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

Effects of hypothalamic knife cuts and experience on maternal behavior in the rat

Recent investigations suggest that the disruption of placentophagia, pup-directed maternal behavior, and nestbuilding seen after lesions of the medial preoptic area (MPO) or the lateral hypothalamus may be due to the interruption at different points of a single longitudinal neural system mediating these behaviors. To test this, we compared the effects of knife cuts on the lateral border of the MPO, and of the posterior medial forebrain bundle (MFB), with asymmetrical cuts combining a unilateral MPO cut with a contralateral MFB cut. We observed placentophagia, nestbuilding, and pup-directed maternal behaviors at, and after, parturition in both primiparous and biparous rats. In primiparae, MPO cuts (a) disrupted placentophagia, (b) delayed the onset of crouching and pup-licking, and (c) eliminated retrieval and nestbuilding. Asymmetrical cuts (a) disrupted placentophagia, and (b) delayed the onset of maternal behavior. In biparous rats, MPO cuts eliminated nestbuilding and retrieval. MFB cuts (a) disrupted placentophagia, and (b) eliminated nestbuilding. Asymmetrical cuts (a) delayed nestbuilding. These results suggest the involvement of a longitudinal neural system in the production of immediate pup-directed maternal behavior, placentophagia, and nestbuilding in parturient primiparae, but which is not critical for the eventual display of maternal behavior and nestbuilding in maternally naive rats, nor for the immediate onset of placentophagia and maternal behavior in maternally experienced rats

Inflammation in benign prostate tissue and prostate cancer in the finasteride arm of the Prostate Cancer Prevention Trial

BACKGROUND: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here we studied these associations in the PCPT finasteride arm. METHODS: Prostate cancer cases (N=197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N=248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of H&E stained sections. Logistic regression was used for statistical analysis. RESULTS: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas; p < 0.001 for difference compared to placebo arm. Overall, the odds of prostate cancer did not differ by prevalence (OR=0.90, 95% CI 0.44-1.84) or extent (P-trend=0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR=1.07, 95% CI 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammationin either cases or controls. CONCLUSION: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. IMPACT: Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation

Large and seasonally varying biospheric CO₂ fluxes in the Los Angeles megacity revealed by atmospheric radiocarbon

Measurements of Δ¹⁴C and CO₂ can cleanly separate biogenic and fossil contributions to CO₂ enhancements above background. Our measurements of these tracers in air around Los Angeles in 2015 reveal high values of fossil CO₂ and a significant and seasonally varying contribution of CO₂ from the urban biosphere. The biogenic CO₂ is composed of sources such as biofuel combustion and human metabolism and an urban biospheric component likely originating from urban vegetation, including turf and trees. The urban biospheric component is a source in winter and a sink in summer, with an estimated amplitude of 4.3 parts per million (ppm), equivalent to 33% of the observed annual mean fossil fuel contribution of 13 ppm. While the timing of the net carbon sink is out of phase with wintertime rainfall and the sink seasonality of Southern California Mediterranean ecosystems (which show maximum uptake in spring), it is in phase with the seasonal cycle of urban water usage, suggesting that irrigated urban vegetation drives the biospheric signal we observe. Although 2015 was very dry, the biospheric seasonality we observe is similar to the 2006–2015 mean derived from an independent Δ¹⁴C record in the Los Angeles area, indicating that 2015 biospheric exchange was not highly anomalous. The presence of a large and seasonally varying biospheric signal even in the relatively dry climate of Los Angeles implies that atmospheric estimates of fossil fuel–CO₂ emissions in other, potentially wetter, urban areas will be biased in the absence of reliable methods to separate fossil and biogenic CO₂

Large and seasonally varying biospheric CO₂ fluxes in the Los Angeles megacity revealed by atmospheric radiocarbon

Measurements of Δ¹⁴C and CO₂ can cleanly separate biogenic and fossil contributions to CO₂ enhancements above background. Our measurements of these tracers in air around Los Angeles in 2015 reveal high values of fossil CO₂ and a significant and seasonally varying contribution of CO₂ from the urban biosphere. The biogenic CO₂ is composed of sources such as biofuel combustion and human metabolism and an urban biospheric component likely originating from urban vegetation, including turf and trees. The urban biospheric component is a source in winter and a sink in summer, with an estimated amplitude of 4.3 parts per million (ppm), equivalent to 33% of the observed annual mean fossil fuel contribution of 13 ppm. While the timing of the net carbon sink is out of phase with wintertime rainfall and the sink seasonality of Southern California Mediterranean ecosystems (which show maximum uptake in spring), it is in phase with the seasonal cycle of urban water usage, suggesting that irrigated urban vegetation drives the biospheric signal we observe. Although 2015 was very dry, the biospheric seasonality we observe is similar to the 2006–2015 mean derived from an independent Δ¹⁴C record in the Los Angeles area, indicating that 2015 biospheric exchange was not highly anomalous. The presence of a large and seasonally varying biospheric signal even in the relatively dry climate of Los Angeles implies that atmospheric estimates of fossil fuel–CO₂ emissions in other, potentially wetter, urban areas will be biased in the absence of reliable methods to separate fossil and biogenic CO₂