神經(jīng)病理性疼痛的概念與診斷李焰生

1、會(huì)計(jì)學(xué)1神經(jīng)病理性疼痛的概念與診斷李焰生神經(jīng)病理性疼痛的概念與診斷李焰生疼痛的解剖和生理疼痛的解剖和生理傷害性感受器傷害性感受器溫度溫度,機(jī)械機(jī)械,化學(xué)化學(xué)A 和和 C纖維纖維 脊髓后角脊髓后角1,2,5層層對(duì)側(cè)脊髓丘腦束對(duì)側(cè)脊髓丘腦束丘腦丘腦VPL核核感覺(jué)皮質(zhì)感覺(jué)皮質(zhì)邊緣系統(tǒng)邊緣系統(tǒng) 腦腦 干干導(dǎo)水管周?chē)屹|(zhì)導(dǎo)水管周?chē)屹|(zhì) 藍(lán)斑藍(lán)斑 5-HTNADworkin Clin J Pain. 2002;18:343-349Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57同義詞同義詞神經(jīng)病性痛

2、，神經(jīng)病變性痛，神經(jīng)性疼痛，神經(jīng)源神經(jīng)病性痛，神經(jīng)病變性痛，神經(jīng)性疼痛，神經(jīng)源性疼痛，等等性疼痛，等等不同于神經(jīng)痛（不同于神經(jīng)痛（neuralgia）NEUROLOGY 2008;70:1630-1635Neuropathic pain：Redefinition and a grading system for clinical and research purposes R. -D. Treede, MD, T. S. Jensen, MD, PhD, J. N. Campbell, MD, G. Cruccu, MD, J. O. Dostrovsky, PhD, J. W. Griffi

3、n, MD, P. Hansson, MD, DMSc, DDS, R. Hughes, MD, T. Nurmikko, MD, PhD and J. Serra, MD Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of

4、 its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as “pain initiated or caused by a primary lesion or dysfunction in the nervous system.” While this definition has been useful in distinguishing so

5、me characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neurop

6、lasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The referenc

7、e to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is prop

8、osed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposespain a

9、rising as a direct consequence of a lesion or disease affecting the somatosensory system.疼痛的病理生理疼痛的病理生理傷害性痛傷害性痛“正常正常”傷害性感受器和傷害性感受器和”潛在潛在”傷害性感受器的激活和敏傷害性感受器的激活和敏感感; ;炎性致痛物質(zhì)炎性致痛物質(zhì)( (質(zhì)子，前列腺素質(zhì)子，前列腺素, ,緩激肽緩激肽,5-HT,5-HT,組胺，細(xì)組胺，細(xì)胞因子和腺苷等胞因子和腺苷等) )在脊髓水平增高，在脊髓水平增高，NMDANMDA受體激活受體激活神經(jīng)病理性痛神經(jīng)病理性痛炎癥和非炎癥機(jī)制炎癥和非炎癥機(jī)制神經(jīng)

10、系統(tǒng)的異位激活神經(jīng)系統(tǒng)的異位激活后角水平的痛覺(jué)通路重組后角水平的痛覺(jué)通路重組 中樞神經(jīng)系統(tǒng)敏感化中樞神經(jīng)系統(tǒng)敏感化 C C纖維表達(dá)腎上腺素受體纖維表達(dá)腎上腺素受體, ,產(chǎn)生交感傳出活動(dòng)產(chǎn)生交感傳出活動(dòng)(SMP,sympathetically mediated pain(SMP,sympathetically mediated pain ) )神經(jīng)病理性痛神經(jīng)病理性痛疼痛來(lái)自于周?chē)蛑刑弁磥?lái)自于周?chē)蛑袠袀π愿杏X(jué)結(jié)構(gòu)的樞傷害性感覺(jué)結(jié)構(gòu)的異常異常傷害性痛傷害性痛組織損傷后疼痛組織損傷后疼痛完整的周?chē)椭袠型暾闹車(chē)椭袠袀π愿杏X(jué)結(jié)構(gòu)傷害性感覺(jué)結(jié)構(gòu)慢性疼痛慢性疼痛如炎癥、關(guān)節(jié)炎如炎癥、關(guān)節(jié)炎如如

