Scratching inhibits serotonin-evoked responses of rat dorsal horn neurons in a site- and state-dependent manner

- Off-site scratching inhibited spinal neuronal responses to 5-HT but not AITC.
- On-site scratching facilitated neuronal responses to both 5-HT and AITC.
- 5-HT (but not AITC)-evoked firing was inhibited after on-site scratching.
- Results support a spinal cord site for scratch-inhibition of itch transmission.

Scratching inhibits pruritogen-evoked responses of neurons in the superficial dorsal horn, implicating a spinal site for scratch inhibition of itch. We investigated if scratching differentially affects neurons depending on whether they are activated by itchy vs. painful stimuli, and if the degree of inhibition depends on the relative location of scratching. We recorded from rat lumbar dorsal horn neurons responsive to intradermal (id) microinjection of serotonin (5-hydroxytryptamine, 5-HT). During the response to 5-HT, scratch stimuli (3 mm, 300 mN, 2 Hz, 20 s) were delivered at the injection site within the mechanosensitive receptive field (on-site), or 4-30 mm away, outside of the receptive field (off-site). During off-site scratching, 5-HT-evoked firing was significantly attenuated followed by recovery. On-site scratching excited neurons, followed by a significant post-scratch decrease in 5-HT-evoked firing. Most neurons additionally responded to mustard oil (allyl isothiocyanate). Off-site scratching had no effect, while on-site scratching excited the neurons. These results indicate that scratching exerts a state-dependent inhibitory effect on responses of spinal neurons to pruritic but not algesic stimuli. Moreover, on-site scratching first excited neurons followed by inhibition, while off-site scratching immediately evoked the inhibition of pruritogen-evoked activity. This accounts for the suppression of itch by scratching at a distance from the site of the itchy stimulus.