Section of Translational Neurovascular Research, IRCCS Mondino Foundation, Pavia, Italy.
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
J Headache Pain. 2024 Oct 25;25(1):184. doi: 10.1186/s10194-024-01890-4.
In addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors.
In a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague-Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration.
Both doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP.
The findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine.
脑源性神经营养因子（BDNF）除了在神经发生中具有关键作用外，还调节疼痛和抑郁行为。
从转化的角度来看，我们在基于慢性和间歇性 NTG 给药（在九天内总共给予五次注射）的头部疼痛动物模型中测试了高度纯化和表征的重组人 BDNF（rhBDNF）的抗偏头痛活性，用于模拟在给定时间段内的攻击复发。为此，我们评估了两种剂量的 rhBDNF（40 和 80μg/kg）经鼻内给药对成年雄性 Sprague-Dawley 大鼠三叉神经痛觉过敏（通过口腔福尔马林测试）、与偏头痛疼痛相关的特定脑区神经肽和炎症细胞因子的基因表达（通过 rt-PCR）的影响。还评估了血清中 CGRP、PACAP 和 VIP 的水平（通过 ELISA）。rhBDNF 的作用与舒马曲坦（5mg/kg，ip）的作用进行了比较，舒马曲坦在最后一次 NTG 给药前 1 小时给药。
两种剂量的 rhBDNF 均显著减少了口腔福尔马林试验 II 期 NTG 诱导的伤害性行为。在 NTG 处理的动物中，高剂量 rhBDNF 经鼻内给药的抗痛觉过敏作用与三叉神经节、延髓-脑桥和下丘脑区域神经肽（CGRP、PACAP、VIP）和细胞因子（IL-1beta、IL-10）mRNA 水平的显著调节相关。值得注意的是，rhBNDF 治疗的效果可与舒马曲坦给药诱导的效果相媲美。rhBDNF 给药的两种剂量均显著降低了血清中 PACAP 的水平，而较高的剂量也显著降低了 VIP 的水平。
这些发现表明，鼻内 rhBDNF 具有成为治疗原发性头痛（特别是偏头痛）的安全、非侵入性和有效的治疗方法的潜力。
