[Intrathecal clonidine--how does it work in spinal fentanyl analgesia in rats?]

The effects of intrathecal clonidine on spinal fentanyl analgesia were studied by the hot-plate test (52.0 degrees C) in rats. Clonidine (5 micrograms) and/or fentanyl (5 micrograms) were administered alone or combined in volume of 10 microliters through a chronically-implanted polyethylene catheter (PE-10) whose tip was near the lumbar enlargement of the spinal cord. Injections were done repeatedly every two or three days to determine the time course of thermal analgesia. Results were as follows; 1) Intrathecal clonidine (n = 5) produced no thermal analgesia. 2) Intrathecal fentanyl (n = 10) produced a profound thermal analgesia which was attenuated markedly by the repeated injections in six rats before the 9th injection. 3) Two out of six fentanyl tolerated rats responded with remarkable increases in thermal thresholds following the intrathecal clonidine with fentanyl. 4) Rats which were administered with both clonidine and fentanyl from the 1st injection (n = 9) responded with a extended prolongation of the escape latency, compared with the rats which received fentanyl only. In this group, the tolerance developed in only three animals by the 9th injection. In conclusion, combined intrathecal administration of clonidine with fentanyl potentiated the analgesic effect of fentanyl and then definitely suppressed the tolerance formation even if a small dose of clonidine which produces no analgesic effect was used. These results suggest that intrathecal or epidural administration of clonidine with narcotics might be useful in managing intractable pain.