS) to patients with PD and has been effective in pain relief in a subset of these patients. However, up to 74% of patients develop new pain concerns while receiving STN DBS. Here the authors explore whether altering the frequency of STN DBS changes pain perception as measured through quantitative sensory testing (QST).

METHODS

Using QST, the authors measured thermal and mechanical detection and pain thresholds in 19 patients undergoing DBS via HFS, low-frequency stimulation (LFS), and off conditions in a randomized order. Testing was performed in the region of the body with the most pain and in the lower back in patients without chronic pain.

RESULTS

In the patients with chronic pain, LFS significantly reduced heat detection thresholds as compared with thresholds following HFS (p = 0.029) and in the off state (p = 0.010). Moreover, LFS resulted in increased detection thresholds for mechanical pressure (p = 0.020) and vibration (p = 0.040) compared with these thresholds following HFS. Neither LFS nor HFS led to changes in other mechanical thresholds. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick compared with thresholds following HFS (p = 0.032).

CONCLUSIONS

Recent literature has suggested that STN LFS can be useful in treating nonmotor symptoms of PD. Here the authors demonstrated that LFS modulates thermal and mechanical detection to a greater extent than HFS. Low-frequency stimulation is an innovative means of modulating chronic pain in PD patients receiving STN DBS. The authors suggest that STN LFS may be a future option to consider when treating Parkinson's patients in whom pain remains the predominant complaint.

Chronic pain is a major nonmotor symptom of Parkinson's disease (PD). Approximately 40%–85% of patients with PD experience pain,3,14,33,41,55 and in some patients the pain can overshadow the motor symptoms of the disease.44,57 Early after a PD diagnosis, dopaminergic medications may provide some analgesic efficacy;21 however, up to 49% of patients believe their medications do not reduce the severity of their pain.46 In patients with more advanced disease, subthalamic nucleus (STN) deep brain stimulation (DBS), commonly used to treat the motor symptoms of PD, is gaining attention as an effective therapy for PD-related pain. Several studies have shown significant improvements in global pain scores 6 months to 1 year following DBS surgery,12,19,42,43,52 and a recent 8-year follow-up study suggests that preoperative pain can be well managed over time.29 Although STN DBS has been shown to be superior to high-dose levodopa treatment in controlling chronic pain,54 the mechanism by which STN DBS improves pain remains unclear. Further, 74% of patients develop new-onset pain after STN DBS.8

Quantitative sensory testing (QST) provides an objective measure of pain perception through mechanical and thermal threshold assessment, which is used to clinically assess pain sensitivity and/or sensory dysfunction.1 The effects of STN DBS on sensory thresholds are varied;12,26,46,52 however, a study of 25 PD patients has suggested that high-frequency stimulation (HFS) increases mechanical and thermal pain thresholds.26,37,53 Moreover, a recent study in 6OHDA (6-hydroxydopamine)–lesioned rats has suggested that both HFS and low-frequency stimulation (LFS) of the STN increase mechanical and thermal thresholds.24 Thus, this work implies that pain may be modulated with LFS of the STN. Additionally, STN LFS has been shown to improve motor function in PD patients.30,38 We believe that LFS also provides an optional therapeutic strategy for alleviating pain in patients undergoing DBS. Here, we evaluate LFS delivered at 60 Hz and its effects on mechanical and thermal sensory and pain thresholds in PD patients with and without chronic pain.

Methods

Participants

Institutional review board approval was granted by Albany Medical College to conduct this study. All enrolled subjects had undergone STN implantation of a DBS device for the treatment of refractory motor fluctuations in PD. Those who qualified for surgical treatment had completed the Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological testing as part of the routine preoperative workup. Patients who did not improve more than 30% on the Core Assessment Program for Surgical Interventional Therapies (CAPSIT) on/off medication testing were not considered acceptable surgical candidates and neither were those who demonstrated dementia, significant cognitive impairment, or unstable psychiatric disease at baseline testing. From a database of patients who had undergone STN DBS, patients were selected for study participation regardless of their pain status. Chronic pain, defined as 8 weeks of pain despite treatment, was self-reported by the patient at the time of testing. Subjects who could not complete testing because of language barriers and/or dementia were excluded from the study. Informed consent was obtained from all study participants prior to testing.

Outcome Measures

All patients completed the visual analog scale, McGill Pain Questionnaire, Oswestry Disability Index, and Pain Catastrophizing Scale and provided their pain medication usage. Quantitative sensory testing was performed to assess detection and pain thresholds for mechanical and sensory stimuli. Testing was conducted at 3 stimulation settings: 1) the patient's optimized HFS settings for the treatment of motor symptoms, 2) LFS at 60 Hz with the same pulse width and voltage, and 3) off stimulation, with the order of testing randomized. Both patient and examiner were aware of the patient's stimulation setting during testing. A minimum of 10 minutes at the new setting was allotted in between each QST session. Testing was performed on the side of the body receiving therapeutic neuromodulation and at the site where the most pain was reported. If the patient did not report pain, QST was performed on the lower back given the high incidence of low-back pain in this population.8 Once an optimal spot for testing was determined, an “x” was drawn to ensure that all testing was performed on the same area.

