Circuit Mechanisms of Itch in the Brain

Mu, Di; Sun, Yan-Gang

doi:10.1016/j.jid.2021.09.022

Cited by 18 publications

(7 citation statements)

References 118 publications

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“…At the central level, many brain areas are involved in itch processing, including the sensory, emotional and motivational pathways. The sensory component involves various brain regions, such as the thalamus, the praecuneus and the somatosensory cortex 22 . Therefore, these previous studies demonstrate that central mechanisms involved in pruritus are complex and not completely characterised.…”

Section: Discussionmentioning

confidence: 97%

Pruritus and brain tumours: A prospective and descriptive study

Fardel

Brenaut

Guellec

et al. 2022

Skin Health and Disease

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Background Pruritus, especially localised to the nostrils, has been reported as a specific sign of brain tumours. Objectives The main goal of this study was to estimate the prevalence of pruritus in a group of patients with brain tumours. The second outcome was to better characterise this pruritus with a specific questionnaire and a skin examination. Methods From June 2020 to September 2021, all patients with a diagnosis of brain tumour were included in this prospective, monocentric study. If the patient suffered from pruritus, a dermatological examination was performed. Results Two hundred patients with brain tumours were included. Thirty‐five of them suffered from pruritus (17.5%). Among them, 15 patients did not present with any skin disease, and 8 could have neuropathic pruritus according to the NP5 questionnaire. No patients presented with pruritus of the nostrils. Discussion This study did not show clear evidence of specifically localised pruritus induced by brain tumours. Conclusion Pruritus observed in patients with brain tumours seems not to be caused by the brain malignancies in most cases. The specific localization to the nostrils cannot be considered a specific marker.

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Section: Discussionmentioning

confidence: 97%

Pruritus and brain tumours: A prospective and descriptive study

Fardel

Brenaut

Guellec

et al. 2022

Skin Health and Disease

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“…Finally, projection neurons transmit the itch signal along the spinothalamic tract to the brainstem where the signal unfolds to further brain regions and the urge to scratch develops ( Dong and Dong, 2018 ; Chen and Sun, 2020 ). For detailed information on itch circuits and processing in the central nervous system and brain in particular, the following recent reviews are recommended ( Chen and Sun, 2020 ; Najafi et al, 2021 ; Mu and Sun, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

In vitro models for investigating itch

Mießner

Seidel²,

Smith³

2022

Front. Mol. Neurosci.

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Itch (pruritus) is a sensation that drives a desire to scratch, a behavior observed in many animals. Although generally short-lasting and not causing harm, there are several pathological conditions where chronic itch is a hallmark symptom and in which prolonged scratching can induce damage. Finding medications to counteract the sensation of chronic itch has proven difficult due to the molecular complexity that involves a multitude of triggers, receptors and signaling pathways between skin, immune and nerve cells. While much has been learned about pruritus from in vivo animal models, they have limitations that corroborate the necessity for a transition to more human disease-like models. Also, reducing animal use should be encouraged in research. However, conducting human in vivo experiments can also be ethically challenging. Thus, there is a clear need for surrogate models to be used in pre-clinical investigation of the mechanisms of itch. Most in vitro models used for itch research focus on the use of known pruritogens. For this, sensory neurons and different types of skin and/or immune cells are stimulated in 2D or 3D co-culture, and factors such as neurotransmitter or cytokine release can be measured. There are however limitations of such simplistic in vitro models. For example, not all naturally occurring cell types are present and there is also no connection to the itch-sensing organ, the central nervous system (CNS). Nevertheless, in vitro models offer a chance to investigate otherwise inaccessible specific cell–cell interactions and molecular pathways. In recent years, stem cell-based approaches and human primary cells have emerged as viable alternatives to standard cell lines or animal tissue. As in vitro models have increased in their complexity, further opportunities for more elaborated means of investigating itch have been developed. In this review, we introduce the latest concepts of itch and discuss the advantages and limitations of current in vitro models, which provide valuable contributions to pruritus research and might help to meet the unmet clinical need for more refined anti-pruritic substances.

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“…Thus, the intensity theory of itch-pain discrimination has also been proposed, claiming that the same group of polymodal neurons can be strongly or weakly stimulated to generate pain or itch sensations in the DRG and spinal cord, respectively (18,22). Besides the intensity and selectivity theories, other theories also try to explain the relationship between itch and pain processing and to clarify mechanisms underlying itch (7,(23)(24)(25). Although different theories have been proposed to explain itch encoding in the DRG and spinal cord, they all targeted into one important direction-the difference between itch and pain encoding and transmission.…”

Section: Introductionmentioning

confidence: 99%

“…The studies on brain mechanisms underlying itch may be helpful in addressing these disputes. It is encouraging that more detailed studies have increasingly focused on the brain mechanisms underlying itch processing ( 23 ). For example, a recent study has shown that GABAergic (γ-aminobutyric acid–releasing) neurons in the ventral tegmental area (VTA) play an important role in encoding the aversive component of itch, while VTA dopaminergic (DA) neurons modulate reward from itch relief ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Itch-specific neurons in the ventrolateral orbital cortex selectively modulate the itch processing

et al. 2022

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Itch is a cutaneous sensation that is critical in driving scratching behavior. The long-standing question of whether there are specific neurons for itch modulation inside the brain remains unanswered. Here, we report a subpopulation of itch-specific neurons in the ventrolateral orbital cortex (VLO) that is distinct from the pain-related neurons. Using a Tet-Off cellular labeling system, we showed that local inhibition or activation of these itch-specific neurons in the VLO significantly suppressed or enhanced itch-induced scratching, respectively, whereas the intervention did not significantly affect pain. Conversely, suppression or activation of pain-specific neurons in the VLO significantly affected pain but not itch. Moreover, fiber photometry and immunofluorescence verified that these itch- and pain-specific neurons are distinct in their functional activity and histological location. In addition, the downstream targets of itch- and pain-specific neurons were different. Together, the present study uncovers an important subpopulation of neurons in the VLO that specifically modulates itch processing.

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Circuit Mechanisms of Itch in the Brain

Cited by 18 publications

References 118 publications

Pruritus and brain tumours: A prospective and descriptive study

Pruritus and brain tumours: A prospective and descriptive study

In vitro models for investigating itch

Itch-specific neurons in the ventrolateral orbital cortex selectively modulate the itch processing

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