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Placental Opioid-Enhancing Factor (POEF) - generalizability of effects

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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.
... To mothers delivering litters (polytocous species), both amniotic fluid and placenta are available to provide POEF before and throughout the entire delivery (Kristal, 1991). Furthermore, POEF, itself, is apparently not absorbed into the system and must be ingested to work: first, systemic injection (1.0 ml amniotic fluid, IP or SC) was not effective in producing a POEF effect (Abbott et al., 1991); and second, the POEF effect requires intact gastric vagus afferents (Tarapacki et al., 1992;Robinson et al., 1995)(see Table 1). One apparent outlier in the literature is a study conducted in mice, in which a large intraperitoneal injection of "human placental extract" (also called HPE, and marketed as Placentrex®) was observed to enhance morphine hypoalgesia (Gurgel et al., 2000). ...
... POEF seems to exist only in afterbirth tissue (Abbott et al., 1991) and is therefore not produced in males; however, male rats can experience enhancement of hypoalgesia produced by POEF ingestion (see Table 1). In male rats that received an intraperitoneal injection of morphine, the morphine hypoalgesia was significantly greater in the males that received a concurrent orogastric infusion of amniotic fluid than it was in those that received a concurrent orogastric infusion of beef bouillon Table 1 Results of Tests for POEF Effects and Possible POEF Effects. ...
... Female rats tested unless otherwise noted. (Abbott et al., 1991). This, in addition to the presence of POEF activity in afterbirth of various taxonomic groups, suggests to us that the POEF effect may be a universal mammalian phenomenon. ...
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Placentophagia, ingestion of placenta and amniotic fluid, usually during parturition, is a behavioral feature of nearly all nonaquatic, placental mammals, and is a nexus for several interlocking behavioral phenomena. Placentophagia has not been typical of human cultures, but in recent years, some women in affluent societies have engaged in it, thereby bringing publicity to the behavior. First, we summarized benefits of placentophagia for nonhuman mammals, which include increased attractiveness of neonates, enhanced onset of maternal behavior, suppression of pseudopregnancy, and enhancement of opioid hypoalgesia by Placental Opioid-Enhancing Factor (POEF), a benefit that may extend well outside the context of parturition. The research on POEF in animals was discussed in detail. Then we discussed placentophagia (placentophagy) in humans, and whether there is validity to the claims of various benefits reported primarily in the pro-placentophagy literature, and, although human afterbirth shows POEF activity, the POEF effect has not yet been tested in humans. Finally, we discussed the general possible implications, for the management of pain and addiction, of isolating and characterizing POEF.
... Abbott et al. [45] found that the POEF effect is generalizable to other species since it was observed in rats (Rattus norvegicus) that consume placental material from humans, dolphins, and cattle. It is also suggested that POEF is a product of the gastrointestinal system's enzymatic or hydrochloric acid action. ...
... The time to produce analgesia after ingesting placental material varies within species. In Holstein cows (Bos taurus) [41] and male rats (Rattus norvegicus) [45], analgesia occurs immediately and lasts up to 60 min; while in female rats (Rattus norvegicus), only a 30 min duration of the analgesic effect was registered [46]. Likewise, the dosage in the ingestion of placental material with an analgesic effect differs among mammal species. ...
... Amniotic fluid and placenta act as morphinic inducers, facilitating analgesia, and activating the release of endorphins [37][38][39][40][41][42][43]45] Women ...
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Placentophagia is a common mammalian behavior, and the first scientific study of the potential effects of human maternal placentophagia on lactation was in 1917. More recently, in the 1970s, human placentophagia was reported in North America with a trend toward increased consumption. There are different hypotheses about the women and nonhuman mammals’ motivation towards placentophagia, but few have been subject to hypotheses testing. In women, the controversy continues; on the one hand, researchers attribute benefits like increased breast milk, weight gain in newborns, decreased postpartum depression and fatigue, and improved mothers’ mood. In contrast, bacterial or viral infections, hormonal, or trace elements that could become toxic for both the mother and baby are reported as possible health risks. Other reports argue a lack of scientific rigor to support the self-reported benefits of placentophagia. Also, the way the placenta is prepared (raw, cooked, dehydrated, processed, or encapsulated) alters its components, and thus the desired effects. This review provides relevant information and the different hypotheses and points of view around placentophagia. However, there are still questions to be resolved, and more studies are needed to confirm or reject the data generated so far about placentophagia in humans and nonhuman mammals.
