Placentophagia and the Tao of POEF.

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.

Placentophagia in humans and nonhuman mammals: causes and consequences.

Afterbirth ingestion by nonhuman mammalian mothers has a number of benefits: (1) increasing the interaction between the mother and infant; (2) potentiating pregnancy-mediated analgesia in the delivering mother; (3) potentiating maternal brain opioid circuits that facilitate the onset of caretaking behavior; and (4) suppressing postpartum pseudopregnancy. Childbirth is fraught with additional problems for which there are no practical nonhuman animal models: postpartum depression, failure to bond, hostility toward infants. Ingested afterbirth may contain components that ameliorate these problems, but the issue has not been tested empirically. The results of such studies, if positive, will be medically relevant. If negative, speculations and recommendations will persist, as it is not possible to prove the negative. A more challenging anthropological question is "why don't humans engage in placentophagia as a biological imperative?" Is it possible that there is more adaptive advantage in not doing so?

Low doses of risperidone and morphine interact to produce more analgesia and greater extrapyramidal effects in rats.

The search for non-narcotic drugs that will enhance the analgesic effects of opiates without enhancing their side effects has included the investigation of psychoactive drugs already approved for other uses. Some research has supported an analgesic effect of risperidone (RIS), an atypical neuroleptic. However, the analysis of the analgesic efficacy of RIS alone or as an adjuvant to morphine (MOR) has not considered the production of adverse motor effects that would limit its usefulness as a treatment for pain. We tested whether low doses of RIS would enhance the analgesic action of opiates without inducing untoward motor effects. The analgesia induced by a range of RIS doses (0.1-1.0 mg/kg, SC) was assessed alone and in combination with MOR (5 mg/kg, IP) in male Long-Evans (hooded) rats using two different algesiometric assays: hotplate and tail-flick test. The presence or absence of ptosis, vacuous chewing, and abnormal stationary postures was recorded to evaluate dyskinetic effects. No dose of RIS alone altered pain threshold. However, the highest dose of RIS, 1.0 mg/kg SC, significantly increased the analgesic effects of MOR. Dyskinetic effects of RIS were dose-dependent and enhanced in RIS+MOR treatment. These results do not support the hypothesis that RIS, alone or in combination with MOR, elevates pain threshold without also inducing motor side effects. These findings suggest caution in the use of RIS as either a primary treatment or opiate adjuvant treatment for pain.

Evaluation of buprenorphine in a postoperative pain model in rats.

We evaluated the commonly prescribed analgesic buprenorphine in a postoperative pain model in rats, assessing acute postoperative pain relief, rebound hyperalgesia, and the long-term effects of postoperative opioid treatment on subsequent opioid exposure. Rats received surgery (paw incision under isoflurane anesthesia), sham surgery (anesthesia only), or neither and were treated postoperatively with 1 of several doses of subcutaneous buprenorphine. Pain sensitivity to noxious and nonnoxious mechanical stimuli at the site of injury (primary pain) was assessed at 1, 4, 24, and 72 h after surgery. Pain sensitivity at a site distal to the injury (secondary pain) was assessed at 24 and 72 h after surgery. Rats were tested for their sensitivity to the analgesic and locomotor effects of morphine 9 to 10 d after surgery. Buprenorphine at 0.05 mg/kg SC was determined to be the most effective; this dose induced isoalgesia during the acute postoperative period and the longest period of pain relief, and it did not induce long-term changes in opioid sensitivity in 2 functional measures of the opioid system. A lower dose of buprenorphine (0.01 mg/kg SC) did not meet the criterion for isoalgesia, and a higher dose (0.1 mg/kg SC) was less effective in pain relief at later recovery periods and induced a long-lasting opioid tolerance, indicating greater neural adaptations. These results support the use of 0.05 mg/kg SC buprenorphine as the upper dose limit for effective treatment of postoperative pain in rats and suggest that higher doses produce long-term effects on opioid sensitivity.

Lack of analgesic efficacy in female rats of the commonly recommended oral dose of buprenorphine.

Previous work in our laboratory showed that the recommended oral dose of buprenorphine (0.5 mg/kg) was not as effective as the standard therapeutic subcutaneous dose for postoperative analgesia in male Long-Evans (hooded) and Sprague-Dawley (albino) rats. The aim of the current study was to extend this analysis to female rats. We measured the pain threshold in adult female rats in diestrus or proestrus before and 30 and 60 min after oral buprenorphine (0.5 mg/kg,), the standard subcutaneous dose of buprenorphine (0.05 mg/kg), or vehicle only (1 ml/kg each orally and subcutaneously). Female rats showed an increased pain threshold (analgesia) after subcutaneous buprenorphine but no change in pain threshold after either oral buprenorphine or vehicle only. Estrous cycle stage (proestrus versus diestrus) did not affect the analgesic effects of buprenorphine, but rats in proestrus showed significantly lower pain thresholds (less tolerance to pain) than did those in diestrus. These results show that the oral dose of buprenorphine recommended for postoperative analgesic care does not induce significant analgesia in female rats and therefore is not as effective as the standard subcutaneous dose.

Placenta ingestion by rats enhances delta- and kappa-opioid antinociception, but suppresses mu-opioid antinociception.

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 (mu, delta, kappa) in the antinociception-modulating effects of Placental Opioid-Enhancing Factor (POEF-presumably the active substance). Antinociception was measured on a 52 degrees C 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 kappa-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 POEF as an adjunct to opioids in pain management.