Research on Insomnia and Neuropeptides

Research on Insomnia and Neuropeptides
6 min read
07 September 2023

Insomnia is a sleep disorder characterized by frequent and persistent difficulty falling asleep or maintaining sleep, leading to insufficient sleep satisfaction. According to the International Classification of Sleep Disorders (ICSD-3), insomnia is classified as acute and chronic sex and unclassified. 

According to a meta-analysis report by scholars such as Cao in 2022, the overall prevalence of insomnia worldwide is 15.0%, with France and Italy accounting for 37.2%, and the United States accounting for 27.1%.

The risk of insomnia occurring in the general population is high and the relief rate is low, which seriously affects the quality of life of patients, increases the risk of anxiety and depression, leads to an increase in the consumption of healthcare resources, increases the risk of resignation and absenteeism, and brings serious consequences to individuals and society.

Article Category: Biomedical Research

Keywords: neuropeptides, substance P, insomnia

Neuropeptide Y (NPY) and Substance P

Insomniacs suffer from circadian circadian rhythms, especially in the sleep/wakefulness cycle. Neuropeptide Y (NPY) and substance P (SP) are highly expressed in the emotion regulating brain region, coordinating with monoamine neurotransmitters and participating in the regulation of circadian biological rhythms.

Some existing studies have shown changes in peripheral NPY and SP levels in patients with insomnia. Therefore, the dysfunction of NPY and SP neurons may be one of the pathological mechanisms of insomnia.

Neuropeptide Y and Insomnia

NPY (Neuropeptide ) is a peptide composed of 36 amino acids, belonging to the NPY bioactive peptide family along with the other two member peptides YY (PYY) and pancreatic polypeptide (PP). 

It is expressed in multiple peripheral and brain regions, including the hypothalamus, amygdala, hippocampus, solitary tract nucleus, locus coeruleus, nucleus accumbens, and cerebral cortex.

Neuropeptide is a kind of peptide and currently available for research after chemical synthesis. References for peptide synthesis: Omizzur - Custom peptide synthesis companies

NPY has complex target tissue specific effects on different physiological processes, including regulating cortical excitability, circadian rhythm, pain management, eating, cardiovascular function, neuroprotection, and neurogenesis.

Research on Insomnia and Neuropeptides

How does NPY Affect Sleep?

  1. NPY affects sleep through electrophysiology:

Sleep is a fundamental and evolutionarily conserved behavioral state, characterized by non rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) cycles in its electrophysiology.

Normal adults first enter NREMS at the beginning of sleep, and then enter REMS after about 60-90 minutes. It lasts for about 10-15 minutes and then turns into NREM. This cycle of interaction occurs 4-6 times a night until they wake up.

Through experiments, it was found that NPY affects the sleep cycle rhythm through its electrophysiological effects on the central nervous system of rats, leading to increased levels of arousal and ultimately insomnia.

  1. NPY affects sleep through endocrine regulation: 

Various hormones (peptides and steroids) participate in sleep regulation. Currently, a large amount of literature has shown that insomnia is closely related to the function of the hypothalamic pituitary adrenal axis (HPA)

  1. NPY affects sleep through neuroprotective effects: 

The hippocampus, as the region with the highest concentration of NPY in the central nervous system, plays a central role in neural development and the risk of insomnia.

Substance P and insomnia

SP is a neuropeptide isolated from the peripheral and central nervous systems, and is the highest content of tachykinin in the central nervous system of mammals. It plays a neurotransmitter and neuromodulatory role, regulating various behaviors such as systemic motor activity, pain, food and water intake, anxiety, reward/reinforcement, and memory consolidation.

SP works by binding to neurokinin receptors, which are G protein coupled receptors and can be divided into three types: neurokinin 1 receptor (NK1R), neurokinin 2 receptor (NK2R), and neurokinin 3 receptor (NK3R). 

Among them, NK1R is the most widely distributed and sensitive to SP, widely distributed in various parts of the brain, including the striatum, amygdala, hippocampus, and brainstem monoamine nuclei

  1. The structural basis for SP's involvement in regulating sleep: SP is co located with known sleep regulating cells and neurotransmitters in brain regions, such as serotonin in the raphe nucleus, dopamine in the midbrain and striatum, and CRH in the hypothalamus.
  1. SP's role in promoting arousal and sleep: Andersen et al. investigated whether SP participates in the mechanism of sleep arousal and found through animal experiments that SP can reduce sleep efficiency, increase sleep latency and wake-up frequency to interfere with sleep. They also found that pre administration of NK1R antagonists can prevent sleep disorders. Similar results were found in experiments with healthy young people, where SP increased sleep latency and wakefulness time. These results are consistent with the conclusion that SP is involved in regulating the structural basis of sleep.
  1. SP and pain induced insomnia: SP plays an important role in the neurobiological process of nociception. A large number of animal research results support that SP is an indispensable part of the nociceptive process, which can enhance the excitatory input of nociceptive neurons, leading to excessive excitation and increased pain sensitivity in the central nervous system.

In March 2015, the National Sleep Foundation of the United States launched a nationwide public opinion survey on sleep quality and pain. The results show that pain has become one of the main causes of insomnia.

Summary & Pittsburgh Sleep Quality Index

In recent years, the adverse effects of insomnia on patients' physical, psychological, and social functions have attracted people's attention. Insomnia, as the most common sleep disorder, is mainly diagnosed using subjective scales such as the Pittsburgh Sleep Quality Index (PSQI) in clinical practice.

As an objective diagnostic standard for insomnia, multi-channel sleep monitoring has drawbacks such as complex operation. With the progress of relevant research and the presentation of more effective evidence, NPY and SP level detection may become more convenient and auxiliary clinical diagnostic standards with guidance.

 

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