Impairment in Pain Perception in Adult Rats Lesioned as Neonates with 5.7-Dihydroxytryptamine

Whereas some studies have demonstrated the essential role of 5-hydroxytryptamine (5-HT) in tramadol and acetaminophen analgesia, other research has presented conflicting results. To dispel doubts, some aspects of the involvement of 5-HT in the antinociceptive properties of these drugs remain to be clarified.

The aim of this study was to determine whether the serotoninergic system dysfunction produced by neonatal 5-HT lesion in rats may affect the antinociceptive effects of tramadol and acetaminophen administered in adulthood.

Three days after birth, the control rats were pretreated with desipramine HCl (20 mg/kg i.p.) 30 min before intraventricular saline--vehicle injection. A separate group received 5.7-DHT; 2×35 µg in each lateral ventricle. At the age of 8 weeks, 5-HT and 5-hydroxyidoleaceticacid (5-HIAA) concentrations were determined in the thalamus and spinal cord by an HPLC/ED method. The antinociceptive effects of tramadol (20 mg/kg i.p.) or acetaminophen (100 mg/kg i.p.) were evaluated by a battery of tests.

5.7-DHT lesioning was associated with a reduction in 5-HT and 5-HIAA content of the thalamus (>85% and >90%) and spinal cord (>58% and 70%). Neonatal 5.7-DHT treatment produced a significant reduction in the antinociceptive effect of tramadol in the hot plate, tail-immersion, paw withdrawal and writhing tests. In the formalin hind paw test, the results were ambiguous. 5-HT lesion was also associated with a decrease in the analgesic effect of acetaminophen in the hot plate and writhing tests. A similar relationship wasn't found in the other assessments conducted with the use of acetaminophen.

The present study provides evidence that (1) an intact serotoninergic system is required for the adequate antinociceptive action of tramadol, and (2) the serotoninergic system exerts a negligible influence on acetaminophen-induced analgesia in rats. We hypothesize that similar abnormalities in nociception may occur in patients with 5-HT dysfunction (e.g. depression), so these results should be complied in analgesic dosage adjustment.