Finamor Fabrício, Scarabelot Vanessa Leal, Medeiros Liciane Fernandes, Stein Dirson João, da Silva Morgana Duarte, Callai Etiane, Caumo Wolnei, de Souza Andressa, Torres Iraci L S
Nucleus of Pain Pharmacology and Neuromodulation. Hospital de Clínicas de Porto Alegre, RS, Brazil.
Nucleus of Pain Pharmacology and Neuromodulation. Hospital de Clínicas de Porto Alegre, RS, Brazil; Universidade La Salle, Canoas, RS, Brazil.
Neurosci Lett. 2023 Jan 10;793:136970. doi: 10.1016/j.neulet.2022.136970. Epub 2022 Nov 17.
Trigeminal neuropathic pain (TNP) is an intense pain condition characterized by hyperalgesia and allodynia; however, its neural mechanisms are not completely understood. Its management is complex, and studies that investigate its biochemical mechanisms are important for improving clinical approaches. This study aimed to evaluate the involvement of GABAergic, glutamatergic, and opioidergic systems and brain-derived neurotrophic factor (BDNF) levels in the TNP process in rats. TNP is induced by chronic constriction injury of the infraorbital nerve (CCI-ION). Nociceptive responses were evaluated using the facial von Frey test before and after the administration of GABAergic and opioidergic agonists and glutamatergic antagonists. The rats were divided into vehicle-treated control (C), sham-surgery (SS), and CCI-ION groups, and then subdivided into the vehicle (V)-treated SS-V and CCI-ION-V groups, SS-MK801 and CCI-ION-MK801, treated with the N-methyl-d-aspartate receptor selective antagonist MK801; SS-PB and CCI-ION-PB, treated with phenobarbital; SS-BZD and CCI-ION-BZD, treated with diazepam; SS-MOR and CCI-ION-MOR, treated with morphine. BDNF levels were evaluated in the cerebral cortex, brainstem, trigeminal ganglion, infraorbital branch of the trigeminal nerve, and serum. CCI-ION induced facial mechanical hyperalgesia. Phenobarbital and morphine reversed the hyperalgesia induced by CCI-ION, and the CCI-BZD group had an increased nociceptive threshold until 60 min. CCI-ION-GLU increased the nociceptive threshold at 60 min. Cerebral cortex and brainstem BDNF levels increased in the CCI-ION and SS groups. Only the CCI group presented high levels of BDNF in the trigeminal ganglion. Our data suggest the involvement of GABAergic, glutamatergic, and opioidergic systems and peripheral BDNF in the TNP process.
三叉神经病理性疼痛（TNP）是一种以痛觉过敏和异常性疼痛为特征的剧烈疼痛病症；然而，其神经机制尚未完全明确。其治疗较为复杂，研究其生化机制对于改进临床治疗方法具有重要意义。本研究旨在评估γ-氨基丁酸能、谷氨酸能和阿片样物质能系统以及脑源性神经营养因子（BDNF）水平在大鼠TNP过程中的作用。通过眶下神经慢性压迫损伤（CCI-ION）诱导TNP。在给予γ-氨基丁酸能和阿片样物质能激动剂以及谷氨酸能拮抗剂前后，使用面部von Frey试验评估伤害性反应。将大鼠分为溶剂处理对照组（C）、假手术组（SS）和CCI-ION组，然后再细分为溶剂（V）处理的SS-V和CCI-ION-V组、用N-甲基-D-天冬氨酸受体选择性拮抗剂MK801处理的SS-MK801和CCI-ION-MK801组、用苯巴比妥处理的SS-PB和CCI-ION-PB组、用地西泮处理的SS-BZD和CCI-ION-BZD组、用吗啡处理的SS-MOR和CCI-ION-MOR组。在大脑皮层、脑干、三叉神经节、三叉神经眶下支和血清中评估BDNF水平。CCI-ION诱导面部机械性痛觉过敏。苯巴比妥和吗啡可逆转CCI-ION诱导的痛觉过敏，且CCI-BZD组在60分钟内伤害性阈值升高。CCI-ION-GLU在60分钟时提高了伤害性阈值。CCI-ION组和SS组大脑皮层和脑干中的BDNF水平升高。仅CCI组三叉神经节中BDNF水平较高。我们的数据表明γ-氨基丁酸能、谷氨酸能和阿片样物质能系统以及外周BDNF参与了TNP过程。
