The anxiolytic effects of midazolam during anticipation to pain revealed using fMRI

Wise, Richard Geoffrey ORCID: https://orcid.org/0000-0003-1700-2144, Lujan, Brandon J., Schweinhardt, Petra, Peskett, Guy D., Rogers, Richard and Tracey, Irene 2007. The anxiolytic effects of midazolam during anticipation to pain revealed using fMRI. Magnetic Resonance Imaging 25 (6) , pp. 801-810. 10.1016/j.mri.2007.03.016

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Abstract

Background and Purpose Functional neuroimaging can distinguish components of the pain experience associated with anticipation to pain from those associated with the experience of pain itself. Anticipation to pain is thought to increase the suffering of chronic pain patients. Inappropriate anxiety, of which anticipation is a component, is also a cause of disability. We present a pharmacological functional magnetic resonance imaging (fMRI) study in which we investigate the selective modulation by midazolam of brain activity associated with anticipation to pain compared to pain itself. Methods Eight right-handed male volunteers underwent fMRI combined with a thermal pain conditioning paradigm and midazolam (30 μg/kg) or saline administration on different occasions, with order randomized across volunteers. Volunteers learned to associate a colored light with either painful, hot stimulation or nonpainful, warm stimulation to the back of the left hand. Results Comparison of the period during thermal stimulation (pain−warm) revealed a network of brain activity commonly associated with noxious stimulation, including activities in the anterior cingulate cortex (ACC), the bilateral insular cortices (anterior and posterior), the thalamus, S1, the motor cortex, the brainstem, the prefrontal cortex and the cerebellum. Comparison of the periods preceding thermal stimulation (anticipation to pain−anticipation to warm) revealed activity principally in the ACC, the contralateral anterior insular cortex and the ipsilateral S2/posterior insula. Detected by a region-of-interest analysis, midazolam reduced the activity associated specifically with anticipation to pain while controlling for anticipation to warm. This was most significant in the contralateral anterior insula (P<.05). There were no significant drug effects on the activity associated with pain itself. Conclusion In identifying a pharmacological effect on activity preceding but not during pain, we have successfully demonstrated an fMRI assay that can be used to study the action of anxiolytic agents in a relatively small cohort of humans.

Item Type:	Article
Status:	Published
Schools:	Medicine Psychology Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	Pain; fMRI; Midazolam; Anxiolysis; Anxiety; Neuroimaging
Publisher:	Elsevier
ISSN:	0730-725X
Last Modified:	20 Oct 2022 09:35
URI:	https://orca.cardiff.ac.uk/id/eprint/32551

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