帕金森氏症(Parkinson’s disease)是一種進行性神經退化性疾病，主要原因是患者腦部中產生的神經傳導物質多巴胺)dopamine)不足所致，然而，其具體明確的機制直至目前為止仍然未知。儘管有許多的研究及治療方式陸續發展，但目前仍缺乏肌肉僵硬情形進程的相關研究，因此從電生理學及生物力學的觀點，發展一個適當的動物模型及動物實驗用之評估工具，對於研究帕金森氏症產生之肌肉僵硬情形的改變發展進程是迫切需要的。本研究首先以一種多巴胺D2受體拮抗劑raclopride來建立帕金森氏症動物模型。發展我們先前表面多點電極肌電訊號的研究，取代侵入式針電極或線電極，來量測肌肉僵硬。另外，以微小化的肌肉張力系統，以五種不同頻率(1/3，1/2，1，3/2，2赫茲)牽張大白鼠後肢，記錄其反應阻力(resistance)。在電生理學多點電極的部分，從我們的結果顯示，施打藥物之後其均方根值(RMS)、中間頻率(median frequency)及振福(amplitude)其值皆比施打藥物前大，但是收縮期間(duration)施打藥物後變小。此外，從時間進程來看，施打藥物後兩小時，黏性(B)及剛性(stiffness)達到最高值，可持續至五小時。因此，對於動物肌肉張力的量化，一個有適當的量化方法及儀器的動物模型，在未來能夠用來評估新的藥物或治療方法，更了解其病理學的機制，或發展新的治療程序。

　　Parkinson’s disease (PD) is a common progressive neurodegenerative disorder, resulting from lesion of the nigrostriatal dopamine system. Although various treatments and investigations have been developed, there is a lack of time-course approach to quantitatively assess the alternations of muscle rigidity. Therefore, it is desirable to develop muscle tone assessment device from physiological and biomechanical aspects that can be utilized to assess the rigidity resulting from PD. Firstly, we adopted the acute PD animal model by injecting raclopride, a dopamine D2 receptor antagonist, in this study. Extension from our previous studies, multielectrode surface electromyography (EMG), instead of invasive needle or wire EMG electrodes, was developed to measure the muscle activity. A miniature muscle tone device measured the reactive torque from varied frequencies of sinusoidal stretch (1/3, 1/2, 1, 3/2 and 2 Hz) of rats’ hindlimb under awake condition. Our electrophysiological observations showed that the root mean square (RMS), amplitude and median frequency of multielectrode EMG in post-injection were larger than those of pre-injection, but the contraction duration was decreased. Besides, from the time-course studies, the viscosity and stiffness had a peak value at two hours post-injection and the effect of the drug was sustained for five hours. Current study demonstrated that a relevant animal model with reliable quantitative methods and apparatus for the assessment of muscle tone in PD animals should be valuable to evaluate the new drugs,, to advance the knowledge of the pathophysiological mechanisms, and to develop a new treatment protocols in the future.

[1]T. M. Dawson, "New animal models for parkinson's disease," Cell, vol. 101, pp. 115-118, 2000.
[2]http://www.holistic-online.com/Remedies/Parkinson/pd_brain.htm
[3]C. D. Marsden, "The mysterious motor function of the basal ganglia: the Robert Wartenberg lecture," Neurology, vol. 32, pp. 514-539, 1982.
[4]M. R. Diaz, P. Abdala, P. Barroso-Chinea, J. Obeso, and T. Gonzalez-Hernandez, "Motor behavioural changes after intracerebroventricular injection of 6-hydroxydopamine in the rat: an animal model of Parkinson's disease," Behav Brain Res, vol. 122, pp. 79-92, 2001.
[5]M. A. Cenci, I. Q. Whishaw, and T. Schallert, "Animal models of neurological deficits: how relevant is the rat?," Neuroscience, vol. 3, pp. 574-579, 2002.
[6]D. Dumitru, Electrodiagnostic medicine. Philadephia: Hanley and Belfus, 1995.
[7]D. Dumitru, J. C. King, and M. J. Zwarts, "Determinants of motor unit potential duration," Clin Neurophysiol, vol. 110, pp. 1876-1882, 1999.
[8]D. F. Stegeman, J. H. Blok, H. J. Hermens, and K. Roeleveld, "Surface EMG model: properties and applications," J Electromyogr Kinesiol, vol. 10, pp. 313-326, 2000.
[9]G. Rau and C. Disselhorst-Klug, "Principles of high-spatial-resolution surface EMG (HSR-EMG): single motor unit detection and application in the diagnosis of neuromuscular disorders," J Electromyogr Kinesiol, vol. 7, pp. 233-239, 1997.
[10]M. J. Zwarts and D. F. Stegeman, "Multichannel surface EMG: basic aspects and clinical utility," Muscle & Nerve, vol. 28, pp. 1-17, 2003.
