Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2014 Jan;77(1):3-9. doi: 10.1016/j.jcma.2013.08.008. Epub 2013 Oct 1.
Chronic visceral pain is the predominant symptom of functional gastrointestinal disorders and chronic pancreatitis. Such pain can impair the patients' quality of life, and can also serve as one of the principal reasons for these patients to seek medical help. Nevertheless, the underlying mechanisms of chronic visceral pain have remained unclear, and much of what we know about visceral pain has been derived from studies of somatic nociception. Current treatment of chronic visceral pain has continued to be unsatisfactory, because of unclear pathophysiology. However, recent progress in pain research has identified the important role of spinal microglia in the development of somatic nociception. For visceral pain, several animal studies have demonstrated that spinal cord microglia is activated during the development of visceral hyperalgesia, which can be induced by neonatal colorectal irritation, psychological stress, and trinitrobenzene sulfonic acid-induced pancreatitis. This visceral hyperalgesia is also associated with elevated phosphorylation of p38 mitogen-activated protein kinase. Minocycline (a microglia inhibitor) reversed the hyperalgesia in rat models of chronic visceral pain, whereas fractalkine (FKN, a microglia activator) reproduced the visceral nociception in naïve rats. These preliminary results support the pronociceptive role of spinal microglia in mediating visceral hyperalgesia. Consequently, spinal microglia may serve as a promising target for controlling the chronic visceral pain.
慢性内脏痛是功能性胃肠疾病和慢性胰腺炎的主要症状。这种疼痛会降低患者的生活质量，也是这些患者寻求医疗帮助的主要原因之一。然而，慢性内脏痛的潜在机制仍不清楚，我们对内脏痛的了解大多来自躯体伤害感受的研究。由于病理生理学不明确，目前慢性内脏痛的治疗仍不尽如人意。然而，疼痛研究的最新进展已经确定了脊髓小胶质细胞在躯体伤害感受发展中的重要作用。对于内脏痛，几项动物研究表明，内脏痛觉过敏发展过程中脊髓小胶质细胞被激活，这种内脏痛觉过敏可以通过新生儿结直肠刺激、心理应激和三硝基苯磺酸诱导的胰腺炎来诱导。这种内脏痛觉过敏也与 p38 丝裂原活化蛋白激酶的磷酸化升高有关。米诺环素（一种小胶质细胞抑制剂）逆转了慢性内脏痛大鼠模型中的痛觉过敏，而 fractalkine（FKN，一种小胶质细胞激活剂）在未处理的大鼠中再现了内脏痛觉。这些初步结果支持脊髓小胶质细胞在介导内脏痛觉过敏中的伤害感受作用。因此，脊髓小胶质细胞可能是控制慢性内脏痛的一个有前途的靶点。
