Measuring expectation of pain: Contingent negative variation in placebo and nocebo effects.

BACKGROUND: Expectation is an important mechanism underlying placebo response. Here, we analysed expectation of placebo hypoalgesia and nocebo hyperalgesia by using, for the first time, the contingent negative variation (CNV), also known as expectancy wave. METHODS: Subjects were presented a green or red cue followed by a train of either non painful or painful electrical stimuli, and expected hypoalgesia after the green and hyperalgesia after the red cue. In experiment 1, expectation was reinforced using a conditioning procedure whereby the green and red cues were paired with non painful and painful stimuli, respectively (acquisition). In a second session (test) the intensity of the stimuli was kept constant, regardless of cue. In experiment 2 no conditioning was performed and participants expected an altered pain perception indicated by the visual cues. CNV mean amplitude, time necessary to stop the train of stimuli (reaction time) and pain ratings were measured. RESULTS: A difference in pain perception occurred when electrical stimuli followed the presentation of the green cue compared to the red in the test session, whereas reaction times showed no changes. The same difference occurred in the early CNV component, related to cognitive stimulus anticipation, whereas the late CNV component, related to motor preparation, did not change. Moreover, these differences in pain perception and CNV amplitude were less robust in the experiment 2. CONCLUSION: Placebo hypoalgesia and nocebo hyperalgesia differently affect sensory (pain perception) and motor components (pain avoidance) of pain. Furthermore, CNV is an electrophysiological objective measure capable of dissecting these components. SIGNIFICANCE: Dissection of placebo hypoalgesia, differentiating the sensory component (pain perception) from the motor component (pain avoidance). Study of these components using the contingent negative variation (CNV) as an electrophysiological objective measure.

Nature of the placebo and nocebo effect in relation to functional neurologic disorders.

Placebos have long been considered a nuisance in clinical research, for they have always been used as comparators for the validation of new treatments. By contrast, today they represent an active field of research, and, due to the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. There is not a single placebo effect, but many, with different mechanisms across different medical conditions and therapeutic interventions. Expectation, anxiety, and reward are all involved, as well as a variety of learning phenomena and genetic variants. The most productive models to better understand the neurobiology of the placebo effect are pain and Parkinson's disease. In these medical conditions, several neurotransmitters have been identified, such as endogenous opioids, cholecystokinin, dopamine, as well as lipidic mediators, for example, endocannabinoids and prostaglandins. Since the placebo effect is basically a psychosocial context effect, these data indicate that different social stimuli, such as words and therapeutic rituals, may change the chemistry of the patient's brain, and these effects are similar to those induced by drugs.

Different contexts, different pains, different experiences.

Pain is an ambiguous perception: the same pain stimulation can be perceived differently in different contexts, producing different experiences, ranging from mild to unbearable pain. It can be even experienced as a rewarding sensation within the appropriate context. Overall, placebo and nocebo effects appear to be very good models to understand how the psychosocial context modulates the experience of pain. In this review, we examine the effects of different contexts on pain, with a specific focus on the neurobiological mechanisms. Positive and rewarding contexts inform the patients that an effective treatment is being delivered and are capable of producing pain relief through the activation of specific systems such as opioids, cannabinoids and dopamine. Conversely, a negative context can produce pain exacerbation and clinical worsening through the modulation of different systems, such as the activation of cholecystokinin and the deactivation of opioids and dopamine. In addition, when a therapy is delivered unbeknownst to the patient, its effects are reduced. A better understanding of the neurobiological underpinnings of the context-pain interaction is a challenge both for future pain research and for good clinical practice.

Role of explicit verbal information in conditioned analgesia.

BACKGROUND: The exact role of expectation in conditioned analgesia is still elusive as it is not clear whether conditioning is an automatic process or rather it is cognitively mediated. This study is aimed at understanding the role of explicit verbal information in conditioned analgesia. METHODS: Two groups of healthy subjects received a conditioning procedure whereby two visual cues were paired with increase and decrease in stimulus intensity. In the 'conditioning/verbal information' group (VER), subjects were informed about the meaning of the cues, whereas no information was given to the second group (noVER). After two conditioning blocks, an evocation session was run in which the stimulus intensity was the same, irrespective of the cues. Pain perception was assessed according to a numerical rating scale from 0 (no pain) to 10 (maximal pain). The N2-P2 component of laser-evoked potentials (LEP) was used as an index of index of brain responses to nociceptive stimuli. RESULTS: In the evocation session, only the VER group reported a decrease in pain rating and LEP amplitude when the cues were presented, suggesting that the visual-analgesic association does not occur without explicit verbal information. CONCLUSIONS: In line with the cognitive theory of conditioning, our results indicate that just pairing a cue with different pain stimulus intensities is not sufficient, per se, to produce a learning process. What matters is the informational cognitive content of the cue, i.e. the meaning assigned to the cue itself. These findings may help understand the mechanisms of conditioned analgesia and more in general of learning.

