Sengupta Jyoti N
Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53051, USA.
Handb Exp Pharmacol. 2009(194):31-74. doi: 10.1007/978-3-540-79090-7_2.
The mechanism of visceral pain is still less understood compared with that of somatic pain. This is primarily due to the diverse nature of visceral pain compounded by multiple factors such as sexual dimorphism, psychological stress, genetic trait, and the nature of predisposed disease. Due to multiple contributing factors there is an enormous challenge to develop animal models that ideally mimic the exact disease condition. In spite of that, it is well recognized that visceral hypersensitivity can occur due to (1) sensitization of primary sensory afferents innervating the viscera, (2) hyperexcitability of spinal ascending neurons (central sensitization) receiving synaptic input from the viscera, and (3) dysregulation of descending pathways that modulate spinal nociceptive transmission. Depending on the type of stimulus condition, different neural pathways are involved in chronic pain. In early-life psychological stress such as maternal separation, chronic pain occurs later in life due to dysregulation of the hypothalamic-pituitary-adrenal axis and significant increase in corticotrophin releasing factor (CRF) secretion. In contrast, in early-life inflammatory conditions such as colitis and cystitis, there is dysregulation of the descending opioidergic system that results excessive pain perception (i.e., visceral hyperalgesia). Functional bowel disorders and chronic pelvic pain represent unexplained pain that is not associated with identifiable organic diseases. Often pain overlaps between two organs and approximately 35% of patients with chronic pelvic pain showed significant improvement when treated for functional bowel disorders. Animal studies have documented that two main components such as (1) dichotomy of primary afferent fibers innervating two pelvic organs and (2) common convergence of two afferent fibers onto a spinal dorsal horn are contributing factors for organ-to-organ pain overlap. With reports emerging about the varieties of peptide molecules involved in the pathological conditions of visceral pain, it is expected that better therapy will be achieved relatively soon to manage chronic visceral pain.
与躯体痛相比，内脏痛的机制仍鲜为人知。这主要是由于内脏痛具有多样性，且受多种因素影响，如性别差异、心理压力、遗传特征以及易感疾病的性质等。由于存在多种促成因素，开发能够理想地模拟确切疾病状况的动物模型面临巨大挑战。尽管如此，人们普遍认识到内脏超敏反应可能由于以下原因发生：（1）支配内脏的初级感觉传入神经的敏化；（2）接受来自内脏突触输入的脊髓上行神经元的过度兴奋（中枢敏化）；（3）调节脊髓伤害性传递的下行通路失调。根据刺激条件的类型，不同的神经通路参与慢性疼痛。在早期生活中的心理应激，如母婴分离，慢性疼痛会在后期因下丘脑 - 垂体 - 肾上腺轴失调和促肾上腺皮质激素释放因子（CRF）分泌显著增加而出现。相比之下，在早期生活中的炎症性疾病，如结肠炎和膀胱炎，下行阿片能系统失调会导致过度的疼痛感知（即内脏痛觉过敏）。功能性肠病和慢性盆腔痛代表无法解释的疼痛，与可识别的器质性疾病无关。疼痛常常在两个器官之间重叠，约35%的慢性盆腔痛患者在接受功能性肠病治疗时症状显著改善。动物研究表明，两个主要因素，即（1）支配两个盆腔器官的初级传入纤维的二分法和（2）两条传入纤维在脊髓背角的共同汇聚，是器官间疼痛重叠的促成因素。随着有关参与内脏痛病理状况的肽分子种类的报道不断涌现，预计不久将实现更好的治疗方法来管理慢性内脏痛。