... Decreased pain sensitivity during parturition may facilitate labor, as neonates are expelled more quickly (Kristal, 1991). Interestingly, POEF is found in placental tissues even of species that typically do not ingest placenta (i.e., dolphins, humans), suggesting that this substance is highly conserved among placental mammals (Abbott et al., 1991). ...
... In the uniparental (i.e., only one parent, the mother, provides offspring care) Siberian hamster (Phodopus sungorus), males ingest experimentally presented placenta only if they are present at the birth of their pups (Gregg and Wynne-Edwards, 2006). Similarly, male rats, which are commonly averse towards the afterbirth, will begin to eat placenta after continuous exposure to it (Abbott et al., 1991). In several biparental (i.e., both males and females care for their young) mammals, males, in addition to females, sometimes ingest placenta during the birth of their offspring. ...
... MPOAmedial preoptic area of the hypothalamus, dBSTdorsal bed nucleus of the stria terminalis, vBSTventral bed nucleus of the stria terminalis, PVNparaventricular nucleus of the hypothalamus, BLAbasolateral amygdala, CeAcentral nucleus of the amygdala. Studies on the consequences of placenta ingestion suggest that placentophagia by mothers may trigger behavioral and physiological changes that positively affect their offspring (e.g., Abbott et al., 1991;González-Mariscal et al., 1998). In the case of males, a study on rats, which are uniparental, showed that virgin males experience hypoalgesia after ingesting placenta (Abbott et al., 1991). ...
Article
s Placentophagia increases parental motivation in sexually inexperienced adult female rodents. We hypothesized that placenta ingestion has similar effects in virgin male California mice (Peromyscus californicus), a monogamous rodent in which fathers provide extensive care for their offspring. To test this hypothesis, we administered either a conspecific’s placenta in oil or oil alone to adult virgin males via oral gavage. One, 7 or 24 hours later, each male underwent a 1-hour behavior test with either an unfamiliar pup or a novel object marble), immediately after which the mouse was perfused and the brain collected. Neural activation (Fos-immunoreactivity) was quantified in brain regions involved in parental care (bed nucleus of the stria terminalis, medial preoptic area, amygdala). We found few significant effects of placenta treatment, but at 7 h post-gavage, placenta-treated males had decreased latencies to approach both pups and marbles, compared to oil-treated controls (p = 0.05). Placenta-treated males also showed lower Fos-immunoreactivity in the dorsal bed nucleus of the stria terminalis, irrespective of stimulus type, compared to controls, both 1 h (p = 0.04) and 7 h (p = 0.05) post-treatment. These results suggest that placentophagia does not directly affect paternal motivation but might increase willingness to interact with novel stimuli in virgin male California mice.
... After ingesting placenta, mothers may undergo specific physiological changes that can potentially affect maternal responsiveness and opioid signaling. For example, placentophagia increases opioid-mediated analgesia in female rats [1]. In addition to pain sensitivity, this effect on the opioid system may influence maternal behavior, as ingestion of placenta and amniotic fluid by adult sexually naïve female rats enhances the stimulatory effect of intracerebroventricular morphine treatment on maternal sensitization (i.e., pup-induced maternal responsiveness: [26]). ...
... Only two studies have investigated the physiological and behavioral changes in males after ingestion of placenta, one in the uniparental rat and another in the biparental California mouse. Both studies suggest that males can undergo neural and behavioral changes after ingesting placenta ( [1]; Perea-Rodriguez, unpub. Ph.D. dissertation). ...
... Ph.D. dissertation). Adult male rats, similar to adult females, experience an increase in opioid-mediated analgesia, suggesting that placentophagia may modify opioid signaling pathways [1]. Adult virgin male California mice administered placenta homogenized in sesame oil via oral gavage showed lower latencies to approach novel stimuli (i.e., an unrelated pup or a pup-sized-marble), than mice administered oil vehicle only. ...
