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The Journal of Neuroscience, November 26, 2003, 23(34):10784-10790

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Behavioral/Systems/Cognitive
Opioid Modulation of Scratching and Spinal c-fos Expression Evoked by Intradermal Serotonin

Hiroshi Nojima,¹ Christopher T. Simons,² Jason M. Cuellar,² Mirela Iodi Carstens,² Justin A. Moore,² and Earl Carstens²

¹Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan, and ²Section of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, California 95616

We investigated a spinal site for opioid modulation of itch-related scratching behavior in rats. Intradermal 5-HT (2%, 10 µl) elicited intermittent bouts of hindlimb scratching directed toward the injection site (nape of neck) beginning within minutes and lasting >1 hr. 5-HT-evoked scratching was significantly reduced by systemic administration of the opiate antagonist naltrexone but was not affected by systemic morphine at a dosage (3 mg/kg) that induces analgesia. Intradermal 5-HT elicited a significant increase in c-fos-like immunoreactivity (FLI) in superficial laminas I-III at the lateral aspect of the cervical C3-C6 dorsal horn compared with controls receiving intradermal saline. Neither systemic morphine nor naltrexone significantly affected counts of 5-HT-evoked FLI. The lack of effect of morphine suggests that intradermal 5-HT activates dorsal horn neurons, signaling itch but not pain. Attenuation of 5-HT-evoked scratching but not spinal FLI by naltrexone suggests a supraspinal site for its antipruritic action. In contrast, morphine significantly attenuated FLI elicited by intradermal capsaicin, a chemical that induces pain but not scratching.

Key words: itch; serotonin; scratching; c-fos immunoreactivity; naltrexone; morphine; rat

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Received July 29, 2003; revised September 3, 2003; accepted September 12, 2003.

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