Sex-specific effects of subthalamic nucleus stimulation on pain in Parkinson’s disease

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  • 1 Departments of Neuroscience and Experimental Therapeutics,
  • 2 Neurosurgery, and
  • 3 Neurology, Albany Medical College, Albany, New York
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OBJECTIVE

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to reduce motor symptoms of Parkinson’s disease (PD). The effects of DBS on various nonmotor symptoms often differ from patient to patient. The factors that determine whether or not a patient will respond to treatment have not been elucidated. Here, the authors evaluated sex differences in pain relief after DBS for PD.

METHODS

The authors prospectively evaluated 20 patients preoperatively and postoperatively after bilateral STN DBS with the validated numeric rating scale (NRS), Revised Oswestry Disability Index for low-back pain (RODI), and King’s Parkinson’s Disease Pain Scale (KPDPS) and assessed the impact of sex as a biological variable.

RESULTS

The cohort consisted of 6 female and 14 male patients with a mean duration of 11.8 ± 2.0 months since DBS surgery. Females were significantly older (p = 0.02). Covariate analysis, however, showed no effect of age, stimulation settings, or other confounding variables. KPDPS total scores statistically significantly improved only among males (p < 0.001). Males improved more than females in musculoskeletal and chronic subsets of the KPDPS (p = 0.03 and p = 0.01, respectively). RODI scores significantly improved in males but not in females (p = 0.03 and p = 0.30, respectively). Regarding the NRS score, the improvements seen in both sexes in NRS were not significant.

CONCLUSIONS

Although it is well recognized that pain complaints in PD are different between men and women, this study is unique in that it examines the sex-specific DBS effects on this symptom. Considering sex as a biological variable may have important implications for DBS pain outcome studies moving forward.

ABBREVIATIONS ADL = activity of daily living; BDI = Beck Depression Inventory; DBS = deep brain stimulation; KPDPS = King’s Parkinson’s Disease Pain Scale; LEDD = levodopa equivalent daily dose; NRS = numeric rating scale; PD = Parkinson’s disease; QOL = quality of life; rACC = rostral anterior cingulate cortex; RODI = Revised Oswestry Disability Index for low-back pain; STN = subthalamic nucleus; UPDRS = Unified Parkinson’s Disease Rating Scale.

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Contributor Notes

Correspondence Julie G. Pilitsis: Albany Medical College, Albany, NY. jpilitsis@yahoo.com.

INCLUDE WHEN CITING Published online October 9, 2020; DOI: 10.3171/2020.6.JNS201126.

Disclosures Dr. Sukul is a consultant for Boston Scientific and Medtronic. Dr. Durphy is on the speaker’s bureau and is a member of the working group for Acorda Pharmaceuticals. Dr. Hanspal is supported by the Dake Chair. Dr. Adam has served as a consultant for Abbott. Dr. Molho is supported by the Riley Family Chair in Parkinson’s Disease; he receives consulting fees from Neurocrine Biosciences; he receives grant support from CHDI/HSG, Civitas Therapeutics, MJF/PSG, and Biogen; and he is on the Neurocrine Biosciences speaker’s bureau. Dr. Pilitsis is a consultant for Boston Scientific, Nevro, TerSera, and Abbott and receives grant support from Medtronic, Boston Scientific, Abbott, Nevro, TerSera, and NIH (grant nos. 2R01CA166379-06 and NIH U44NS115111); and she is a medical advisor for and has stock equity in Aim Medical Robotics and Karuna.

  • 1

    Moro E, Lozano AM, Pollak P, Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson’s disease. Mov Disord. 2010;25(5):578586.

    • Search Google Scholar
    • Export Citation
  • 2

    Zesiewicz TA, Sullivan KL, Hauser RA. Nonmotor symptoms of Parkinson’s disease. Expert Rev Neurother. 2006;6(12):18111822.

  • 3

    Chaudhuri KR, Healy DG, Schapira AHV. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol. 2006;5(3):235245.

    • Search Google Scholar
    • Export Citation
  • 4

    Valkovic P, Harsany J, Hanakova M, Nonmotor symptoms in early- and advanced-stage Parkinson’s disease patients on dopaminergic therapy: how do they correlate with quality of life? ISRN Neurol. 2014;2014:587302.

    • Search Google Scholar
    • Export Citation
  • 5

    Martinez-Martin P, Falup Pecurariu C, Odin P, Gender-related differences in the burden of non-motor symptoms in Parkinson’s disease. J Neurol. 2012;259(8):16391647.

    • Search Google Scholar
    • Export Citation
  • 6

    Zagni E, Simoni L, Colombo D. Sex and gender differences in central nervous system-related disorders. Neurosci J. 2016;2016:2827090.

