School of Medicine, Federal University of Delta do Parnaíba, Parnaíba, Brazil; Department of Pharmaceutical Products, School of Pharmacy, Federal University of Minas Gerais, Avenida Antônio Carlos 6627, 31270-901, Belo Horizonte, Brazil.
Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Avenida Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
Biomed Pharmacother. 2021 Mar;135:111210. doi: 10.1016/j.biopha.2020.111210. Epub 2021 Feb 1.
Serotonin (5-HT) acts as a neurotransmitter in the central nervous system (CNS) and as a mediator released by enterochromaffin cells to regulate intestinal motility. However, this amine also plays an important role as an inflammatory mediator and induces phenotypic changes of nociceptors. Despite the wide knowledge of the role of 5-HT in nociception, most studies have focused on its role in the CNS, while a clear information about its role in peripheral tissues is still lacking. In the present study, we investigated the role of peripheral 5-HT receptors in the nociceptive response induced by 5-HT or carrageenan in mice by using antagonists that target different 5-HT receptors. Mechanical nociceptive threshold was measured with an analgesimeter and evaluated after intraplantar (i.pl.) injection of 5-HT or carrageenan. 5-HT antagonists were injected via the i.pl. route. 5-HT (10, 20, 40 or 80 μg/paw) or carrageenan (100 μg/paw) induced mechanical allodynia. Pretreatment with isamoltane (5 μg; 5-HT antagonist) or ketanserine (1 μg; 5-HT antagonist) did not affect the mechanical allodynia induced by 5-HT. This response was inhibited by BRL 15572 (10 μg; 5-HT antagonist) or SB 269970 (25 μg; 5-HT antagonist). On the other hand, mechanical allodynia induced by 5-HT or carrageenan was exacerbated by ondansetron (10, 20 or 40 μg; 5-HT antagonist). The results indicate that activation of 5-HT and 5-HT receptors plays a role in the mechanical allodynia induced by 5-HT in mice. This study also demonstrates the inhibitory role of peripheral 5-HT receptors in the nociceptive response induced by 5-HT or carrageenan.
5-羟色胺（5-HT）作为一种神经递质在中枢神经系统（CNS）和作为一种介质由肠嗜铬细胞释放以调节肠道运动。然而，这种胺也作为一种炎症介质发挥重要作用，并诱导伤害感受器的表型变化。尽管 5-HT 在伤害感受中的作用得到了广泛的认识，但大多数研究都集中在它在中枢神经系统中的作用，而对其在外周组织中的作用仍缺乏明确的信息。在本研究中，我们通过使用针对不同 5-HT 受体的拮抗剂，研究了外周 5-HT 受体在 5-HT 或角叉菜胶诱导的小鼠伤害感受反应中的作用。通过疼痛测定仪测量机械性痛觉阈值，并在足底（i.pl.）注射 5-HT 或角叉菜胶后进行评估。5-HT 拮抗剂通过 i.pl. 途径注射。5-HT（10、20、40 或 80 μg/爪）或角叉菜胶（100 μg/爪）诱导机械性痛觉过敏。伊萨姆洛坦（5 μg；5-HT 拮抗剂）或酮色林（1 μg；5-HT 拮抗剂）预处理不影响 5-HT 诱导的机械性痛觉过敏。该反应被 BRL 15572（10 μg；5-HT 拮抗剂）或 SB 269970（25 μg；5-HT 拮抗剂）抑制。另一方面，5-HT 或角叉菜胶诱导的机械性痛觉过敏被昂丹司琼（10、20 或 40 μg；5-HT 拮抗剂）加剧。结果表明，5-HT 和 5-HT 受体的激活在小鼠 5-HT 诱导的机械性痛觉过敏中发挥作用。本研究还表明，外周 5-HT 受体在 5-HT 或角叉菜胶诱导的伤害感受反应中具有抑制作用。
