Lu Ching-Liang, Pasricha Pankaj J, Hsieh Jen-Chuen, Lu Ray-Hwa, Lai Chun-Ru, Wu Learn-Long, Chang Full-Young, Lee Shou-Dong
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 11217, Taiwan.
Regul Pept. 2005 Nov;131(1-3):66-73. doi: 10.1016/j.regpep.2005.06.008.
Visceral pain/hypersensitivity is a cardinal symptom of functional gastrointestinal disorders. With their peripheral and central (spinal) projections, sensory neurons in the dorsal root ganglia (DRG) are the "gateway" for painful signals emanating from both somatic and visceral structures. In contrast to somatic pain, the neurochemical pathways involved in visceral pain/hypersensitivity have not been well studied. We hypothesized the neuropeptide changes in spinal cord and DRG during visceral pain would mirror similar changes in somatic nociception. Noxious (painful) colorectal distension (CRD) was done by distending a rectal balloon up to 60 mm Hg phasically for 1 h in Sprague-Dawley rats. The spinal content of calcitonin gene-related peptide (CGRP), substance P (SP), galanin and vasoactive intestinal peptide (VIP) as well as their mRNAs in DRG were measured at 0, 4 and 24 h after the CRD. Visceromotor reflex (VMR) was measured by recording the electromyogram at the abdominal muscle in response to CRD. Distal colorectum was removed for evaluating the presence of inflammation. No significant evidence of histological inflammation was seen in the colonic mucosa/submucosa after repeated CRD, which is confirmed by myeloperoxidase assay. The spinal content of CGRP and SP decreased significantly 4 h after CRD, while galanin and VIP levels increased gradually and reached highest level at 24 h (p<0.05). The mRNAs in DRG of the neuropeptides were significantly upregulated after CRD (p<0.05). VMR recording showed the rat's colon became hypersensitive 4 h after CRD, a sequence parallel to the spinal changes of CGRP and SP in timeframe. Noxious mechanical distension of the colorectum causes an acute change in the spinal levels of excitatory neurotransmitters (CGRP and SP), probably reflecting central release of these peptides from sensory neurons and contributing to the hypersensitivity following the noxious CRD. This is followed by a slower change in the levels of the inhibitory neurotransmitter galanin and VIP. Such stimulation results in significant alternation of the gene expression in DRG, reflecting the plasticity of the neuronal response. In the absence of visceral inflammation, the aforementioned neuropeptides are important mediators in the processing of visceral pain/hypersensitivity.
内脏痛觉过敏是功能性胃肠疾病的主要症状。背根神经节（DRG）中的感觉神经元通过其外周和中枢（脊髓）投射，成为源自躯体和内脏结构的疼痛信号的“门户”。与躯体痛不同，内脏痛觉过敏所涉及的神经化学通路尚未得到充分研究。我们推测，内脏痛期间脊髓和DRG中的神经肽变化将反映躯体痛觉感受中的类似变化。通过在Sprague-Dawley大鼠中阶段性地将直肠球囊扩张至60 mmHg并持续1小时来进行有害（疼痛性）结肠扩张（CRD）。在CRD后的0、4和24小时测量脊髓中降钙素基因相关肽（CGRP）、P物质（SP）、甘丙肽和血管活性肠肽（VIP）的含量以及它们在DRG中的mRNA。通过记录腹部肌肉对CRD的肌电图来测量内脏运动反射（VMR）。切除远端结肠以评估炎症的存在。重复CRD后，结肠黏膜/黏膜下层未发现明显的组织学炎症证据，髓过氧化物酶测定证实了这一点。CRD后4小时，脊髓中CGRP和SP的含量显著降低，而甘丙肽和VIP水平逐渐升高，并在24小时达到最高水平（p<0.05）。CRD后，神经肽在DRG中的mRNA显著上调（p<0.05）。VMR记录显示，CRD后4小时大鼠结肠变得过敏，这一顺序在时间框架上与CGRP和SP的脊髓变化平行。结肠的有害机械扩张导致兴奋性神经递质（CGRP和SP）的脊髓水平发生急性变化，这可能反映了这些肽从感觉神经元的中枢释放，并导致有害CRD后的过敏反应。随后，抑制性神经递质甘丙肽和VIP的水平发生较慢变化。这种刺激导致DRG中的基因表达发生显著改变，反映了神经元反应的可塑性。在内脏无炎症的情况下，上述神经肽是内脏痛觉过敏处理过程中的重要介质。