  • 7

    Georgiev D, Hamberg K, Hariz M, Gender differences in Parkinson’s disease: a clinical perspective. Acta Neurol Scand. 2017;136(6):570584.

    • Search Google Scholar
    • Export Citation
  • 8

    Chandran S, Krishnan S, Rao RM, Gender influence on selection and outcome of deep brain stimulation for Parkinson’s disease. Ann Indian Acad Neurol. 2014;17(1):6670.

    • Search Google Scholar
    • Export Citation
  • 9

    Chaudhuri KR, Rizos A, Trenkwalder C, King’s Parkinson’s disease pain scale, the first scale for pain in PD: an international validation. Mov Disord. 2015;30(12):16231631.

    • Search Google Scholar
    • Export Citation
  • 10

    Fairbank JC, Couper J, Davies JB, O’Brien JP. The Oswestry low back pain disability questionnaire. Physiotherapy. 1980;66(8):271273.

    • Search Google Scholar
    • Export Citation
  • 11

    Hudson-Cook N, Tomes-Nicholson K, Breen A. A revised Oswestry disability questionnaire. In: Roland MO, Jenner JR, eds. Back Pain: New Approaches to Rehabilitation and Education. Manchester University Press, 1989:187204.

    • Search Google Scholar
    • Export Citation
  • 12

    Przybyszewski AW, Ravin P, Pilitsis JG, Multi-parametric analysis assists in STN localization in Parkinson’s patients. J Neurol Sci. 2016;366:3743.

    • Search Google Scholar
    • Export Citation
  • 13

    Rashid T, Hwang R, DiMarzio M, Evaluating the role of 1.5T quantitative susceptibility mapping for subthalamic nucleus targeting in deep brain stimulation surgery. J Neuroradiol. Published online May 28, 2019. doi:10.1016/j.neurad.2019.04.007

    • Search Google Scholar
    • Export Citation
  • 14

    Novak P, Przybyszewski AW, Barborica A, Localization of the subthalamic nucleus in Parkinson disease using multiunit activity. J Neurol Sci. 2011;310(1-2):4449.

    • Search Google Scholar
    • Export Citation
  • 15

    Peng S, Levine D, Ramirez-Zamora A, A comparison of unilateral deep brain stimulation (DBS), simultaneous bilateral DBS, and staged bilateral DBS lead accuracies. Neuromodulation. 2017;20(5):478483.

    • Search Google Scholar
    • Export Citation
  • 16

    Roediger J, Artusi CA, Romagnolo A, Effect of subthalamic deep brain stimulation on posture in Parkinson’s disease: a blind computerized analysis. Parkinsonism Relat Disord. 2019;62:122127.

    • Search Google Scholar
    • Export Citation
  • 17

    Romito LM, Contarino FM, Albanese A. Transient gender-related effects in Parkinson’s disease patients with subthalamic stimulation. J Neurol. 2010;257(4):603608.

    • Search Google Scholar
    • Export Citation
  • 18

    Chiou SM. Sex-related prognostic predictors for Parkinson disease undergoing subthalamic stimulation. World Neurosurg. 2015;84(4):906912.

    • Search Google Scholar
    • Export Citation
  • 19

    Kim R, Yoo D, Choi JH, Sex differences in the short-term and long-term effects of subthalamic nucleus stimulation in Parkinson’s disease. Parkinsonism Relat Disord. 2019;68:7378.

    • Search Google Scholar
    • Export Citation
  • 20

    Kim YE, Kim HJ, Yun JY, Musculoskeletal problems affect the quality of life of patients with Parkinson’s disease. J Mov Disord. 2018;11(3):133138.

    • Search Google Scholar
    • Export Citation
  • 21

    Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci. 2012;13(12):859866.

    • Search Google Scholar
    • Export Citation
  • 22

    Sorge RE, Totsch SK. Sex differences in pain. J Neurosci Res. 2017;95(6):12711281.

  • 23

    Legorreta-Herrera M, Mosqueda-Romo NA, Nava-Castro KE, Sex hormones modulate the immune response to Plasmodium berghei ANKA in CBA/Ca mice. Parasitol Res. 2015;114(7):26592669.

    • Search Google Scholar
    • Export Citation
  • 24

    Xiong X, Xu L, Wei L, IL-4 is required for sex differences in vulnerability to focal ischemia in mice. Stroke. 2015;46(8):22712276.

  • 25

    Cabello N, Mishra V, Sinha U, Sex differences in the expression of lung inflammatory mediators in response to ozone. Am J Physiol Lung Cell Mol Physiol. 2015;309(10):L1150L1163.

