左侧空间忽略患者关联性注意捕捉效应的研究

目的:探讨脑损伤后致左侧空间忽略患者的注意捕捉效应。方法:本研究对右侧大脑半球损伤伴左侧忽略的患者及健康被试各20例,分别进行神经心理学背景测试及关联性注意捕捉效应测试,观察左侧空间忽略患者与健康被试之间注意捕捉效应的差异,分析影响关联性注意捕捉效应强度的因素。结果:①与健康对照组相比,左侧空间忽略组的数字捕捉正确率明显降低(P<0.01)。②健康对照组:无论干扰刺激颜色与目标刺激颜色是否一致,左侧视野出现干扰刺激时的数字捕捉正确率均明显低于右侧视野出现干扰刺激时(P<0.01);无论干扰刺激在目标刺激的左侧或右侧,当干扰刺激颜色与目标刺激颜色一致时,数字捕捉正确率低于干扰刺激颜色与目标刺激颜色不一致时(P<0.01,0.05)。③左侧空间忽略组:无论干扰刺激颜色与目标刺激颜色是否一致,右侧视野出现干扰刺激时的数字捕捉正确率均低于左侧视野出现干扰刺激时(P<0.05);左侧视野出现的干扰刺激颜色与目标刺激颜色一致或不一致时,对数字捕捉正确率的影响差异无统计学意义,而右侧视野出现的干扰刺激颜色与目标刺激颜色一致时,数字捕捉正确率低于颜色不一致时(P<0.05)。结论:左侧空间忽略患者的注意功能下降,但无论对于健康受试者或者左侧空间忽略患者,符合目标刺激颜色特征的干扰刺激均能够增强非随意性地注意捕捉效应。     

Thermal sensibility changes during ischemic nerve block

Changes in perception of pure thermal stimuli delivered to the hand at threshold intensity were observed during ischemic nerve block in 27 healthy subjects in order to study the significance of unmyelinated cutaneous cold receptors for thermal sensibility.

Paresthesias and an increasing feeling of numbness were followed by a sudden change in cold sensation which developed a clearly dysesthetic quality. When complete motor block was reached and no myelinated axon functions were left, cold stimuli were still clearly but abnormally perceived. Warm sensation was little affected during the whole course of nerve block.

The results indicate that the information from unmyelinated low threshold cold receptors alone leads to a dysesthetic cold sensation which normally is suppressed by the activity of myelinated cold afferents. Obviously these receptors are not needed for the discrimination of minor cold stimuli but they seem to be essential for the perception of the first burning cold pain.     

Thermal sensibility changes during ischemie nerve block

Changes in perception of pure thermal stimuli delivered to the hand at threshold intensity were observed during ischemic nerve block in 27 healthy subjects in order to study the significance of unmyelinated cutaneous cold receptors for thermal sensibility.Paresthesias and an increasing feeling of numbness were followed by a sudden change in cold sensation which developed a clearly dysesthetic quality. When complete motor block was reached and no myelinated axon functions were left, cold stimuli were still clearly but abnormally perceived. Warm sensation was little affected during the whole course of nerve block.The results indicate that the information from unmyelinated low threshold cold receptors alone leads to a dysesthetic cold sensation which normally is suppressed by the activity of myelinated cold afferents. Obviously these receptors are not needed for the discrimination of minor cold stimuli but they seem to be essential for the perception of the first burning cold pain.     

Investigation of the paradoxical painful sensation ('illusion of pain') produced by a thermal grill

