Pregabalin Influences Insula and Amygdala Activation During Anticipation of Emotional Images

Abstract

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.

Evaluation of the German Guideline for Chronic Pruritus: Results of a Retrospective Study on 385 Patients

“…Several areas of the brain are involved in pruritus processing and perception, such as the primary sensory cortex, prefrontal cortex, premotor areas, cerebellum, anterior cingulum, and dorsal insular cortex [12]. Substances such as pregabalin and gabapentin have been described to inhibit calcium currents via high-voltage-activated channels containing the a2d-1 subunit, to reduce the release of various neurotransmitters and to attenuate amygdala and insula activation in the central nervous system, possibly resulting in suppression of itch neuron activity [13,14]. The concept of interfering with pruritus transmission and perception was successful in 71.3% of patients treated in the third step (29.6% of the total cohort).…”

Temporal profile of brain response to alprazolam in patients with generalized anxiety disorder

“…The STIMEX is a continuous performance task that has reliably activated the anterior insula in prior studies (Simmons et al, 2006;Aupperle et al, 2011). The STIMEX assesses the impact of anticipating affective stimuli on attention to a response signal and on the subsequent response ( Figure 1) (Simmons et al, 2006).…”

“…Square frames were presented every two seconds. The number of consecutively cued trials presented prior to presentation of an affectively valenced picture varied from picture to picture jittering trials on which affectively loaded stimuli were presented (Aupperle et al, 2011). Two versions of the STIMEX were administered to each subject during each session.…”

“…Slices from volumes showing excessive movement were censored. In a previous study inclusion of a global, white matter, temporal covariate improved activation contrast to noise for the STIMEX task (Aupperle et al, 2011). Consequently, a global white matter regressor was added to the STIMEX model.…”

Neurotransmitters & Networks

“…These effects vary among AEDs [67,68] and depend on the specific task performed during the measurements [69]. While AEDs mainly attenuate the activation patterns, as can be expected from their mechanisms of action, also enhanced activation during AED use has been reported [70]. This seemingly contradictory result could be an indirect effect of attenuated activation in other brain areas, or result directly from AED mechanisms, as a computer simulation showed that modulation of the sodium channels by phenytoin or carbamazepine can also lead to increased excitation [71].…”