Thresholds for mechanical sensation were detected using von Frey filaments, which allow forces between 0.25 and 512 mN to be applied to the skin with a consistent and uniform contact surface area and shape. Mechanical pain was detected using standardized 10- and 40-g weighted pinprick stimulators. Patients were asked to rate the pain felt after each 10- and 40-g pinprick on a scale of 0–10, with 10 being the highest level of pain. Pressure pain was detected through a standard pressure gauge device allowing 1–10 kg of pressure to be applied. Patients were asked to notify the researcher when the pressure became uncomfortable. Vibration detection was assessed using a Rydel-Seiffer tuning fork. Using the Medoc Pathway thermode (device range 0°C–50°C), we assessed cool and warm thermal detection and determined when the temperature became painful.

Data Analysis

For the demographic and medical information collected, statistical analysis was performed in SPSS (IBM SPSS Statistics for Windows, version 22.0, IBM Corp.) using paired t-tests and regression analysis to assess differences, in which p < 0.05 was considered significant.

Results

Demographics

Nineteen PD patients who had undergone surgery for STN DBS were included in this study. Thirteen patients had unilateral STN DBS surgery and 6 had bilateral surgery. Eleven patients reported chronic pain. Additional demographic information as well as the QST testing sites is listed in Table 1.

TABLE 1.

Demographic distribution of PD patients with and without chronic pain

Patient No.Age (yrs), SexYrs Since DiagnosisChronic PainQST Testing Location
168, F15YesLt dorsal medial hand
263, F7YesLt low back
370, F20YesLt low back
466, M7YesLt posterior shoulder
555, M20YesLt low back
671, F17YesLt lat ankle
766, M6YesRt posterior shoulder
858, M5YesRt hip
961, M11YesRt dorsal thumb
1050, M10YesBilat epigastric region
1143, F23YesLt anterior chest
1271, F71NoLt low back
1375, F75NoLt low back
1436, M36NoBilat low back
1572, M72NoBilat low back
1667, F67NoBilat low back
1757, M57NoBilat low back
1879, M79NoLt low back
1968, M68NoBilat low back

Results of Sensory Threshold Testing

Patients with chronic pain who received STN LFS had significantly reduced heat detection thresholds, compared with thresholds following HFS (p = 0.029) or in the off state (p = 0.010; Fig. 1A). In addition, LFS significantly increased mechanical detection thresholds (p = 0.020; Fig. 1B) and vibration detection (p = 0.040; Fig. 1C) compared with thresholds following HFS. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick as compared with HFS (p = 0.032; Fig. 1D). Combining all patients regardless of pain status, we found that LFS significantly reduced heat detection thresholds compared with HFS (p = 0.044). The mean mechanical and thermal detection values and p values are listed in Table 2.

FIG. 1.
FIG. 1.

In PD patients with chronic pain, LFS significantly reduced heat detection thresholds (A) compared with HFS (p = 0.029) or no stimulation (p = 0.010), LFS increased mechanical detection thresholds (B) compared with HFS (p = 0.020), and LFS increased vibration detection (C) compared with HFS (p = 0.040). In PD patients without chronic pain, LFS significantly increased mechanical pain thresholds (D) compared with HFS (p = 0.032).

TABLE 2.

Thermal and mechanical thresholds in patients receiving STN DBS*

ThresholdPatients w/Chronic Pain (11 patients)Patients w/o Chronic Pain (8 patients)
HFSLFSOffp Value, HFS vs LFSHFSLFSOffp Value, HFS vs LFS
Cold detection27.36364 ± 0.72473128.66182 ± 0.47969825.78455 ± 2.3007760.11928.03 ± 0.60053827.98769 ± 0.63714628.39231 ± 0.3698840.916
Heat detection37.65364 ± 1.24651836.33 ± 0.89009537.80273 ± 1.0287680.02935.83538 ± 0.59126735.22385 ± 0.37796135.06462 ± 0.2756730.365
Cold pain18.91182 ± 3.12476322.14364 ± 2.99784718.69364 ± 2.738340.14320.07423 ± 2.69202417.16077 ± 3.24268715.24385 ± 3.2770040.133
Heat pain42.33091 ± 1.82013641.83 ± 1.53588143.07818 ± 1.5082930.40039.85308 ± 1.13151640.82923 ± 1.31122241.64231 ± 1.5152660.382
Mechanical detection3.431818 ± 0.346893.990909 ± 0.2016143.816364 ± 0.2500770.0204.044615 ± 0.2502733.791538 ± 0.2864993.528462 ± 0.2789560.333
Pressure pain2.472727 ± 0.3242032.581818 ± 0.5016012.236364 ± 0.3292620.5593.527273 ± 0.7878743.290909 ± 0.7272133.581818 ± 0.868050.328
Mechanical pain, 10 g0.2 ± 0.046710.2 ± 0.042640.209091 ± 0.0314920.4260.115385 ± 0.037290.130769 ± 0.0429440.153846 ± 0.038590.721
Mechanical pain, 40 g0.427273 ± 0.0775660.409091 ± 0.0530090.409091 ± 0.0624570.8040.215385 ± 0.0478330.338462 ± 0.0729760.215385 ± 0.0516970.032
Vibration detection0.636364 ± 0.152120.909091 ± 0.0909090.727273 ± 0.1408360.0400.846154 ± 0.1041540.846154 ± 0.1041541 ± 01.000

Values expressed as the means ± standard error of the mean.

