Endorphin-Mediated Increases in Pain Threshold During Pregnancy

Gintzler, Alan R.

doi:10.1126/science.7414330

Cited by 339 publications

(119 citation statements)

References 13 publications

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“…Presumably, parturient female mammals benefit from ingest ing amniotic fluid immediately prior to delivery by experienc ing an enhancement of endorphin-mediated analgesia. (Such an endorphin-mediated analgesia, "analgesia of pregnancy," was described elsewhere (2,5), and has been observed in our laboratory.) Subsequently, ingestion of the placenta in the period after the delivery of the infant may afford an additional short-term enhancement of endogenous-opioid-mediated analgesia.…”

Section: Discussionsupporting

confidence: 74%

Dose-dependent enhancement of morphine-induced analgesia by ingestion of amniotic fluid and placenta

Kristal

Abbott

Thompson

1988

Pharmacology Biochemistry and Behavior

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. Dose-dependent enhancement oJmorphine-induced analgesia by ingestion oj amniotic fluid and placenta. PHARMACOL BIOCHEM BEHAV 31(2) [351][352][353][354][355][356] 1988.-Ingestion of amniotic fluid and placenta by rats has been shown to enhance opioid-mediated analgesia. The present studies were designed to examine the effect of several doses and volumes of placenta and amniotic fluid on tail-flick latency in rats treated with 3 mg/kg morphine. The optimal dose of amniotic fluid was found to be 0.25 ml, although 0.50 and 1.0 ml also produced significant enhancement. Doses of 0.125 and 2 ml of amniotic fluid were ineffective, as was a dose of 0.25 ml diluted to 2 ml with saline. The optimal dose of placenta was found to be 1 placenta, although the resulting enhancement was not significantly greater than that produced by 0.25, 0.50, 2.0 or 4.0 placentas. Doses smaller than 0.25 placenta or larger than 4.0 placentas were ineffective. The most effective doses of amniotic fluid and placenta correspond to the amounts delivered with each pup during parturition.

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Section: Discussionsupporting

confidence: 74%

Dose-dependent enhancement of morphine-induced analgesia by ingestion of amniotic fluid and placenta

Kristal

Abbott

Thompson

1988

Pharmacology Biochemistry and Behavior

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“…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). The putative component of ingested afterbirth material that affects central opioid phenomena has been termed Placental Opioid-Enhancing Factor (POEF) (Kristal et al, 1988).…”

Section: Introductionsupporting

confidence: 89%

“…Plasma and brain levels of endogenous opioids increase over the course of pregnancy, peak during parturition, and then decline to pre-pregnancy levels during lactation (Petraglia et al, 1985;Wardlaw and Frantz, 1983). These changes in endogenous opioids are consistent with "pregnancy-mediated analgesia", the elevation in pain threshold (hypoalgesia) during labor and delivery (Gintzler, 1980), which is greatly enhanced in the periparturitional period by the opioidmodifying effect of afterbirth ingestion (Kristal, 1998;Kristal et al, 1990aKristal et al, , 1990b.…”

Section: Introductionmentioning

confidence: 91%

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

et al. 2009

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Previous research has shown that injection of morphine into the ventral tegmental area (VTA) facilitates the onset of maternal behavior in virgin female rats, and injection of the opioid antagonist naltrexone into the VTA disrupts the onset of maternal behavior in parturient rats. Placentophagia -ingestion of placenta and amniotic fluid, usually at parturition -modifies central opioid processes. Ingestion of the active substance in placenta and amniotic fluid, Placental Opioid-Enhancing Factor (POEF), enhances the hypoalgesic effect of centrally administered morphine, and more specifically, enhances δ-and κ-opioidreceptor-mediated hypoalgesia and attenuates μ-opioid-receptor-mediated hypoalgesia. POEF (in placenta or amniotic fluid) ingestion does not, by itself, produce hypoalgesia. In the present study, we tested the hypothesis that ingestion of amniotic fluid enhances the facilitative effect of opioid activity (unilateral morphine injection) in the VTA on the rate of onset of maternal behavior. Virgin female Long-Evans rats were given one intra-VTA injection of morphine sulfate (0.0, 0.01, or 0.03 μg, in saline) and an orogastric infusion of 0.25 ml amniotic fluid or saline once each day of the first three days of the 10-day testing period. Subjects were continuously exposed to foster pups that were replaced every 12 h; replacement of pups was followed by a 15-min observation period. Maternal behavior latency was determined by the first of two consecutive tests wherein the subject displayed pup retrieval, pup licking in the nest, and crouching over all foster pups, during the 15-min observation. We confirmed the previous finding that the VTA injection, alone, of 0.03 μg IntroductionRats at parturition show an almost immediate onset of appropriate maternal behavior. In contrast, the onset of maternal behavior in virgin rats that are continuously exposed to relatively constant-age foster pups (a procedure referred to as "concaveation", i.e., "with pups") is slow to appear, and is usually measured as the latency, in days, to the appearance of B R A I N R E S E A R C H 1 2 6 1 ( 2 0 0 9 ) 2 9 -3 6 ⁎ Corresponding author.

