The HTR3A polymorphism c. -42C>T is associated with amygdala responsiveness in patients with irritable bowel syndrome.

Background & Aims: 5-Hydroxytryptamine (5-HT)3 receptor (5-HT3R) antagonists are effective in treating patients with irritable bowel syndrome (IBS) and have anxiolytic effects. Their therapeutic effects are related, in part, to reducing amygdala engagement during expected visceral pain. A single nucleotide polymorphism in HTR3A, c.

Impact of Mindfulness-Based Stress Reduction training on intrinsic brain connectivity.

The beneficial effects of mindful awareness and mindfulness meditation training on physical and psychological health are thought to be mediated in part through changes in underlying brain processes. Functional connectivity MRI (fcMRI) allows identification of functional networks in the brain. It has been used to examine state-dependent activity and is well suited for studying states such as meditation.

Regional gray matter density changes in brains of patients with irritable bowel syndrome.

Background & Aims: Several studies have examined structural brain changes associated with chronic pain syndromes, including irritable bowel syndrome (IBS), but study sample sizes have been small and heterogeneous.

Methods: We used magnetic resonance imaging-based techniques, voxel-based morphometry, and cortical thickness analysis to examine brain anatomical differences in a relatively large, tightly screened sample of IBS patients (n = 55); we compared data with that from healthy persons (controls; n = 48).

Results: IBS was associated with decreased gray matter density (GMD) in widespread areas of the brain, including medial prefrontal and ventrolateral prefrontal cortex, posterior parietal cortex, ventral striatum, and thalamus.

Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome.

Cognitive factors such as fear of pain and symptom-related anxiety play an important role in chronic pain states. The current study sought to characterize abnormalities in preparatory brain response before aversive pelvic visceral distention in irritable bowel syndrome (IBS) patients and their possible relationship to the consequences of distention. The brain functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to anticipated and delivered mild and moderate rectal distention was recorded from 14 female IBS patients and 12 healthy controls.

Altered central micro-opioid receptor binding after psychological trauma.

Background: Functional neuroimaging studies have detected abnormal limbic and paralimbic activation to emotional probes in posttraumatic stress disorder (PTSD), but few studies have examined neurochemical mechanisms that underlie functional alterations in regional cerebral blood flow. The mu-opioid neurotransmitter system, implicated in responses to stress and suppression of pain, is distributed in and is thought to regulate the function of brain regions that are implicated in affective processing.

Methods: Here we examined the micro-opioid system with positron emission tomography and the micro-opioid receptor-selective radiotracer [11C] carfentanil in 16 male patients with PTSD and two non-PTSD male control groups, with (n = 14) and without combat exposure (n = 15).

Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women.

Prominent interindividual and sex-dependent differences have been described in responses to sustained pain and other stressful stimuli. Variations in mu-opioid receptor-mediated endogenous opioid neurotransmission may underlie some of these processes. We examined both baseline mu-opioid receptor levels and the activation of this neurotransmitter system during sustained pain using positron emission tomography in a sample of young healthy men and women.

Sex differences in regional brain response to aversive pelvic visceral stimuli.

To explore sex differences in the response of seven brain regions to an aversive pelvic visceral stimulus, functional magnetic resonance images were acquired from 13 healthy adults (6 women) during 15 s of cued rectal distension at two pressures: 25 mmHg (uncomfortable), and 45 mmHg (mild pain), as well as during an expectation condition (no distension). Random-effects analyses combining subject data voxelwise found 45-mmHg pressure significantly activated the insular and anterior cingulate cortices in both sexes. In men only, the left thalamus and ventral striatum were also activated.

BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects.

Background: A frequent polymorphism of the brain-derived neurotrophic factor (BDNF) gene (val(66)met) has been suggested to modulate hippocampal neuronal plasticity and has been associated with individual variations in emotional reactivity traits and episodic memory.

Methods: The hippocampal formation was outlined in high-resolution anatomical magnetic resonance imaging (MRI) data in a sample of 36 healthy volunteers and compared between individuals as a function of the presence of the met-BDNF allele. Both whole-brain volume corrected and uncorrected data were tested for effects of genotype, sex, and age.

Placebo effects mediated by endogenous opioid activity on mu-opioid receptors.

Reductions in pain ratings when administered a placebo with expected analgesic properties have been described and hypothesized to be mediated by the pain-suppressive endogenous opioid system. Using molecular imaging techniques, we directly examined the activity of the endogenous opioid system on mu-opioid receptors in humans in sustained pain with and without the administration of a placebo. Significant placebo-induced activation of mu-opioid receptor-mediated neurotransmission was observed in both higher-order and sub-cortical brain regions, which included the pregenual and subgenual rostral anterior cingulate, the dorsolateral prefrontal cortex, the insular cortex, and the nucleus accumbens.

Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission.

Background: Human affective responses appear to be regulated by limbic and paralimbic circuits. However, much less is known about the neurochemical systems engaged in this regulation. The mu-opioid neurotransmitter system is distributed in, and thought to regulate the function of, brain regions centrally implicated in affective processing.

COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor.

Responses to pain and other stressors are regulated by interactions between multiple brain areas and neurochemical systems. We examined the influence of a common functional genetic polymorphism affecting the metabolism of catecholamines on the modulation of responses to sustained pain in humans. Individuals homozygous for the met158 allele of the catechol-O-methyltransferase (COMT) polymorphism (val158met) showed diminished regional mu-opioid system responses to pain compared with heterozygotes.

mu-opioid receptor-mediated antinociceptive responses differ in men and women.

Sex differences in the experience of clinical and experimental pain have been reported. However, the neurobiological sources underlying the variability in pain responses between sexes have not been adequately explored, especially in humans. The endogenous opioid neurotransmitters and mu-opioid receptors are centrally implicated in responses to stress, in the suppression of pain, and in the action of opiate analgesic drugs.