疼痛机理与临床学习班—培训课件.pptVIP

Glu SP nociceptors do not adapt 连续刺激continued stimulation ↓ 1.感受器反复放电→自发性疼痛 continuous or repetitive firing of the nociceptor 2.感受器反应域值下降 a decrease in the threshold ↓ 外周(感受器)敏化sensitization of nociceptors 传入纤维持续放电可引起投射神经元的反应发生改变 中枢敏化 “central sensitization” ↓ 痛觉过敏 hyperalgesia 痛觉倒错 allodynia. Mechanisms of peripheral and central sensitization in neuropathic pain. Primary Afferent pathways ←descending modulatory Systems（NE/5-HT） opioid noxiousstimulus, such as an injury or disease 持续伤害性刺激 手术 炎症 神经损伤 外周敏化Peripheral sensitization to pain: 1.感受器反复放电continuous or repetitive firing of the nociceptor 2.异位从动 背根神经节的电位震荡 →自发性疼痛 3.感受器反应域值下降a decrease in the threshold →对热 冷 静态机械刺激 交感神经释放的NE敏感 一炎症汤“inflammatory soup” nociceptor function is altered by the “inflammatory soup” that characterises a region of tissue injury. CGRP CGRP Peripheral sensitization to pain: neurogenic inflammation degranulation →nitric oxide Plasmae xtravasation phospholipaseA2 1.Bradykinin:powerful algogenic substance, from kininogens in the circulation, activates nociceptors in a way that is dependent on protein kinase C and calcium 2.cytokines (interleukins interferon tumour necrosis factor) ↓ Spontaneous pain (ongoing)瘙痒 走蚁感 TNF-α 拮抗剂 阿达木单抗 （Adalimumab） 依那西普(Etanercept) 因福利美Infliximab NSAIDS?治疗 PKA phosphorylates Nav1.8/1.9; PKC phosphorylates noxious stimuli receptors (TRPV, ASIC)4. Result: increased ion influx per depolarization; lowered activation threshold Upregulated 3.Nerve growth factor(fibroblastsandSchwann Cells) →tyrosine kinase receptors increases the excitability of nociceptors which leads to hyperalgesia Capsaicin receptor 4.purines receptorP2X3 (a ligand-gated ion channel triggered by ATP) which is selectively expressed by small-diameter sensory neurons 5.acid-sensing ion channelis rapidly activated by conditions of acidity below pH →静态不痛的机械压力刺激:用手轻压皮肤→钝痛 6. prostagl