Itch elicited by intradermal injection of serotonin, intracisternal injection of morphine, and their synergistic interactions in rats

• Intradermal injection of serotonin into facial skin of rats causes scratching.
• Intracisternal injection of morphine produces scratching and reduces the nociceptive behavior of wiping.
• Combining the two types of injections produces a synergistic, super-additive increase in scratching.
• The results indicate that application of small doses of morphine to the CNS causes itch and hyperknesis.

We used the cheek model of itch and pain in rats to determine the dose–response relationships for intradermal injection of serotonin and α methylserotonin on scratching behavior. We also determined the dose-related effects of intracisternally injected morphine on scratching, effects that were greatly reduced by administration of the opiate antagonist naloxone. We then examined the interactions of intradermal injection of serotonin and intracisternal injection of morphine on scratching and found that the two procedures act synergistically to increase itch. These results suggest that morphine applied to the CNS is capable of producing itch and greatly increasing itch originating in the skin (hyperknesis).