Brainstem changes in 5-HT1A receptor availability during migraine attack.

BACKGROUND: Among serotonin receptors, 5-HT(1A) receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT(1A) receptors' availability during migraine attacks. METHODS: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [(18)F]MPPF PET tracer, a selective 5-HT(1A) antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study. RESULTS: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [(18)F]MPPF binding potential (BP(ND)) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [(18)F]MPPF BP(ND) in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [(18)F]MPPF BP(ND) was observed between headache-free migraineurs and controls. CONCLUSIONS: Our results emphasize the role of 5HT(1A) receptors in the pontine raphe nuclei during the early stage of migraine attacks.

Comorbidity between temporal lobe epilepsy and depression: a [18F]MPPF PET study.

Brain and brainstem changes of serotoninergic 5-hydroxytryptophan (5-HT)(1A) receptor density have been reported in patients with major depressive disorder as well as in patients with temporal lobe epilepsy (TLE), using PET and the selective antagonist radiotracers [(11)C]WAY-100635 or [(18)F]FC-WAY. We used a distinct 5-HT(1A) antagonist, [(18)F]MPPF, whose binding potential depends on both receptor density and extracellular serotonin concentration, in 24 patients with drug-resistant TLE and MRI evidence of hippocampal sclerosis but without prior antidepressant exposure. Their Beck Depression Inventory (BDI-2) score ranged from 0 to 34, with nine patients having a score >11. We used a simplified reference tissue model, statistical parametric mapping and anatomical regions of interest (ROIs) to correlate parametric images of [(18)F]MPPF BP with the total BDI score and its four subclasses. The total BDI score, as well as symptoms of psychomotor anhedonia and negative cognition, correlated positively with [(18)F]MPPF BP in the raphe nuclei and in the insula contralateral to seizure onset, whereas somatic symptoms correlated positively with [(18)F]MPPF binding potential in the hippocampal/parahippocampal region ipsilateral to seizure onset, the left mid-cingulate gyrus and the inferior dorsolateral frontal cortex, bilaterally. We confirm an association of depressive symptoms in TLE patients with changes of the central serotoninergic pathways, in particular within the raphe nuclei, insula, cingulate gyrus and epileptogenic hippocampus. These changes are likely to reflect lower extracellular serotonin concentration in more depressed patients, with an upregulation of receptors a less likely alternative.

Interictal brain 5-HT1A receptors binding in migraine without aura: a 18F-MPPF-PET study.

In this study we aimed to assess the brain distribution of 5-HT(1A) receptors in migraine patients without aura. Ten female migraine patients and 24 female healthy volunteers underwent magnetic resonance imaging and positron emission tomography using a radioligand antagonist of 5-HT(1A) receptors [4-(2'-methoxyphenyl)-1-[2'-(N-2-pirydynyl)-p-fluorobenzamido]-ethylpiperazine ((18)F-MPPF)]. A simplified reference tissue model was used to generate parametric images of 5-HT(1A) receptor binding potential (BP) values. Statistical Parametrical Mapping (SPM) analysis showed increased MPPF BP in posterior cortical areas and hippocampi bilaterally in patients compared with controls. Region of interest (ROI) analysis showed a non-significant trend in favour of a BP increase patients in cortical regions identified by the SPM analysis except in hippocampi, left parietal areas and raphe nuclei. During the interictal period of migraine patients without aura, the increase of MPPF BP in posterior cortical and limbic areas could reflect an increase in receptor density or a decrease of endogenous serotonin, which could explain their altered cortical excitability.

Deformation and failure of rock samples probed by T1 and T2 relaxation.

The objective of the study was to pinpoint the effect of stress induced rock matrix alterations on NMR-wireline-log measurements by means of laboratory T1 and T2 relaxation time measurements. The research activities were subdivided into two major parts: NMR relaxation measurements on a brine saturated outcrop sandstone (Red Wildmoor Sandstone) during uniaxial compressional tests and NMR relaxation measurements on artificial sandstone samples prepared with defined crack patterns. T1-measurements performed on Red Wildmoor samples during compaction showed a decrease in the mean relaxation rate 1/exp

Spinal cholinergic alpha-2 adrenergic interactions in analgesia and hemodynamic control: role of muscarinic receptor subtypes and nitric oxide.

Intrathecal injection of neostigmine enhances antinociception from clonidine while it counteracts clonidine-induced hypotension. This study further examined the pharmacology of neostigmine-clonidine interactions in the spinal cord and focused on the roles of muscarinic receptor subtypes and local nitric oxide synthesis. Spinal neostigmine counteracted clonidine-induced decreases in blood pressure and heart rate in conscious sheep and this effect was blocked by spinal injection of the M2 muscarinic antagonist, AFDX-116, but not by the M1 muscarinic antagonist, pirenzepine. Carbamylcholine injected spinally alone increased blood pressure and heart rate and these effects and neostigmine's hemodynamic interaction with clonidine were blocked by spinal injection of the nitric oxide synthase inhibitor, N-methyl-L-arginine. The authors also investigated antinociceptive interactions by using a mechanical pressure stimulus on the forelimb of conscious sheep. Spinal clonidine produced dose-dependent antinociception, which was enhanced by neostigmine and antagonized by N-methyl-L-arginine. NADPH diaphorase staining of sheep spinal cord revealed dense localization to the superficial dorsal horn and the intermediolateral cell column. These results suggest that counteraction of spinal clonidine-induced hypotension by neostigmine is due to stimulation of spinal M2 muscarinic receptors and synthesis of nitric oxide. Nitric oxide synthesis is also necessary for clonidine-induced antinociception in sheep.