Molecular Pain | |
Pain perception in acute model mice of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) | |
Kyungmin Lee3  Bong-Kiun Kaang1  Min Zhuo2  Chung-Ah Park3  Hyunhyo Seo3  Chae-Seok Lim1  Jihye Park1  | |
[1] Neurobiology Laboratory, College of Natural Sciences, Seoul National University, 599 Gwanangno, Seoul 151-747, South Korea;Department of Physiology, Faculty of Medicine, University of Toronto, The center for the study of pain, 1 King’s College Circle, Toronto M5S 1A8, ON, Canada;Behavioral Neural Circuitry and Physiology Laboratory, Department of Anatomy, Brain Science & Engineering Institute, Kyungpook National University Graduate School of Medicine, 2-101, Dongin-dong, Jung-gu, Daegu 700-842, South Korea | |
关键词: Astrogliosis; Inflammation; Subthalamic nucleus; Dopaminergic pathway; | |
Others : 1208582 DOI : 10.1186/s12990-015-0026-1 |
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received in 2015-01-16, accepted in 2015-05-11, 发布年份 2015 | |
【 摘 要 】
Background
Pain is the most prominent non-motor symptom observed in patients with Parkinson’s disease (PD). However, the mechanisms underlying the generation of pain in PD have not been well studied. We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD to analyze the relationship between pain sensory abnormalities and the degeneration of dopaminergic neurons.
Results
The latency to fall off the rotarod and the total distance traveled in round chamber were significantly reduced in MPTP-induced PD mice, consistent with motor dysfunction. MPTP-treated mice also showed remarkably shorter nociceptive response latencies compared to saline-treated mice and the subcutaneous injection of L-3,4-dihydroxyphenylalanine (L-DOPA) partially reversed pain hypersensitivity induced by MPTP treatment. We found that degeneration of cell bodies and fibers in the substantia nigra pars compacta and the striatum of MPTP-treated mice. In addition, astrocytic and microglial activation was seen in the subthalamic nucleus and neuronal activity was significantly increased in the striatum and globus pallidus. However, we did not observe any changes in neurons, astrocytes, and microglia of both the dorsal and ventral horns in the spinal cord after MPTP treatment.
Conclusions
These results suggest that the dopaminergic nigrostriatal pathway may have a role in inhibiting noxious stimuli, and that abnormal inflammatory responses and neural activity in basal ganglia is correlated to pain processing in PD induced by MPTP treatment.
【 授权许可】
2015 Park et al.; licensee BioMed Central.
【 预 览 】
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【 参考文献 】
- [1]Chaudhuri KR, Healy DG, Schapira AH: Non-motor symptoms of Parkinson’s disease: Diagnosis and management. Lancet Neurol 2006, 5:235-45.
- [2]Beiske AG, Loge JH, Rønningen A, Svensson E: Pain in Parkinson’s disease: prevalence and characteristics. Pain 2009, 141:173-7.
- [3]Jackson-Lewis V, Przedborski S: Protocol for the MPTP mouse model of Parkinson’s disease. Nat Protoc 2007, 2:141-51.
- [4]Magnusson JE, Fisher K: The involvement of dopamine in nociception: the role of D1 and D2 receptors in the dorsolateral striatum. Brain Res 2000, 855:260-6.
- [5]Chudler EH, Lu Y: Nociceptive behavioral responses to chemical, thermal and mechanical stimulation after unilateral, intrastriatal administration of 6-hydroxydopamine. Brain Res 2008, 1213:41-7.
- [6]Rosemann M, Ivashkevich A, Favor J, Dalke C, Hölter SM, Becker L, et al.: Microphthalmia, parkinsonism, and enhanced nociception in Pitx3 416insG mice. Mamm Genome 2010, 21(1–2):13-27.
- [7]Shimizu T, Iwata S, Morioka H, Masuyama T, Fukuda T, Nomoto M: Antinociceptive mechanism of L-DOPA. Pain 2004, 110:246-9.
- [8]Jenner P: Molecular mechanisms of L-DOPA-induced dyskinesia. Nat Rev Neurosci 2008, 9:665-77.
- [9]Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, et al.: Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 2003, 349:1925-34.
- [10]Dellapina E, Ory-Magne F, Regragui W, Thalamas C, Lazorthes Y, Rascol O, et al.: Effect of subthalamic deep brain stimulation on pain in Parkinson’s disease. Pain 2012, 153:2267-73.
- [11]Pellaprat J, Ory-Magne F, Canivet C, Simonetta-Moreau M, Lotterie JA, Radji F, et al.: Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson’s disease. Parkinsonism and Related Disorders 2014, 20:662-4.
- [12]Stern Y, Mayeux R, Rosen J, Ilson J: Perceptual motor dysfunction in Parkinson’s disease: a deficit in sequential and predictive voluntary movement. J Neurol Neurosurg Psychiatry 1983, 46:145-51.
- [13]Brooks SP, Dunnett SB: Tests to assess motor phenotype in mice: a user’s guide. Nat Rev Neurosci 2009, 10:519-29.
- [14]Luchtman DW, Shao D, Song C: Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson’s disease. Physiol Behav 2009, 98:130-8.
- [15]Marchetti B, L’Episcopo F, Morale MC, Tirolo C, Testa N, Caniglia S, et al.: Uncovering novel actors in astrocyte–neuron crosstalk in Parkinson’s disease: the Wnt/b-catenin signaling cascade as the common final pathway for neuroprotection and self-repair. Eur J Neurosci 2013, 37:1550-63.
- [16]Halliday GM, Stevens CH: Glia: initiators and progressors of pathology in Parkinson’s disease. Mov Disord 2011, 26:6-17.
