Jean C. Doerr

Amniotic-fluid ingestion by parturient rats enhances pregnancy-mediated analgesia

Amniotic fluid and placenta contain a substance (POEF, for Placental Opioid-Enhancing Factor) that, when ingested, enhances opioid-mediated analgesia in nonpregnant rats; ingestion of the substance by rats not experiencing opioid-mediated analgesia, however, does not produce analgesia. It is highly likely that periparturitional analgesia-enhancement is a significant benefit of ingestion of the afterbirth (placentophagia) during delivery. Here we report that prepartum ingestion of amniotic fluid (via orogastric infusion) does indeed enhance the endogenous-opioid-mediated analgesia evident at the end of pregnancy and during delivery; that the degree of enhancement is greater with 0.75 ml than with 0.25 ml; and that the prepartum enhancement of analgesia can be blocked with the opioid antagonist naloxone.

Placental opioid-enhancing factor (POEF): Generalizability of effects

A substance in amniotic fluid and placenta (POEF for Placental Opioid-Enhancing Factor) has been shown to enhance opiate- or opioid-mediated analgesia in rats. Recent studies have only touched on the generalizability of the phenomenon. The present studies further tested the generalizability of the POEF effect: they examined sex specificity of the mechanism; whether POEF activity exists in afterbirth material of species other than the rat; whether POEF activity exists in tissue other than afterbirth material; whether POEF activity could be demonstrated after injection rather than ingestion of afterbirth material; and whether POEF enhances all opioid-mediated phenomena. We found that (a) POEF is effective in male rats as well as in female rats; (b) POEF activity exists in human and dolphin afterbirth material; (c) ingestion of pregnant-rat liver does not produce enhancement of opioid-mediated analgesia; (d) POEF does not seem to be effective when amniotic fluid is injected either IP or SC; and (e) POEF does not modify morphine-induced hyperthermia.

Enhancement of opioid-mediated analgesia by ingestion of amniotic fluid: Onset latency and duration

Ingestion of placenta and amniotic fluid has been shown to enhance opioid-mediated analgesia produced by morphine injection, footshock, vaginal/cervical stimulation, and during late pregnancy in rats. The present study was designed to determine how soon after ingestion the enhancement begins and how long it lasts. Tail-flick latencies in Long-Evans rats were determined before and during vaginal/cervical stimulation; analgesia was measured as the percent increase in tail-flick latency during vaginal stimulation. After determination of baseline, rats were intubated with 0.25 ml of either amniotic fluid or beef bouillon. We found that analgesia enhancement was detectable as early as 5 minutes after ingestion of amniotic fluid, and the effect lasted at least 30 minutes, but no longer than 40 minutes.

Insect venom allergy: a prospective case study showing lack of correlation between immunologic reactivity and clinical sensitivity

This case report demonstrates the lack of correlation between clinical sensitivity to insect venoms and immunologic reactivity as indicated by the presence of venom-specific IgG. A 20-yr-old venom collector was monitored over a 3-yr period with measurements of venom-specific IgE (skin test and RAST) and venom-specific IgG. In the first year of venom collection, multiple stings were tolerated with no reaction. In the second season, she had an anaphylactic reaction after a yellow jacket sting. Subsequently, there was a rising titer of serum yellow jacket and bee venom-specific IgE and positive skin-test reactions. In the third season, yellow jacket, hornet, and bee venom skin tests remained positive and serum IgE antibody titers remained elevated. Stings from all three insects were tolerated with no reaction. Throughout the 3-yr course, serum venom-specific IgG remained low and unchanged. The factors other than IgE-modulating clinical anaphylaxis, perhaps responsible for this clinical and immunologic dichotomy, are unknown. These observations add a further complication to the choice of patients for venom immunotherapy.

