The antinociceptive effects of morphine, desipramine, and serotonin and their combinations after intrathecal injection in the rat

Antinociception can be produced at the spinal level by activation of opioid ergic, noradrenergic, and serotonergic systems. We tested the antinocicepti ve effects of combined activation of all three systems. Antinociception was assessed in the rat tail-flick test, and drugs were administered via an in trathecal catheter. Morphine, the norepinephrine uptake inhibitor desiprami ne, and serotonin produced antinociception of their own. The combination of subthreshold doses of morphine 1 mu g and of desipramine 3 mu g produced p ronounced antinociception that was antagonized by yohimbine. The combinatio n of subthreshold morphine with serotonin 50 mu g or desipramine with serot onin caused only small antinociceptive effects. When morphine combined with desipramine was decreased to a subthreshold dose, we observed pronounced a ntinociception when a subthreshold dose of serotonin was added. A complex i nteraction can be supposed by results obtained with antagonists. The activa tion of all three neurotransmitter systems with small doses of agonists may represent an effective principle for pain control at the spinal level. Imp lications: Pain sensations are modulated at the spinal level by opioids, no radrenergic drugs, and serotonin. Using a rat model, we showed that the con current use of drugs from each of these classes produces good pain control at doses that should avoid the side effects associated with larger doses of each individual drug.