A paradoxical painful sensation can be elicited by the simultaneous application of innocuous warm and cold stimuli to the skin. In the present study, we analyzed the conditions of production of this unique experimental illusion of pain in 52 healthy volunteers (27 men, 25 women). The stimuli were produced by a thermode composed of six bars whose temperature was controlled by Peltier elements. The temperature of alternate (even- and odd-numbered) bars could be controlled independently to produce various patterns of the 'thermal grill'. After measuring the cold and heat pain thresholds, a series of combinations of warm and cold stimuli, whose distance to the thermal pain threshold was at least 4 degrees C, were applied on the palmar surface of the right hand during 30s. After each stimulus, the subjects had to describe and rate their sensations on visual analog scales. Paradoxical painful sensations, mostly described as burning, were reported by all the subjects but three. However, the phenomenon was less frequent in approximately one third of ('low responder') volunteers. The frequency and intensity of such painful sensations were directly related to the magnitude (i.e. 5-25 degrees C) of the difference of the temperature between the warm and cold bars of the grill. The combination of increasingly colder temperature to a given warm temperature induces similar effects as combining increasingly warmer temperature to a given cold temperature. These results suggest that pain can be the result of a simple addition of non-noxious warm and cold signals.     

The context of a noxious stimulus affects the pain it evokes

The influence of contextual factors on the pain evoked by a noxious stimulus is not well defined. In this study, a -20 degrees C rod was placed on one hand for 500 ms while we manipulated the evaluative context (or 'meaning') of, warning about, and visual attention to, the stimulus. For meaning, a red (hot, more tissue damaging) or blue (cold, less tissue damaging) visual cue was used. For warning, the stimulus occurred after the cue or they occurred together. For visual attention, subjects looked towards the stimulus or away from it. Repeated measures ANCOVA was significant (alpha=0.0125). Stimuli associated with a red cue were rated as hot, with the blue cue as cold (difference on an 11 point scale approximately 5.5). The red cue also meant the pain was rated as more unpleasant (difference approximately 3.5) and more intense (difference approximately 3). For stimuli associated with the red cue only, the pain was more unpleasant when the stimulus occurred after the cue than when it didn't (difference approximately 1.1). Pain was rated as more intense, and the stimulus as hotter, when subjects looked at the red-cued stimulus than when they didn't (difference approximately 0.9 for pain intensity and approximately 2 for temperature). We conclude that meaning affects the experience a noxious stimulus evokes, and that warning and visual attention moderate the effects of meaning when the meaning is associated with tissue-damage. Different dimensions of the stimulus' context can have differential effects on sensory-discriminative and affective-emotional components of pain.     

Cold and heat pain assessment of the human oesophagus after experimental sensitisation with acid

The aim of the present study was to investigate the effect of thermal stimulation of the oesophagus before and after sensitisation with acid. In 17 healthy subjects a stimulation bag was used to re-circulate water at 5 and 60 degrees C for up to 90 s in the lower part of the oesophagus. The area under the temperature curve was used to assess the caloric load. The thermal stimuli were repeated after perfusion of the oesophagus with acid. The evoked pain intensity and referred pain areas (at the pain threshold) were assessed. At baseline the subjects were able to tolerate less caloric load (42%) for the heat compared to the cold stimuli (P = 0.007). The heat stimuli resulted in an increased referred pain area as compared with the cold stimuli (P = 0.03). Following acid perfusion there was a selective sensitisation to the heat pain stimuli as only 36% of the initial caloric load was tolerated (P = 0.012) whereas the sensation to the cold stimuli was unchanged. After acid perfusion, the referred pain area to the heat pain stimulation increased 49% (P = 0.04) but was not changed to cold stimulation (P = 0.82). After sensitisation the words used to describe the sensations to heat pain stimuli shifted from a warmth quality towards a more burning quality in most subjects. This multi-modal sensory testing study showed that acid sensitises the oesophagus to heat but not to cold pain. This may account for the modality-specific symptoms and hypersensitivity reported in patients suffering from, e.g. gastro-oesophageal reflux disease.     