Using ordinary least-squares regression analysis, we evaluated each QST test on the 3 categorical factors (patient sex, pain status, and testing site) for significance. At the 5% level of significance, there was a statistically significant difference between male and female patients receiving HFS or LFS for both the pressure pain and 40-g pinprick tests. Specifically, women were more sensitive to pressure pain and less sensitive to mechanical pain. We also found a significant difference between testing the lower back and other sites for patients receiving HFS or LFS for the 10-g Neuropen test and for patients receiving HFS for the 40-g Neuropen test. The lower back was less sensitive. Results are summarized in Table 3.

TABLE 3.

Regression analyses p values for each QST test on patient sex, pain status, and testing site

TestFrequencyPatient SexPain StatusTesting Site
Cold detectionHFS0.2650.6840.726
LFS0.7420.1480.293
Heat detectionHFS0.2670.9640.152
LFS0.2080.6900.071
Cold painHFS0.0800.4410.142
LFS0.1680.0700.160
Heat painHFS0.3720.8500.103
LFS0.4050.5020.128
Mechanical detectionHFS0.2450.9560.118
LFS0.8500.3910.569
Pressure painHFS0.0240.6660.069
LFS0.0110.4560.064
Mechanical pain, 10 gHFS0.4330.4640.031
LFS0.4020.3950.0392
Mechanical pain, 40 gHFS0.0020.0880.000
LFS0.0300.3320.101
Vibration detectionHFS0.6920.9070.314
LFS0.6520.5500.956

Discussion

In this study, we demonstrated that LFS, as compared with traditional HFS, can differentially alter sensory thresholds for specific sensory modalities. Low-frequency stimulation significantly reduced heat detection thresholds, regardless of patient pain status. However, when patients were analyzed by pain status, LFS had different effects, suggesting that pain status may play an important role in the mechanism underlying low-frequency DBS symptom relief. Although chronic pain patients receiving LFS were less sensitive to mechanical and vibrational stimuli, they were more sensitive to heat. In contrast, patients without chronic pain who received LFS showed increased tolerance for mechanical pain, allowing this subset of patients to potentially exhibit greater pain relief than without the stimulator.

Mechanical and thermal detection thresholds were generally independent of patient sex; however, a stark difference between men and women appeared to persist across stimulation settings for both pressure pain and mechanical pain with the 40-g pinprick. According to our results, men appeared to have a higher threshold for pressure pain than women for both HFS and LFS. On the other hand, women had a higher threshold for mechanical pain with the 40-g pinprick. Current literature has mixed results regarding sex differences in pain sensitivity. Some studies suggest that women have a less efficient pain inhibition capacity than men,23,27,28 while other studies report no change.2,22,35 One study suggests that behavioral and psychological factors may influence the perception of pain differently among men and women.10

Quantitative sensory testing location only had an influence on the 10-g and 40-g mechanical pain pinprick tests. According to our results, the lower back is less sensitive to mechanical pain. However, the correlation (r) between the patient's report of chronic pain and using the lower back as a testing site was −0.678, which indicates a strong relationship between patients without pain and less sensitivity in the lower back. This finding indicated that the lower-back test site may have influenced the results of these tests.

Little evidence exists for the efficacy of other common chronic pain treatments such as antiepileptics (for example, gabapentin, pregabalin), antispasmodics (for example, baclofen), antidepressants, or opioids for the treatment of PD-related chronic pain. However, in 2007, Djaldetti et al. did provide some evidence of pain relief after 6 weeks of duloxetine (serotonin-norepinephrine reuptake inhibitor) treatment in PD patients.18 Interestingly, the efficacy of STN DBS for the treatment of different types of pain is still debated. For example, in a cohort of 41 patients, significant improvements in dystonic and musculoskeletal pain occurred at 1 year, while neuropathic and central pain remained unchanged.13 In another study, dystonic and central pain were relieved, while musculoskeletal and radicular pain were not.32

Extensive evidence suggests that a variety of sensory functions are altered in PD, and recent studies have shown that patients and animal models exhibit lower mechanical42,46,48,60 and thermal21,42,46,48 thresholds than those in healthy controls. Unfortunately, treatment for PD-related pain is particularly difficult as it can manifest in a variety of ways (musculoskeletal, dystonic, radiculoneuritic, or central) and patients can suffer from pain from different origins at the same time.20 Given that pain in PD is under-recognized, undertreated, and understudied, there is a critical need to develop new therapies in patients whose pain is refractory to dopaminergic medications or traditional STN HFS. Traditional STN DBS is delivered at a high frequency typically ranging from 130 to 185 Hz.51 However, recent literature has demonstrated the efficacy of STN LFS in improving motor function in PD patients.9,30,38,39,45,47,58

Our data are novel in showing that LFS can be used as an optional therapeutic strategy for pain relief in PD patients undergoing DBS. In addition, given our results, there could be a relationship between chronic pain in DBS and specific sensory threshold modalities. Among patients receiving STN DBS, mechanical pain changes were evident in those without pain, whereas thermal and mechanical changes were evident in those with pain. It is uncertain whether LFS is more sensitive to specific sensory modalities depending on whether or not there is chronic pain. However, our analysis suggests there may be some connection.

We acknowledge that QST has limitations. Its results may be subject to patient behavior, including boredom, distraction, or mental fatigue.50 Although QST results have been shown to be reproducible over a period of weeks for healthy subjects,50 we performed testing at a single visit. Moreover, we performed mechanical testing only once but thermal testing twice to minimize patient confusion when conducting these tests. In addition, the participants' self-assessments on their areas of chronic pain are subjective since their levels of current pain often change from day to day. This could cause a bias on their level of response to QST and stimulation setting changes. Moreover, neither patients nor examiners were blinded to the stimulation settings during testing. Changing the stimulation settings can have a profound effect on patient motor symptoms, and patients often felt when their stimulator settings were adjusted. We acknowledge this as a potential limitation of the study.

We examined alterations in sensory thresholds following acute LFS in PD patients with and without complaints of chronic pain. We did not address whether these patients would report changes in chronic pain since they were only stimulated with LFS for 15 minutes. However, sensory thresholds have been used as quantitative measures of changes in sensory processing in other studies and suggest changes in pain states.5–7,16,17,25,34,40,49,59 Although the analgesic effects of STN DBS in PD are not well understood, the current literature suggests that STN DBS alters sensory processing in the central nervous system, including the basal ganglia,11,31,49 through increased pain thresholds.12,15,36 Since dopamine can also modify pain perception through increased pain thresholds in PD6,25,36 and levodopa dosing is typically reduced following STN DBS, it is conceivable that STN DBS modulates neurotransmission in midbrain circuits that are altered in PD.

Conclusions

In summary, although traditional STN HFS has proven efficacy in treating the motor symptoms of PD,4 patients can develop new pain symptoms or continue to have chronic pain.56 Given the changes in sensory detection and pain thresholds in our patient cohort, we suggest that STN LFS may be a future option to consider in the treatment of PD-related pain refractory to other therapies. Further studies should address whether long-term STN LFS improves chronic pain status in these patients. In addition, patients receiving STN DBS who have a history of chronic pain may respond differently to specific mechanical and thermal stimuli compared with those who do not have chronic pain. Tailoring stimulation parameters to address specific symptoms of PD is critical for the optimization of DBS therapy.

Acknowledgments

The Phyllis E. Dake Endowed Chair in Movement Disorders (J.G.P. and A.R.Z.) supported this study. We thank our colleague, Damian Shin, PhD, for providing his insight and expertise to greatly improve the quality of this paper.

References

  • 1

    Arendt-Nielsen LYarnitsky D: Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. J Pain 10:5565722009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Baad-Hansen LPoulsen HFJensen HMSvensson P: Lack of sex differences in modulation of experimental intraoral pain by diffuse noxious inhibitory controls (DNIC). Pain 116:3593652005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Beiske AGLoge JHRønningen ASvensson E: Pain in Parkinson's disease: prevalence and characteristics. Pain 141:1731772009

  • 4

    Benabid ALChabardes SMitrofanis JPollak P: Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease. Lancet Neurol 8:67812009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Bouhassira DAttal NAlchaar HBoureau FBrochet BBruxelle J: Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114:29362005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Brefel-Courbon COry-Magne FThalamas CPayoux PRascol O: Nociceptive brain activation in patients with neuropathic pain related to Parkinson's disease. Parkinsonism Relat Disord 19:5485522013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Brefel-Courbon CPayoux PThalamas COry FQuelven IChollet F: Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study. Mov Disord 20:155715632005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Broetz DEichner MGasser TWeller MSteinbach JP: Radicular and nonradicular back pain in Parkinson's disease: a controlled study. Mov Disord 22:8538562007

  • 9

    Brozova HBarnaure IAlterman RLTagliati M: STN-DBS frequency effects on freezing of gait in advanced Parkinson disease. Neurology 72:7707712009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Bulls HWFreeman ELAnderson AJRobbins MTNess TJGoodin BR: Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition. J Pain Res 8:3113202015

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Chudler EHDong WK: The role of the basal ganglia in nociception and pain. Pain 60:3381995

  • 12

    Ciampi de Andrade DLefaucheur JPGalhardoni RFerreira KSBrandão Paiva ARBor-Seng-Shu E: Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease. Pain 153:110711132012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Cury RGGalhardoni RFonoff ETDos Santos Ghilardi MGFonoff FArnaut D: Effects of deep brain stimulation on pain and other nonmotor symptoms in Parkinson disease. Neurology 83:140314092014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Defazio GBerardelli AFabbrini GMartino DFincati EFiaschi A: Pain as a nonmotor symptom of Parkinson disease: evidence from a case-control study. Arch Neurol 65:119111942008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Dellapina EOry-Magne FRegragui WThalamas CLazorthes YRascol O: Effect of subthalamic deep brain stimulation on pain in Parkinson's disease. Pain 153:226722732012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Derbyshire SWJones AKCreed FStarz TMeltzer CCTownsend DW: Cerebral responses to noxious thermal stimulation in chronic low back pain patients and normal controls. Neuroimage 16:1581682002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Djaldetti RShifrin ARogowski ZSprecher EMelamed EYarnitsky D: Quantitative measurement of pain sensation in patients with Parkinson disease. Neurology 62:217121752004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Djaldetti RYust-Katz SKolianov VMelamed EDabby R: The effect of duloxetine on primary pain symptoms in Parkinson disease. Clin Neuropharmacol 30:2012052007

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Drake DFHarkins SQutubuddin A: Pain in Parkinson's disease: pathology to treatment, medication to deep brain stimulation. NeuroRehabilitation 20:3353412005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Fil ACano-de-la-Cuerda RMuñoz-Hellín EVela LRamiro-González MFernández-de-Las-Peñas C: Pain in Parkinson disease: a review of the literature. Parkinsonism Relat Disord 19:2852942013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Ford B: Pain in Parkinson's disease. Mov Disord 25:Suppl 1S98S1032010

  • 22

    France CRSuchowiecki S: A comparison of diffuse noxious inhibitory controls in men and women. Pain 81:77841999

  • 23

    Ge HYMadeleine PArendt-Nielsen L: Sex differences in temporal characteristics of descending inhibitory control: an evaluation using repeated bilateral experimental induction of muscle pain. Pain 110:72782004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Gee LEChen NRamirez-Zamora AShin DSPilitsis JG: The effects of subthalamic deep brain stimulation on mechanical and thermal thresholds in 6OHDA-lesioned rats. Eur J Neurosci 42:206120692015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Gerdelat-Mas ASimonetta-Moreau MThalamas COry-Magne FSlaoui TRascol O: Levodopa raises objective pain threshold in Parkinson's disease: a RIII reflex study. J Neurol Neurosurg Psychiatry 78:114011422007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Gierthmühlen JArning PBinder AHerzog JDeuschl GWasner G: Influence of deep brain stimulation and levodopa on sensory signs in Parkinson's disease. Mov Disord 25:119512022010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Goodin BRMcGuire LAllshouse MStapleton LHaythornthwaite JABurns N: Associations between catastrophizing and endogenous pain-inhibitory processes: sex differences. J Pain 10:1801902009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Granot MWeissman-Fogel ICrispel YPud DGranovsky YSprecher E: Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: do conditioning stimulus painfulness, gender and personality variables matter?. Pain 136:1421492008

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Jung YJKim HJJeon BSPark HLee WWPaek SH: An 8-year follow-up on the effect of subthalamic nucleus deep brain stimulation on pain in Parkinson disease. JAMA Neurol 72:5045102015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Khoo HMKishima HHosomi KMaruo TTani NOshino S: Low-frequency subthalamic nucleus stimulation in Parkinson's disease: a randomized clinical trial. Mov Disord 29:2702742014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Kim HJJeon BSPaek SH: Effect of deep brain stimulation on pain in Parkinson disease. J Neurol Sci 310:2512552011

  • 32

    Kim HJPaek SHKim JYLee JYLim YHKim MR: Chronic subthalamic deep brain stimulation improves pain in Parkinson disease. J Neurol 255:188918942008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Lee MAWalker RWHildreth TJPrentice WM: A survey of pain in idiopathic Parkinson's disease. J Pain Symptom Manage 32:4624692006

  • 34

    Lim SYFarrell MJGibson SJHelme RDLang AEEvans AH: Do dyskinesia and pain share common pathophysiological mechanisms in Parkinson's disease?. Mov Disord 23:168916952008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Locke DGibson WMoss PMunyard KMamotte CWright A: Analysis of meaningful conditioned pain modulation effect in a pain-free adult population. J Pain 15:119011982014

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Marques AChassin OMorand DPereira BDebilly BDerost P: Central pain modulation after subthalamic nucleus stimulation: A crossover randomized trial. Neurology 81:6336402013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Maruo TSaitoh YHosomi KKishima HShimokawa THirata M: Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease. Pain 152:8608652011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Moreau CDefebvre LDestée ABleuse SClement FBlatt JL: STN-DBS frequency effects on freezing of gait in advanced Parkinson disease. Neurology 71:80842008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Moreau CPennel-Ployart OPinto SPlachez AAnnic AViallet F: Modulation of dysarthropneumophonia by low-frequency STN DBS in advanced Parkinson's disease. Mov Disord 26:6596632011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Mylius VEngau ITeepker MStiasny-Kolster KSchepelmann KOertel WH: Pain sensitivity and descending inhibition of pain in Parkinson's disease. J Neurol Neurosurg Psychiatry 80:24282009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Nègre-Pagès LRegragui WBouhassira DGrandjean HRascol OGroup DS: Chronic pain in Parkinson's disease: the cross-sectional French DoPaMiP survey. Mov Disord 23:136113692008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Oshima HKatayama YMorishita TSumi KOtaka TKobayashi K: Subthalamic nucleus stimulation for attenuation of pain related to Parkinson disease. J Neurosurg 116:991062012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Pellaprat JOry-Magne FCanivet CSimonetta-Moreau MLotterie JARadji F: Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease. Parkinsonism Relat Disord 20:6626642014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Quittenbaum BHGrahn B: Quality of life and pain in Parkinson's disease: a controlled cross-sectional study. Parkinsonism Relat Disord 10:1291362004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Ramdhani RAPatel ASwope DKopell BH: Early use of 60 Hz frequency subthalamic stimulation in Parkinson's disease: a case series and review. Neuromodulation 18:6646692015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46

    Rana ASaeed UMasroor MSYousuf MSSiddiqui I: A cross-sectional study investigating clinical predictors and physical experiences of pain in Parkinson's disease. Funct Neurol 28:2973042013

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Ricchi VZibetti MAngrisano SMerola AArduino NArtusi CA: Transient effects of 80 Hz stimulation on gait in STN DBS treated PD patients: a 15 months follow-up study. Brain Stimulat 5:3883922012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48

