Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Interdipartimental University Center of Research "Adaptation and Regeneration of Tissues and Organs (ARTO)", University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Biomed Res Int. 2022 Mar 11;2022:1326885. doi: 10.1155/2022/1326885. eCollection 2022.
Physiology of orofacial pain pathways embraces primary afferent neurons, pathologic changes in the trigeminal ganglion, brainstem nociceptive neurons, and higher brain function regulating orofacial nociception. The goal of this study was to investigate the nitroxidergic system alteration at brainstem level (spinal trigeminal nucleus), and the role of peripheral P2 purinergic receptors in an experimental mouse model of pediatric inflammatory orofacial pain, to increase knowledge and supply information concerning orofacial pain in children and adolescents, like pediatric dentists and pathologists, as well as oro-maxillo-facial surgeons, may be asked to participate in the treatment of these patients. The experimental animals were treated subcutaneously in the perioral region with pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a P2 receptor antagonist, 30 minutes before formalin injection. The pain-related behavior and the nitroxidergic system alterations in the spinal trigeminal nucleus using immunohistochemistry and western blotting analysis have been evaluated. The local administration of PPADS decreased the face-rubbing activity and the expression of both neuronal and inducible nitric oxide (NO) synthase isoforms in the spinal trigeminal nucleus. These results underline a relationship between orofacial inflammatory pain and nitroxidergic system in the spinal trigeminal nucleus and suggest a role of peripheral P2 receptors in trigeminal pain transmission influencing NO production at central level. In this way, orofacial pain physiology should be elucidated and applied to clinical practice in the future.
口腔颌面疼痛通路的生理学包括初级传入神经元、三叉神经节的病理变化、脑干伤害感受神经元和调节口腔颌面伤害感受的高级大脑功能。本研究的目的是探讨脑干水平（三叉神经脊束核）的硝态氮系统改变，以及外周 P2 嘌呤能受体在小儿炎症性口腔颌面疼痛实验模型中的作用，以增加有关儿童和青少年口腔颌面疼痛的知识和提供信息，如儿科牙医和病理学家，以及口腔颌面外科医生，可能被要求参与这些患者的治疗。实验动物在口周区域皮下接受吡哆醛-6-偶氮苯-2'，4'-二磺酸（PPADS），一种 P2 受体拮抗剂，在福马林注射前 30 分钟。通过免疫组织化学和 Western 印迹分析评估了疼痛相关行为和三叉神经脊束核中硝态氮系统的改变。局部给予 PPADS 可减少面部摩擦活动和脊髓三叉神经核中神经元型和诱导型一氧化氮合酶同工型的表达。这些结果表明口腔颌面炎症性疼痛与脊髓三叉神经核中的硝态氮系统之间存在关系，并提示外周 P2 受体在三叉神经疼痛传递中影响中央水平的 NO 产生中的作用。通过这种方式，未来应阐明口腔颌面疼痛生理学并将其应用于临床实践。
