Role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behaviors in mice

Song, Yong-tang; Pan, Xu-chu; Liu, Cheng; Xiang, Hong‐Bing

doi:10.1007/s11596-012-1058-7

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…Microinjections of intradermal CQ led to increased itch behavior and increased c‐fos expression, co‐localized with GRPR in arcuate nucleus neurons in mice . Further, CQ itch in mice is inhibited by NMDA receptor antagonists D‐AP5 IN Y142F Knock‐in mice, with associated increase in c‐fos colocalized with GRPR in same neurons …”

Section: Inferences and Potential Therapeutic Intervention Approachesmentioning

confidence: 94%

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Itching, chloroquine, and malaria: a review of recent molecular and neuroscience advances and their contribution to mechanistic understanding and therapeutics of chronic non‐histaminergic pruritus

Ajayi

2018

Int J Dermatology

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Chloroquine (CQ) is an antimalarial drug that elicits severe pruritus in black Africans with malaria fever. This acute itching (2-7 days duration) exhibits age dependency and a racial and genetic predilection. CQ itch is non-histaminergic, which makes it both a good model and a tool to probe the mechanisms of chronic itch. This review focuses on recently discovered mechanisms, neuroscience, mediators, and receptors that are implicated in molecular studies of CQ pruritus. CQ pruritus mechanisms are also compared to that of itching following other systemic diseases, such as chronic kidney disease, chronic liver disease, skin disorders, and burns. There are striking similarities between CQ itching pathways and other chronic itch secondary to systemic disease with or without skin lesions, which have not been previously highlighted. Prominent among these are the shared roles of skin, neural and spinal l opiate receptors, kappa opiate receptor, nitric oxide, serotonin via 5HT1B/D receptors, cytokines, especially interleukins, and tumor necrosis factor. There is elaborate "cross talk" among the diverse mediators and receptors involved in CQ-induced pruritus. CQ also binds to the mas-related G protein coupled receptors MrgprA3/MrgprX1 present in a small proportion (4-5%) of dorsal root ganglion neurons and skin. The mrgprA3 CQ receptors are coupled to PLC-b3 and a chloride channel to initiate skin itch action potentials in C nerve fibers. Mrgpra3/X1 couples to TRPA1 for calcium influx into neuronal cells at noncutaneous sites. Central CQ itch occurs via gastrin-related peptide (GRP) and its receptor (GRPR) in the dorsal spinothalamic tracts, as well as glutamic mediated GRP projection to parabrachial nucleus. The possibility of chronic itch therapy based on personalized medicine, genetics, and transcriptomics or the use of itch "polypill/polycream" are discussed.Itching is the commonest symptom of dermatologic diseases and also a manifestation of many systemic disorders, without associated skin lesions. Itching, which provokes scratching, increases the morbidity and reduces the quality of life associated with chronic itching. 1 Itching or pruritus is an orphan symptom, without a specific efficacious treatment, such as there is for analgesics.The mechanisms and neuroscience of itch are being actively investigated, and we have studied the itching associated with antimalarial drugs, especially chloroquine (CQ). 2,3 CQ causes pruritus both in healthy volunteers, 4 as well as severe scratching in rodents, rats, 5 and mice. 6,7 The pruritus associated with CQ is greatly accentuated and generalized in patients with malaria fever, compared to the severity following CQ in people without malaria. 4,8,9 There is evidence of a genetic contribution, as the CQinduced pruritus is much more severe and generalized in blacks and people of Negroid descent, whereas pruritus is extremely rare in white patients with malaria fever receiving CQ. 2,10 Further, there is a positive correlation between the area under the intensity-time curve follow...

