Catastrophizing thinking towards itch and pain in chronic itch patients

Granot, Michal; Yakov, Sarit; Kuperman, Pora; Yosipovitch, Gil; Ramon, Michal

doi:10.1111/jdv.16975

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…Moreover, compared to control mice, CQ induced scratching was especially enhanced in CD model mice (68 ± 8.9 SADBE vs. 43 ± 5.7 Control) (Figure 1 E), while no difference in wiping responses was detected (Figure 1 D). This finding is consistent with common reports of hyperkinesis in chronic itch patients 21 . Vehicle injection did not produce any detectible effects on scratching or wiping behavior in CD model mice ( Figure S2 B).…”

Section: Resultssupporting

confidence: 93%

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3⁺ neurons in chronic dermatitis

Yu,

Liu,

Huang

et al. 2024

Theranostics

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Rationale: Noxious stimuli are often perceived as itchy in patients with chronic dermatitis (CD); however, itch and pain mechanisms of CD are not known. Methods: TRPV1 involvement in CD was analyzed using a SADBE induced CD-like mouse model, and several loss-and gain-of-function mouse models. Trigeminal TRPV1 channel and MrgprA3 + neuron functions were analyzed by calcium imaging and whole-cell patch-clamp recordings. Lesional CD-like skin from mice were analyzed by unbiased metabolomic analysis. 20-HETE availability in human and mouse skin were determined by LC/MS and ELISA. And finally, HET0016, a selective 20-HETE synthase inhibitor, was used to evaluate if blocking skin TRPV1 activation alleviates CD-associated chronic itch or pain. Results: While normally a pain inducing chemical, capsaicin induced both itch and pain in mice with CD condition. DREADD silencing of MrgprA3 + primary sensory neurons in these mice selectively decreased capsaicin induced scratching, but not pain-related wiping behavior. In the mice with CD condition, MrgprA3 + neurons showed elevated ERK phosphorylation. Further experiments showed that MrgprA3 + neurons from MrgprA3;Braf mice, which have constitutively active BRAF in MrgprA3 + neurons, were significantly more excitable and responded more strongly to capsaicin. Importantly, capsaicin induced both itch and pain in MrgprA3;Braf mice in an MrgprA3 + neuron dependent manner. Finally, the arachidonic acid metabolite 20-HETE, which can activate TRPV1, was significantly elevated in the lesional skin of mice and patients with CD. Treatment with the selective 20-HETE synthase inhibitor HET0016 alleviated itch in mice with CD condition. Conclusion:Our results demonstrate that 20-HETE activates TRPV1 channels on sensitized MrgprA3 + neurons, and induces allokinesis in lesional CD skin. Blockade of 20-HETE synthesis or silencing of TRPV1-MrgprA3 + neuron signaling offers promising therapeutic strategies for alleviating CD-associated chronic itch.

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Section: Resultssupporting

confidence: 93%

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3⁺ neurons in chronic dermatitis

Yu,

Liu,

Huang

et al. 2024

Theranostics

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“…[1][2][3] These patients frequently think of or recall unpleasant sensory experiences of itch; thus, researchers have considered the possibility that the itch sensation is provoked more frequently and amplified when patients' minds are preoccupied by itch. [4][5][6] Addressing this question is important to better understand the pathology of chronic itch. To do this, it is essential to develop a method for capturing the moment when the mind is preoccupied by itch.…”

Section: Machine Learning Using Brain Activity Can Capture the State ...mentioning

confidence: 99%

Machine learning using brain activity can capture the state of mind when a person is preoccupied by the unpleasant sensory experience of itch

Mochizuki,

Yosipovitch

2024

Acad Dermatol Venereol

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Pain Catastrophizing: Controversies, Misconceptions and Future Directions

Sullivan

Tripp

2024

The Journal of Pain

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Catastrophizing thinking towards itch and pain in chronic itch patients

Cited by 3 publications

References 10 publications

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3⁺ neurons in chronic dermatitis

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3⁺ neurons in chronic dermatitis

Machine learning using brain activity can capture the state of mind when a person is preoccupied by the unpleasant sensory experience of itch

Pain Catastrophizing: Controversies, Misconceptions and Future Directions

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Catastrophizing thinking towards itch and pain in chronic itch patients

Cited by 3 publications

References 10 publications

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3+ neurons in chronic dermatitis

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3+ neurons in chronic dermatitis

Machine learning using brain activity can capture the state of mind when a person is preoccupied by the unpleasant sensory experience of itch

Pain Catastrophizing: Controversies, Misconceptions and Future Directions

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20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3⁺ neurons in chronic dermatitis

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3⁺ neurons in chronic dermatitis