Setting the tone: Superficial dorsal horn projection neurons regulate pain sensitivity

The neurokinin-1 receptor is expressed by lamina I projection neurons of the spinal cord that are crucial for regulating pain behavior. These neurons are nocispecific, support long-term potentiation and appear to downregulate the K ⁺-Cl ^- exporter channel KCC2 following peripheral nerve damage, leading to increased excitability. These lamina I neurons project to the brainstem and thalamus and modulate descending inhibitory and excitatory pathways to the dorsal horn that regulate nociceptive traffic.