Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Department of Experimental and Clinical Medicine-DMSC, Anatomy and Histology Section, University of Florence, L. go Brambilla 3, 50134 Florence, Italy.
Cells. 2020 Jul 24;9(8):1772. doi: 10.3390/cells9081772.
The management of visceral pain is a major clinical problem in patients affected by gastrointestinal disorders. The poor knowledge about pain chronicization mechanisms prompted us to study the functional and morphological alterations of the gut and nervous system in the animal model of persistent visceral pain caused by 2,4-dinitrobenzenesulfonic acid (DNBS). This agent, injected intrarectally, induced a colonic inflammation peaking on day 3 and remitting progressively from day 7. In concomitance with bowel inflammation, the animals developed visceral hypersensitivity, which persisted after colitis remission for up to three months. On day 14, the administration of pain-relieving drugs (injected intraperitoneally and intrathecally) revealed a mixed nociceptive, inflammatory and neuropathic pain originating from both the peripheral and central nervous system. At this time point, the colonic histological analysis highlighted a partial restitution of the , transmural collagen deposition, infiltration of mast cells and eosinophils, and upregulation of substance P (SP)-positive nerve fibers, which were surrounded by eosinophils and MHC-II-positive macrophages. A significant activation of microglia and astrocytes was observed in the dorsal and ventral horns of spinal cord. These results suggest that the persistence of visceral pain induced by colitis results from maladaptive plasticity of the enteric, peripheral and central nervous systems.
内脏疼痛的管理是受胃肠道疾病影响的患者的一个主要临床问题。我们对疼痛慢性化机制的了解甚少，促使我们在 2,4-二硝基苯磺酸（DNBS）引起的持续性内脏疼痛动物模型中研究肠道和神经系统的功能和形态改变。该试剂通过直肠内注射，在第 3 天引起结肠炎症高峰，并从第 7 天开始逐渐缓解。与肠道炎症同时发生的是内脏高敏性，这种高敏性在结肠炎缓解后可持续长达三个月。在第 14 天，给予止痛药物（腹腔内和鞘内注射）后，发现源自外周和中枢神经系统的混合伤害感受、炎症和神经病理性疼痛。此时，结肠组织学分析突出显示，黏膜下胶原沉积、肥大细胞和嗜酸性粒细胞浸润以及 P 物质（SP）阳性神经纤维的部分恢复，这些神经纤维被嗜酸性粒细胞和 MHC-II 阳性巨噬细胞包围。在脊髓背角和腹角中观察到小胶质细胞和星形胶质细胞的显著激活。这些结果表明，结肠炎引起的内脏疼痛持续存在是由于肠、外周和中枢神经系统的适应性可塑性。
