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Placenta ingestion by rats enhances d- and k-opioid antinociception, but suppresses m-opioid antinociception

By Jean M. DiPirro and Dr. Mark B. Kristal


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

Topics: Psychobiology, Neuropharmacology, Behavioral Neuroscience
Publisher: Elsevier
Year: 2004
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  1. (1993). 17-h-Estradiol and progesterone modulate an intrinsic opioid analgesic system,
  2. (1979). A Stereotaxic Atlas of the Rat Brain,
  3. (1990). Amniotic fluid ingestion enhances opioid-mediated but not nonopioid-mediated analgesia,
  4. (1990). Amniotic-fluid ingestion by parturient rats enhances pregnancy-mediated analgesia,
  5. (1991). Amniotic-fluid ingestion enhances morphine analgesia during morphine tolerance and withdrawal in rats, doi
  6. (1991). Amniotic-fluid ingestion enhances the central analgesic effect of morphine,
  7. (1989). An in vitro profile of activity for the (+) and ( ) enantiomers of spiradoline and PD117302,
  8. (1990). Analgesia produced by intrathecal administration of the kappa opioid agonist, U-50,488H, on formalin-evoked cutaneous pain in the rat,
  9. (1992). Analgesic and discriminative properties of U-62,066E, the selective kappa-opioid receptor agonist, in the rat,
  10. (1981). Analogues of beta-LPH61-64 possessing selective agonist activity at mu-opiate receptors, doi
  11. (1994). and kappa opioid receptor mRNA expression in the rat CNS: an in situ hybridization study,
  12. (1995). Antinociception and delta-1 receptors in the rat spinal cord: studies with intrathecal 7-benzylidenenaltrexone,
  13. (1993). Behavioral effects of A-opioid peptide agonists DAMGO, DALDA, and PL017 on locomotor activities,
  14. (1993). Behavioral effects of opioid peptide agonists DAMGO, DPDPE, and DAKLI on locomotor activities,
  15. (1987). Binding selectivity profiles for ligands of multiple receptor types: focus on opioid receptors, doi
  16. (1995). Biochemical and pharmacological characterization of multiple h-endorphinergic antinociceptive systems in the rat periaqueductal gray,
  17. (1983). Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors,
  18. (1989). Blockade of dopamine receptors reverses the behavioral effects of endogenous enkephalins in the nucleus caudatus but not in the nucleus accumbens: differential involvement of y and A opioid receptors,
  19. (1997). Body temperature and analgesic effects of selective mu and kappa opioid receptors microdialyzed into rat brain, doi
  20. (1988). Body temperature response profiles for selective mu, delta and kappa opioid agonists in restrained and unrestrained rats,
  21. (1983). Brain beta-endorphin during pregnancy, parturition and the postpartum period, doi
  22. (1997). Cellular mechanism for antianalgesic action of agonists of the n-opioid receptor,
  23. (1995). Characterization of supraspinal antinociceptive actions of opioid delta agonists in the rat,
  24. (1990). Differences in physical dependence induced by selective A or y opioid agonists and by endogenous enkephalins protected by peptidase inhibitors, Brain Res.
  25. (1991). Differential cross-tolerance to mu and kappa opioid agonists in morphine-tolerant rats responding under a schedule of food presentation,
  26. (1984). Differential tolerance and cross-tolerance to repeated daily injections of mu and kappa agonists in the rat, doi
  27. (1988). Dose-dependent enhancement of morphine-induced analgesia by ingestion of amniotic fluid and placenta,
  28. (1992). Effects of mu-, kappa-, and delta-selective opioid agonists on thermoregulation in the rat, doi
  29. (1980). Endorphin-mediated increase in pain threshold during pregnancy, doi
  30. (1996). Estrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms,
  31. (1987). Evidence for the interaction of morphine with kappa and delta opioid receptors to induce analgesia in hFunaltrexamine-treated mice,
  32. (1996). Gastric vagotomyantinociception induced by intracerebroventricularly administered delta-, but not mu-, epsilon-, or kappa-opioid receptor agonists in the mouse,
  33. (1991). Hypothalamic opiatergic tone during pregnancy, parturition and lactation in the rat, doi
  34. (2000). Ingested bovine amniotic fluid enhances morphine antinociception in rats,
  35. (1986). Ingestion of amniotic fluid enhances opiate analgesia in rats,
  36. (1997). Involvement of spinal cord y opiate receptors in the antinociception of gestation and its hormonal simulation, Brain Res.
  37. (1992). Kappa opiate receptors mediate tail-shock induced antinociception at spinal levels, Brain Res. doi
  38. (1990). Kappa-opioid receptors and analgesia,
  39. (1996). Kappa-opioids produce significantly greater analgesia in women than in men, doi
  40. (1996). Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene,
  41. (1996). Medial frontal cortex lesions selectively attenuate the hot plate response: possible nocifensive apraxia in the rat,
  42. (1987). Mu opioid receptor involvement in enkephalin activation of dopamine neurons in the ventral tegmental area,
  43. (1989). Multiple opioid receptors: ligand profiles and binding signatures,
  44. (1990). n- and y-opioid agonists synergize to produce potent analgesia, Brain Res.
  45. (1997). Opiate receptor knockout mice define A receptor roles in endogenous nociceptive responses and morphine-induced analgesia, doi
  46. (1985). Opioid peptides of the pituitary and hypothalamus: changes in pregnant and lactating rats,
  47. (1991). Opioid receptor-subtype involvement in maternal behavior in lactating rats,
  48. (1991). Opioid y agonists and endogenous enkephalins induce different emotional reactivity than A agonists after injection in the rat ventral tegmental area,
  49. (1995). Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications,
  50. (1986). Pain discomfort thresholds in late pregnancy,
  51. (1993). Pharmacological mechanisms of opioid analgesics,
  52. (1986). Placenta ingestion enhances analgesia produced by vaginal/cervical stimulation in rats,
  53. (1997). Placenta ingestion facilitates locomotion and antinociception induced by activation of delta-opioid receptors in the rat,
  54. (1981). Placenta on pups’ skin accelerates onset of maternal behavior in nonpregnant rats,
  55. (1987). Preoptic area opioids and opiate receptors increase during pregnancy and decrease during lactation, Brain Res. doi
  56. (1989). Spinal analgesic actions of kappa receptor agonists, U-50,488H and spiradoline (U-62066),
  57. (1944). The evaluation of analgesic action of pethidine hydrochloride
  58. (1987). The selective kappa-opioid agonist, U-50,488H, produces antinociception in the rat via a supraspinal action,
  59. (1985). U-69593 a highly selective ligand for the opioid kappa receptor,