Itch represents an important somatosensory defensive mechanism. Both mechanical and chemical pruritic stimuli evoke the sensation of itch, and the molecular mechanisms for its peripheral signal transduction have been revealed. Local neuronal networks in the spinal cord are essential for central processing and gating of these transduced itch signals, which are then transmitted to the brain via several types of spinal projection neuron. Both the thalamus and the parabrachial nucleus are essential for the central relay of itch information. In the brain, several neural circuits between brain areas can use this encoded information to alter affective states, which in turn motivate defensive responses such as scratching behaviour. Itch signal processing in the spinal cord is regulated by both neuromodulatory systems and descending pathways. In this Review, progress in the understanding of the neural circuits that underlie itch signal processing, transmission and encoding within the CNS is synthesized. Neural circuit mechanisms in the brain for itch perception and the modulation of itch processing in the spinal cord via descending and neuromodulatory pathways are also discussed.
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