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Ingestion of placenta by mammalian mothers can lead to changes in pain sensitivity, hormone levels, and behavioral responses to newborns. In some biparental mammals, males, in addition to females, ingest placenta when their offspring are born. In the monogamous, biparental California mouse (Peromyscus californicus), males first become attracted to placenta when cohabitating with their pregnant mate, and virgin males administered placenta are less neophobic than males given oil vehicle. In this study, we investigated the effects of placentophagia on pain sensitivity, anxiety-like behavior, behavioral responses to pups, and circulating corticosterone levels of both breeding and nonbreeding male California mice. We orally administered either a conspecific placenta or oil vehicle to male mice from three reproductive conditions (first-time fathers, first-time expectant fathers, and virgin males) and tested their pain sensitivity 1 h later, as well as their exploratory behavior and paternal responsiveness in an open field 4 h post-treatment. We measured plasma corticosterone immediately after the open-field test. We found that placenta-treated males, independent of reproductive condition, traveled significantly longer distances in the open field than males treated with oil, indicative of lower anxiety. Additionally, fathers had shorter latencies to approach and to care for pups (i.e., huddling and licking pups), and spent more time engaging in these behaviors, than did age-matched expectant fathers and virgin males, independent of treatment. We found no effect on plasma corticosterone levels or pain sensitivity as a result of either treatment or reproductive condition. These findings indicate that placenta ingestion decreases anxiety-related behaviors in male California mice, but might not influence pain sensitivity, paternal responsiveness, or plasma corticosterone concentrations.
... The active substance(s) in placenta and amniotic fluid has been termed Placental Opioid-Enhancing Factor (POEF) [43]. The antinociception-enhancing effect of POEF has been well documented in rats of both sexes, in different reproductive states (in virgin and parturient females), and in several algesiometric tests (radiant heat tail-flick test, hot water tail-immersion test, formalin test, and hotplate test) [1,39,41,44,45,73]. In addition, antinociception enhancement has been observed in rats that eat placenta or amniotic fluid of all other species tested to date, including that of humans, dolphins [1], and cows [12], and has been observed in cows after ingestion of bovine amniotic fluid [71]. ...
... The antinociception-enhancing effect of POEF has been well documented in rats of both sexes, in different reproductive states (in virgin and parturient females), and in several algesiometric tests (radiant heat tail-flick test, hot water tail-immersion test, formalin test, and hotplate test) [1,39,41,44,45,73]. In addition, antinociception enhancement has been observed in rats that eat placenta or amniotic fluid of all other species tested to date, including that of humans, dolphins [1], and cows [12], and has been observed in cows after ingestion of bovine amniotic fluid [71]. At parturition, changing levels of ovarian sex steroids and uterine afferent activity produce ''pregnancy-mediated analgesia'', an opioid-mediated increase in maternal pain threshold that is particularly pronounced in the periparturitional period [11,23,31,33,95]. ...
... However, the effects of POEF do not extend equally to all opioid-mediated phenomena. POEF ingestion does not affect morphine-mediated hyperthermia [1], and it suppresses contralateral circling produced by unilateral morphine injection into the ventral tegmental area (VTA) [90]. ...
Article
Ingestion of placenta or amniotic fluid produces a dramatic enhancement of centrally mediated opioid antinociception in the rat. The present experiments investigated the role of each opioid receptor type (p, 6, K) in the antinociception-modulating effects of Placental Opioid-Enhancing Factor (POEF-presumably the active substance). Antinociception was measured on a 52degreesC hotplate in adult, female rats after they ingested placenta or control substance (1.0 g) and after they received an intracerebroventricular injection of a delta-specific ([D-Pen2,D-Pen5]enkephalin (DPDPE); 0, 30, 50, 62, or 70 nmol), mu-specific ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO); 0, 0.21, 0.29, or 0.39 nmol), or K-specific (U-62066; spiradoline; 0, 100, 150, or 200 nmol) opioid receptor agonist. The results showed that ingestion of placenta potentiated delta- and kappa-opioid antinociception, but attenuated mu-opioid antinociception. This finding of POEF action as both opioid receptor-specific and complex provides an important basis for understanding the intrinsic pain-suppression mechanisms that are activated during parturition and modified by placentophagia, and important information for the possible use of POET as in adjunct to opioids in pain management.
... Since placental tissues are not available to humans until after the child is born and no studies were found that systematically studied placental consumption in conjunction with opiate intake in humans, the relevance of these findings to reducing pain in labor or postpartum in humans is unclear. Abbott et al. (1991) conducted a series of studies investigating the generalizability and specificity of mechanisms of action of POEF on enhancing analgesia in rodents. To evaluate the generalizability of effects of POEF, the authors investigated effects of human and dolphin placental ingestion on pain thresholds in female rats experiencing partially opioidmediated analgesia produced by vaginal-cervical stimulation. ...
... In another study in this series, Abbott et al. (1991) did not find POEF to be contained in rat liver tissue and concluded that POEF is localized to placental tissue. Rats were fed pregnant-rat liver, beef or no meat, after injections of morphine and compared to rats given saline. ...
