Papers of the Week

Spinal gastrin-releasing peptide receptor-expressing (GRPR) neurons play an essential role in itch signal processing. However, the circuit mechanisms underlying the modulation of spinal GRPR neurons by direct local and long-range inhibitory inputs remain elusive. Using viral tracing and electrophysiological approaches, we dissected the neural circuits underlying the inhibitory control of spinal GRPR neurons. We found that spinal galanin GABAergic neurons form inhibitory synapses with GRPR neurons in the spinal cord and play an important role in gating the GRPR neuron-dependent itch signaling pathway. Spinal GRPR neurons also receive inhibitory inputs from local neurons expressing neuronal nitric oxide synthase (nNOS). Moreover, spinal GRPR neurons are gated by strong inhibitory inputs from the rostral ventromedial medulla. Thus, both local and long-range inhibitory inputs could play important roles in gating itch processing in the spinal cord by directly modulating the activity of spinal GRPR neurons.