    Saadé NEAtweh SFBahuth NBJabbur SJ: Augmentation of nociceptive reflexes and chronic deafferentation pain by chemical lesions of either dopaminergic terminals or midbrain dopaminergic neurons. Brain Res 751:1121997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49

    Schestatsky PKumru HValls-Solé JValldeoriola FMarti MJTolosa E: Neurophysiologic study of central pain in patients with Parkinson disease. Neurology 69:216221692007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50

    Siao PCros DP: Quantitative sensory testing. Phys Med Rehabil Clin N Am 14:2612862003

  • 51

    Sidiropoulos CWalsh RMeaney CPoon YYFallis MMoro E: Low-frequency subthalamic nucleus deep brain stimulation for axial symptoms in advanced Parkinson's disease. J Neurol 260:230623112013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52

    Smith HGee LKumar VRamirez-Zamora ADurphy JHanspal E: Deep brain stimulation significantly decreases disability from low back pain in patients with advanced Parkinson's disease. Stereotact Funct Neurosurg 93:2062112015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53

    Spielberger SWolf EKress MSeppi KPoewe W: The influence of deep brain stimulation on pain perception in Parkinson's disease. Mov Disord 26:136713692011

  • 54

    Sürücü OBaumann-Vogel HUhl MImbach LLBaumann CR: Subthalamic deep brain stimulation versus best medical therapy for L-dopa responsive pain in Parkinson's disease. Pain 154:147714792013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55

    Tinazzi MDel Vesco CFincati EOttaviani SSmania NMoretto G: Pain and motor complications in Parkinson's disease. J Neurol Neurosurg Psychiatry 77:8228252006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56

    Toda KHarada T: Prevalence, classification, and etiology of pain in Parkinson's disease: association between Parkinson's disease and fibromyalgia or chronic widespread pain. Tohoku J Exp Med 222:152010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57

    Uebelacker LAEpstein-Lubow GLewis TBroughton MKFriedman JH: A survey of Parkinson's disease patients: most bothersome symptoms and coping preferences. J Parkinsons Dis 4:7177232014

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58

    Xie TVigil JMacCracken EGasparaitis AYoung JKang W: Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD. Neurology 84:4154202015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59

    Zambito Marsala STinazzi MVitaliani RRecchia SFabris FMarchini C: Spontaneous pain, pain threshold, and pain tolerance in Parkinson's disease. J Neurol 258:6276332011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 60

    Zengin-Toktas YFerrier JDurif FLlorca PMAuthier N: Bilateral lesions of the nigrostriatal pathways are associated with chronic mechanical pain hypersensitivity in rats. Neurosci Res 76:2612642013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Disclosures

Dr. Pilitsis is a consultant for Medtronic, Boston Scientific, and St. Jude; receives grant support from Jazz, Medtronic, Boston Scientific, St. Jude, TEVA Pharmaceuticals, and the NIH (No. 1R01CA166379) for non–study-related clinical or research effort; and is a consultant for and has equity in Centauri. Dr. Ramirez-Zamora has received research grant support from Boston Scientific and Medtronic and honoraria from TEVA Pharmaceuticals.

Author Contributions

Conception and design: Pilitsis, Belasen. Acquisition of data: Pilitsis, Belasen, Yeung, Hanspal, Paiva, Durphy. Analysis and interpretation of data: Pilitsis, Belasen, Rizvi, Gee. Drafting the article: Pilitsis, Belasen, Rizvi, Gee, Yeung. Critically revising the article: Pilitsis, Belasen, Gee, Yeung, Ramirez-Zamora. Reviewed submitted version of manuscript: Pilitsis, Belasen, Rizvi, Gee, Prusik, Ramirez-Zamora, Hanspal, Paiva, Durphy, Argoff. Approved the final version of the manuscript on behalf of all authors: Pilitsis. Statistical analysis: Pilitsis, Belasen, Rizvi, Gee, Prusik. Administrative/technical/material support: Pilitsis, Gee, Prusik, Ramirez-Zamora, Hanspal, Paiva, Durphy, Argoff. Study supervision: Pilitsis, Prusik, Ramirez-Zamora.

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Article Information

INCLUDE WHEN CITING Published online April 22, 2016; DOI: 10.3171/2016.2.JNS152231.

Correspondence Julie G. Pilitsis, AMC Neurosurgery Group, 47 New Scotland Ave., MC 10, Physicians Pavilion, 1st Fl., Albany, NY 12208. email: jpilitsis@yahoo.com.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    In PD patients with chronic pain, LFS significantly reduced heat detection thresholds (A) compared with HFS (p = 0.029) or no stimulation (p = 0.010), LFS increased mechanical detection thresholds (B) compared with HFS (p = 0.020), and LFS increased vibration detection (C) compared with HFS (p = 0.040). In PD patients without chronic pain, LFS significantly increased mechanical pain thresholds (D) compared with HFS (p = 0.032).

