Activation of the opioidergic descending pain control system underlies placebo analgesia
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Activation of the opioidergic descending pain control system underlies placebo analgesia. / Eippert, Falk; Bingel, Ulrike; Schoell, Eszter D; Yacubian, Juliana; Klinger, Regine; Lorenz, Jürgen; Büchel, Christian.
In: NEURON, Vol. 63, No. 4, 27.08.2009, p. 533-43.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Activation of the opioidergic descending pain control system underlies placebo analgesia
AU - Eippert, Falk
AU - Bingel, Ulrike
AU - Schoell, Eszter D
AU - Yacubian, Juliana
AU - Klinger, Regine
AU - Lorenz, Jürgen
AU - Büchel, Christian
PY - 2009/8/27
Y1 - 2009/8/27
N2 - Placebo analgesia involves the endogenous opioid system, as administration of the opioid antagonist naloxone decreases placebo analgesia. To investigate the opioidergic mechanisms that underlie placebo analgesia, we combined naloxone administration with functional magnetic resonance imaging. Naloxone reduced both behavioral and neural placebo effects as well as placebo-induced responses in pain-modulatory cortical structures, such as the rostral anterior cingulate cortex (rACC). In a brainstem-specific analysis, we observed a similar naloxone modulation of placebo-induced responses in key structures of the descending pain control system, including the hypothalamus, the periaqueductal gray (PAG), and the rostral ventromedial medulla (RVM). Most importantly, naloxone abolished placebo-induced coupling between rACC and PAG, which predicted both neural and behavioral placebo effects as well as activation of the RVM. These findings show that opioidergic signaling in pain-modulating areas and the projections to downstream effectors of the descending pain control system are crucially important for placebo analgesia.
AB - Placebo analgesia involves the endogenous opioid system, as administration of the opioid antagonist naloxone decreases placebo analgesia. To investigate the opioidergic mechanisms that underlie placebo analgesia, we combined naloxone administration with functional magnetic resonance imaging. Naloxone reduced both behavioral and neural placebo effects as well as placebo-induced responses in pain-modulatory cortical structures, such as the rostral anterior cingulate cortex (rACC). In a brainstem-specific analysis, we observed a similar naloxone modulation of placebo-induced responses in key structures of the descending pain control system, including the hypothalamus, the periaqueductal gray (PAG), and the rostral ventromedial medulla (RVM). Most importantly, naloxone abolished placebo-induced coupling between rACC and PAG, which predicted both neural and behavioral placebo effects as well as activation of the RVM. These findings show that opioidergic signaling in pain-modulating areas and the projections to downstream effectors of the descending pain control system are crucially important for placebo analgesia.
KW - Adult
KW - Analgesia
KW - Analgesics, Opioid
KW - Double-Blind Method
KW - Humans
KW - Male
KW - Naloxone
KW - Pain
KW - Pain Measurement
KW - Placebo Effect
KW - Pyramidal Tracts
KW - Receptors, Opioid
KW - Signal Transduction
KW - Young Adult
KW - Comparative Study
KW - Journal Article
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.neuron.2009.07.014
DO - 10.1016/j.neuron.2009.07.014
M3 - SCORING: Journal article
C2 - 19709634
VL - 63
SP - 533
EP - 543
JO - NEURON
JF - NEURON
SN - 0896-6273
IS - 4
ER -