Highlights
- •Oxytocin (OT) modulates pain processing in the ventral striatum.
- •OT counteracts sensitization to repeated pain stimuli via the anterior insula.
- •OT acts on pain anticipation in the posterior insula, boostering associative learning.
- •OT enhances the conditioned fear of pain response mediated in the ventral striatum.
Abstract
There is an ongoing debate whether the neuropeptide oxytocin (OT) modulates pain processing
in humans. This study differentiates behavioral and neuronal OT effects on pain perception
and pain anticipation by using a Pavlovian conditioning paradigm. Forty-six males
received intranasally administered OT in a randomized, double-blind, placebo-controlled
group design. Although OT exerted no direct effect on perceived pain, OT was found
to modulate the blood oxygen level-dependent response in the ventral striatum for
painful versus warm unconditioned stimuli and to decrease activity in the anterior
insula (IS) with repeated thermal pain stimuli. Regarding pain anticipation, OT increased
responses to CSpain versus CSminus in the nucleus accumbens. Furthermore, in the OT condition increased correct expectations,
particularly for the most certain conditioned stimuli (CS)–unconditioned stimuli associations
(CSminus and CSpain) were found, as well as greatest deactivations in the right posterior IS in response
to the least certain condition (CSwarm) with posterior IS activity and correct expectancies being positively correlated.
In conclusion, OT seems to have both a direct effect on pain processing via the ventral
striatum and by inducing habituation in the anterior IS as well as on pain anticipation
by boostering associative learning in general and the neuronal conditioned fear of
pain response in particular.
Perspective
The neuropeptide OT has recently raised the hope to offer a novel avenue for modulating
pain experience. This study found OT to modulate pain processing and to facilitate
the anticipation of pain, inspiring further research on OT effects on the affective
dimension of the pain experience.
Key words
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Article info
Publication history
Published online: April 19, 2019
Accepted:
April 2,
2019
Received in revised form:
February 11,
2019
Received:
December 27,
2018
Footnotes
S.C.H. and M.M.S. contributed equally to this work.
Supported by a grant from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) within the Collaborative Research Center (SFB) 1158 (subproject B02 to S.C.H. and V.G.) and the Chica and Heinz Schaller Research Foundation (to V.G.). There are no competing financial interests in relation to the work described. All authors declare no conflict of interest.
Supplementary data accompanying this article are available online at www.jpain.org and www.sciencedirect.com.
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© 2019 by the American Pain Society
