Site-dependent and state-dependent inhibition of pruritogen-responsive spinal neurons by scratching

The relief of itch by scratching is thought to involve inhibition of pruritogen-responsive neurons in the spinal cord. We recorded the responses of superficial dorsal horn neurons in mice to intradermal injection of the pruritogens chloroquine and histamine. Scratching within an area 5-17 mm distant from the injection site, outside of the units' mechanoreceptive fields (off-site), significantly inhibited chloroquine-evoked and histamine-evoked responses without affecting capsaicin-evoked firing. This is consistent with observations that scratching at a distance from a site of itch is antipruritic. In contrast, scratching directly at the injection site (within the receptive field; on-site) had no effect on chloroquine-evoked neuronal firing, but enhanced the same neurons' responses to intradermal injection of the algogen capsaicin. Moreover, neuronal responses to histamine were enhanced during on-site scratching, and this was followed by suppression of firing below baseline levels after termination of scratching. Scratching thus inhibits pruritogen-responsive neurons in a manner that depends on the input modality (i.e. pain vs. histamine-dependent or histamine-independent itch) and skin location.