References

  • 1

    Arendt-Nielsen LYarnitsky D: Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. J Pain 10:5565722009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Baad-Hansen LPoulsen HFJensen HMSvensson P: Lack of sex differences in modulation of experimental intraoral pain by diffuse noxious inhibitory controls (DNIC). Pain 116:3593652005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Beiske AGLoge JHRønningen ASvensson E: Pain in Parkinson's disease: prevalence and characteristics. Pain 141:1731772009

  • 4

    Benabid ALChabardes SMitrofanis JPollak P: Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease. Lancet Neurol 8:67812009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Bouhassira DAttal NAlchaar HBoureau FBrochet BBruxelle J: Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114:29362005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Brefel-Courbon COry-Magne FThalamas CPayoux PRascol O: Nociceptive brain activation in patients with neuropathic pain related to Parkinson's disease. Parkinsonism Relat Disord 19:5485522013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Brefel-Courbon CPayoux PThalamas COry FQuelven IChollet F: Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study. Mov Disord 20:155715632005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Broetz DEichner MGasser TWeller MSteinbach JP: Radicular and nonradicular back pain in Parkinson's disease: a controlled study. Mov Disord 22:8538562007

  • 9

    Brozova HBarnaure IAlterman RLTagliati M: STN-DBS frequency effects on freezing of gait in advanced Parkinson disease. Neurology 72:7707712009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Bulls HWFreeman ELAnderson AJRobbins MTNess TJGoodin BR: Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition. J Pain Res 8:3113202015

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Chudler EHDong WK: The role of the basal ganglia in nociception and pain. Pain 60:3381995

  • 12

    Ciampi de Andrade DLefaucheur JPGalhardoni RFerreira KSBrandão Paiva ARBor-Seng-Shu E: Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease. Pain 153:110711132012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Cury RGGalhardoni RFonoff ETDos Santos Ghilardi MGFonoff FArnaut D: Effects of deep brain stimulation on pain and other nonmotor symptoms in Parkinson disease. Neurology 83:140314092014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Defazio GBerardelli AFabbrini GMartino DFincati EFiaschi A: Pain as a nonmotor symptom of Parkinson disease: evidence from a case-control study. Arch Neurol 65:119111942008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Dellapina EOry-Magne FRegragui WThalamas CLazorthes YRascol O: Effect of subthalamic deep brain stimulation on pain in Parkinson's disease. Pain 153:226722732012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Derbyshire SWJones AKCreed FStarz TMeltzer CCTownsend DW: Cerebral responses to noxious thermal stimulation in chronic low back pain patients and normal controls. Neuroimage 16:1581682002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Djaldetti RShifrin ARogowski ZSprecher EMelamed EYarnitsky D: Quantitative measurement of pain sensation in patients with Parkinson disease. Neurology 62:217121752004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Djaldetti RYust-Katz SKolianov VMelamed EDabby R: The effect of duloxetine on primary pain symptoms in Parkinson disease. Clin Neuropharmacol 30:2012052007

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Drake DFHarkins SQutubuddin A: Pain in Parkinson's disease: pathology to treatment, medication to deep brain stimulation. NeuroRehabilitation 20:3353412005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Fil ACano-de-la-Cuerda RMuñoz-Hellín EVela LRamiro-González MFernández-de-Las-Peñas C: Pain in Parkinson disease: a review of the literature. Parkinsonism Relat Disord 19:2852942013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Ford B: Pain in Parkinson's disease. Mov Disord 25:Suppl 1S98S1032010

  • 22

    France CRSuchowiecki S: A comparison of diffuse noxious inhibitory controls in men and women. Pain 81:77841999

  • 23

    Ge HYMadeleine PArendt-Nielsen L: Sex differences in temporal characteristics of descending inhibitory control: an evaluation using repeated bilateral experimental induction of muscle pain. Pain 110:72782004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Gee LEChen NRamirez-Zamora AShin DSPilitsis JG: The effects of subthalamic deep brain stimulation on mechanical and thermal thresholds in 6OHDA-lesioned rats. Eur J Neurosci 42:206120692015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Gerdelat-Mas ASimonetta-Moreau MThalamas COry-Magne FSlaoui TRascol O: Levodopa raises objective pain threshold in Parkinson's disease: a RIII reflex study. J Neurol Neurosurg Psychiatry 78:114011422007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Gierthmühlen JArning PBinder AHerzog JDeuschl GWasner G: Influence of deep brain stimulation and levodopa on sensory signs in Parkinson's disease. Mov Disord 25:119512022010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Goodin BRMcGuire LAllshouse MStapleton LHaythornthwaite JABurns N: Associations between catastrophizing and endogenous pain-inhibitory processes: sex differences. J Pain 10:1801902009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Granot MWeissman-Fogel ICrispel YPud DGranovsky YSprecher E: Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: do conditioning stimulus painfulness, gender and personality variables matter?. Pain 136:1421492008

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Jung YJKim HJJeon BSPark HLee WWPaek SH: An 8-year follow-up on the effect of subthalamic nucleus deep brain stimulation on pain in Parkinson disease. JAMA Neurol 72:5045102015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Khoo HMKishima HHosomi KMaruo TTani NOshino S: Low-frequency subthalamic nucleus stimulation in Parkinson's disease: a randomized clinical trial. Mov Disord 29:2702742014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Kim HJJeon BSPaek SH: Effect of deep brain stimulation on pain in Parkinson disease. J Neurol Sci 310:2512552011

  • 32

    Kim HJPaek SHKim JYLee JYLim YHKim MR: Chronic subthalamic deep brain stimulation improves pain in Parkinson disease. J Neurol 255:188918942008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Lee MAWalker RWHildreth TJPrentice WM: A survey of pain in idiopathic Parkinson's disease. J Pain Symptom Manage 32:4624692006

