Effects of a Nociceptin Receptor Antagonist on Experimentally Induced Scratching Behavior in Mice

Itch and pain are two distressing sensations sharing a lot in common. In addition to the periphery, the central nervous system is proposed as a therapeutic target for the development of antipruritic drugs. The contribution of the most recently discovered opioid peptide, nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) in pain transmission is controversial. It seems to be pronociceptive when given supraspinally, but elicits an antinociceptive action when injected spinally. Here, we examined whether the N/OFQ system plays a role in experimentally induced pruritus. Scratching behavior was produced by intradermal administration of serotonin (50 μg/50 μl/mouse) or nociceptin (30 nmol/50 μl/mouse) to Balb/c mice. JTC-801 (1, 3 or 10 mg/kg, i.p.), a NOP receptor antagonist, attenuated both serotonin- and nociceptin-induced scratches. When given intradermally, JTC-801 (100 nmol) significantly reduced serotonin-induced but not nociceptin-induced scratches. We propose that antagonizing NOP receptors either systemically or localy may be a novel approach in the development of antipruritic agents.

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