Dynamic Spatial Coding within the Dorsal Frontoparietal Network during a Visual Search Task

To what extent are the left and right visual hemifields spatially coded in the dorsal frontoparietal attention network? In many experiments with neglect patients, the left hemisphere shows a contralateral hemifield preference, whereas the right hemisphere represents both hemifields. This pattern of spatial coding is often used to explain the right-hemispheric dominance of lesions causing hemispatial neglect. However, pathophysiological mechanisms of hemispatial neglect are controversial because recent experiments on healthy subjects produced conflicting results regarding the spatial coding of visual hemifields. We used an fMRI paradigm that allowed us to distinguish two attentional subprocesses during a visual search task. Either within the left or right hemifield subjects first attended to stationary locations (spatial orienting) and then shifted their attentional focus to search for a target line. Dynamic changes in spatial coding of the left and right hemifields were observed within subregions of the dorsal front-parietal network: During stationary spatial orienting, we found the well-known spatial pattern described above, with a bilateral hemifield representation in the right hemisphere and a contralateral preference in the left hemisphere. However, during search, the right hemisphere had a contralateral preference and the left hemisphere equally represented both hemifields. This finding leads to novel perspectives regarding models of visuospatial attention and hemispatial neglect.     

Visual neglect and extinction: a new test

A new computerized test for visual neglect and extinction was developed and evaluated by testing twenty-five patients with right-hemisphere cerebrovascular accidents. The test consisted of a series of unilateral or bilateral lights on a semicircular array to which the subject responded by pushing a button. A computer controlled the sequence of stimuli and stored the responses. Results of the computer test were compared to conventional occupational therapy and beside clinical tests. Extinction was present in 16 subjects on the computerized test, and in 11 on the clinical test. Neglect was present in 13 subjects on the computerized test, in seven subjects on the occupational therapy test, and in five subjects on the clinical test. The computerized test was more sensitive than the other tests. On both computerized and clinical testing, all subjects with left-sided neglect also had left-sided extinction, but not all subjects with extinction had neglect. Neglect may represent a more severe manifestation of an underlying perceptual defect that produces both neglect and extinction.     

Subjective sensitization to tonic heat as an indicator of thermal pain

In 144 healthy subjects tonic heat stimuli were applied with a contact thermode and systematically varied with respect to 3 parameters: temperature T, rate of temperature change RTC, and duration D. In addition, the stimulus temperature at which the first sensation of pain occurred was produced by some subjects. In both types of experiments, subjects compared heat intensity felt at the beginning and the end of the stimulus and then set stimulus temperature to correspond with their initial sensation. The direction of this temperature change (delta T) indicates whether the subject senses an augmentation or a diminution of heat intensity. There was a parallel occurrence of pain and sensitization to sustained heat. The average skin temperature of the point of transition from adaptation to sensitization was equal to the average pain threshold temperature. The temperature change response maintained individual differences of thermal and pain sensitivity and was highly consistent for each subject. Potential applications of the procedure in clinical and experimental pain research are discussed.     

fMRI of thermal pain: effects of stimulus laterality and attention.

Brain activity was studied by fMRI in 18 healthy subjects during stimulation of the thenar eminence of the hand with either warm (non-painful, 40 degrees C) or hot (painful, 46-49 degrees C) stimuli using a contact thermode. Experiments were performed on the right and left hand independently and with two attentional contexts: subjects either attended to pain or attended to a visual global motion discrimination task (to distract them from pain). Group analysis demonstrated that attended warm stimulation of the right hand did not produce any significantly activated clusters. Painful thermal stimulation of either hand elicited significant activity over a large network of brain regions, including insula, inferior frontal gyrus, cingulate gyrus, secondary somatosensory cortex, cerebellum, and medial frontal gyrus (corrected P < 0.05). Insula activity was distributed along its anterior-posterior axis and depended on the hand stimulated and attentional context. In particular, activity within the posterior insula was contralateral to the site of stimulation, tested using regions of interest (ROI) analysis: significant side x site interaction (P = 0.001). With attention diverted from the painful stimulus bilateral anterior insula activity moved posteriorly to midinsula and decreased in extent (ROI analysis: significant main effect of attention (P = 0.03)). The role of the insula in thermosensation and attention is discussed.     

Spatial summation in human thermal pain perception: comparison within and between dermatomes.

