Effect of Nebulized Dexmedetomidine on Central Sensitization and Chronification in Migraine: A Randomized Controlled Trial Using Calcitonin Gene Related Peptide and Trigeminal Neurophysiological Biomarkers
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 146
- 试验地点
- 1
- 主要终点
- Treatment of Chronic Migraine
研究概览
简要总结
Migraine is a debilitating neurological disorder characterized by recurrent headaches episodes, often accompanied by amplified perception of multiple sensory inputs such as cutaneous allodynia, photophobia, and phonophobia. The suggested mechanism in migraine is likely through sensitized trigeminovascular and dysfunctional pain modulatory systems.
Dexmedetomidine, a selective α2-adrenergic receptor agonist, exerts central antinociceptive effects by reducing neuronal hyperexcitability, glial activation, and CGRP expression. Nebulized administration provides a non-invasive alternative to intravenous use, with rapid CNS absorption and minimal sedation .
详细描述
Chronic migraine: This is defined as a headache that occurs on 15 or more days in a month for more than 3 months, with migraine features present on at least 8 or more days in a month. Episodic syndromes that may be associated with migraine include recurrent gastrointestinal disturbances, involving recurrent attacks of abdominal pain, discomfort, nausea, and vomiting that may be associated with migraines; benign paroxysmal vertigo involving brief, recurrent attacks of vertigo, or benign paroxysmal torticollis is characterized by recurrent episodes of head tilt to one side.
Migraine chronification is strongly associated with central sensitization of the trigeminovascular system, a process mediated by the upregulation of calcitonin gene-related peptide (CGRP) and enhanced excitability of both brainstem and cortical pain-processing structures. Elevated CGRP plays a pivotal role in migraine pathophysiology by promoting vasodilation, neurogenic inflammation, and nociceptive facilitation.
Calcitonin gene-related peptide is a 37-amino acid neuropeptide and a potent vasodilator produced by neurons in both the central and peripheral nervous systems. Activation of CGRP-R in the trigeminovascular system plays a critical role in peripheral and central events that ultimately lead to the experience of migraine pain .
Following nerve stimulation, CGRP is released from its storage vesicles through the process of calcium-dependent exocytosis.This peripheral release of CGRP from trigeminal nerve endings is thought to trigger multiple responses induced by CGRP-R binding, which eventually lead to the sensitization of nociceptor trigeminal neurons.
The stimulation of peripheral nociceptive trigeminal neurons is hypothesized to relay the migraine pain signal through the brainstem into the brain, ultimately leading to the experience of migraine pain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Early chronic migraine (<6 months of ≥15 headache days/month), per ICHD-3 criteria.
- •No preventive migraine therapy in the prior 8 weeks.
排除标准
- •Presence of cardiopulmonary, psychiatric, or neurological comorbidities.
- •Current use of sedatives, opioids, or CGRP-targeting therapies.
- •Pregnancy or breastfeeding.
研究组 & 干预措施
Group A (Nebulized dexmedetomidine ):
About 73 cases suffering from Chronic Migraine will undergo Nebulized dexmedetomidine (1 mcg/kg in 4 mL normal saline) Administered via jet nebulizer for 3 sessions per week for 2weeks
干预措施: Dexmedetomidine (Drug)
Group B (Placebo):
About 73 cases suffering from Chronic Migraine will undergo Nebulized 4 mL normal saline Administered via jet nebulizer for 3 sessions per week for 2weeks
干预措施: Dexmedetomidine (Drug)
结局指标
主要结局
Treatment of Chronic Migraine
时间窗: 6 Months
Assessment of the patients whom suffering from Chronic Migraine treated by Nebulized Dexmedetomidine on Central Sensitization and Chronification in Migraine
次要结局
未报告次要终点
研究者
Ibthal Osama Fathy Ibrahim
Assistant lecturer at Anesthesiology, surgical intensive care, and pain managemen Departmentt
Beni-Suef University