【正文】 destroy cartilage and excite the nociceptors TNFα can be inhibited by specific antibody interrupting immune system perpetuation of inflammation a basis for new antirheumatic drugs such as Adalimumab *TNFα = Tumor Necrosis Factor Alpha 雙向的相互作用 神經(jīng)系統(tǒng) – 免疫系統(tǒng) : 炎癥和疼痛的放大 Nerve Cells Immune Cells Cytokines, . TNFα Neuropeptides, NO + + 關(guān)節(jié)傷害性感受器的敏化 work by Schaible and Schmidt 19831998 Sensitization by ? 前列腺素 ? 緩激肽 ? 神經(jīng)肽 ? 細(xì)胞因子 ? ..... 炎癥前的放電 炎癥后的放電 Unphysiological range Flexion Extension Joint capsule Nociceptor 炎癥激活的靜息的傷害性感受器 Afferent fibers Time 脊髓和神經(jīng)受壓迫的多個(gè)部位 R252。疼痛治療研究進(jìn)展 首都醫(yī)科大學(xué)麻醉學(xué)系 北京三博腦科醫(yī)院 王保國 控制疼痛 醫(yī)生的職責(zé)，患者的權(quán)利！ 疼痛的定義 Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage , or described in terms of such damage. The international Association for the study of pain (IASP) 疼痛是一種與真正的或潛在的組織損傷有關(guān)的令人不愉快的感覺和情緒方面的經(jīng)歷。ckgrats Vertebral disk and protrusion Nerve sensitization by nucleus pulposus material Facet joint Spinal nerve Dura 一氧化氮合酶 mRNA在軸突損傷部位蓄積 Ventral caudal thalamus 皮層 間腦 中腦 髓質(zhì) 脊髓 背角 傳遞 A 疼痛的中樞傳遞 外周神經(jīng)纖維 Brain 交感神經(jīng)纖維 疼痛信息的中樞處理過程 ? 神經(jīng)系統(tǒng)的可塑性和中樞神經(jīng)系統(tǒng)的敏化 坐骨神經(jīng)痛的多樣生理病理機(jī)制 Baron 2022 傷害性成份 : 受到刺激的 C類傷害性感受器 Cfiber A?fiber 神經(jīng)病理性成份 1: 椎間盤突出導(dǎo)致的神經(jīng)根受壓 神經(jīng)病理性成份 2: 炎性介質(zhì) TNFα 損壞神經(jīng)根 Intervertebral disc Central sensitization Cfiber “混合性疼痛” , 一個(gè)新的臨床術(shù)語 雖然所有的傷害性感受器都是游離的神經(jīng)末梢 ,但是依據(jù)軸突可以將它們分為兩大類。 痛覺的傳遞 Central sensitizationLTP Peripheral injury triggers a change in the excitability of the CNS so that normal inputs evoked exaggerated responses leading to pain hypersensitivity (Sturge, 1883). Woolf et al (1983) provided the first evidence demonstrating that strong noxious stimulation to peripheral nerve or tissue leads to a lasting increase in excitability of spinal neurons. 正常的初級(jí)傳入纖維末梢終止于脊髓背角較深的位置 神經(jīng)損傷后， C纖維末梢萎縮，A纖維末梢芽生進(jìn)入脊髓背角的較淺部位 Neuronal circuits established in the rat spinal superficial dorsal horn Lu Y amp。35:45 慢性疼痛是一種疾病 慢性疼痛的病理生理學(xué) 外周沖動(dòng)產(chǎn)生 ... 參與 : ? 殘肢痛 ? 感覺異常和多神經(jīng)病痛 ? 感覺異常和椎間盤突出引起的痛 Ectopic excitation at site of axonal injury IIIIIII I II IIII 外周神經(jīng)損傷后中樞延遲痛產(chǎn)生 ... 參與 : ? 幻覺痛 ? 皰疹痛 ? 三叉神經(jīng)痛 Transient injurydischarge following nerve trauma Spinal Sensitization IIIIIIIIII Hyperactivity II III IIIII Delayed apoptosis Inhibitory Neuron 損傷 疼痛和感染 損傷治愈但疼痛信號(hào)持續(xù)存在 CNS結(jié)構(gòu)發(fā)生改變引起神經(jīng)傳遞變化 慢性疼痛 觸摸痛 疼痛過敏 疼痛播散 （摘自 Marcus , 2022） 慢性疼痛是一種疾病 痛與大腦 Following arm amputation, face area expands into hand area on the ?cortical map“ 皮 層 上的 軀 體感 覺 分布 圖 截肢者 Following arm amputation the face area is expanding into the hand area, as assessed by brain imaging. This reanization of sensory topography is correlated with the incidence and severity of phantom limb pain Flor et al. 1995 中樞神經(jīng)運(yùn)動(dòng)控制系統(tǒng)異化痛覺可能需要多種神經(jīng)塑形 運(yùn)動(dòng)控制系統(tǒng)的正反饋導(dǎo)致痛覺的上調(diào) M. Zimmermann, 19781999 Sensitization of reflex transmission From brain: ? Guarding behavior ? Behavioral therapy ? Positive cognitions Joint nociceptors Trigger point infiltration Positive feedback by increased muscle contraction Motor neuron Inhibitory neurons activated by: ?Analgesic drugs ?Antispastic drugs ?TENS Nociceptors of muscle and tendon 運(yùn)動(dòng)控制系統(tǒng)的失調(diào)放大痛 ... ? 過度的肌緊張 ? 關(guān)節(jié)強(qiáng)直 ? 收縮肌與拮抗肌的失平衡 ? 防護(hù)行為 ? 沒有運(yùn)動(dòng)的學(xué)習(xí)行為 ? 日常生活的千篇一律 發(fā)射控制 學(xué)習(xí)行為 ... 均增加了痛敏 慢性持續(xù)痛的軀體動(dòng)力學(xué)和心理放大反饋 Hasenbring et al., Der Schmerz 15, 2022, 442 K 鰎 p e r l i ch e F o l g e nE i n sch r 鋘 ku n g d e r B e w e g l i ch ke i tS ch o n h a l t u n gM u ske l u n d L e i st u n g ssch