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.

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.

Low-rate repetitive TMS allays central pain.

Only about 50% of central pain patients respond to motor cortex stimulation in the long run. There is a need for prognostic factors. Here we show that propofol test and TMS both predict short-term effect in nine patients with central pain. This may help reduce the number of failures.

Transcranial magnetic cortical stimulation relieves central pain.

Extradural cortical stimulation for neurogenic pain is a recent addition to the field of functional neurosurgery. About 50% of patients with central pain draw benefit in the long run. However, there is an urgent need for prognostic factors in order to cut the costs of the procedure. In this paper we report a statistically significant correlation between the subhypnotic propofol test, transcranial magnetic cortical stimulation (TMS) and the actual short-term outcome of extradural cortical stimulation in 9 patients. The propofol test and TMS appear to predict short-term effects of extradural cortical stimulation.

Quantitative EEG responses to ischaemic arm stress in migraine.

Several studies suggest that patients with migraine respond physiologically to stress differently from controls, yet experimental data are scarce. In order to evaluate the reactivity to stress in migraine, we recorded the quantitative electroencephalogram (qEEG) during non-noxious and noxious ischaemic arm stress in two groups of healthy controls and compared the results with the effects of non-noxious ischaemic arm stress in a group of patients with migraine. In the controls, non-noxious mild stress did not produce any qEEG change but noxious stress induced a significant decrease of the alpha power. By contrast, in migraine patients the non-noxious mild stress was sufficient to induce a significant decrease of the alpha power in all brain regions. The results of our study show that migraine sufferers display a lower threshold to physical stress and confirm previous studies indicating that migraine is a disease characterized by a state of altered neuronal excitability.

Neuropsychological and neurophysiological evaluation after anterior communicating artery (ACoA) aneurysm surgery.

BACKGROUND: We evaluated high cerebral functions 6 months after surgery for bleeding ACoA aneurysms comparing neurophysiological and neuropsycological tests. METHODS: Twelve patients were chosen among a series of cases operated on in the first 48 hours after ACoA aneurysm bleeding. All of them were in Hunt-Hess grade I or II. We excluded patients over 65 years, or with intracranial haematomas, intraventricular haemorrhage, hydrocephalus, or with multiple or giant aneurysms. All of them underwent neurophysiological evaluation with recording and mapping of long latency (P300) auditory and visual event-related potentials (ERPs) and a neuropsychological assessment for memory, intelligence, frontal lobe functions and language. RESULTS: Neuropsychological assessment: All patients were severely damaged on phonemic fluency. In a first group (group A: 3 cases) tests were all in a normal range. In a second (group B: 3 cases) the tests showed severe impairment on learning and long term memory. In a third (group C: 6 cases) tests showed memory and "frontal lobe" deficits. Neurophysiological assessment: The whole group of patients showed significant delay in ERPs recordings compared to controls. ERPs of patients in group A and B showed no significant differences from controls, while being significantly delayed in 5 patients out of 6 of group C. CONCLUSIONS: All patients had difficulties in the phonemic task in which a notable cognitive effort is necessary, while intelligence, short term memory, attention and language were within normal limits. Patients in group C showed severe frontal lobe type cognitive impairment. Those ones in groups A and B did not present cognitive derangements (A) or only memory and learning impairment (B). ERPs may be an objective parameter in the follow-up of cases with cognitive impairment, even if neurophysiological tests cannot be replaced.

Autonomic responses and pain perception in Alzheimer's disease.

We analysed the effects of electrical noxious stimulation on the autonomic nervous system of Alzheimer's disease (AD) patients who were assessed by means of the Mini Mental State Examination test (MMSE). To do this, we used electrical stimuli at two different intensities: just above pain threshold and twice pain threshold. We recorded heart rate and systolic blood pressure by using conventional electrocardiography and finger photo-plethysmography. When a pain stimulus just above threshold was delivered, AD patients were found to have blunted autonomic responses compared to controls of the same age. Similarly, prestimulus expectation produced a less pronounced increase of the responses in AD patients compared to the controls. However, when the painful stimulus was increased to twice the pain threshold, the systolic blood pressure increase of AD patients did not differ from the controls, whereas heart rate increase was still slightly diminished. By contrast, pain perception was similar in the two groups when the stimulus was at pain threshold, whereas it was blunted in AD patients when the stimulus was twice the pain threshold. These findings show that in AD mild noxious stimulation produces blunted autonomic responses and normal pain perception, whereas strong noxious stimulation produces quasi-normal autonomic responses and blunted pain perception. These results indicate that AD patients have an increased threshold for both autonomic activation and pain tolerance.

Pain threshold and tolerance in Alzheimer's disease.

We tested both pain thresholds and pain tolerance in patients with Alzheimer's disease (AD) by means of phasic and tonic noxious stimuli. In the first case, electrical stimulation was used, whereas in the second case arm ischemia was studied. By comparing AD patients with normal subjects of the same age, we found no differences in stimulus detection and pain thresholds, whereas a clearcut increase in pain tolerance was present in AD patients. The severity of AD was assessed by means of the Mini Mental State Examination test (MMSE) and the spectral analysis of the electroencephalogram (EEG). There was a straightforward correlation between MMSE scores and pain tolerance such that the more severe the cognitive impairment the higher the tolerance to pain. In addition, analysis of the EEG power spectra indicated that patients with low alpha and high delta peaks showed an increase in pain tolerance to both electrical stimulation and ischemia. These findings show that, whereas the sensory-discriminative component of pain is maintained in AD patients, pain tolerance is altered and depends on cognitive and affective factors. Thus, pain tolerance is tightly related to the severity of the disease according to the rule, 'the more severe the MMSE and EEG changes, the higher the tolerance to pain'.

