Corticotropin-releasing factor receptor 1 (CRF-R1) antagonists: Promising agents to prevent visceral hypersensitivity in irritable bowel syndrome

Lv, Yuanxia; Wen, Jing; Fang, Yunxia; Zhang, Haoyuan; Zhang, Jianwu

doi:10.1016/j.peptides.2021.170705

Cited by 9 publications

(6 citation statements)

References 151 publications

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“…However, these models have also their limitation. Though CRH (generally administered intracerebroventricularly) can initiate visceral hyperalgesia and changes in colonic motility, as observed in IBS, CRH antagonists seem to have limited clinical effect in IBS patients (yet some new CRH drugs are still under development) 55 . Irritant substances models could mimic some characteristics of IBS but may cause microstructural damages of the intestine tissue (as the mechanical stimulation) which are at variance of the complex pathophysiology of the disease 15,16 .…”

Section: Discussionmentioning

confidence: 99%

“…Though CRH (generally administered intracerebroventricularly) can initiate visceral hyperalgesia and changes in colonic motility, as observed in IBS, CRH antagonists seem to have limited clinical effect in IBS patients (yet some new CRH drugs are still under development). 55 Irritant substances models could mimic some characteristics of IBS but may cause microstructural damages of the intestine tissue (as the mechanical stimulation) which are at variance of the complex pathophysiology of the disease. 15,16 Stress-related models, like neonatal maternal deprivation or repeated water avoidance stress, are well-recognized models of visceral hypersensitivity that can precipitate IBS symptoms, and cause depression-like symptoms in the animals.…”

Section: Net Response Additional Spikes/10 Smentioning

confidence: 99%

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Menthacarin treatment attenuates nociception in models of visceral hypersensitivity

Omoloye,

Weisenburger,

Lehner

et al. 2024

Neurogastroenterology Motil

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BackgroundChronic visceral hypersensitivity is closely associated with irritable bowel syndrome (IBS), a very common disorder which significantly impairs quality of life, characterized by abdominal pain, and distension. Imaging studies have found that IBS patients show higher metabolic activities and functional differences from normal controls in the anterior cingulate cortex (ACC), in response to visceral pain stimulation. Non‐clinical data and clinical data suggest that medicinal products containing essential oils such as peppermint or caraway oil exert beneficial effects on IBS symptoms.MethodsWe assessed acute and long‐term treatment effects of a mixture of peppermint and caraway essential oils (Menthacarin) on brain electrophysiological markers of gut pain sensitivity in two rat models of visceral hypersensitivity.Key ResultsChronic administration of corticosteroids and acute repeated mechanical hyperstimulation under anesthesia induced hyperalgesia and hypersensitivity, characterized by an increase in electrophysiological excitatory responses of ACC neurons to colorectal distension (CRD) and an increase in the proportion of neurons responding to otherwise subthreshold stimulation, respectively.Long‐term, but not acute, oral administration of Menthacarin (60 mg kg−1 day−1) significantly reduced the net excitatory response to CRD in normally responsive control animals and counteracted the development of visceral hyperalgesia and hypersensitivity induced by repeated corticosterone administration and acute mechanical stimulation.Conclusions & InferencesThe present study shows that, using the CRD method, chronic Menthacarin administration at a clinically relevant dose attenuates the neuronal discharge associated with visceral pain stimuli in the rat ACC, particularly in models of hypersensitivity, suggesting a potential for treating exaggerated visceral pain sensitivity.

