Low-dose clonidine enhances pregnancy-induced analgesia to visceral but not somatic stimuli in rats.
This is one of a series of experiments designed to examine the possible pharmacologic basis for analgesia normally associated with pregnancy. The antinociceptive effects of low-dose (0.1 mg/kg) subcutaneous clonidine on analgesia associated with pregnancy were evaluated in rats. Colorectal distention thresholds and tail-flick latencies were determined in timed pregnant rats (n = 27) before mating, on days 7 and 21 of gestation, and on postpartum day 7. Immediately after baseline testing on each of those days, animals received 0.1 mg/kg clonidine subcutaneously and were retested 30 min later. On day 21 of gestation, 20 micrograms/kg naloxone (n = 9) and 0.2 mg/kg yohimbine (n = 5) were intravenously administered after clonidine testing, and animals were retested 15 min later. In the absence of clonidine, pregnant animals demonstrated a statistically significant increase in their tolerance of colorectal distention pressures and longer latencies to tail-flick withdrawal on day 21 of gestation. Clonidine produced a further significant increase in distention thresholds on day 21 of gestation but did not change these thresholds on any other day, nor did it change tail-flick latencies. Naloxone and yohimbine reversed the effect of clonidine on the distention thresholds on day 21. Systemic clonidine, at a dose lower than that required to produce antinociception in nonpregnant rats, enhanced pregnancy-induced analgesia to visceral stimulation late in pregnancy, an effect that was reversed by naloxone and yohimbine. These results suggest a synergistic antinociceptive effect of clonidine due to an interaction with an endogenous opiate system that is only activated late in pregnancy.
Iwasaki
H
H
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Collins
J G
JG
Saito
Y
Y
Uchida
H
H
Kerman-Hinds
A
A
D016362:Analgesia, Obstetrical; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D010147:Pain Measurement / Q000187:drug effects*; D010812:Physical Stimulation; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000700:Analgesics; D003000:Clonidine