Headache Group, Wolfson Centre for Age-Related Disease, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
Department of Nutrition and Metabolism, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa; Lisboa, Portugal.
Cephalalgia. 2022 Nov;42(13):1359-1374. doi: 10.1177/03331024221110111. Epub 2022 Oct 18.
Imaging migraine premonitory studies show increased midbrain activation consistent with the ventral tegmental area, an area involved in pain modulation and hedonic feeding. We investigated ventral tegmental area pharmacological modulation effects on trigeminovascular processing and consequent glycemic levels, which could be involved in appetite changes in susceptible migraine patients.
Serotonin and pituitary adenylate cyclase-activating polypeptide receptors immunohistochemistry was performed in ventral tegmental area parabrachial pigmented nucleus of male Sprague Dawley rats. trigeminocervical complex neuronal responses to dura mater nociceptive electrical stimulation, and facial mechanical stimulation of the ophthalmic dermatome were recorded. Changes in trigeminocervical complex responses following ventral tegmental area parabrachial pigmented nucleus microinjection of glutamate, bicuculline, naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole were measured, and blood glucose levels assessed pre- and post-microinjection.
Glutamatergic stimulation of ventral tegmental area parabrachial pigmented nucleus neurons reduced nociceptive and spontaneous trigeminocervical complex neuronal firing. Naratriptan, pituitary adenylate cyclase-activating polypeptide-38 and quinpirole inhibited trigeminovascular spontaneous activity, and trigeminocervical complex neuronal responses to dural-evoked electrical and mechanical noxious stimulation. Trigeminovascular sensory processing through modulation of the ventral tegmental area parabrachial pigmented nucleus resulted in reduced circulating glucose levels.
Pharmacological modulation of ventral tegmental area parabrachial pigmented nucleus neurons elicits changes in trigeminovascular sensory processing. The interplay between ventral tegmental area parabrachial pigmented nucleus activity and the sensory processing by the trigeminovascular system may be relevant to understand associated sensory and homeostatic symptoms in susceptible migraine patients.
偏头痛先兆的影像学研究表明，中脑激活增加，与参与疼痛调节和愉悦性摄食的腹侧被盖区一致。我们研究了腹侧被盖区-臂旁核色氨酸区神经元的药理学调制对三叉血管系统处理的影响，以及随之而来的血糖水平变化，这可能与易感偏头痛患者的食欲变化有关。
对雄性 Sprague Dawley 大鼠的腹侧被盖区-臂旁核色氨酸区进行 5-羟色胺和垂体腺苷酸环化酶激活肽受体免疫组织化学染色。记录三叉颈复合体神经元对硬脑膜伤害性电刺激和眶皮区机械性刺激的反应。测量腹侧被盖区-臂旁核色氨酸区微量注射谷氨酸、荷包牡丹碱、那拉曲坦、垂体腺苷酸环化酶激活肽-38 和喹吡罗后三叉颈复合体反应的变化，并在微注射前后评估血糖水平。
腹侧被盖区-臂旁核色氨酸区神经元的谷氨酸刺激减少了伤害性和自发性三叉颈复合体神经元的放电。那拉曲坦、垂体腺苷酸环化酶激活肽-38 和喹吡罗抑制三叉血管自发性活动以及三叉颈复合体神经元对硬脑膜诱发电刺激和机械性伤害刺激的反应。通过调节腹侧被盖区-臂旁核色氨酸区神经元，三叉血管感觉处理导致循环血糖水平降低。
腹侧被盖区-臂旁核色氨酸区神经元的药理学调制会引起三叉血管感觉处理的变化。腹侧被盖区-臂旁核色氨酸区神经元活动与三叉血管系统的感觉处理之间的相互作用可能与理解易感偏头痛患者相关的感觉和稳态症状有关。