... However, no significant differences in pain thresholds were found in the experimental groups. When comparing effects of different administration locations (enteral, intraperitoneal, subcutaneous), enhancement of opioidmediated analgesia occurred only when afterbirth was administered through the gastrointestinal tract (Abbott et al. 1991). Based on these findings, the authors suggested that the enhancing effect of POEF is localized to placental tissue and associated with biochemical events in the gastrointestinal system. ...
Article
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Postpartum women are consuming their placentas encapsulated, cooked, and raw for the prevention of postpartum depression (PPD), pain relief, and other health benefits. Placentophagy is supported by health advocates who assert that the placenta retains hormones and nutrients that are beneficial to the mother. A computerized search was conducted using PubMed, Medline Ovid, and PsychINFO between January 1950 and January 2014. Keywords included placentophagy, placentophagia, maternal placentophagia, maternal placentophagy, human placentophagia, and human placentophagy. A total of 49 articles were identified. Empirical studies of human or animal consumption of human placentas were included. Editorial commentaries were excluded. Animal placentophagy studies were chosen based on their relevance to human practice. Ten articles (four human, six animal) were selected for inclusion. A minority of women in developed countries perceive placentophagy to reduce PPD risk and enhance recovery. Experimental animal research in support of pain reduction has not been applied in humans. Studies investigating placenta consumption for facilitating uterine contraction, resumption of normal cyclic estrogen cycle, and milk production are inconclusive. The health benefits and risks of placentophagy require further investigation of the retained contents of raw, cooked, and encapsulated placenta and its effects on the postpartum woman.
... The way the afterbirth enters the body seems to be important for exerting its effects. Subcutaneous or intraperitoneal injection of the amniotic fluid did not change the pain sensitivity of rats, whereas the orogastric infusion did (Abbott et al., 1991). Interestingly, the gastric vagus nerve is necessary for analgesic effects of placentophagy as gastric vagotomy blocks the effects (Tarapacki et al., 1992). ...
... The putative components in the placenta that enhance analgesia are still unknown. One of these putative components has been named placental opioid-enhancing factor (POEF) (Abbott et al., 1991) and predicted to be a peptide that a temperature above 40 degrees Celsius can inactivate it (Kristal et al., 2012). Like most peptides, it seems that POEF does not pass the blood-brain barrier in physiologically significant amounts and, thus, its effects depend on indirect activation of central mechanisms. ...
Article
The first clinical applications of oxytocin (OT) were in obstetrics as a hormone to start and speed up labor and to control postpartum hemorrhage. Discoveries in the 1960s and 1970s revealed that the effects of OT are not limited to its peripheral actions around birth and milk ejection. Indeed, OT also acts as a neuromodulator in the brain affecting fear memory, social attachment, and other forms of social behaviors. The peripheral and central effects of OT have been separately subject to extensive scrutiny. However, the effects of peripheral OT—particularly in the form of administration of synthetic OT (synOT) around birth—on the central nervous system are surprisingly understudied. Here, we provide a narrative review of the current evidence, suggest putative mechanisms of synOT action, and provide new directions and hypotheses for future studies to bridge the gaps between neuroscience, obstetrics, and psychiatry.
... 17 Researchers started using the term placental opioid-enhancing factor (POEF) to refer to the placental component that induces this enhancement. 56 The idea that the POEF effect reduces pain sensitivity explains why most mammals engage in placentophagy. The molecular structure of POEF has not yet been identified; however, it is suggested that it is a relatively small peptide of 6000e8000 Daltons that can easily be inactivated at temperatures above 104 F (40 C). 17,56 The only available randomized, double-blinded, placebo-controlled trial in women who ate their placenta compared the effect of placenta pills on maternal postpartum iron status. ...
... 56 The idea that the POEF effect reduces pain sensitivity explains why most mammals engage in placentophagy. The molecular structure of POEF has not yet been identified; however, it is suggested that it is a relatively small peptide of 6000e8000 Daltons that can easily be inactivated at temperatures above 104 F (40 C). 17,56 The only available randomized, double-blinded, placebo-controlled trial in women who ate their placenta compared the effect of placenta pills on maternal postpartum iron status. 57 Hemoglobin, transferrin, and ferritin were measured at 36 gestational weeks, within web 4C=FPO ajog.org ...
