Summary: Researchers implicate the neuropeptide NPPB in generating the itching sensation characteristic of eczema.
Source: North Carolina State University.
Researchers at North Carolina State University have identified a specific neuropeptide that contributes to transmitting itch signals in a mouse model of atopic dermatitis. The findings add clarity to the signaling pathway that conveys itch from the skin through peripheral neurons to the spinal cord.
“You can think of itch being transmitted from the skin to the brain as a series of switches that get flipped,” says Santosh Mishra, assistant professor of neuroscience at NC State. “The signal goes from neuronal projections in the skin through the dorsal root ganglia (DRG) – which are clusters of sensory cells located at the root of the spinal nerves – then to the spinal cord. We’re interested in finding out how the portion of this pathway from DRG to spinal cord works in terms of signaling itchiness in chronic skin disease.”
Atopic dermatitis, commonly called eczema, is a chronic inflammatory skin disease that causes persistent and often severe itching. The intense and ongoing itch can substantially reduce quality of life. To better understand the molecular signals that drive this sensation, Mishra and colleagues focused on interleukin-31 (IL-31), a cytokine known to be overproduced in people with atopic dermatitis and known to trigger itch-related neuronal activity.
“We know that when IL-31 binds to the receptor present on neuronal projections in the skin, those neurons signal a subset of neurons in the DRG called the TRPV-1, which then signal the spinal cord,” Mishra explains. “We wanted to figure out which neuropeptide was involved in the ‘switch’ between the DRG and the spinal cord.”
The team investigated the role of the neuropeptide natriuretic polypeptide B (NPPB). NPPB is released by TRPV-1–expressing neurons in the DRG after IL-31 acts on sensory nerve endings in the skin. To determine whether NPPB mediates itch signaling to the spinal cord, the researchers used IL-31 to stimulate itch responses in mice and compared behavioral and neuronal responses across different genetic models.
Specifically, the study compared normal (wild-type) mice to mice lacking the receptor for NPPB and to mice genetically engineered not to produce NPPB. The investigators observed that animals without NPPB or without its receptor exhibited a 70 to 80 percent reduction in scratching behavior in response to IL-31. This large decrease strongly indicates that NPPB and its receptor are important components of the signaling chain that carries itch information from the DRG into the spinal cord.
“Our work shows that NPPB does act on neurons in the spinal cord, and that it plays an important role in this signaling pathway,” Mishra says. The results point to NPPB as a key messenger between peripheral sensory neurons and central spinal circuits involved in itch sensation.
The researchers emphasize that the neural circuitry for chronic itch is complex. Neurons that express NPPB can also express additional neuropeptides, and multiple signaling molecules may work together to shape the itch response. “Our next steps will be to build on this work, because the neurons that express NPPB can express more than one neuropeptide,” Mishra notes. “Perhaps we will be able to identify another receptor involved in the link between the peripheral and central nervous system for chronic itch associated with eczema.”
The research is reported in Acta Dermato-Venereologica. Santosh Mishra is corresponding author. Contributors to the work include NC State postdoctoral scholar Saumitra Pitake, research technician Jennifer DeBrecht, and undergraduate student Patrick Ralph from William Peace College.
Source: Julia Wandt, North Carolina State University.
Publisher: Organized by NeuroscienceNews.com.
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Original research: The study is published in Acta Dermato-Venereologica.
North Carolina State University. “Neuropeptide Involved in Transmitting Itch Signal in Eczema Identified.” NeuroscienceNews, June 13, 2018. Acta Dermato-Venereologica (publication).
This summary emphasizes the role of IL-31, TRPV-1–expressing dorsal root ganglion neurons, NPPB, and NPPB receptors in the transmission of itch signals in an atopic dermatitis mouse model. The findings highlight a potential molecular target for therapies aimed at reducing chronic itch in conditions such as eczema, while further research will be needed to explore additional neuropeptides and receptors that participate in this signaling pathway.