Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5(-/-) mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.
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http://dx.doi.org/10.1016/j.neuron.2014.02.046 | DOI Listing |
J Neurosci
April 2018
Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai 201203, China,
Itch is an unpleasant sensation that initiates scratching behavior. The itch-scratch reaction is a complex phenomenon that implicates supraspinal structures required for regulation of sensory, emotional, cognitive, and motivational aspects. However, the central mechanisms underlying the processing of itch and the interplay of the supraspinal regions and spinal cord in regulating itch-scratch processes are poorly understood.
View Article and Find Full Text PDFPain
March 2016
Department of Neurobiology Pittsburgh Center for Pain Research, University of Pittsburgh Medical Scientist Training Program, University of Pittsburgh Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA, USA.
Handb Exp Pharmacol
July 2015
Departments of Neurobiology and Anesthesiology, The Center for Pain Research, University of Pittsburgh, 200 Lothrop Street, BSTW1465, Pittsburgh, PA, 15213, USA.
Recent studies have made significant progress in the knowledge of how itch sensation is processed, especially the molecular identity of neurons involved in itch signaling, both in the dorsal root ganglion and spinal cord. Despite these advances, the organization of these neurons in dorsal spinal cord circuits and how they interact with other somatosensory modalities, such as pain or temperature, remain relatively unexplored. Recent work from our lab and others has begun to shed light on these questions and will be the focus of this chapter.
View Article and Find Full Text PDFNeuron
May 2014
Department of Neurobiology, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; University of Pittsburgh Pain Center, University of Pittsburgh, 200 Lothrop St. Pittsburgh, PA 15213, USA; Department of Anesthesiology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Electronic address:
Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5(-/-) mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!