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Hippocampus mediates nocebo impairment of opioid analgesia through changes in functional connectivity

Abstract:
The neural mechanisms underlying placebo analgesia have attracted considerable attention over the recent years. In contrast, little is known about the neural underpinnings of a nocebo-induced increase in pain. We previously showed that nocebo-induced hyperalgesia is accompanied by increased activity in the hippocampus that scaled with the perceived level of anxiety. As a key node of the neural circuitry of perceived threat and fear, the hippocampus has recently been proposed to coordinate defensive behaviour in a context-dependent manner. Such a role requires close interactions with other regions involved in the detection of and responses to threat. Here, we investigated the functional connectivity of the hippocampus during nocebo-induced hyperalgesia. Our results show an increase in functional connectivity between hippocampus and brain regions implicated in the processing of sensory-discriminative aspects of pain (posterior insula and primary somatosensory/motor cortex) as well as the periaqueductal gray (PAG). This nocebo-induced increase in connectivity scaled with an individual's increase in anxiety. Moreover, hippocampus connectivity with the amygdala was negatively correlated with the pain intensity reported during nocebo hyperalgesia relative to the placebo condition. Our findings suggest that the hippocampus links nocebo-induced anxiety to a heightened responsiveness to nociceptive input through changes in its crosstalk with pain-modulatory brain areas.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1111/ejn.15687

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0002-9528-3204
More by this author
Role:
Author
ORCID:
0000-0001-8899-6444


Publisher:
Wiley
Journal:
European Journal of Neuroscience More from this journal
Volume:
56
Issue:
2
Pages:
3967-3978
Publication date:
2022-06-16
Acceptance date:
2022-05-04
DOI:
EISSN:
1460-9568
ISSN:
0953-816X
Pmid:
35537867


Language:
English
Keywords:
Pubs id:
1259095
Local pid:
pubs:1259095
Deposit date:
2022-06-06

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