Dynorphin Acts as a Neuromodulator to Inhibit Itch in the Dorsal Horn of the Spinal Cord
نویسندگان
چکیده
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.
منابع مشابه
Glutamate acts as a neurotransmitter for gastrin releasing peptide-sensitive and insensitive itch-related synaptic transmission in mammalian spinal cord
Itch sensation is one of the major sensory experiences of human and animals. Recent studies have proposed that gastrin releasing peptide (GRP) is a key neurotransmitter for itch in spinal cord. However, no direct evidence is available to indicate that GRP actually mediate responses between primary afferent fibers and dorsal horn neurons. Here we performed integrative neurobiological experiments...
متن کاملRole of nitric oxide and Jun N-terminal kinase in the development of dark neurons in the dorsal horn of the spinal cord following induction of inflammatory pain
Introduction: Dark neurons which their morphological characteristics are consistent with those of cells undergoing apoptosis, are generated as an acute or delayed consequence of several pathological situations. The present study was designed to evaluate whether inflammatory pain regarding the role of NO and JNK lead to the formation of dark neurons in the dorsal horn of the lumbar spinal cor...
متن کاملPropofol differentially inhibits the release of glutamate, γ-aminobutyric acid and glycine in the spinal dorsal horn of rats
Objective(s): Propofol (2, 6-diisopropylphenol) is an intravenous anesthetic that is commonly used for the general anesthesia. It is well known that the spinal cord is one of the working targets of general anesthesia including propofol. However, there is a lack of investigation of the effects of propofol on spinal dorsal horn which is important for the sensory transmission of nociceptive signal...
متن کاملPain and itch: insights into the neural circuits of aversive somatosensation in health and disease.
Although pain and itch are distinct sensations, most noxious chemicals are not very specific to one sensation over the other, and recent discoveries are revealing that Trp channels function as transducers for both. A key difference between these sensations is that itch is initiated by irritation of the skin, whereas pain can be elicited from almost anywhere in the body; thus, itch may be encode...
متن کاملImmunoreactive dynorphin B in sacral primary afferent fibers of the cat.
Immunocytochemical analysis of the distribution of dynorphin B terminals in the sacral spinal cord of the cat revealed a pattern of staining very similar to that produced with antisera directed against the primary afferent derived, putative neurotransmitter, vasoactive intestinal polypeptide. Labeled axons and terminals were concentrated in lamina I and V and there was dense fiber staining in t...
متن کامل