    • Search Google Scholar
    • Export Citation
  • 26

    Rosen S, Ham B, Mogil JS. Sex differences in neuroimmunity and pain. J Neurosci Res. 2017;95(1-2):500508.

  • 27

    Campos ACP, Kikuchi DS, Paschoa AFN, Unraveling the role of astrocytes in subthalamic nucleus deep brain stimulation in a Parkinson’s disease rat model. Cell Mol Neurobiol. 2020;40(6):939954.

    • Search Google Scholar
    • Export Citation
  • 28

    Picillo M, Palladino R, Moccia M, Gender and non motor fluctuations in Parkinson’s disease: a prospective study. Parkinsonism Relat Disord. 2016;27:8992.

    • Search Google Scholar
    • Export Citation
  • 29

    Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care. 2014;8(2):143151.

    • Search Google Scholar
    • Export Citation
  • 30

    Hilker R, Voges J, Weisenbach S, Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson’s disease. J Cereb Blood Flow Metab. 2004;24(1):716.

    • Search Google Scholar
    • Export Citation
  • 31

    Albaugh DL, Shih YY. Neural circuit modulation during deep brain stimulation at the subthalamic nucleus for Parkinson’s disease: what have we learned from neuroimaging studies? Brain Connect. 2014;4(1):114.

    • Search Google Scholar
    • Export Citation
  • 32

    Dai YJ, Zhang X, Yang Y, Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures. J Headache Pain. 2018;19(1):24.

    • Search Google Scholar
    • Export Citation
  • 33

    Schofield P. Pain in older adults: epidemiology, impact and barriers to management. Rev Pain. 2007;1(1):1214.

  • 34

    Cerri S, Mus L, Blandini F. Parkinson’s disease in women and men: What’s the difference? J Parkinsons Dis. 2019;9(3):501515.

  • 35

    Colombo D, Abbruzzese G, Antonini A, The “gender factor” in wearing-off among patients with Parkinson’s disease: a post hoc analysis of DEEP study. ScientificWorldJournal. 2015;2015:787451.

    • Search Google Scholar
    • Export Citation
  • 36

    Beiske AG, Loge JH, Rønningen A, Svensson E. Pain in Parkinson’s disease: prevalence and characteristics. Pain. 2009;141(1-2):173177.

    • Search Google Scholar
    • Export Citation
  • 37

    Nègre-Pagès L, Regragui W, Bouhassira D, Chronic pain in Parkinson’s disease: the cross-sectional French DoPaMiP survey. Mov Disord. 2008;23(10):13611369.

    • Search Google Scholar
    • Export Citation
  • 38

    Defazio G, Berardelli A, Fabbrini G, Pain as a nonmotor symptom of Parkinson disease: evidence from a case-control study. Arch Neurol. 2008;65(9):11911194.

    • Search Google Scholar
    • Export Citation
  • 39

    Broetz D, Eichner M, Gasser T, Radicular and nonradicular back pain in Parkinson’s disease: a controlled study. Mov Disord. 2007;22(6):853856.

    • Search Google Scholar
    • Export Citation
  • 40

    Rustøen T, Wahl AK, Hanestad BR, Age and the experience of chronic pain: differences in health and quality of life among younger, middle-aged, and older adults. Clin J Pain. 2005;21(6):513523.

    • Search Google Scholar
    • Export Citation
  • 41

    Gaenslen A, Swid I, Liepelt-Scarfone I, The patients’ perception of prodromal symptoms before the initial diagnosis of Parkinson’s disease. Mov Disord. 2011;26(4):653658.

    • Search Google Scholar
    • Export Citation
  • 42

    Chaudhuri KR, Prieto-Jurcynska C, Naidu Y, The nondeclaration of nonmotor symptoms of Parkinson’s disease to health care professionals: an international study using the nonmotor symptoms questionnaire. Mov Disord. 2010;25(6):704709.

    • Search Google Scholar
    • Export Citation
  • 43

    Marceglia S, Mrakic-Sposta S, Foffani G, Gender-related differences in the human subthalamic area: a local field potential study. Eur J Neurosci. 2006;24(11):32133222.

    • Search Google Scholar
    • Export Citation
  • 44

    Belasen A, Rizvi K, Gee LE, Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson’s disease. J Neurosurg. 2017;126(2):397403.

    • Search Google Scholar
    • Export Citation
  • 45

    Siao P, Cros DP. Quantitative sensory testing. Phys Med Rehabil Clin N Am. 2003;14(2):261286.

  • 46

    Marques A, Chassin O, Morand D, Central pain modulation after subthalamic nucleus stimulation: a crossover randomized trial. Neurology. 2013;81(7):633640.

    • Search Google Scholar
    • Export Citation

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