Exacerbation of Pain by Anxiety Is Associated with Activity in a Hippocampal Network

By Alexander Ploghaus, C. Narain, Christian F. Beckmann, Stuart Clare, Susanna Bantick, Richard G. Wise, Paul M. Matthews, J. Rawlins, Irene Tracey. Journal of Neuroscience, 2001

815 citations recorded by the source corpus.

It is common clinical experience that anxiety about pain can exacerbate the pain sensation. Using event-related functional magnetic resonance imaging (FMRI), we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety. One visual signal, which reliably predicted noxious stimulation of moderate intensity, came to evoke low anxiety about the impending pain. Another visual signal was followed by the same, moderate-intensity stimulation on most of the trials, but occasionally by discriminably stronger noxious stimuli, and came to evoke higher anxiety. We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli, dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety. During this emotional pain modulation, entorhinal responses predicted activity in closely connected, affective (perigenual cingulate), and intensity coding (mid-insula) areas. Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus. It supports the proposal that during anxiety, the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome.

Subfields: Anesthesiology and Pain Medicine, Cognitive Neuroscience, Physiology

View Paper: https://www.semanticscholar.org/paper/75a087cffca68c21d0e1c2b48dde4e9da638c890

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Citations in the corpus

Increased activation in the right insula during risk-taking decision making is related to harm avoidance and neuroticism (2003, background): “…insula in instantiating aversive somatic markers are based on findings linking insula activation to the degree of noxious heat (Becerra et al., 1999) or cold (Tracey et al., 2000; Davis, 2000) stimuli, which is consistent with pain intensity coding activation in the insula (Ploghaus et al., 2001).”
Predictors of Postoperative Pain and Analgesic Consumption: A Qualitative Systematic Review (2009, background): “An anxious state has been advocated as a factor in lowering pain threshold,(69) facilitating overestimation of pain intensity,(70) and activation in the entorhinal cortex of the hippocampal formation.(71) The”
Stress-induced analgesia. (2009, background): “In an interesting human study, subjects were given visual cues to an impending noxious stimulus (Ploghaus et al., 2001).”
The effect of pain on cognitive function: a review of clinical and preclinical research. (2011, background): “In addition, pain-evoked activity in the ACC can be altered in healthy volunteers by hypnotic suggestions (Faymonville et al., 2000; Rainville et al., 1997), pain anxiety (Ploghaus et al., 2001) and anticipation of pain (Hsieh et al., 1999).”
Clinical biomarkers in drug discovery and development (2003, background): “In pain research, fMRI-based psychophysical studies can assess brain activation by pain, its anticipation and modulation by attentio”
The perception and categorisation of emotional stimuli: A review (2010, background): “…should be conceptualised as reflecting an interaction between the person and the stimulus, as demonstrated by interindividual differences in pain perception related to factors such as race, sex, catastrophism or anxiety level (Ploghaus et al., 2001; Sheffield, Biles, Orom, Maixner, & Sheps, 2000).”
The neural architecture of emotion regulation (2007, background): “…receive only a nonpainful one, they nonetheless show activa - tion of pain-related regions of midcingulate cortex (Sawamoto et al., 2000), rostral cingulate/MPFC regions likely related to expectations about how it might feel, and medial temporal regions related to memory (Ploghaus et al., 2001).”
The cerebral signature for pain perception and its modulation. (2007, background): “Many studies aimed at understanding how anticipation and anxiety cause a heightened pain experience have been performed over the past decade (Hsieh et al., 1999; Ploghaus et al., 1999, 2000, 2001; Porro et al., 2002, 2003; Song et al., 2006).”
The placebo effect: From concepts to genes. (2015, positive): “This finding is particularly interesting as the hippocampus has been associated with increased anticipatory anxiety during the processing of painful stimuli (Ploghaus et al., 2001).”
Anxiety Reduction through Detachment: Subjective, Physiological, and Neural Effects (2005, background): “We show that a cognitive strategy of detachment attenuates subjective and physiological measures of anticipatory anxiety for pain and reduces reactivity to receipt of pain itself.”
Cognitive modulation of pain: how do attention and emotion influence pain processing? (2002, background): “A recent study showing activation of entorhinal cortex during the modulation of pain by anxiety (Ploghaus et al., 2001) at least indirectly implicates this circuitry in anxietyrelated pain modulation, since there are strong reciprocal connections between amygdala and entorhinal cortex (Pitkanen et…”
The influence of negative emotions on pain: Behavioral effects and neural mechanisms (2009, neutral): “In the context of pain, the entorhinal cortex has been found to exhibit a stronger response to anxiety-associated noxious stimuli compared to physically identical stimuli unrelated to pain without associated anticipatory anxiety (Ploghaus et al., 2001).”
The cognitive control of emotion. (2005, background): “The second approach has examined how expectations about how a stimulus might feel influence neural responses to it. Studies have shown that nonpainful stimuli are perceived as painful when participants expect pain, and that this expectation leads to activation of midcingulate regions [45] as well as”
Human brain mechanisms of pain perception and regulation in health and disease (2005, background): “…or decreased pain sensation Longe et al. (2001) fMRI Attention, distraction ACC, IC, Th Distracting vibratory stimulus reduced pain- evoked activity Ploghaus et al. (2001) fMRI Anxiety Hippo, peri-genual ACC, mid-IC Anxiety amplified pain-related responses Bantick et al. (2002) fMRI…”