Pharmacology and physiology of pregnancy induced analgesia

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Pregnancy-induced analgesia is of interest to anesthesiologists because of the observation that parturients may require less anesthetic or analgesic drugs. This is one of series of experiments to examine the pharmacology of pregnancy-induced analgesia in rats.In pregnant animals, a significant increase in tail-flick latency(TFL) was demonstrated on day 21 of gestation. Intrathecally administered ketamine (50 and 100 microg) produced a dose dependent prolongation of TFL on day 21 of gestation. However, this potentiative effect in TFL after ketamine injection were not observed on days 7 and 17 of gestation, and post-partum day 7 (Fig 1). A similar pattern of augmentation in AUC after ketamine was observed on day 21 of gestation. The main finding of this study was that intrathecally administered ketamine potentiated the degree of pregnant-induced analgesia to thermal noxious stimulation late in pregnancy. These results suggest a synergistic antinociceptive effect of ketamine due to an interaction with an endogenous opiate system that is only activated late in pregnancy. (Journal of Anesthesia 13:74:1999, Anesthesiology 91:A778:1999).Then we investigated, in rats, the effects of pregnancy on pain behaviorous induced by electrical stimulation of the peripheral fields, or by subcutaneous injection of formalin into the hind paw. This study demonstrated that pregnancy can increase cutaneous pain thresholds to electrical as well as chemical stimuli (Anesthesiology 2001;95:A748).Endomorphine-1 is a novel endogenous u-opioid ligand. The potent antinociceptive effect of endomorphine-1 microinjected into the ventrolateral periaqueductal gray is mediated through the u-opioid receptor and is potentiated by concomitant administration of L-type calcium channel blocker, nifedipine (Anesth Analg 2003;96:1065-71)