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

AbstractThe 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.