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The effect of central administration of delta-sleep-inducing peptide (DSIP) on nociceptive responses was evaluated in mice and rats. DSIP, administered intracerebroventricularly or intracisternally to mice, produced a significant dose-dependent antinociceptive effect in the tail-pinch and hot-plate tests. Intrathecal administration of DSIP did not produce such an effect. The antinociceptive effect of DSIP was blocked by pretreatment with the opioid antagonist, naloxone. Moreover, DSIP did not produce an antinociceptive effect in morphine-tolerant mice. Similar antinociceptive effects of DSIP were observed in rats. These results suggest that DSIP produces an antinociceptive effect by acting at the supraspinal level and that this effect is mediated via the opioid receptor, either directly or indirectly. DSIP may play an important role in pain regulation in the central nervous system.
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