Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy.
Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy.
Toxins (Basel). 2019 Jul 31;11(8):449. doi: 10.3390/toxins11080449.
Visceral pain, of which the pathogenic basis is currently largely unknown, is a hallmark symptom of both functional disorders, such as irritable bowel syndrome, and inflammatory bowel disease. Intrinsic sensory neurons in the enteric nervous system and afferent sensory neurons of the dorsal root ganglia, connecting with the central nervous system, represent the primary neuronal pathways transducing gut visceral pain. Current pharmacological therapies have several limitations, owing to their partial efficacy and the generation of severe adverse effects. Numerous cellular targets of visceral nociception have been recognized, including, among others, channels (i.e., voltage-gated sodium channels, VGSCs, voltage-gated calcium channels, VGCCs, Transient Receptor Potential, TRP, and Acid-sensing ion channels, ASICs) and neurotransmitter pathways (i.e., GABAergic pathways), which represent attractive targets for the discovery of novel drugs. Natural biologically active compounds, such as marine toxins, able to bind with high affinity and selectivity to different visceral pain molecular mediators, may represent a useful tool (1) to improve our knowledge of the physiological and pathological relevance of each nociceptive target, and (2) to discover therapeutically valuable molecules. In this review we report the most recent literature describing the effects of marine toxin on gastrointestinal visceral pain pathways and the possible clinical implications in the treatment of chronic pain associated with gut diseases.
内脏痛目前其发病基础在很大程度上尚不清楚，是功能性疾病（如肠易激综合征和炎症性肠病）和炎症性肠病的标志性症状。肠神经系统中的固有感觉神经元和与中枢神经系统相连的背根神经节中的传入感觉神经元是将肠道内脏痛转化为初级神经元途径的主要途径。由于其部分疗效和严重不良反应的产生，目前的药物治疗方法存在多种局限性。内脏伤害感受的许多细胞靶点已被识别，包括通道（即电压门控钠离子通道、VGSCs、电压门控钙通道、VGCCs、瞬时受体电位、TRP 和酸敏离子通道、ASICs）和神经递质途径（即 GABA 能途径），这些都是发现新型药物的有吸引力的靶点。天然生物活性化合物，如海洋毒素，能够与不同的内脏痛分子介质以高亲和力和选择性结合，可能是一种有用的工具：（1）提高我们对每个伤害性靶点的生理和病理相关性的认识；（2）发现有治疗价值的分子。在这篇综述中，我们报告了最近描述海洋毒素对胃肠道内脏痛途径影响的文献，并描述了其在治疗与肠道疾病相关的慢性疼痛方面的可能临床意义。
