Brain Research 1014 (2004) 22-33

Research report

BRAIN

RESEARCH

www.elsevier.com/locate/brainres

Placenta ingestion by rats enhances y- and n-opioid antinociception,
but suppresses A-opioid antinociception

Jean M. DiPirro ^*, Mark B. Kristal

Behavioral Neuroscience Program, Department of Psychology, University at Buffalo, Buffalo, NY 14260, USA

Accepted 1 April 2004

Available online 28 May 2004

Abstract

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 (A, y, n) in the antinociception-modulating effects of Placental Opioid-Enhancing
Factor (POEF—presumably the active substance). Antinociception was measured on a 52 jC hotplate in adult, female rats after they ingested
placenta or control substance (1.0 g) and after they received an intracerebroventricular injection of a y-specific ([D-Pen2,D-Pen5]enkephalin
(DPDPE); 0, 30, 50, 62, or 70 nmol), A-specific ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO); 0, 0.21, 0.29, or 0.39 nmol), or n-specific
(U-62066; spiradoline; 0, 100, 150, or 200 nmol) opioid receptor agonist. The results showed that ingestion of placenta potentiated y- and
n-opioid antinociception, but attenuated A-opioid antinociception. This finding of POEF action as both opioid receptor-specific and complex
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.

D 2004 Elsevier B.V. All rights reserved.

Theme: Neurotransmitters, modulators, transporters and receptors

Topic: Opioid receptors

Keywords: Placentophagia; POEF; Antinociception; Opioid; Parturition; DPDPE; DAMGO; Spiradoline; Rat; Opioid receptor

1. Introduction

Ingestion of placenta or amniotic fluid enhances opi-
oid-mediated antinociception [39]. The active substance(s)
in placenta and amniotic fluid has been termed Placental
Opioid-Enhancing Factor (POEF) [43]. The antinocicep-
tion-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 ob-
served 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

* Corresponding author. Department of Psychology, State University
College at Buffalo, 1300 Elmwood Avenue, Buffalo, NY 14222, USA. Tel.:
+1-716-878-4317; fax: +1-716-878-6228.

E-mail address: [email protected] (J.M. DiPirro).

0006-8993/$ - see front matter D 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.brainres.2004.04.006
cows after ingestion of bovine amniotic fluid [71]. At
parturition, changing levels of ovarian sex steroids and
uterine afferent activity produce ‘‘pregnancy-mediated
analgesia’’, an opioid-mediated increase in maternal pain
threshold that is particularly pronounced in the periparturi-
tional period [11,23,31,33,95]. A likely benefit derived
from ingestion of afterbirth materials—placentophagia—
is the augmentation of this parturitional antinociception
[39].

As yet, little is known of the intervening steps by
which placentophagia ultimately modifies pain suppres-
sion. The data indicate that the effect of ingested placenta
or amniotic fluid is strictly modulatory; ingested POEF
does not generate antinociception, but rather potentiates
antinociception that is already present [39]. Furthermore,
this modulatory influence appears to be specific to opioid
mechanisms. In the rat, the ingestion of POEF as either
placenta or amniotic fluid produces significant elevation
of antinociception resulting from a number of opioid-
mediated or at least partly opioid-mediated mechanisms,

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