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“…Endogenous opiate levels rise during pregnancy and de livery in both humans and rats [4,6,9,12,13,[19][20][21][22][23]. Pain threshold has been observed to rise over the course of preg nancy in rats, and this "analgesia of pregnancy" has been demonstrated to be opiate mediated [1,7,8]. Enhancement of such analgesia, therefore, may be one of the principal benefits of parturitional placentophagia, and, in contrast to other hypotheses about advantages (e.g., nest hygiene, mother-infant attachment, reduction of predator-attracting stimuli [14,17]), this hypothesis suggests a benefit that would apply to virtually all species of mammals.…”

mentioning

confidence: 99%

Ingestion of amniotic fluid enhances opiate analgesia in rats

Kristal

Thompson

Abbott

1986

Physiology & Behavior

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. Ingestion ofllmnioticfluid enhances opiate analgesia in rats. PHYSIOL BEHAV 38(6) [809][810][811][812][813][814][815] 1986.-Placenta ingestion has recently been shown to enhance opiate-mediated analgesia produced by morphine injection, footshock, or vaginal/cervical stimulation. The enhancement of the effect of endogenous opiates (especially analgesia) may be one of the principal benefits to mammalian mothers of placentophagia at delivery. During labor and delivery, however, mothers also ingest amniotic fluid (AF) which, unlike placenta, becomes available during, or even before expulsion of the infant. The present experiments were undertaken to determine (a) whether AF ingestion, too, enhances analgesia; if so, (b) whether the effect requires ingestion of, or merely exposure to, AF; (c) whether the effect can be produced by AF delivered directly to the stomach by tube; and (d) whether the enhancement, if it exists, can be blocked by administering an opiate antagonist. Nulliparous Long-Evans rats were tested for analgesia using tail-flick latency. We found that (a) rats that ingested AF after receiving a morphine injection showed significantly more analgesia than did rats that ingested a control substance;' (b) AF ingestion, alone, did not produce analgesia; (c) ingestion of AF, rather than just smelling and seeing it, was necessary to produce analgesia enhancement; (d) AF produced enhance ment when oropharyngeal factors were eliminated by delivering it through an orogastric tube; and (e) treatment of the rats with naltrexone blocked the enhancement of morphine-induced analgesia that results from AF ingestion. . Furthermore, placenta does not seem to contain a substance that, by itself, is analgesic, since in gestion of placenta in the absence of an analgesia-producing treatment does not elevate pain threshold [15,16]. We have also demonstrated that the analgesia-enhancing effect of placenta ingestion seems to be specific to opiate-mediated analgesia, since treatment with naltrexone, an opiate antagonist, not only attenuates the analgesia produced by footshock, as expected, but also blocks the enhancing effect of placenta ingestion [15]. Endogenous opiate levels rise during pregnancy and de livery in both humans and rats [4,6,9,12,13,[19][20][21][22][23]. Pain threshold has been observed to rise over the course of preg nancy in rats, and this "analgesia of pregnancy" has been demonstrated to be opiate mediated [1,7,8]. Enhancement of such analgesia, therefore, may be one of the principal benefits of parturitional placentophagia, and, in contrast to other hypotheses about advantages (e.g., nest hygiene, mother-infant attachment, reduction of predator-attracting stimuli [14,17]), this hypothesis suggests a benefit that would apply to virtually all species of mammals.However, if placenta, alone, contains the substance that enhances opiate-mediated analgesia during the perinatal period, the fact that placenta is delivered after the neonate (anywhere from 5 to 75 min after) would render it effective only during th...

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Endorphin-Mediated Increases in Pain Threshold During Pregnancy

Cited by 339 publications

References 13 publications

Dose-dependent enhancement of morphine-induced analgesia by ingestion of amniotic fluid and placenta

Dose-dependent enhancement of morphine-induced analgesia by ingestion of amniotic fluid and placenta

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

Ingestion of amniotic fluid enhances opiate analgesia in rats

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