title: Dissociable neural mechanisms underlying the modulation of pain and anxiety? An FMRI pilot study.
abstract: The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a "behavioral control" paradigm, which involves the ability to terminate a noxious stimulus, and a "safety signaling" paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.
authors.affiliation: Nuffield Department of Clinical Neurosciences (Nuffield Division Anaesthetics), University of Oxford, John Radcliffe Hospital, Headley Way, OX3 9DU, Oxford, United Kingdom; Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Headley Way, OX3 9DU, Oxford, United Kingdom.
authors.forename: Katja
authors.initials: K
authors.lastname: Wiech
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School, Brigham & Women's Hospital, Chestnut Hill, Massachusetts, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Edwards
authors.affiliation: Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Headley Way, OX3 9DU, Oxford, United Kingdom; Sansom Institute for Health Research, University of South Australia, Adelaide 5000, Australia & Neuroscience Research Australia, Sydney, Australia.
authors.forename: Graham Lorimer
authors.initials: GL
authors.lastname: Moseley
authors.affiliation: Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Headley Way, OX3 9DU, Oxford, United Kingdom; Department of Psychiatry, University of Oxford, OX3 7JX, Oxford, United Kingdom.
authors.forename: Chantal
authors.initials: C
authors.lastname: Berna
authors.affiliation: Department of Neurology, Technische Universität München, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ploner
authors.affiliation: Nuffield Department of Clinical Neurosciences (Nuffield Division Anaesthetics), University of Oxford, John Radcliffe Hospital, Headley Way, OX3 9DU, Oxford, United Kingdom; Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Headley Way, OX3 9DU, Oxford, United Kingdom.
authors.forename: Irene
authors.initials: I
authors.lastname: Tracey
mesh_terms: D000328:Adult; D001007:Anxiety / Q000503:physiopathology*; D001931:Brain Mapping; D000066498:Emotional Adjustment; D004644:Emotions; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology*; D010865:Pilot Projects; D017397:Prefrontal Cortex / Q000502:physiology* / Q000503:physiopathology*; D055815:Young Adult