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

Wise, Richard G.; Lujan, Brandon J.; Schweinhardt, Petra; Peskett, G. D.; Rogers, Richard; Tracey, Irene

doi:10.1016/j.mri.2007.03.016

Cited by 54 publications

(32 citation statements)

References 37 publications

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“…Attenuation of insula activation during anticipation of painful or emotional stimuli has previously been reported for the benzodiazepine, midazolam (Wise et al, 2007) and the SSRI, escitalopram ). To our knowledge, this is the first study to report amygdala attenuation by an anxiolytic during an anticipation paradigm.…”

Section: Discussion Pgb Fmri Effectsmentioning

confidence: 69%

“…fMRI studies with healthy controls report acute benzodiazepine administration to attenuate activation of insula, amygdala, and medial prefrontal cortex (mPFC) during paradigms involving processing of emotional faces (Paulus et al, 2005), anticipation of painful stimuli (Wise et al, 2007), and punishment during risk-based decision making (Arce et al, 2006). Sub-chronic SSRI administration (eg, 3-30 days) has been associated with decreased amygdala, insula, and/or mPFC and anterior cingulate (ACC) activation during anticipation ) and processing of aversive pictures (Takahashi et al, 2005) and emotional faces (Anderson et al, 2007;Arce et al, 2008;Del-Ben et al, 2005;Harmer et al, 2006;Windischberger et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Anticipatory anxiety is thought to be a cardinal symptom of anxiety disorders (Craske et al, 2009) and anticipation paradigms are sensitive to insula, amygdala, and PFC activation (Nitschke et al, 2006;Simmons et al, 2004) as well as to pharmacologic effects of benzodiazepines and SSRIs Wise et al, 2007). The primary aim of this study was to delineate potential neuroanatomical mechanisms of action for PGB during anticipatory processing.…”

Section: Introductionmentioning

confidence: 99%

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Pregabalin Influences Insula and Amygdala Activation During Anticipation of Emotional Images

Aupperle

Ravindran

Tankersley

et al. 2011

Neuropsychopharmacol

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Pregabalin (PGB) has shown potential as an anxiolytic for treatment of generalized and social anxiety disorder. PGB binds to voltagedependent calcium channels, leading to upregulation of GABA inhibitory activity and reduction in the release of various neurotransmitters. Previous functional magnetic resonance imaging (fMRI) studies indicate that selective serotonin reuptake inhibitors and benzodiazepines attenuate amygdala, insula, and medial prefrontal cortex activation during anticipation and emotional processing in healthy controls. The aim of this study was to examine whether acute PGB administration would attenuate activation in these regions during emotional anticipation. In this double-blind, placebo-controlled, randomized crossover study, 16 healthy controls completed a paradigm involving anticipation of negative and positive affective images during fMRI approximately 1 h after administration of placebo, 50, or 200 mg PGB. Linear mixed model analysis revealed that PGB was associated with (1) decreases in left amygdala and anterior insula activation and (2) increases in anterior cingulate (ACC) activation, during anticipation of positive and negative stimuli. There was also a region of the anterior amygdala in which PGB dose was associated with increased activation during anticipation of negative and decreased activation during anticipation of positive stimuli. Attenuation of amygdala and insula activation during anticipatory or emotional processing may represent a common regional brain mechanism for anxiolytics across drug classes. PGB induced increases in ACC activation could be a unique effect related to top-down modulation of affective processing. These results provide further support for the viability of using pharmaco-fMRI to determine the anxiolytic potential of pharmacologic agents.

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Section: Discussion Pgb Fmri Effectsmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pregabalin Influences Insula and Amygdala Activation During Anticipation of Emotional Images

Aupperle

Ravindran

Tankersley

et al. 2011

Neuropsychopharmacol

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“…We also predicted an interaction with activity in the anterior insula (aIns), a region involved in emotional responses (Kober et al, 2008) and associated with benzodiazepine-induced blood oxygenation level-dependent (BOLD) effects on pain (Wise et al, 2007) and face emotion processing (Paulus et al, 2005). Based on postmortem work, we hypothesized that when subjects viewed salient emotional images, LRZ would have a reduced inhibitory effect on neurocircuits in these regions, which would be correlated with greater negative affect.…”

Section: Introductionmentioning

confidence: 99%

Abnormal GABAergic Function and Negative Affect in Schizophrenia

Taylor

Demeter

Phan

et al. 2013

Neuropsychopharmacol

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Deficits in the g-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.

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“…Wise et al have investigated the anxiolytic action of midazolam during pain-related anxiety [44]. They hypothesized that fMRI would reveal changes related to the modulation of anxiety related to a conditioned painful stimulus, however, pain related fMRI activity would remain unchanged.…”

Section: Neuroimaging the Pharmacologic Modulation Of Painmentioning

confidence: 99%

Role of Neuroimaging in Analgesic Drug Development

Lawrence

Mackey

2008

Drugs in R & D

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Rapidly developing, non-invasive, neuroimaging methods provide increasingly detailed structural and functional information about the nervous system, helping advance our understanding of pain processing, chronic pain conditions, and the mechanisms of analgesia. However, effective treatment for many chronic pain conditions remains a large, unmet medical need. In this review, we examine how the neuroimaging of pain has enhanced our understanding of the mechanisms of chronic pain, our current understanding of the central neural correlates of pharmacologic modulation of pain, and the role of neuroimaging in analgesic development, discussing both current limitations and future directions

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

Cited by 54 publications

References 37 publications

Pregabalin Influences Insula and Amygdala Activation During Anticipation of Emotional Images

Pregabalin Influences Insula and Amygdala Activation During Anticipation of Emotional Images

Abnormal GABAergic Function and Negative Affect in Schizophrenia

Role of Neuroimaging in Analgesic Drug Development

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