11、DPN、三叉神經(jīng)痛、三叉神經(jīng)痛、卒中后疼痛、卒中后疼痛、PHN混合性痛混合性痛坐骨神經(jīng)痛，坐骨神經(jīng)痛，腫瘤痛腫瘤痛 burning, pins and needles, pricklingstabbinghyperalgesiaallodynia touch sensation pain sensation position sensation vibration sensation cold / warm 中樞敏感化中樞敏感化 周?chē)舾谢車(chē)舾谢?CNSPNS CNS“正常正?！?傷害性感受器傷害性感受器正常傳遞正常傳遞 中樞重組中樞重組異常傷害性感受器異常傷害性感受器PNSPappaga

12、llo M. 2001.病理狀態(tài)病理狀態(tài)神經(jīng)病理性疼痛神經(jīng)病理性疼痛傷害性痛傷害性痛生理狀態(tài)生理狀態(tài)神經(jīng)病理性痛可能涉及的生理生化改變神經(jīng)病理性痛可能涉及的生理生化改變 門(mén)控學(xué)說(shuō)門(mén)控學(xué)說(shuō)Wall & Melzack 1965中間神經(jīng)元由A-beta 纖維激活起門(mén)控作用，抑制由 C 纖維向高級(jí)中樞的疼痛傳入搓揉損害周?chē)つw可減輕疼痛.經(jīng)皮電神經(jīng)刺激(TENS).后柱刺激.針灸 centralperipheralMechanical hyperalgesia is due to spinal sensitizationEctopic dischargesPar/dyssthesias(so

13、dium channel)Decreased central inhibitionSpinal hyperexcitability / sensitizationallodynia / mech. hyperalgesia(glutamate) Peripheral sensitization of nociceptors (inflammatory substances)涉及持續(xù)神經(jīng)病理性痛的可能機(jī)制涉及持續(xù)神經(jīng)病理性痛的可能機(jī)制腦腦脊髓脊髓周?chē)窠?jīng)周?chē)窠?jīng)交感神經(jīng)交感神經(jīng)通道改變分子改變基因表達(dá)改變接受場(chǎng)改變通道改變（鈉）通道改變（鈉）分子改變后角失神經(jīng)后超敏基因表達(dá)改變接受場(chǎng)改變異位發(fā)放

14、（鈉通道異常聚集異位發(fā)放（鈉通道異常聚集）機(jī)械敏感假突觸交連（假突觸交連（A ）假突觸交連中樞性抑制降低中樞性抑制降低正常神經(jīng)沖動(dòng)的中樞處正常神經(jīng)沖動(dòng)的中樞處理過(guò)程改變（放大和持理過(guò)程改變（放大和持續(xù)）續(xù)）低強(qiáng)度刺激低強(qiáng)度刺激溫度、機(jī)械溫度、機(jī)械敏感化的高閾值傳敏感化的高閾值傳入入 AA，C C脊髓脊髓疼痛疼痛原發(fā)痛覺(jué)過(guò)敏原發(fā)痛覺(jué)過(guò)敏高強(qiáng)度刺激高強(qiáng)度刺激機(jī)械、化學(xué)、溫度機(jī)械、化學(xué)、溫度高閾值傳入高閾值傳入AA，C C后根神經(jīng)節(jié)后根神經(jīng)節(jié)疼痛疼痛原發(fā)痛覺(jué)過(guò)敏原發(fā)痛覺(jué)過(guò)敏低強(qiáng)度刺激低強(qiáng)度刺激觸摸、壓、刷觸摸、壓、刷低閾值傳入低閾值傳入 AA敏感化敏感化DRGDRG疼痛疼痛機(jī)械性機(jī)械性allodyn

