Neurology and Preclinical Neurological Studies - Original Article
In patients with Parkinson’s disease (PD), abnormal activations of nociceptive brain areas and lowered pain thresholds were reported, probably reflecting a central modification of pain processing. The aim of this study was to investigate the possible correlation between the striatal and extrastriatal dopaminergic system and pain threshold in PD patients. We included 25 PD patients with various intensities of central pain (visual analog scale). Subjective pain threshold (thermotest) and a motor examination (UPDRS III) were performed. Patients underwent SPECT imaging with [123I]-FP-CIT. We analyzed the correlation between [123I]-FP-CIT binding and subjective pain threshold, using a simple linear regression model for striatal uptake and a voxel-based approach for extrastriatal uptake. The covariables were age, sex, duration of PD, and UPDRS motor score. A pain matrix mask was also used to identify clusters in relation with pain matrix. Striatal analysis revealed that [123I]-FP-CIT binding was negatively correlated with age (p = 0.02), duration of PD (p = 0.0002) and UPDRS motor score (p = 0.006), but no correlation with pain threshold was observed. The extrastriatal analysis showed a positive correlation between [123I]-FP-CIT binding and subjective heat pain threshold for the left posterior cingulate cortex (PCC) (p < 0.001) and negative correlations for the right secondary visual cortex (p < 0.001) and left insula (p < 0.001). When applying the pain matrix mask, correlations remained significant only in the left PCC and the left insula. We suggest that pain perception abnormalities in PD are not directly related to striatal dopaminergic dysfunction. Painful sensations may be related to extrastriatal monoaminergic systems.
Parkinson’s disease Central pain [123I]-FP-CIT Dopaminergic system
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This work was supported by a Toulouse University Hospital grant.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Becerra LR et al (1999) Human brain activation under controlled thermal stimulation and habituation to noxious heat: an fMRI study. Magn Reson Med 41:1044–1057CrossRefPubMedGoogle Scholar
Beiske AG, Loge JH, Ronningen A, Svensson E (2009) Pain in Parkinson’s disease prevalence characteristics. Pain 141:173–177CrossRefGoogle Scholar
Benamer HT, Patterson J, Wyper DJ, Hadley DM, Macphee GJ, Grosset DG (2000) Correlation of Parkinson’s disease severity and duration with 123I-FP-CIT SPECT striatal uptake. Mov Disord 15:692–698CrossRefGoogle Scholar
Brefel-Courbon C et al (2005) Effect of levodopa on pain threshold in Parkinson’s disease: a clinical and positron emission tomography study. Mov Disord 20:1557–1563CrossRefPubMedGoogle Scholar
Brefel-Courbon C et al (2009) Comparison of chronic analgesic drugs prevalence in Parkinson’s disease other chronic diseases the general population. Pain 141:14–18CrossRefPubMedGoogle Scholar
Brefel-Courbon C, Ory-Magne F, Thalamas C, Payoux P, Rascol O (2013) Nociceptive brain activation in patients with neuropathic pain related to Parkinson’s disease. Parkinsonism Relat Disord 19:548–552CrossRefPubMedGoogle Scholar
Defrin R, Pick CG, Peretz C, Carmeli E (2004) A quantitative somatosensory testing of pain threshold in individuals with mental retardation. Pain 108:58–66CrossRefPubMedGoogle Scholar
Dellapina E et al (2012) Effect of subthalamic deep brain stimulation on pain in Parkinson‘s disease. Pain 153:2267–2273CrossRefPubMedGoogle Scholar
Djaldetti R, Shifrin A, Rogowski Z, Sprecher E, Melamed E, Yarnitsky D (2004) Quantitative measurement of pain sensation in patients with Parkinson disease. Neurology 62:2171–2175CrossRefPubMedGoogle Scholar
Hsieh JC, Belfrage M, Stone-Elander S, Hansson P, Ingvar M (1995) Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain 63:225–236CrossRefPubMedGoogle Scholar
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184CrossRefPubMedPubMedCentralGoogle Scholar
Hurd YL, Suzuki M, Sedvall GC (2001) D1 and D2 dopamine receptor mRNA expression in whole hemisphere sections of the human brain. J Chem Neuroanat 22:127–137CrossRefPubMedGoogle Scholar
Kas A et al (2007) Validation of a standardized normalization template for statistical parametric mapping analysis of 123I-FP-CIT images. J Nucl Med 48:1459–1467CrossRefPubMedGoogle Scholar
Kumru H, Soler D, Vidal J, Tormos JM, Pascual-Leone A, Valls-Sole J (2012) Evoked potentials and quantitative thermal testing in spinal cord injury patients with chronic neuropathic pain. Clin Neurophysiol 123:598–604CrossRefPubMedGoogle Scholar
Lim SY, Farrell MJ, Gibson SJ, Helme RD, Lang AE, Evans AH (2008) Do dyskinesia and pain share common pathophysiological mechanisms in Parkinson’s disease? Mov Disord 23:1689–1695CrossRefPubMedGoogle Scholar
Mylius V et al (2009) Pain sensitivity and descending inhibition of pain in Parkinson’s disease. J Neurol Neurosurg Psychiatry 80:24–28CrossRefPubMedGoogle Scholar
Negre-Pages L, Regragui W, Bouhassira D, Grandjean H, Rascol O (2008) Chronic pain in Parkinson’s disease: the cross-sectional French DoPaMiP survey. Mov Disord 23:1361–1369CrossRefPubMedGoogle Scholar
Nielsen FA, Balslev D, Hansen LK (2005) Mining the posterior cingulate: segregation between memory pain components. Neuroimage 27:520–532CrossRefPubMedGoogle Scholar
Peyron R, Laurent B, Garcia-Larrea L (2000) Functional imaging of brain responses to pain. A review and meta-analysis. Neurophysiol Clin 30:263–288CrossRefPubMedGoogle Scholar
Schestatsky P, Kumru H, Valls-Sole J, Valldeoriola F, Marti MJ, Tolosa E, Chaves ML (2007) Neurophysiologic study of central pain in patients with Parkinson disease. Neurology 69:2162–2169CrossRefPubMedGoogle Scholar
Slaoui T, Mas-Gerdelat A, Ory-Magne F, Rascol O, Brefel-Courbon C (2007) [Levodopa modifies pain thresholds in Parkinson’s disease patients]. Rev Neurol (Paris) 163:66–71 (MDOI-RN-01-2007-163-1-0035-3787-101019-200604714 [pii])CrossRefGoogle Scholar