1、Translational research in rehabilitation medicine:What we can learn from biomedical research?康复医学中的转化医学研究康复医学中的转化医学研究从生物医学科研中的心得从生物医学科研中的心得Dr.rer.biol.hum.Boya Nugraha,MSPost Congress-9th ISPRM 2015Hanover,25 June 2015Content Chronic pain syndromes:epidemiology and characteristics 慢性疼痛 特征 Mechanisms
2、 of pain chronification(Fibromyalgia as model of chronic pain)疼痛的慢性损伤 肌肉纤维疼痛 Neuroplasticity 神经重塑 Pain mediators 疼痛因子 Conclusion and Future Direction 讨论及未来展望Chronic pain(characteristics and epidemiology)Pain in musculoskeletal system is very frequent symptom:肌肉骨骼系统疼痛为主 with tissue damage:e.g.Osteoar
3、thritis,disc herniation 实质性损伤 without(specific)tissue damage:joint dysfunction,irritation caused by overstrain,muscle hypertension and others Many of these syndrome are not very severe(or dangerous)and self limiting but in some cases they can become chronicThe impact of musculoskeletal pain on quali
4、ty of life,and health expenses is very highImportant question:how to prevent(and treat)chronic pain syndromes 无特殊性损伤 关节功能丧失 其中一些并不危险，并且有自身受限，但某些情况下会变成慢性重要问题-如何预防并治疗转化成慢性疼痛Symptoms症状 Decreased overall pain thresholds increased sensitivity of muscles and tendons to pressure 肌肉及肢体对压力的敏感性增加Autonomous dy
5、sfunction(Fibromyalgia)自主神经功能紊乱 sleep disturbances,睡眠终止 fatigue 疲劳 and others 其他Psycho-social aspects high intensity of suffering 集中病痛感同身受 strong focus of attention to symptoms 高度关注 high demand for health interventions 高度健康关注CountryPrevalence(%)ReferenceUSA2.0Lawrence et al.1998Canada3.3White et al.
6、1999Germany3.0Raspe et al.1992Poland4.5Gagliese and Katz.2000Spain2.4Carmona et al.2001Italy2.2Salaffi et al.2005Sweden2.5Cster et al.2008France1.6Perrot et al.2011Finland0.8Mkel and Heliovaara,1991Denmark0.7Prescott et al.1993Prevalence of FMS in several western countriesMechanisms of pain chronifi
7、cationMay,Pain 2008;137:715Different level of plasticity in chronic painNeuroplasticity:Alteration1.Function 功能2.Structure 结构3.Chemical profile 化学指标Central sensitization(Coghill RC 2005)中枢patient with chronic pain 慢性疼痛 normal subject 正常人Central sensitization:functional imagingGuedj et al.:J Nucl Med
8、 2008;49:17981803May,2008May,2011.The NeuroscientistChemical profile(pain mediators)化学剖面（疼痛因子）Pain mediators:Brain Derived Neurotropic Factor,BDNF脑源性神经营养因子Correlation of BDNF and age in Healthy Controls and FMS patientsPain mediators:Brain Derived Neurotropic Factor,BDNFNugraha et al.2013:Neurochem
9、IntNugraha et al.2012Rheumatol IntPain mediators:Brain Derived Neurotropic Factor,BDNF(n total=39;HADS-D score 10:n=8;Data are shown in mean SEM;The JocnkheereTerpstra test:p 0.05)(n total=39;HADS-A score 10:n=18;Data are shown in mean SEM;The JocnkheereTerpstra test:p 0.05).Level of serum BDNF in F
10、MS patients based on depression score groupLevel of serum BDNF in FMS patients based on anxiety score groupCorrelation:R=0.434;p=0.006Pain Mediators:CD3+CD56+NKT Cells:FMS and depression%CD3+CD56+NKT CellsHADS-D ScoreR=-0.297;p=0.03ANOVA:p=0.02Post-hoc:Bonferroni test:HADS-D 10(p=0.018)CorrelationNu
11、graha et al.2013Clin Exp RheumPain mediators:Anandamide花生四烯酸乙醇胺Kaufman et al.:Psychoneuroendocrinology 2008;33,676685How to manage chronic pain?如何处理慢性疼痛010203040506070ExCBTEx+CBTNTFIQ ScoreGroupFibromyalgia impact questionnaireT0T1*024681012ExCBTEx+CBTNTHADS-A ScoreGroupLevel of AnxietyT0T1012345678
12、910ExCBTEx+CBTNTHADS-D ScoreGroupLevel of DepressionT0T1*Exercise and biomediatorsBiomediatorsEffect of ExerciseHumanAnimalAnandamideIncreased after running and cycling(Sparling et al.,2003;Raicheln et al.2012)Increased after running(Raicheln et al.2012)BDNFIncreased BDNF mRNA in hippocampus volunta
13、ry running wheel(Neeper et al.,1995)SerotoninIncresead in humansIncreased in rat hippocampus(Bequet et al.,2008)Cytokinesincreased of IL-1,IL-6 and TNF-(Ostrowski et al.,1999;Vassilakopoulos et al.,2003)ConclusionTranslational research in rehabilitation medicine can help elucidate the pathomechanism
14、s of diseases which can be used to diagnose,monitor the treatment在康复中的转化医学研究可以帮助疾病的诊断及治疗More studies are needed to investigate the effectiveness of treatments in rehabilition medicine through biomedicine通过生化方式研究康复医学治疗的影响有更多内容需要进行Thank youBoya Nugraha,MS,PhDNugraha.Boyamh-hannover.de Dept.Rehabilitat
15、ion Medicine,Hannover Medical SchoolHannover,GermanyENVIRONMENTAL FACTORS,GENETICSPERIPHERALCENTRALH P A AXIS:Cortisol,etcP A I NImmune system and inflammatory mediators:cytokinesMuscle dysfunctionMood-related disorderFatigueAn inter-related network of FMS clinical symptoms with inflammatory and mol
16、ecular mediatorsFibromyalgia Syndrome.Nugraha and Gutenbrunner,2013Aetiology and Pathomechanism of Fibromyalgia syndromeNot clear aetiologyChronic generalized pain syndrome(reduce pain threshold),stress related disorderDysregulation of Hypothalamus-Pituitary-Adrenal(HPA)-axis,immune system dysfunction
