Placenta ingestion by rats enhances d- and k-opioid antinociception, but suppresses m-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 (m, d, k) in the antinociception-modulating effects of Placental Opioid-Enhancing Factor (POEF—presumably the active substance). Antinociception was measured on a 52 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 d-specific ([D-Pen2,D-Pen5]enkephalin (DPDPE); 0, 30, 50, 62, or 70 nmol), m-specific ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO); 0, 0.21, 0.29, or 0.39 nmol), or k-specific\ud (U-62066; spiradoline; 0, 100, 150, or 200 nmol) opioid receptor agonist. The results showed that ingestion of placenta potentiated d- and k-opioid antinociception, but attenuated m-opioid antinociception. This finding of POEF action as both opioid receptor-specific and complex\ud 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

Amniotic-Fluid Ingestion Enhances the Central\ud Analgesic Effect of Morphine

Amniotic fluid and placenta contain a substance (POEF) that when ingested enhances opioid-mediated analgesia produced by several agents (morphine injection, vaginal/cervical stimulation, late pregnancy, footshock), but not that produced by aspirin injection. The present series of experiments employed quaternary naltrexone, an opioid antagonist that does not readily cross the blood-brain barrier, in conjunction with either peripheral or central administration of morphine, to determine whether amniotic-fluid ingestion (and therefore POEF ingestion) enhances opioid-mediated analgesia by affecting the central and/or peripheral actions of morphine. The results suggest that POEF affects only the central analgesic effects of morphine

The Analgesia-Enhancing Component of\ud Ingested Amniotic Fluid Does Not Affect\ud Nicotine-Induced Antinociception in\ud Naltrexone-Treated Rats

Ingestion of amniotic fluid and placenta by rats has been shown to enhance opioid-mediated antinociception but not affect the nonopioid-mediated antinociception produced by aspirin, suggesting spccificity for opioid-mediated processes. However, enhancement by the active substance(s) in amniotic fluid and placenta1 (POEF, for placental opioid-enhancing factor) of antinociception produced by other nonopioid mechanisms has yet to be examined. The present experiments tested whether ingestion of amniotic fluid enhances the antinociception produced by nicotine injection. In Experiment IA, Enhancement of morphine-mediated antinociception by ingestion of amniotic fluid was demonstrated in a hot-plate assay. In Experiment IB, rats pretreated with naltrexone were given an orogastric infusion of amniotic fluid or control (0.25 ml), then injected with nicotine (0, 0.075, 0.125, or 0.225 mg/kg subcutaneously), then tested for antinociception in a hot-plate assay. Amniotic fluid ingestion did not enhance the antinociception produced by various doses of nicotine. In Experiment 2, rats pretreated with naltrexone were given an orogastric infusion of amniotic fluid (0, 0.125,\ud 0.25, or 0.50 ml) and then injectcd with 0.125 mg/kg nicotine. None of the doses of amniotic fluid enhanced the nicotine-induced antinociception. The findings of these experiments lend support to our contention that the enhancement by POEF of antinociception is specific to opioid-mediated processes

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

Previous work in our laboratory showed that the recommended oral dose of buprenorphine (0.5 mg/kg) was not as effective\ud 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

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