【正文】 LTP Cfiber evoked spinal field potential LTP, a model for long term sensitization in the central nervous system Tetanic Cfiber stimulation 100 Hz, 5 sec ... any prolonged nociceptive input may induce spinal LTP! 軸突信號將損傷信息傳遞到細(xì)胞核 痛導(dǎo)致神經(jīng)塑性 .... ? 導(dǎo)致神經(jīng)元的基因轉(zhuǎn)錄 ? 類鴉片系統(tǒng)的弱化 ? 中樞神經(jīng)系統(tǒng)運(yùn)動控制系統(tǒng)的失調(diào) ? 皮層拓?fù)涞闹亟M ? 痛相關(guān)認(rèn)知和行為可以持久化和放大痛 ? 多種社會效應(yīng) 傷害性刺激的跨膜基因誘導(dǎo)導(dǎo)致復(fù)雜的神經(jīng)塑形響應(yīng) NMDAreceptors * IEGs = Immediate Early Genes Transcriptional regulation of: Neurotransmitters Synaptic receptor proteins Trophic substances Adverse functional modifications in the pain system, .: Neuronal Sensitization Attenuation of inhibitory cells Neuronal cell death * Induction of such as 重復(fù)傷害性刺激后在大鼠脊髓神經(jīng)元出現(xiàn) “ Immediate Early Genes”如 cfos轉(zhuǎn)錄標(biāo)志著痛通路中長時程可塑性 Herdegen, Zimmermann et al. 1993 Dorsal horn Laminae 1 3 Laminae 4 7 Afferent Cfibers to brain Attenuation of cFos, LTP, sensitization, apoptosis by OligoDesoxynucleotides against cfos Block of either NMDA, NK1, NOS, TNF? ... 參與 神 經(jīng)損傷 后多 處 痛 發(fā) 生的 細(xì) 胞機(jī)制 Zimmermann et al., 1989 2022 Transynaptic gene induction Deficiency of neurotrophic factors from target Abnormal excitability, Stump pain Sensitization, Impaired inhibition, Apoptosis, Phantom pain cFos cJun LTP, Long term potentiation cJun Bcl2 Regeneration, Apoptosis DR ganglion Nerve sprouts Spinal cord Axonal transport Brookoff D. Hosp Pract (Off Ed) 2022。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)動控制系統(tǒng)異化痛覺可能需要多種神經(jīng)塑形 運(yùn)動控制系統(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 w 鋍 heP sy ch o so zi a l e F o l g e nV e r l u st d e r S e l b st w i r ksa m ke i tA n g st / D e p r e ssi o nK r a n kh e i t sg e w i n nS ch m e r zSt 鋜 ke , D a u e rA u sl 鰏 e r e i n e r S ch m e r ze p i so d e Trigger by Initial Pain Episode Pain Intensity, Duration Somatic Consequences Guarding Behavior Decreased Mobilty Decreased Muscle Strength Psychosocial Consequences Loss of Self Efficacy Anxiety/Depression Secondary Social Gain Examples: Low Back Pain, Fibromyalgia 痛與抑郁 , 通常并存的疾病 誰為先 ? 慢性痛 – 抑郁的癥狀 Blumer and Heilbronn 1981, Pain a variant of depression ? 抑郁 – 慢性痛的轉(zhuǎn)歸 W246。