- [17]Henning J, Strauss U, Wree A, Gimsa J, Rolfs A, Benecke R, et al.: Differential astroglial activation in 6-hydroxydopamine models of Parkinson’s disease. Neurosci Res 2008, 62:246-53.
- [18]Hamby ME, Sofroniew MV: Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 2010, 7:494-506.
- [19]Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D: Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol 1999, 46:598-605.
- [20]Niranjan R, Nath C, Shukla R: The mechanism of action of MPTP-induced neuroinflammation and its modulation by melatonin in rat astrocytoma cells, C6. Free Radic Res 2010, 44:1304-16.
- [21]Petroske E, Meredith G, Callen S, Totterdell S, Lau Y-S: Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic MPTP/probenecid treatment. Neuroscience 2001, 106(3):589-601.
- [22]Sedelis M, Schwarting RK, Huston JP: Behavioral phenotyping of the MPTP mouse model of Parkinson’s disease. Behav Brain Res 2001, 125(1):109-25.
- [23]Vivacqua G, Biagioni F, Yu S, Casini A, Bucci D, D’Este L, et al.: Loss of spinal motor neurons and alteration of alpha-synuclein immunostaining in MPTP induced Parkinsonism in mice. J Chem Neuroanat 2012, 44:76-85.
- [24]Tagliati M, Martin C, Alterman R: Lack of motor symptoms progression in Parkinson’s disease patients with long-term bilateral subthalamic deep brain stimulation. Int J Neurosci 2010, 120(11):717-23.
- [25]Pani L, Porcella A, Gessa G: The role of stress in the pathophysiology of the dopaminergic system. Mol Psychiatry 2000, 5:14.
- [26]Teicher MH, Anderson CM, Polcari A, Glod CA, Maas LC, Renshaw PF: Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry. Nat Med 2000, 6:470-3.
- [27]Nieoullon A: Dopamine and the regulation of cognition and attention. Prog Neurobiol 2002, 67:53.
- [28]Chudler EH, Dong WK: The role of the basal ganglia in nociception and pain. Pain 1995, 60:3-38.
- [29]Chesselet M-F, Delfs JM: Basal ganglia and movement disorders: an update. Trends Neurosci 1996, 19:417-22.
- [30]Hagelberg N, Jääskeläinen SK, Martikainen IK, Mansikka H, Forssell H, Scheinin H, et al.: Striatal dopamine D2 receptors in modulation of pain in humans: a review. Eur J Pharmacol 2004, 500:187-92.
- [31]Levant B, McCarson KE: D3 dopamine receptors in rat spinal cord: implications for sensory and motor function. Neurosci Lett 2001, 303:9-12.
- [32]Gao K, Mason P: Serotonergic Raphe magnus cells that respond to noxious tail heat are not ON or OFF cells. J Neurophysiol 2000, 84(4):1719-25.
- [33]Heikkila RE, Sieber B-A, Manzino L, Sonsalla PK: Some features of the nigrostriatal dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in the mouse. Mol Chem Neuropathol 1989, 10:171-83.
- [34]Rosland JH, Hunskaar S, Broch OJ, Hole K: Acute and Long Term Effects of 1‐Methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP) in Tests of Nociception in Mice. Pharmacol Toxicol 1992, 70:31-7.
- [35]Orega-Legaspi JM, de Gortari P, Garduño-Gutiérrez R, Amaya MI, León-Olea M, Coffeen U, et al.: Expression of the dopaminergic D1 and D2 receptors in the anterior cingulate cortex in a model of neuropathic pain. Mol Pain 2011, 7:1-10. BioMed Central Full Text
- [36]Coffeen U, Ortega-Legaspi JM, de Gortari P, Simón-Arceo K, Jaimes O, Amaya MI, et al.: Inflammatory nociception diminishes dopamine release and increases dopamine D2 receptor mRNA in the rat’s insular cortex. Mol Pain 2010, 6:1-8. BioMed Central Full Text
- [37]Bourgoin S, Pohl M, Mauborgne A, Benoliel JJ, Collin E, Hamon M, et al.: Monoaminergic control of the release of calcitonin gene-related peptide- and substance P-like materials from rat spinal cord slices. Neuropharmacology 1993, 32(7):633-40.
- [38]Wiesenfeld-Hallin Z: Sex differences in pain perception. Gend Med 2005, 2:137-45.
- [39]Rozas G, López-Martın E, Guerra M, Labandeira-Garcıa J: The overall rod performance test in the MPTP-treated-mouse model of Parkinsonism. J Neurosci Methods 1998, 83:165-75.
- [40]Jiang H, Fang D, Kong LY, Jin ZR, Cai J, Kang XJ, et al.: Sensitization of neurons in the central nucleus of the amygdala via the decreased GABAergic inhibition contributes to the development of neuropathic pain-related anxiety-like behaviors in rats. Mol Brain 2014, 7:72. BioMed Central Full Text
- [41]Zhang MM, Liu SB, Chen T, Koga K, Zhang T, Li YQ, et al.: Effects of NB001 and gabapentin on irritable bowel syndrome-induced behavioral anxiety and spontaneous pain. Mol Brain 2014, 7:47. BioMed Central Full Text
- [42]Chen T, Wang W, Dong YL, Zhang MM, Wang J, Koga K, et al.: Postsynaptic insertion of AMPA receptor onto cortical pyramidal neurons in the anterior cingulate cortex after peripheral nerve injury. Mol Brain 2014, 7:76. BioMed Central Full Text
- [43]Liu MG, Zhuo M: No requirement of TRPV1 in long-term potentiation or long-term depression in the anterior cingulate cortex. Mol Brain 2014, 7:27. BioMed Central Full Text
- [44]Yu D, Thakor DK, Han I, Ropper AE, Haragopal H, Sidman RL, et al.: Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A. Proc Natl Acad Sci U S A 2013, 110:E746-55.