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