Article
Placentophagy or placentophagia, the postpartum ingestion of the placenta, is widespread among mammals; however, no contemporary human culture incorporates eating placenta postpartum as part of its traditions. Nevertheless, there is an increasing interest in placentophagy among postpartum women, especially in the United States. The placenta can be eaten raw, cooked, roasted, dehydrated, encapsulated, or through smoothies and tinctures. The most frequently used preparation appears to be placenta encapsulation after steaming and dehydration. Numerous companies offer to prepare the placenta for consumption. The evidence for positive effects of human placentophagy is anecdotal, and limited to self-reported surveys. Without any scientific evidence, individuals promoting placentophagy, especially in the form of placenta encapsulation, claim that it is associated with certain physical and psychosocial benefits. We found that there is no scientific evidence of any clinical benefit of placentophagy among humans, and no placental nutrients and hormones are retained in sufficient amounts after placenta encapsulation to be potentially helpful to the mother, postpartum. In contrast to the belief of clinical benefits associated with placenta encapsulation, the Centers for Disease Control and Prevention recently issued a warning owing to a case where a newborn infant developed recurrent neonatal group B Streptococcus sepsis after the mother ingested contaminated placenta capsules containing Streptococcus agalactiae. The Centers for Disease Control and Prevention recommended that the intake of placenta capsules should be avoided owing to inadequate eradication of infectious pathogens during the encapsulation process. Therefore, in response to a woman who expresses an interest in placentophagy, physicians should inform her about the reported risks and the absence of clinical benefits associated with the ingestion. In addition, clinicians should inquire regarding a history of placenta ingestion in cases of postpartum maternal or neonatal infections such as group B Streptococcus sepsis. In conclusion, owing to the harmful effects of placentophagy, there is no professional responsibility on clinicians to offer placentophagy to pregnant women. Moreover, because placentophagy is potentially harmful with no documented benefit, counseling women should be directive: physicians should discourage this practice. Healthcare organizations should develop clear clinical guidelines to implement a scientific and professional approach to placentophagy.
... The enhancing effect of POEF was shown in both male and female subjects, and has been demonstrated in rats, mice, and cows (Gurgel et al., 2000;Kristal et al., 2012;Pinheiro-Machado et al., 1997). POEF must be ingested to be effective, and POEF activity is found in both AF and placenta of all species tested, suggesting that the mechanism for responding to POEF may be ubiquitous among mammals (Abbott et al., 1991;Kristal et al., 2012). DiPirro et al. found that POEF actions are centrally rather than peripherally mediated (DiPirro et al., 1991), and that the effect is to enhance d-and j-opioid-induced events (hypoalgesia) while attenuating m-receptor-mediated events (DiPirro and Kristal, 2004). ...
Article
Placental Opioid Enhancing Factor (POEF) is found in amniotic fluid (AF) and placenta. When ingested, it enhances opioid-mediated pain relief. Our laboratory has shown that ingestion of AF specifically enhances the hypoalgesia associated with δ-opioid receptor activation in the brain. The specific biochemical compound in AF responsible for the enhancement of δ-opioid activity is of great interest as an analgesic adjunct for pain but is unknown at this time. Research efforts to isolate and characterize this biochemical compound are hampered by the lack of an algesiometric assay that allows repeated measurement of pain threshold and repeated exposure to δ-opioid receptor activation. The cold water tail-flick assay (CWTF) may be a sensitive and reliable pain threshold test of (a) all species of opioids that is (b) not subject to repeated-testing effects. Therefore the CWTF test is potentially ideal for the study of δ opioid systems in a repeated measures design. Here, we confirm these attributes of the CWTF test, and determined that (a) there are no repeated-exposure effects associated with the CWTF assay; (b) there are no repeated-exposure effects associated with repeated central injections of DPDPE ([D-Pen2,D-Pen5]-Enkephalin, a selective δ-opioid agonist) as measured by the CWTF assay; and (c) ingestion of AF in conjunction with a central injection of DPDPE produced the same hypoalgesic enhancement as previously found using another assay.
... Although enhancement of opioid-mediated analgesia has been welldocumented in rats, there have been no studies conducted on humans to evaluate this phenomenon. The effects of POEF do not appear to be species-specific, and human placenta and amniotic fluid exhibit POEF activity when tested in rats (Abbott et al., 1991). Given its presences across species, it is plausible that the substance may also have similar activity in response to ingestion by humans. ...
Article
Postpartum women are consuming their placentas to achieve claimed health benefits, including improved mood, energy, and lactation. Strong scientific evidence to substantiate these claims is lacking. Self-reported benefits from some women include improved mood and lactation; animal models suggest there may be an analgesic effect. Possible risks include infection, thromboembolism from estrogens in placental tissue, and accumulation of environmental toxins. Women’s health care providers should be aware of this practice to help women make informed decisions.