Growth of ultrathin epitaxial Fe/MgO spin injector on (0, 0, 1) (Ga, Mn)As.

We have grown an ultrathin epitaxial Fe/MgO bilayer on (Ga, Mn)As by e-beam evaporation in UHV. The system structure has been investigated by high resolution transmission electron microscopy (TEM) experiments which show that the Fe and MgO films, covering completely the (Ga, Mn)As, grow with the epitaxial relationship Fe[100](001) [parallel] MgO[110](001) [parallel] (Ga,Mn)As[110](001). The magnetic reversal process, studied by the magneto-optical Kerr effect (MOKE) at room temperature, demonstrates that the iron is ferromagnetic and possesses a cubic anisotropy, confirming the epitaxy relationship found with TEM. Resistivity measurements across the barrier display a non-Ohmic behavior characterized by cubic conductance as a function of the applied voltage suggesting tunneling-dominated transport across the barrier.

Hidden administration of drugs.

In placebo-controlled trials, the placebo component of treatments is usually assessed by simulating a therapy through the administration of a dummy treatment (placebo) in order to eliminate the specific effects of the therapy. Recently, a radically different approach to the analysis of placebo responses has been implemented in which placebo responses are assessed without placebo groups. To do this, the placebo (psychological) component is eliminated by conducting hidden (unexpected) administrations of the active treatment. Compelling experimental evidence now shows that when the psychological component is eliminated through the administration of therapies unbeknownst to the patient, the effects of a variety of treatments are significantly reduced. Overall, the experimental data show that the action of different pharmacological agents can be modulated by cognitive and affective factors that can increase or decrease the effects of drugs. This experimental approach is thus a window into the complex interactions between psychology and pharmacodynamics.

Morphology and composition of InAs/GaAs quantum dots.

Surface compositional maps of self-organized InAs/GaAs quantum dots were obtained with laterally resolved photoemission spectroscopy. We found a surface In concentration of about 0.85 at the center of the islands which decreases to 0.75 on the wetting layer. Comparison with concentration values found in the core of similar dots suggests a strong In segregation on the topmost surface layers of the dots and on the surrounding wetting layer. Furthermore, the morphological properties of the dots such as size and density have been measured with plan-view transmission electron microscopy and low energy electron microscopy.

Detection of magnetic circular dichroism using a transmission electron microscope.

A material is said to exhibit dichroism if its photon absorption spectrum depends on the polarization of the incident radiation. In the case of X-ray magnetic circular dichroism (XMCD), the absorption cross-section of a ferromagnet or a paramagnet in a magnetic field changes when the helicity of a circularly polarized photon is reversed relative to the magnetization direction. Although similarities between X-ray absorption and electron energy-loss spectroscopy in a transmission electron microscope (TEM) have long been recognized, it has been assumed that extending such equivalence to circular dichroism would require the electron beam in the TEM to be spin-polarized. Recently, it was argued on theoretical grounds that this assumption is probably wrong. Here we report the direct experimental detection of magnetic circular dichroism in a TEM. We compare our measurements of electron energy-loss magnetic chiral dichroism (EMCD) with XMCD spectra obtained from the same specimen that, together with theoretical calculations, show that chiral atomic transitions in a specimen are accessible with inelastic electron scattering under particular scattering conditions. This finding could have important consequences for the study of magnetism on the nanometre and subnanometre scales, as EMCD offers the potential for such spatial resolution down to the nanometre scale while providing depth information--in contrast to X-ray methods, which are mainly surface-sensitive.

High resolution transmission electron microscopy to study very thin crystalline layers buried at an amorphous-crystalline interface

Structure characterisation of interfaces is a field of widespread application of high resolution transmission electron microscopy for its very high spatial resolution. Specimen thickness and electron optical condition have a deep influence on the high resolution electron transmission microscopy image contrast. Hence, in many cases, the real structure of the sample can be understood from experimental images only by comparison with the relevant simulation. Moreover, the understanding of the contrast variation of a few A at an interface is a task in which even the use of simulation could not produce an unequivocal solution of the experimental result. In this paper high resolution transmission electron microscopy image simulations show that two monolayers of crystalline material buried at an amorphous-crystalline interface can be successfully revealed and interpreted. The simulated images reproduce the experimental results as obtained from the Al/Si-As/n-GaAs (001) heterostructure.