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

Abstract

PHA RM ACOL BlOCH FM HEHA Y 511( I) 147-15 I. IlJ'I7.-lngestion of ;1I1111iotic fluid and placenta by rats h;ls been shown to enh;lllce opioid-mediated ,Intinociception but not arrect the nonopioid-mediated antinociception pl'llduced bv aspirin. su~ csting spccificity for opioid-mediated proccsses. Ilowcver. enhanccment hy the active substancc(s) in amniotic fluid and pia cc'nta (POEF. for placental o[Jioid-enhancing factor) of antinociception produced bv other nonopioidmech,lllisms 1m.. yet to be examine'll. Thc present experiments tested whether ingestion of amniotic fluid enlwnees thc antinociecption produced by nicotine injection. In ExperimLOnt I A. LOnhancelllent of morphine-mediated antinociception by ingestionl>f amniotic fluid W;h den]()nstrared in ,I hot-plate assay. In Experiment I B. rats prdreated with naltrexone werc given an orogastric infusion of amniotic fluid m contl'lll (0.25 ml). then injected with nicotine (0.0.075.0.125, or 0.225 mglkg subcut'lncously). then tested for antinocicc'ption in a hot-pl;lte 'ISS;ly. Amniotic fluid ingestion did not enhance the antinociccption produccd by v;nious doscs of nicotinLO. In Expcrimcnt 2. rats pretrcated with naltrcxone were given an orogaslric infusion of amniotic fluid (0.0.125. 11.25. or 0.50 ml) ;\Ild then injcctcd with n.125 m~lk~ nicotinc. None of the doscs of amniotic fluid enhanced thc nicotinc induccd <1n1 inocicept ion. Thc'findings of these expcr;'illents lend support 10 our contcntion that thc enhancemcnt bv POEF of <Int i nociecpl ion is speciric 10 opioid-mediatcd pmcesses. I.D 1'il)7 Elsevier Science Inc.

Ingested bovine amniotic fluid enhances morphine antinociception in rats

“…I, salinc-injecteu groups). Both the dose dependent efficacy anu the inability of BAF to produce anti nociception independent of opioid antinociception are con sistent with previous findings [4,[12][13][14]16,17,23,25].…”

“…More recent mammals is the presence of placenta as a secretory substrate evidence indicates that placenta ingestion preferentially en and as a pathway for selective physiological exchange be hances antinociception produced by activation of 5 or K opioid tween parent and offspring [20]. Of particular interest in the receptors, but inhibits antinociception produced by activation comparative study of mammalian behavior is the fact that at of J.L opioid receptors [3,5,11], Ingestion of placenta or AF parturition, females of almost all eutherian species engage does not, however, affect morphine-induced hyperthermia [I J in placentophagia-ingestion of placenta and amniotic fluid or nonopioid antinociception [13,23], nor does it produce anti (AF) [9]. nociception by itself [4,[12][13][14]16,17,23,251.…”

“…Of particular interest in the receptors, but inhibits antinociception produced by activation comparative study of mammalian behavior is the fact that at of J.L opioid receptors [3,5,11], Ingestion of placenta or AF parturition, females of almost all eutherian species engage does not, however, affect morphine-induced hyperthermia [I J in placentophagia-ingestion of placenta and amniotic fluid or nonopioid antinociception [13,23], nor does it produce anti (AF) [9]. nociception by itself [4,[12][13][14]16,17,23,251. Because opioid The desire to understand the proximate and ultimate action is a prerequisite for the enhancing activity of ingested causes of placentophagia has inspired a variety of explana placenta and AF, Kristal et al r14] have named the enhancing tions for the phenomenon.…”

Placenta ingestion by rats enhances δ- and κ-opioid antinociception, but suppresses μ-opioid antinociception

“…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].…”

Ingestion of amniotic fluid enhances the facilitative effect of VTA morphine on the onset of maternal behavior in virgin rats

“…Placentophagia (ingestion of afterbirth material) occurs in most nonhuman and non-aquatic mammalian species at parturition (Kristal, 1980(Kristal, , 1991(Kristal, , 1998. Ingestion of placenta or amniotic fluid modulates opioid-mediated events: (a) it enhances opioid-induced hypoalgesia (Kristal et al, 1985(Kristal et al, , 1986a(Kristal et al, , 1986b whether the pain relief is produced by endogenous (Kristal et al, 1990a(Kristal et al, , 1990b(Kristal et al, , 1986a(Kristal et al, , 1986b or exogenous opioids (Kristal et al, 1985(Kristal et al, , 1986a(Kristal et al, , 1986b, (b) it does not affect nonopioid-induced hypoalgesia (Kristal et al, 1990a(Kristal et al, , 1990bRobinson-Vanderwerf et al, 1997), and (c) it does not produce hypoalgesia by itself (without the existence of an underlying opioid hypoalgesia) (Kristal, 1991(Kristal, , 1998. Furthermore, ingestion of placenta enhances δ-and κ-opioid-receptor-mediated hypoalgesia and attenuates μ-opioid-receptor-mediated hypoalgesia (DiPirro and Kristal, 2004), which is consistent with Gintzler's research (Gintzler, 1980;Gintzler and Liu, 2001) showing that the spinal mechanisms of periparturitional hypoalgesia (pregnancy-mediated analgesia) are mediated by δ-and κ-opioid receptors, but not by μ-opioid receptors (Gintzler and Liu, 2001).…”