15、iaBouhassira D, Attal N, Alchaar H et al. Pain 2005; 114: 2936.83% 83% 敏感性敏感性, 90% , 90% 特異性特異性神經(jīng)病理性痛診斷分級(jí)流程神經(jīng)病理性痛診斷分級(jí)流程主訴疼痛主訴疼痛可能的神經(jīng)解剖分布的疼痛，可能的神經(jīng)解剖分布的疼痛，及及病史提示相關(guān)疾病或病變病史提示相關(guān)疾病或病變不像是不像是非是可能神經(jīng)病理性痛可能神經(jīng)病理性痛證實(shí)檢查：證實(shí)檢查：A 感覺(jué)體征，位于病變神經(jīng)分布區(qū)感覺(jué)體征，位于病變神經(jīng)分布區(qū)B 診斷性檢查證實(shí)有能解釋神經(jīng)病理性痛的疾病或病變?cè)\斷性檢查證實(shí)有能解釋神經(jīng)病理性痛的疾病或病變無(wú)兩者皆有兩者皆有:肯

16、定肯定一項(xiàng)符合：一項(xiàng)符合：很可能很可能伴隨痛性神經(jīng)病的其他表現(xiàn)伴隨痛性神經(jīng)病的其他表現(xiàn)失眠失眠焦慮焦慮抑郁抑郁體重下降體重下降生命質(zhì)量下降生命質(zhì)量下降Gilron, I. et al. CMAJ 2006;175:265-275神經(jīng)病理性痛治療流程神經(jīng)病理性痛治療流程考慮非藥物治療（如理療、心理干預(yù)）早期選擇考慮非藥物治療（如理療、心理干預(yù)）早期選擇封閉治療以促進(jìn)康復(fù)（如復(fù)雜區(qū)域疼痛綜合癥）封閉治療以促進(jìn)康復(fù)（如復(fù)雜區(qū)域疼痛綜合癥）如是如是PHN或局灶神經(jīng)病或局灶神經(jīng)病可以表面用利多卡因可以表面用利多卡因起始一線治療：起始一線治療：加巴噴丁、普加巴林、加巴噴丁、普加巴林、TCA、SNRI無(wú)效、

17、部分有效或其他診斷無(wú)效、部分有效或其他診斷無(wú)效、不能耐受無(wú)效、不能耐受部分有效部分有效轉(zhuǎn)換其他一線藥轉(zhuǎn)換其他一線藥增加其他一線藥增加其他一線藥無(wú)效、不能耐受無(wú)效、不能耐受部分有效部分有效單用曲馬多或阿片類(lèi)單用曲馬多或阿片類(lèi)加用曲馬多或阿片類(lèi)加用曲馬多或阿片類(lèi)轉(zhuǎn)診、三線藥、介入干預(yù)等轉(zhuǎn)診、三線藥、介入干預(yù)等無(wú)效、不能耐受無(wú)效、不能耐受謝謝謝謝同義詞同義詞神經(jīng)病性痛，神經(jīng)病變性痛，神經(jīng)性疼痛，神經(jīng)源神經(jīng)病性痛，神經(jīng)病變性痛，神經(jīng)性疼痛，神經(jīng)源性疼痛，等等性疼痛，等等不同于神經(jīng)痛（不同于神經(jīng)痛（neuralgia） 中樞敏感化中樞敏感化 周?chē)舾谢車(chē)舾谢?CNSPNS CNS“正常正?！?傷害性感受器傷害性感受器正常傳遞正常傳遞 中樞重組中樞重組異常傷害性感受器異常傷害性感受器PNSPappagallo M. 2001.病理狀態(tài)病理狀態(tài)神經(jīng)病理性疼痛神經(jīng)病理性疼痛傷害性痛傷害性痛生理狀態(tài)生理狀態(tài)神經(jīng)病理性痛可能涉及的生理生化改變神經(jīng)病理性痛可能涉及的生理生化改變centralperipheralMe