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Section: Inferences and Potential Therapeutic Intervention Approachesmentioning

confidence: 94%

“…Central itch mechanisms need to be probed further, as inhibition of itch at rostral brain levels may abolish itch regardless of the initiating cause. It appears that central NMDA mechanisms may be involved in CQ itch and act at a trigeminal region cephalic to spinal cord GRPR …”

Section: Inferences and Potential Therapeutic Intervention Approachesmentioning

confidence: 99%

Itching, chloroquine, and malaria: a review of recent molecular and neuroscience advances and their contribution to mechanistic understanding and therapeutics of chronic non‐histaminergic pruritus

Ajayi

2018

Int J Dermatology

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“…They were briefly anesthetized with isoflurane (2% in 100% oxygen), and received an intradermal microinjection of 100 µl compound 48/80 (100 µg/100 µl) or saline in the nape of the neck (via a 0.3 ml insulin syringe with a 31 gauge needle). As previously described (12)(13)(14), immediately after the injection, the mouse was placed into the arena and videotaped from above for 30 minutes. Videotapes were reviewed by the observers of the pruritic behaviors.…”

Section: Behavioral Assaymentioning

confidence: 99%

Altered Expression Profiling of Spinal Genes Modulated by Compound 48/80 in A Mouse Itch Model

He¹,

Liu²,

Li³

et al. 2017

J Anesth Perioper Med

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Background: The molecular mechanisms underlying itch are constantly being studied to create new opportunities to prevent or alleviate itch. The aim of our study was to determine the spinal gene expression changes induced by compound 48/80 in a mouse itch model. Methods: Mice were divided into saline group (control group, n=12) and compound 48/80 group (48/80 group, n=12). 100 µl saline or compound 48/80 was microinjected intradermally in the nape of the neck. After injection, pruritic behavior was immediately measured every 5 minutes. 30 minutes after injection, tissue was prepared to carry out mRNA profiling microarray and reverse transcription polymerase chain reaction (RT-qPCR) analyses. Results: The total numbers of scratching bout after compound 48/80 injection (100 µg/100 µl) were significantly increased in 48/80 group (190 ± 11.33) as compared with control group (6.83 ± 1.17). We screened the dorsal part of the cervical spinal cord of the mouse itch model for differentially expressed genes. Out of 45037 studied transcripts, the abundance levels of 15 transcripts were altered following compound 48/80 injection. 9 and 6 genes were up-and down-regulated in 48/80 group, respectively. We validated the reliability of the microarray results by RT-qPCR, and found 6 up-regulated mRNA, including Sgk1, Bag4, Fos, Ehd2, Edn3 and Wdfy, were significantly increased, whereas 3 down-regulated mRNA, including Corin, 4921511E18Rik and 4930423020Rik, were significantly decreased. Conclusions: These findings indicate that the alterations of spinal gene expression are involved in acute itch, and provide a translational bridge for spinal drugs targeting their signaling pathway to prevent or alleviate itch.

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“…Itch has been defined as an unpleasant skinspecific sensation with negative affective component, and produces a characteristic desire or reflex of scratching behavior [1][2][3]. The mechanisms that generate itch are poorly understood and effective treatment for chronic itch is lacking despite its clinical importance.…”

Section: Introductionmentioning

confidence: 99%

“…Behavioral data suggest that scratching behavior may be used as an index for the study of itch in experimental rodents [2,14]. Several lines of evidence suggested that 5, 7-dihydroxytriptamine (5,7-DHT), a serotonergic neurotoxin, selectively diminished tissue 5-HT content [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

(334) Inhibition of itch-related responses by selectively ablated serotonergic signals at the rostral ventromedial medulla in mice

Xiang

Liu

et al. 2014

The Journal of Pain

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Role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behaviors in mice

Cited by 8 publications

References 23 publications

Itching, chloroquine, and malaria: a review of recent molecular and neuroscience advances and their contribution to mechanistic understanding and therapeutics of chronic non‐histaminergic pruritus

Itching, chloroquine, and malaria: a review of recent molecular and neuroscience advances and their contribution to mechanistic understanding and therapeutics of chronic non‐histaminergic pruritus

Altered Expression Profiling of Spinal Genes Modulated by Compound 48/80 in A Mouse Itch Model

(334) Inhibition of itch-related responses by selectively ablated serotonergic signals at the rostral ventromedial medulla in mice

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