VISCERAL PAIN

内脏疼痛导致癌症和癌症患者的痛苦和功能障碍 炎症状态。对其机制和神经机制知之甚少 涉及内脏的系统多于涉及皮肤疼痛的系统。尽管 脊髓丘脑束同时发出皮肤和内脏疼痛的信号， 神经外科背柱中线损伤可缓解骨盆症状 癌痛，省去皮肤感和疼痛。假设1是 一条发出内脏胀痛信号的通路在 背柱。具体的目的1是看看病变是否会降低反应 VPL神经元对伤害性结直肠扩张的反应。假设2是 内脏伤害性感受通路是突触后背柱的一部分 路径。具体目标2是确定源、目的地和 该途径的多肽含量。解剖学和电生理学 计划进行实验，以记录对结直肠扩张的反应 突触后背柱神经元和背柱核及TO 确定细小神经元的内脏反应是否通过 突触后背柱神经元而不是通过直接初级传入 投射。假设3是该通路也负责 内脏发炎痛的信号。具体的目标3是点燃 并确定1)神经元的反应是否增强 内脏炎症后；2)室旁核神经元反应增强 通过阻断通路的损伤来减少或阻止；3)相同 损伤会阻止脑干细胞群对c-fos进行染色。假设 内脏炎性痛引起中枢敏感化。 特异性目的是探讨致敏作用的机理。 通过测定1)释放到内脏的氨基酸来预防内脏炎症 结肠炎时的背角；2)如果背根反射 在结肠炎期间发生；3)是否可以减少敏感度 通过输注兴奋性氨基酸、GABA(A)或多肽的拮抗剂 位于L6-S1的受体进入背角；4)肽基因 药理作用前后的调控与表达 操纵。长期目标是制定新的战略， 内脏痛的治疗。

Visceral pain causes suffering and dysfunction in malignant and inflammatory states. Less is known about the mechanisms and neural systems involved in visceral than in cutaneous pain. Although the spinothalamic tract signals both cutaneous and visceral pain, a neurosurgical midline lesion in the dorsal column can relieve pelvic cancer pain, sparing cutaneous sensation and pain. HYPOTHESIS 1 is that a pathway that signals the pain of visceral distention ascends in the dorsal column. SPECIFIC AIM 1 is to see if a lesion reduces the responses of VPL neurons to noxious colorectal distention. HYPOTHESIS 2 is that the visceral nociceptive pathway is a part of the postsynaptic dorsal column pathway. SPECIFIC AIM 2 is to determine the source, destination, and peptide content of the pathway. Anatomical and electrophysiological experiments are planned to record responses to colorectal distention of postsynaptic dorsal column neurons and dorsal column nucleus and to determine if visceral responses of gracile neurons are signaled by postsynaptic dorsal column neurons rather than by direct primary afferent projections. HYPOTHESIS 3 is that the pathway is also responsible for signaling visceral inflammatory pain. SPECIFIC AIM 3 is to inflame the colon and to determine if 1) the responses of neurons become enhanced following visceral inflammation; 2) the enhanced responses of VPL neurons are reduced or prevented by a lesion interrupting the pathway; 3) the same lesions prevent brainstem cell groups from staining for c-FOS. HYPOTHESIS 4 is that visceral inflammatory pain causes central sensitization. SPECIFIC AIM 4 is to investigate mechanisms of the sensitization resulting from visceral inflammation by determining 1) the amino acids released into the dorsal horn during colon inflammation; 2) if dorsal root reflexes develop during colon inflammation; 3) if the sensitization can be reduced by infusing antagonists of excitatory amino acid, GABA(A) or peptide receptors into the dorsal horn at L6-S1; and 4) the peptide gene regulation and expression before and after the pharmacological manipulations. The long-term goal is to develop new strategies for therapy of visceral pain.