Inhibition of itch-related responses at spinal level in rats

The goal was to develop a rat model for determination of the effects of intrathecally administered drugs on the peripherally induced pruritic behaviors. After chronic intrathecal catheterization, a serotonin derivative (5-methoxytryptamine: MeOT, 200 μg on both sides) was injected into the lower leg skin. After the first period (phase 0: 0-30 min) MeOT injection was repeated and opioid antagonist naltrexone (10 μg), NMDA receptor antagonists ketamine (10-100 μg), kynurenic acid (1-10 μg) or their combinations were injected intrathecally. The second observational period lasted for 60 min (phases I and II, 30-60 and 60-90 min, respectively). MeOT produced pruritic behavior with high degree of interindividual differences. The second MeOT injection caused an enhanced pruritic behavior in Phase I. Naltrexone decreased the pruritic activity, while neither doses of ketamine influenced the effects of MeOT. The higher doses of kynurenic acid resulted in notable decreases in the pruritic behavior. The combinations of naltrexone with ketamine or kynurenic acid produced a prolonged antipruritic effect. Our data suggest an important direction for the development of a new itch model in rats that focuses on the spinal mechanism of itching. Besides, the results revealed the role of the spinal opioid and NMDA receptors in this process.