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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).
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Two major consequences of placentophagia, the ingestion of afterbirth materials that occurs usually during mammalian parturition, have been uncovered in the past several years. The first is that increased contact, associated with ingesting placenta and amniotic fluid from the surface of the young, causes an accelerated onset of maternal behavior toward those young. The second, which probably has importance for a broader range of mammalian taxa than the first, is that ingestion of afterbirth materials produces enhancement of ongoing opioid-mediated analgesia. The active substance in placenta and amniotic fluid has been named POEF, for Placental Opioid-Enhancing Factor. Recent research on both consequences is summarized, with particular attention to POEF, the generalizability of the enhancement phenomenon, its locus and mode of action, and its significance for new approaches to the management of pain and addiction. Figures available at http://cogprints.org/180/1/review.html
Article
Although ingestion of the afterbirth during delivery is a reliable component of parturitional behavior of mothers in most mammalian species, we know almost nothing of the direct causes or consequences of the act. Traditional explanations of placentophagia, such as general or specific hunger, are discussed and evaluated in light of recent experimental results. Next, research is reviewed which has attempted to distinguish between placentophagia as a maternal behavior and placentophagia as an ingestive behavior. Finally, consequences of the behavior, which may also be viewed as ultimate causes in an evolutionary sense, are considered, such as the possibility of beneficial effects on maternal behavior or reproductive competence, on protection against predators, and on immunological protection afforded either the mother or the young.
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Stimulation of the vaginal cervix with a glass rod elevated vocalization thresholds to tail shock in ovariectomized rats. As more force (in g) was applied to the cervix, we observed a progressive increase in the threshold of vocalization in response to tail shock. In a second experiment, ovariectomized rats were treated with either estradiol benzoate, progesterone, estradiol plus progesterone, or oil, and tested for vocalization to tail shock. Estradiol treatment enhanced the effect of cervical stimulation on elevating the vocalization threshold. Progesterone had no such effect when given alone, but completely prevented the estrogen effect. These findings demonstrate that a) vocalization in response to noxious stimulation is suppressed by genital tract stimulation, b) the degree of suppression increases with increasing intensity of genital tract stimulation, and c) steroid hormones affect this phenomenon.
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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.
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Of the effects of morphine and endogenous opioid peptides on thermoregulation, the one which is most likely to be of physiologic significance is hyperthermia. This increase in body temperature is the result of coordinated changes in both physiological and behavioral thermoregulatory activities and, like fever, reflects an increase in the level about which body temperature is regulated. Morphine, endogenous opioid peptides and other opioids such as pentazocine all cause hyperthermia, but the considerable variation in the dose of naloxone required to antagonize the different agonists indicates that more than one type of opiate receptor is involved in these pharmacologic responses. The minimal effect of naloxone and naltrexone on normal body temperature and on pyrogen-induced fever indicates that endogenous opioid peptides are unlikely to act physiologically via stimulation of receptors specifically sensitive to morphine. However, methionine-enkephalin is less readily antagonized by naloxone and could have a physiologic role in thermoregulation through stimulation of another type of opiate receptor.
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Changes in Tre were determined in unrestrained rats after injections of morphine into the PO/AH and MED regions. Injections into the former site consistently caused hyperthermia, while medullary injections caused only inconsistent small responses. Destruction of the PO/AH region did not enhance the response to medullary injections of morphine. Restraint reversed responses to PO/AH and ip administration of morphine, resulting in hypothermia. These results provide additional evidence for the concept of a sensitive primary temperature control in the PO/AH region and a secondary control, which responds minimally to drugs, in the medulla.
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Ingestion of amniotic fluid or placenta by rats has been shown to enhance several types of opioid-mediated analgesia: that induced by morphine, footshock, vaginal/cervical stimulation, and late pregnancy. This enhancement has also been blocked by administration of opioid antagonists. The present study was designed to examine further the specificity of the enhancement effect for opioid-mediated analgesia by testing for enhancement following administration of aspirin, a nonopioid analgesic. The formalin test was used as the pain threshold assay. Amniotic fluid or beef bouillon was administered by orogastric tube to rats that were treated either with morphine sulfate or saline, or pretreated with naltrexone, then treated with aspirin or vehicle. Both morphine and aspirin treatments produced analgesia. Amniotic fluid significantly enhanced the analgesia produced by morphine, but did not enhance the analgesia produced by aspirin, further suggesting that the enhancing effect of amniotic fluid ingestion is specific for opioid-mediated analgesia, such as that existing at the start of parturition.