Ingested bovine amniotic fluid enhances morphine antinociception in rats

Ingestion by rats of rat placenta or amniotic fluid enhances opioid-mediated, or partly opioid-mediated, antinociception produced by morphine injection, vaginal or cervical stimulation, late pregnancy, and foot shock. This phenomenon is believed to be produced by a placental opioid-enhancing factor (POEF). Ingestion by rats of human or dolphin placenta has also been shown to enhance opioid antinociception, suggesting that POEF may be common to many mammalian species. We tested bovine amniotic fluid (BAF) for its capacity to enhance morphine antinociception in female Long-Evans rats, as determined by percentage change from baseline tail-flick latency in response to radiant heat, and we report that 0.50 mL BAF effectively enhanced morphine antinociception but did not by itself produce antinociception. The efficacy of POEF across species suggests that POEF may have been functionally (and structurally) conserved during evolution. Furthermore, the availability of POEF at parturition, as well as its ability to enhance pregnancy-mediated antinociception without disrupting maternal behavior, offers a tenable explanation for the long-debated ultimate causality of placentophagia.

Amniotic-fluid ingestion enhances morphine analgesia during morphine tolerance and withdrawal in rats

Ingestion of placenta and amniotic fluid has been shown to enhance opioid-mediated analgesia in rats produced by morphine injection, footshock, vaginal/cervical stimulation, and during late pregnancy. The present study was designed to investigate the effects of amniotic fluid ingestion on the characteristics of morphine dependency and withdrawal. Tail-flick latencies in Long-Evans rats were determined before and after repeated daily injections of morphine sulfate. It was found that ingestion of amniotic fluid after establishment of the morphine dependency, coupled with an injection of an otherwise ineffective dose of morphine, enhanced analgesia in morphine-dependent rats, and reversed hyperalgesia seen during withdrawal from morphine dependency.

Adaptation of the electrical stimulation procedure for the collection of vespid venoms

Abstract Venom was obtained from yellow hornets ( Dolichovepula arenaria ), bald-faced hornets ( D. maculata ) and yellow jacket species ( Vespula spp.) by modification of the electrical “milking” method. Usual venom yields were 20–40 mg per colony. These methods are a substantial improvement over previous techniques employed to obtain pure vespid venoms.

Amniotic fluid ingestion before vaginal/cervical stimulation produces a dose-dependent enhancement of analgesia and blocks pseudopregnancy

A substance in amniotic fluid (AF) and placenta has been shown to enhance analgesia produced by morphine, late pregnancy, footshock, and vaginal/cervical stimulation (VS). When morphine-induced analgesia was assessed previously, the degree of enhancement by ingestion of AF or placenta was found to be a function of the amount of analgesia being generated. We have extended these results to include the analgesia produced by VS. Analgesia induced by 75, 125, 175, or 225 g of vaginal/cervical pressure was measured in rats pretreated with 0.25 ml (by orogastric infusion) of either AF or saline. AF infusion enhanced the analgesia produced by 125 g VS, but did not affect the analgesia produced by 75, 175, or 225 g VS. Unexpectedly, we also found that infusion of AF shortly before the application of VS prevents VS-induced pseudopregnancy (PsP). Whereas the incidence of PsP following 75, 125, or 175 g VS was less than 19% and not statistically different for AF and saline pretreatments, the incidence of PsP after 225 g VS was 44% in saline-pretreated rats, but only 10% in AF-pretreated rats. Protection from the induction of pseudopregnancy, which could be caused by mechanical stimulation of the cervical area during delivery, may be an additional benefit of parturitional ingestion of placenta and amniotic fluid (placentophagia).

Ingested placenta blocks the effect of morphine on gut transit in Long–Evans rats

Opioids produce antinociception, and ingested placenta or amniotic fluid modifies that antinociception. More specifically, ingested placenta enhances the antinociception produced by selective activation of central kappa-opioid or delta-opioid receptors but attenuates that produced by activation of central mu-opioid receptors. Opioids also slow gut transit by acting on central or peripheral mu-opioid receptors. Therefore, we hypothesized that ingested placenta would reverse the slowing of gut transit that is produced by morphine, a preferential mu-opioid-receptor agonist. Rats were injected with morphine either centrally or systemically and fed placenta, after which gastrointestinal transit was evaluated. We report here that ingested placenta reversed the slowing of gut transit produced by centrally administered morphine but did not affect the slowing of gut transit produced by systemically administered morphine. These results suggest another likely consequence of placentophagia at parturition in mammals--reversal of opioid-mediated, pregnancy-based disruption of gastrointestinal function--as well as an important consideration in opioid-based treatments for pain in humans--enhancement of desirable effects with attenuation of adverse effects.