  • 34

    Lim SYFarrell MJGibson SJHelme RDLang AEEvans AH: Do dyskinesia and pain share common pathophysiological mechanisms in Parkinson's disease?. Mov Disord 23:168916952008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Locke DGibson WMoss PMunyard KMamotte CWright A: Analysis of meaningful conditioned pain modulation effect in a pain-free adult population. J Pain 15:119011982014

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Marques AChassin OMorand DPereira BDebilly BDerost P: Central pain modulation after subthalamic nucleus stimulation: A crossover randomized trial. Neurology 81:6336402013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Maruo TSaitoh YHosomi KKishima HShimokawa THirata M: Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease. Pain 152:8608652011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Moreau CDefebvre LDestée ABleuse SClement FBlatt JL: STN-DBS frequency effects on freezing of gait in advanced Parkinson disease. Neurology 71:80842008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Moreau CPennel-Ployart OPinto SPlachez AAnnic AViallet F: Modulation of dysarthropneumophonia by low-frequency STN DBS in advanced Parkinson's disease. Mov Disord 26:6596632011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Mylius VEngau ITeepker MStiasny-Kolster KSchepelmann KOertel WH: Pain sensitivity and descending inhibition of pain in Parkinson's disease. J Neurol Neurosurg Psychiatry 80:24282009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Nègre-Pagès LRegragui WBouhassira DGrandjean HRascol OGroup DS: Chronic pain in Parkinson's disease: the cross-sectional French DoPaMiP survey. Mov Disord 23:136113692008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Oshima HKatayama YMorishita TSumi KOtaka TKobayashi K: Subthalamic nucleus stimulation for attenuation of pain related to Parkinson disease. J Neurosurg 116:991062012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Pellaprat JOry-Magne FCanivet CSimonetta-Moreau MLotterie JARadji F: Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease. Parkinsonism Relat Disord 20:6626642014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Quittenbaum BHGrahn B: Quality of life and pain in Parkinson's disease: a controlled cross-sectional study. Parkinsonism Relat Disord 10:1291362004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Ramdhani RAPatel ASwope DKopell BH: Early use of 60 Hz frequency subthalamic stimulation in Parkinson's disease: a case series and review. Neuromodulation 18:6646692015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46

    Rana ASaeed UMasroor MSYousuf MSSiddiqui I: A cross-sectional study investigating clinical predictors and physical experiences of pain in Parkinson's disease. Funct Neurol 28:2973042013

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Ricchi VZibetti MAngrisano SMerola AArduino NArtusi CA: Transient effects of 80 Hz stimulation on gait in STN DBS treated PD patients: a 15 months follow-up study. Brain Stimulat 5:3883922012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48

    Saadé NEAtweh SFBahuth NBJabbur SJ: Augmentation of nociceptive reflexes and chronic deafferentation pain by chemical lesions of either dopaminergic terminals or midbrain dopaminergic neurons. Brain Res 751:1121997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49

    Schestatsky PKumru HValls-Solé JValldeoriola FMarti MJTolosa E: Neurophysiologic study of central pain in patients with Parkinson disease. Neurology 69:216221692007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50

    Siao PCros DP: Quantitative sensory testing. Phys Med Rehabil Clin N Am 14:2612862003

  • 51

    Sidiropoulos CWalsh RMeaney CPoon YYFallis MMoro E: Low-frequency subthalamic nucleus deep brain stimulation for axial symptoms in advanced Parkinson's disease. J Neurol 260:230623112013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52

    Smith HGee LKumar VRamirez-Zamora ADurphy JHanspal E: Deep brain stimulation significantly decreases disability from low back pain in patients with advanced Parkinson's disease. Stereotact Funct Neurosurg 93:2062112015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53

    Spielberger SWolf EKress MSeppi KPoewe W: The influence of deep brain stimulation on pain perception in Parkinson's disease. Mov Disord 26:136713692011

  • 54

    Sürücü OBaumann-Vogel HUhl MImbach LLBaumann CR: Subthalamic deep brain stimulation versus best medical therapy for L-dopa responsive pain in Parkinson's disease. Pain 154:147714792013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55

    Tinazzi MDel Vesco CFincati EOttaviani SSmania NMoretto G: Pain and motor complications in Parkinson's disease. J Neurol Neurosurg Psychiatry 77:8228252006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56

    Toda KHarada T: Prevalence, classification, and etiology of pain in Parkinson's disease: association between Parkinson's disease and fibromyalgia or chronic widespread pain. Tohoku J Exp Med 222:152010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57

    Uebelacker LAEpstein-Lubow GLewis TBroughton MKFriedman JH: A survey of Parkinson's disease patients: most bothersome symptoms and coping preferences. J Parkinsons Dis 4:7177232014

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58

    Xie TVigil JMacCracken EGasparaitis AYoung JKang W: Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD. Neurology 84:4154202015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59

    Zambito Marsala STinazzi MVitaliani RRecchia SFabris FMarchini C: Spontaneous pain, pain threshold, and pain tolerance in Parkinson's disease. J Neurol 258:6276332011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 60

    Zengin-Toktas YFerrier JDurif FLlorca PMAuthier N: Bilateral lesions of the nigrostriatal pathways are associated with chronic mechanical pain hypersensitivity in rats. Neurosci Res 76:2612642013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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