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Section: Discussionmentioning

confidence: 99%

Section: Net Response Additional Spikes/10 Smentioning

confidence: 99%

Menthacarin treatment attenuates nociception in models of visceral hypersensitivity

Omoloye,

Weisenburger,

Lehner

et al. 2024

Neurogastroenterology Motil

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“…Gut epithelial integrity Anti-angiogenesis Reduced signalling sensitivity (Reul et al, 2015) Immunosuppression (Cohen et al, 2012) Impaired wound healing (Anstead, 1998 (Hauger et al, 2009) Visceral pain (Lv et al, 2022) Enteric nervous system dysfunction (Tache et al, 2018) Impaired gut barrier (Rodiño-Janeiro et al, 2015) Mast cell degranulation (Ayyadurai et al, 2017) CRF2 receptor…”

Section: Corticosteroidsmentioning

confidence: 99%

The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective

Leigh,

Uhlig,

Wilmes

et al. 2023

The Journal of Physiology

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The physiological consequences of stress often manifest in the gastrointestinal tract. Traumatic or chronic stress is associated with widespread maladaptive changes throughout the gut, although comparatively little is known about the effects of acute stress. Furthermore, these stress‐induced changes in the gut may increase susceptibility to gastrointestinal disorders and infection, and impact critical features of the neural and behavioural consequences of the stress response by impairing gut–brain axis communication. Understanding the mechanisms behind changes in enteric nervous system circuitry, visceral sensitivity, gut barrier function, permeability, and the gut microbiota following stress is an important research objective with pathophysiological implications in both neurogastroenterology and psychiatry. Moreover, the gut microbiota has emerged as a key aspect of physiology sensitive to the effects of stress. In this review, we focus on different aspects of the gastrointestinal tract including gut barrier function as well as the immune, humoral and neuronal elements involved in gut–brain communication. Furthermore, we discuss the evidence for a role of stress in gastrointestinal disorders. Existing gaps in the current literature are highlighted, and possible avenues for future research with an integrated physiological perspective have been suggested. A more complete understanding of the spatial and temporal dynamics of the integrated host and microbial response to different kinds of stressors in the gastrointestinal tract will enable full exploitation of the diagnostic and therapeutic potential in the fast‐evolving field of host–microbiome interactions. image

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“…Selective CRHR1 antagonists currently developed include antalarmin, pexacerfont, NBI-30775 (R121919), CP-376, JTC-017, NGD9002, and so on, and the combination of CRHR1 antagonists with CRHR1 in different parts of the body could create diverse effects. 114 For example, R121919 has been successfully used in clinical treatment of depression and anxiety, which is associated with decreased blood oxygen level-dependent signal in brain regions related to emotional arousal circuit (amygdala, hippocampus, and ACC). 115 - 117 JTC-017 could reduce the release of hippocampus NE after acute CRD stress in rats, and relieve visceral hypersensitivity as well as anxiety-like behavior.…”

Section: Crh-related Treatmentmentioning

confidence: 99%

“… 119 - 121 In addition, the balance between receptor affinity and the pharmacokinetic property of CRHR1 antagonists remains the focus of the pharmaceutical industry. 114 Besides, CRHR2 agonists have an anti-anxiety effect in CNS, but can delay gastric empty, therefore, organ-selective CRHR2 agonists should be chosen in clinic. 13…”

Section: Crh-related Treatmentmentioning

confidence: 99%

Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders

et al. 2023

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Irritable bowel syndrome (IBS) is considered a stress disorder characterized by psychological and gastrointestinal dysfunction. IBS patients not only suffer from intestinal symptoms such as abdominal pain, diarrhea, or constipation but also, experience dysthymic disorders such as anxiety and depression. Studies have found that corticotropin-releasing hormone plays a key role in IBS with comorbid dysthymic disorders. Next, we will summarize the effects of corticotropin-releasing hormone from the central nervous system and periphery on IBS with comorbid dysthymic disorders and relevant treatments based on published literatures in recent years.

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Corticotropin-releasing factor receptor 1 (CRF-R1) antagonists: Promising agents to prevent visceral hypersensitivity in irritable bowel syndrome

Cited by 9 publications

References 151 publications

Menthacarin treatment attenuates nociception in models of visceral hypersensitivity

Menthacarin treatment attenuates nociception in models of visceral hypersensitivity

The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective

Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders

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