Neurophysiologic assessment of nerve impairment in posterolateral and muscle-sparing thoracotomy.

OBJECTIVE: This study was aimed at analyzing the degree of intercostal nerve impairment in posterolateral and muscle-sparing thoracotomy and at correlating the nerve damage to the severity of long-lasting postthoracotomy pain. METHODS: Neurophysiologic recordings were performed 1 month after either posterolateral or muscle-sparing thoracotomy to assess the presence of the superficial abdominal reflexes (mediated in part by the intercostal nerves), the somatosensory-evoked responses after electrical stimulation of the surgical scar, and the electrical thresholds for tactile and pain sensations of the surgical incision. RESULTS: The patients who underwent a posterolateral thoracotomy showed a higher degree of intercostal nerve impairment than the muscle-sparing thoracotomy patients as revealed by the disappearance of the abdominal reflexes, a larger reduction in amplitude of the somatosensory-evoked potentials, and a larger increase of the sensory thresholds to electrical stimulation for both tactile perception and pain. In addition, these neurophysiologic parameters were highly correlated to the postthoracotomy pain experienced by the patients 1 month after surgery, indicating a causal role for nerve impairment in the long-lasting postoperative pain. CONCLUSIONS: This study shows for the first time the pathophysiologic differences between posterolateral and muscle-sparing thoracotomy and suggests that the minor long-lasting postthoracotomy pain in muscle-sparing thoracotomy patients is partly due to a minor nerve damage. In addition, because nerve impairment is responsible for the long-lasting neuropathic component of postoperative pain, it is necessary to match specific treatments to the neuropathic pain-generating mechanisms.

Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain.

The treatment of neuropathic pain with opioid analgesics is a matter of controversy among clinicians and clinician scientists. Although neuropathic pain is usually believed to be only slightly responsive to opioids, several studies show that satisfactory analgesia can be obtained if adequate doses are administered. In the present study, we tested the effectiveness of buprenorphine in 21 patients soon after thoracic surgery (nociceptive postoperative pain) and 1 month after surgery in the same 21 patients who developed postthoracotomy neuropathic pain with a burning, electrical and shooting quality. According to a double-blind randomized study, the analgesic dose (AD) of buprenorphine needed to reduce the long-term neuropathic pain by 50% (AD50) was calculated and compared to the AD50 in the immediate postoperative period. We found that long-term neuropathic pain could be adequately reduced by buprenorphine. However, the AD50 in neuropathic pain was significantly higher relative to the AD50 in the short-term postoperative pain, indicating a lower responsiveness of neuropathic pain to opioids. We also found a strict relationship between the short-term and long-term AD50, characterized by a saturating effect. In fact, if the AD50 soon after surgery was low, the AD50 increase in the long-term neuropathic pain was threefold. By contrast, if the AD50 soon after surgery was high, the AD50 in neuropathic pain was only slightly increased. This suggests that, though neuropathic pain is indeed less sensitive to opioids, in some neuropathic patients a large amount of opioid resistance is already present in other painful conditions.

Lack of association between vigabatrin and impaired cognition.

Of 14 patients with a history of partial epilepsy who received vigabatrin 2 g daily for 6 months, eight were newly diagnosed and received vigabatrin as monotherapy, while the remaining six received vigabatrin in addition to pre-existing treatment with phenobarbitone. Neurophysiological and neuropsychological evaluations, done before and after the therapeutic period, included the Luria-Nebraska neuropsychological battery (LNNB), electroencephalograms (EEGs) and evoked potentials. The results for each item of the test battery at baseline were compared with those after 6 months' treatment. There were no statistically significant differences on the functional scales of the LNNB, the EEG or the evoked potentials. There was a significant improvement (P = 0.01) in the LNNB topographic scales for the right frontal lobe and the motor-sensory area following treatment. These results indicate that vigabatrin has no detrimental effects on cognitive function and may improve function.

Chronic triventricular hydrocephalus: morphological and functional study before and after ventriculoperitoneal shunting.

We have neuroradiologically and neuropsycho-physiologically studied a case of chronic hydrocephalus due to congenital acqueductal stenosis, before and after ventriculoperitoneal shunting. The aims of the study were: 1) to point out the correlation between neuroimaging (Computerized Tomography/Magnetic Resonance Imaging) and mapping of Computerized Spectral Analysis EEG (CSA-EEG); 2) to monitor evoked bioelectrical activity by neurophysiological evaluation of acoustic and visual N1 and P3. Both bioelectrical activity and neuroimaging evaluation showed a considerable recovery of the neurobiological substratum after neurosurgical shunting, while neuropsychological investigation showed a slight improvement in all cognitive tasks.

Propofol analgesia in central pain: preliminary clinical observations.

Propofol, an intravenous general anaesthetic, has been reported to relieve some forms of pruritus at subhypnotic doses. We assessed its effectiveness in 32 patients with several kinds of non-malignant chronic pain, in a placebo-controlled, double-blind study. We found that central pain, but not neuropathic pain, is at least partially controlled by propofol at subhypnotic doses, without major side-effects. In particular, allodynia associated with central, but no neuropathic, pain has been completely controlled. Propofol analgesia leads to renormalization of brain metabolism as seen on single photon emission computed tomography. We conclude that propofol may help in the diagnosis of central pain, particularly in unclear cases, and also in treatment. Possible mechanisms of action are discussed.

Time information in Poggendorff visual illusion: visual evoked potentials.

Using the component sets of the Poggendorff visual illusion as optical stimuli (comprising two horizontal and parallel segments intersected by two oblique segments), we recorded the respective visual evoked potentials (VEPs). Depending on the different delta t passing between the constitutive elements of the Poggendorff illusion, it was found that there was a greater latency of VEP components for the visual stimulus presentation sequence in which oblique segments are projected before horizontal segments.