Altered pain processing in children with migraine: An evoked potential study

In adults, evidence is accumulating that migraine is associated with altered central processing of pain stimuli and, possibly, changes in the allocation of attentional resources to such stimuli. In pediatric migraine, however, little is known about altered pain processing. We examined 15 children with migraine and 15 controls (age 10–15) in an oddball standards task. Children had to respond to rare targets (tones) and ignore frequent painful (pain threshold) or non‐painful mechanical standard stimuli while evoked potentials were obtained. Painful as compared to non‐painful stimuli elicited significantly larger N150, P260 and P300 components of the somatosensory evoked potential in all children. The pain‐evoked N150 and P260 components did not differ significantly between groups. However, in children with migraine, both painful and non‐painful standard stimuli were associated with significantly larger P300 amplitudes at significantly shorter latencies. Perceived intensity of the painful and non‐painful stimuli was comparable in both groups. The evoked potentials and reaction times to the target tones did not differ significantly between groups. Habituation across trials was similar in both groups. Hence, children with migraine may display an automatic attentional bias towards painful and potentially painful somatosensory stimuli. Consistent with the psychobiological perspective of chronic pain, such an attentional bias could constitute an important mechanism for migraine becoming a chronic problem.     

The effect of opioids on phantom limb pain and cortical reorganization

The efficacy of oral retarded morphine sulphate (MST) was tested against placebo in a double-blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation. Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST or Placebo. The titration phase was 2 weeks. The dose of MST was titrated to at least 70 mg/day and at highest 300 mg/day. Pain intensity was assessed hourly on visual analog scales during a 4-week treatment-free phase, both treatment phases and at two follow-ups (6 and 12 months). Reorganization of somatosensory cortex, electric perception and pain thresholds as well as selective attention were measured pre- and post-treatment. A significant pain reduction was found during MST but not during placebo. A clinically relevant response to MST (pain reduction of more than 50%) was evident in 42%, a partial response (pain reduction of 25-50%) in 8% of the patients. Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST concurrent with the reduction in pain intensity. Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST. Thus, opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization. These data need to be replicated in larger patient samples.     

Measurement of magnesium absorption in man using stable 26MG as a tracer

The stable isotope ²⁶Mg was compared to the radioisotope ²⁸Mg to estimate magnesium absorption in four healthy male subjects confined to a metabolic ward and consuming a constant diet for 146 days. Two isotopes tests were carried out in each subject on days 66 and 109 of the constant-diet period. In test 1, a solution containing 50 mg ²⁶Mg and 30 μC ²⁸Mg were taken orally during breakfast. In test 2, 50 mg ²⁶Mg were administered orally followed three hours later by an i.v. injection of 20 μC ²⁸Mg.True magnesium absorption was estimated by: (1) oral/i.v. ratios of ²⁸Mg in plasma and urine, or oral/i.v. ²⁶Mg/²⁸Mg ratios in urine; (2) the difference between intake and fecal excretion of total dietary magnesium over a period of 10 days, or of a single dose of either isotope, corrected for endogenous fecal magnesium. Estimates made in individual subjects by different procedures based on data derived solely by use of ²⁸Mg varied as much as estimates made by comparable procedures with data derived from either ²⁶Mg or ²⁸Mg. Measurements of ²⁶Mg enrichment in urine and feces were made by neutron activation analysis which loses precision at enrichment levels below 10% above natural abundance. With the doses used in this investigation only fecal samples collected within 3–4 days and urine samples taken wihin 2–24 h contained adequately detectable ²⁶Mg enrichment levels. Despite this limitation, ²⁶Mg significantly expands the scope of investigation of magnesium absorption in man beyond that possible with the short lived ²⁸Mg alone.     

Liver biopsy complications monitored by ultrasound

Ultrasound (US) was performed in 96 patients (on 108 occasions) 2-4 h after diagnostic liver puncture with a modified Menghini needle. Serious complications (major haemorrhages: one intraparenchymal and one into the abdominal cavity) were seen in two patients, while seven presented with minor bleedings though without any registered clinical abnormality (slight pain in one). On 11 occasions (10 patients) slight to moderate pain was observed though in combination with a normal US. Findings on US and clinical observations showed poor correlation and the number of bleeding complications discovered by US examination seems to depend upon when the study is performed. US does not replace the clinical follow-up but may be helpful in the presence of adverse clinical reactions in order to establish the type of lesion: profuse parenchymal haemorrhage versus bleeding into the abdominal cavity. This information may be helpful in the choice between conservative and surgical therapy.     

Effects of different viewing perspectives on somatosensory activations during observation of touch

Previous studies showed that neurons in the monkey premotor cortex became active when performing a particular action and also when observing the same action performed by others. These findings suggest a mirror system for action observation. Recently, bimodal neurons, sensitive both to visual and tactile stimulation, were reported in the parietal cortex, suggesting a potential mirror neuron system for observing and experiencing tactile stimulation. Subsequently, a mirror neuron system for observed touch has been suggested. The current study was designed to determine whether the activation of a sensory mirror system during touch observation is affected by possible attributions of the observed touch to oneself (subjective view) or to somebody else (objective view). In the study, healthy volunteers observed video clips of a touched or nontouched hand either in an egocentric or in an allocentric perspective during functional magnetic resonance imaging. Results showed activation of somatosensory cortices when observing the hand being touched in egocentric as well as in the allocentric perspectives. Moreover, somatosensory responses differed depending on the perspective of the observed touch. We discuss the results in terms of a possible mirror neuron system for observed and experienced touch. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Emotional learning during dissociative states in borderline personality disorder

Background

Neurobiological findings and clinical data suggest that dissociative experience inhibits conditioning processes, but experimental studies are lacking. The aim of our study was to determine whether high states of dissociative experience would specifically alter emotional learning, but not declarative knowledge.

Methods

We used an aversive differential delay conditioning procedure in 33 unmedicated patients with borderline personality disorder (BPD) and 35 healthy controls.

Results

Patients with BPD who had high state dissociative experiences (BPD D+) showed diminished acquisition of differential aversive delay conditioning with respect to emotional learning compared with those who did not experience dissociative symptoms (BPD D−) and healthy controls (skin conductance response; interaction dissociation × quadratic time × type, p = 0.009). Specifically, the control group and the BPD D− subgroup showed an increase in valence and arousal to the conditioned stimulus (CS+) during the conditioning procedure (all p < 0.012) and demonstrated differential skin conductance responses in the acquisition and extinction phases. In contrast, the BPD D+ subgroup showed no increase in valence and arousal to CS+ or differential response regarding skin conductance. We examined general psychopathology, trauma history, perceptual differences and posttraumatic stress disorder as confounding factors, but we found no evidence of bias.

Limitations

Subdividing the BPD group reduced power. In addition, because our sample included only women, the generalizability of our results is constrained. Furthermore, we performed no separate analysis of the influence of different aspects of dissociation on the learning process.

Conclusion

Emotional, amygdala-based learning processes seem to be inhibited during state dissociative experience. State dissociative experience may alter acquisition and extinction processes and should be closely monitored in exposure-based psychotherapy.     

Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning.