Expression of miR-155 in Migraine: Association With Different Phenotypes and Disease Severity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Comparison of miR-155 expression in peripheral monocytes between the three study groups: chronic migraine, episodic migraine and healthy control.
研究概览
简要总结
Migraine is a common, yet often disabling, neurological disease that affects over 1 billion people around the world. It's the second most disabling disease globally and the leading cause of disability for people under the age of 50, especially women. The effects of migraine aren't limited to the individual, with a tremendous economic impact on families, friends, and employers. To help reduce this burden, research is now focusing on developing biomarkers that can help with diagnosis, predicting response to treatments, and identifying those at risk of developing chronic migraine.
MicroRNAs (miRNAs) are one of the most promising classes, as they can modulate gene expression and affect a wide range of cellular processes. Other studies have already observed different miRNA expression in those with episodic migraine or chronic migraine, but no specific miRNAs have been identified as a strong and specific migraine signature. miRNA-155 is of particular interest, as it has been linked to inflammation and pain, and may be a potential target for migraine treatments.
It is known that the immune system plays a role in migraine headaches. Monocytes, a type of immune cell, may be involved in the development of migraines. Certain medicines, such as aspirin, can affect monocyte function and have been used to treat migraines. Recent research has also shown that microRNAs can regulate the activity of these cells and influence inflammation, which may be linked to migraine attacks.
This study aims to investigate the role of miRNA-155 and monocyte differentiation in migraine patients, and in particular its association with migraine phenotype and severity. We aim to study three groups of subjects: Episodic migraine (EM), Chronic migraine with or without Medication Overuse Headache (CM-MOH) and Healthy Controls (HCs).
详细描述
Background:
Depending on the median frequency of headache, migraine is defined as episodic migraine (EM) (for those who have less than 15 migraine days per month), or chronic migraine (for those who have at least 15 headache days per month, 8 of which with migraine features, for at least three months). The chronification of migraine is often associated with a progressive increase of acute medications intake, leading to a condition known as Medication Overuse Headache (CM-MOH).
So far, there are no validated and reliable biomarkers of migraine, but the headache scientific community is intensely investigating the neurobiological signatures of migraine. Validated biological biomarkers may allow several steps forward in the management of migraine by: (I) refining the diagnosis according to biological features; (II) predicting the response to advanced therapies; (III) predicting which patients are at the greatest risk of migraine chronification and mark different phases of the migraine cycle; (IV) the identification of novel molecular targets for drugs development. Fulfilling these purposes, a class of molecules that has recently gained enormous interest are microRNAs (miRNAs). miRNAs are small endogenous noncoding RNAs that are around 22 nucleotides in length. miRNAs operate as post-transcriptional regulator of gene expression by promoting messenger RNA (mRNA) degradation or repressing mRNA translation. The regulation process performed by miRNAs is complex and articulated since an individual miRNA might target hundreds of different mRNAs, and conversely, each mRNA may be regulated by multiple miRNAs. It has been estimated that more than 60% of all protein-coding genes are regulated by miRNAs which consequentially determine the pleiotropic modulation of a wide variety of cellular processes involving differentiation, development and signaling. miRNAs are involved in the generation and maintenance of pain and several evidence suggest that specific miRNAs could play a role in migraine.
The micro-MIG study corroborated the hypothesis that different miRNAs expression is altered in EM and CM when compared to a control group, although no specific miRNAs were identified as a strong and specific migraine molecular signature.
miRNA-155 can be considered as a master regulator of inflammation since its expression can modulate many inflammatory stimuli such as: interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), alarmins (eg, IL-1α), hypoxia, nuclear factor erythroid 2-related factor 2 (NRF2), pathogen-associated and damage-associated molecular patterns as well as to toll-like receptor ligand (TLR) in various cell types. Recently, several lines of preclinical evidence further highlighted the role of miRNA-155 in inflammation and pain generation and maintenance also as a feasible therapeutic target. The inhibition of miRNA-155 can alleviate hyperalgesia and bone cancer pain as well as neuropathic pain in in-vivo rodent models. Therefore, it can be inferred that miRNA-155 might also play an important role in neurogenic inflammation, a process supposed to take place in the trigeminovascular system, and related to the pathogenic mechanisms underlying migraine pain.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age between >18 and <65 years, of both genders
- •Exclusion criteria:
- •diagnosis of primary and/or secondary headache according to ICHD-III criteria (only diagnosis of sporadic tension type headache is allowed)
- •diagnosis of neurological disorders
- •diagnosis of medical conditions considered clinically relevant by the researcher
- •pregnant and lactating women
- •taking NSAIDs, triptans or opiates in the previous 24 hours
- •Episodic Migraine
- •Inclusion Criteria:
- •diagnosis of migraine without or with aura according to ICHD-III criteria
- •age between >18 and <65 years of both genders
- •have completed a headache diary for at least 3 months at the time of enrollment
- •Exclusion criteria:
- •history of chronic migraine or other chronic headache subtypes according to ICHD-III criteria
- •concomitant diagnosis of other primary and/or secondary headache according to ICHD-III criteria (only diagnosis of sporadic tension headache is allowed)
- •diagnosis of other neurological disorders
- •diagnosis of medical conditions considered clinically relevant by the researcher
- •diagnosis of chronic pain syndrome of any nature
- •pregnant and lactating women
- •use of substances of abuse
- •taking NSAIDs, triptans or opiates in the previous 24 hours
- •Chronic Migraine
- •Inclusion Criteria:
- •diagnosis of chronic migraine with or without concomitant diagnosis of medication overuse headache according to ICHD-III criteria
- •history of chronic migraine for at least 1 year
- •age between >18 and <65 years, of both sexes
- •have completed a headache diary for at least 3 months at the time of enrollment
- •Exclusion criteria:
- •concomitant diagnosis of other primary and/or secondary headache according to ICHD-III criteria (only diagnosis of sporadic tension headache is allowed)
- •concomitant diagnosis of other neurological disorders
- •diagnosis of medical conditions considered clinically relevant by the researcher
- •diagnosis of chronic pain syndrome of any nature
- •pregnant and lactating women
- •use of substances of abuse
- •taking NSAIDs, triptans or opiates within the previous 24 hours
排除标准
- 未提供
结局指标
主要结局
Comparison of miR-155 expression in peripheral monocytes between the three study groups: chronic migraine, episodic migraine and healthy control.
时间窗: Baseline (T0).
miRNA-155 gene expression will be evaluated by real-time reverse transcription (RT-PCR). This assessment will be then normalized with U6 (a type of small nuclear RNA used as housekeeping gene) and expressed as Relative Quantification (RQ).
次要结局
- Cytofluorimetric evaluation of monocytes to determine their phenotype and subtype and the different colocalization of these between the three study groups: chronic migraine, episodic migraine and healthy control.(Baseline (T0).)
- Comparison of gene expression in peripheral monocytes of pro-inflammatory (IL-1B, TNF-alpha) and anti-inflammatory (IL-10) cytokines between the three study groups: chronic migraine, episodic migraine and healthy control.(Baseline (T0).)
- Comparison of miR-382-5p and miR-34a-5p expressions in peripheral monocytes between the three study groups: chronic migraine, episodic migraine and healthy control.(Baseline (T0).)