
Itch & Pruritus
Pruritus, also known as itch, is defined as an unpleasant sensation that elicits the desire or reflex to scratch. Itch manifests in both acute and chronic forms. Acute itch is easily relieved by scratching. By contrast, chronic itch remains a challenge in the clinic as it arises from diseases of the skin or from diseases of the central or peripheral nervous system such as brain tumors, peripheral neuropathy or nerve compression. Similar to pain, the itch sensation is mediated by nociceptive neurons that transmit information from the periphery to the central nervous system. Because of the similarities between pain and itch sensations, itch has been historically considered a submodality of pain.
Models
Intradermal injection of the mast cell degranulator Compound 48/80 produces a local release of histamine and intense scratching of the injected area. Since histamine elicits itch in humans this response is believed to reflect a similar sensation in mice.
TPA (12-O-tetradecanoylphorbol-13-acetate) applied topically to a mouse ear causes a strong local inflammatory response. It activates protein kinase C (PKC), driving inflammatory mediators and leukocyte recruitment, increased vascular permeability, and ultimately ear edema/swelling and erythema.
The chloroquine-induced itch model in mice is an acute, histamine-independent pruritus model. An intradermal injection of chloroquine activates MrgprA3 (Mas-related G-protein-coupled receptor A3) on a subset of peripheral sensory neurons. Signaling through TRPA1 then triggers sensory-neuron activation and a strong, measurable scratching response.
Platforms used
Molecular Biomarkers & Histology Molecular biomarkers and tissue biomarker expression
Electroencephalography (EEG) In-vivo rodent telemetry
MoSeq AI-powered motion sequencing
Operant Platform Motivation, impulsivity, attention, cognition, memory
PK/PD Studies Endpoints for lead optimization
PK-Bridge PK studies for discovery budgets
Humanized Models PXB humanized-liver mice
SPIDAR Rapid analgesic screening
Transgenics Genetically modified mice
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