[11]T.-Y. Lee, M.-J. Fu, T. B. J. Kuo, P.-W. Lui, and S. H. H. Chan, "Power spectral analysis of electromyogrphic and systemic arterial pressure signals during fentanyl-induced muscular rigidity in the rat," Br J Anaesth, vol. 72, pp. 328-334, 1994.
[12]K. M. Hemsley and A. D. Crocker, "Raclopride and Chlorpromazine, but not Clozapine, increase muscle rigidity in the rat: relationship with D2 dopamine receptor occupancy," Neuropsychopharmacology, vol. 21, pp. 101-109, 1999.
[13]E. Lorenc-Koci, S. Wolfarth, and K. Ossowska, "Haloperidol-increased muscle tone in rats as a model of parkinsonian rigidity," Exp Brain Res, vol. 109, pp. 268-276, 1996.
[14]W.G. Tatton, W. Bedingham, M.C. Verrier, and R.D. Blair, "Characteristic alterations in responses to imposed wrist displacements in parkinsonian rigidity and dystonia musculorum deformans," Can J Neurol Sci, vol. 11, pp. 281-287, 1984.
[15]S. L. Dickinson, D. A. Longman, and P. Slater, "A method for measuring drug-induced changes in limb muscle tone in the rat," Journal of Neuroscience Methods., vol. 5, pp. 195-200, 1982.
[16]B. Johnels and G. Steg, "A mechanographic method for measurement of locomotor activity in rats. Effects of dopaminergic drugs and electric stimulation of the brainstem," Journal of Neuroscience Methods., vol. 6, pp. 17-27, 1982.
[17]W. Kolasiewicz, J. Baran, and S. Wolfarth, "Mechanographic analysis of muscle rigidity after morphine and haloperidol: a new methodological approach," Naunyn-Schmiedeberg's Arch Pharmaco, vol. 335, pp. 449-453, 1987.
[18]P. Bose, R. Parmer, and F. J. Thompson, "Velocity-dependent ankle torque in rats after contusion injury of the midthoracic spinal cord: time course," Journal of Neurotrauma., vol. 19, pp. 1231-49, 2002.
[19]H. M. Lee, J. J. Chen, M. S. Ju, C. C. Lin, and P. W. Poon, "Validation of portable muscle tone measurement device for quantifying velocity-dependent properties in elbow spasticity," Journal of Electromyography & Kinesiology., 2004.
[20]A. W. Wiegner and R. L. Watts, "Elastic properties of muscles measured at the elbow in men. I. Normal controls," J Neurol Neurosurg Psychiatry, vol. 49, pp. 1171-1176, 1986.
[21]M. P. Caligiuri, "Portable device for quantifying parkinsonian wrist rigidity," Movement Disorders., vol. 9, pp. 57-63, 1994.
[22]H. M. Lee, Y. Z. Huang, J. J. Chen, and I. S. Hwang, "Quantitative analysis of the velocity related pathophysiology of spasticity and rigidity in the elbow flexor," J Neurol Neurosurg Psychiatry, vol. 72, pp. 621-629, 2002.
[23]H. C. Scholle, N. P. Schumann, F. H. Biedermann, D. F. Stegeman, R. Grassme, K. Roeleveld, N. Schilling, and M. S. Fischer, "Spatiotemporal surface EMG characteristics from rat triceps brachii muscle during treadmill locomotion indicate selective recruitment of functionally distinct muscle regions," Exp Brain Res, vol. 138, pp. 26-36, 2001.
[24]N. P. Schumann, F. H. Biedermann, B. U. Kleine, D. F. Stegeman, K. Roeleveld, R. Hackert, and H. C. Scholle, "Multi-channel EMG of the M. triceps brachii in rats during treadmill locomotion," Clin Neurophysiol. vol. 113, pp. 1142-1151, 2002.
[25]T. Y. Sun , T. S. Lin , and J. J. Chen, "Multielectrode surface EMG for noninvasive estimation of motor unit size," Muscle Nerve. vol. 22, pp. 1063-1070, 1999.
[26]G. L. Soderberg and L. M. Knutson, "A guide for use and interpretation of kinesiologic electromyographic data," Phys Ther, vol. 80, pp. 485-498, 2000.
[27]K. L. Double and A. D. Crocker, "Dopamine receptors in the substantia nigra are involved in the regulation of muscle tone," Neurobiology, vol. 92, pp. 1669-1673, 1995.
[28]R. Cantello, M. Gianelli, C. Civardi, and R. Mutani, "Parkinson's disease rigidity: EMG in a small hand muscle at "rest"," Electroencephalogr Clin Neurophysiol, vol. 97, pp. 215-222, 1995.
[29]L. Q. Zhang, R. Shiavi, M. A. Hunt, and J. J. Chen, "Clustering analysis and pattern discrimination of EMG linear envelopes," IEEE Trans Biomed Eng, vol. 38, pp. 777-84, 1991.
[30]R. L. Watts, A. W. Wiegner, and R. R. Young, "Elastic properties of muscles measured at the elbow in man. II. Patients with Parkinsonian rigidity," J Neurol Neurosurg Psychiatry, vol. 49, pp. 1177-1181, 1986.