Spatial summation of thermal pain has recently been reported when stimulus presentations were restricted within a single dermatome. The present study examined whether the magnitude of spatial summation of human thermal pain perception would vary when stimuli were presented within vs. between adjacent dermatomes. Noxious contact heat stimuli from 43 degrees C to 51 degrees C (5 sec duration) were applied to the forearm using areas of 0.21-2.10 cm2. Subjects rated the intensity and unpleasantness of pain using visual analog scales. For stimuli from 45 degrees C to 51 degrees C, there was a significant increase in ratings with increasing stimulus area for both intensity and unpleasantness. When two thermodes were used simultaneously in adjacent dermatomes, the ratings did not differ significantly from those for the same stimulus area in a single dermatome. We conclude that spatial summation both within and between dermatomes plays a significant role in thermal pain perception across the range from threshold to tolerance.     

Unilateral spatial neglect.

Unilateral spatial neglect is a complex, but fascinating, deficit in attention that may occur following stroke. The phrase "unilateral spatial neglect" belies the complex mixture of disorders in representational memory, hypokinesia in the opposite hemispace, and inattention to sensory stimuli in the opposite hemispace. Unilateral spatial neglect occurs as a result of damage to the posterior parietal cortex, frontal lobe, cingulate gyrus, striatum, thalamus, or specific brain-stem nuclei. This neural network for attention is an excellent example of how different anatomic areas work together to produce a specific behavior. Traditional treatment strategies for USN have focused on training attention in the left hemispace using a variety of techniques, including sensory awareness, visual scanning, and spatial organization. Recently, additional treatment strategies have emerged that focus on representational aspects of brain functioning. These strategies have included visual and movement imagery,30 manipulation of sensory input that conveys perception of the head in space, and manipulation of visual input using prisms and eye patches. The complex nature of USN provides numerous directions for future research. Continued research will play a pivotal role in devising effective treatment strategies for patients with USN.     

Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients

Diffuse noxious inhibitory control (DNIC) is part of a central pain modulatory system that relies on spinal and supraspinal mechanisms. Previous studies have shown that fibromyalgia (FMS) patients are lacking DNIC effects on experimental pain, compared to normal control (NC) subjects. Because DNIC has a greater effect on second pain than on first pain, we hypothesized that wind-up (WU) of second pain should be attenuated by a strong conditioning stimulus. Thus, we compared DNIC's effect on WU in three groups of subjects: 11 NC males, 22 NC females, and 11 FMS females. To separately assess the contributions of distraction related mechanisms to inhibition of second pain, we designed the experiment in such a way that directed the subjects' attention to either the test or conditioning stimulus. Repeated heat taps to the thenar surface of the right hand were used as test stimuli to generate WU of second pain. Immersion of the left hand into a hot water bath was the conditioning stimulus. As previous experiments have shown, DNIC requires a strong conditioning stimulus for pain attenuation, which may be at least partly dependent on a distraction effect. DNIC significantly inhibited thermal WU pain in normal male subjects, but adding distraction to the DNIC effect did not increase the extent of this inhibition. In contrast, neither DNIC nor DNIC plus distraction attenuated thermal WU pain in female NCs. DNIC plus distraction but not DNIC alone produced significant inhibition of thermal WU pain in female FMS patients. Our results indicate that DNIC effects on experimental WU of second pain are gender specific, with women generally lacking this pain-inhibitory mechanism.     

Psychophysical study of stinging pain evoked by brief freezing of superficial skin and ensuing short-lasting changes in sensations of cool and cold pain

Psychophysical methods were used to investigate pain in human subjects elicited by controlled freezing of the skin using a novel vortex thermode. When cooling stimuli delivered with a small thermode (7 mm diameter) exceeded the normal cold pain threshold into the sub-zero temperature range (−5 to −11°C), all subjects reported an intense, sharp stinging pain sensation which occurred suddenly and was readily differentiated from normal cold pain. The onset of this stinging `freezing' pain was closely correlated with a sudden increase in skin temperature beneath the thermode of 4.77±0.86°C (±SD) associated with the phase transition of supercooled water to ice. The mean intensity of freezing pain was rated as 1.7 times as intense as cold pain at threshold. Subjects' mean reaction-time latency to signal stinging pain following the onset of phase transition on the volar forearm was 687±220 ms, which was slower than that for mechanically evoked impact pain. Freezing pain is suggested to be mediated by A-delta fibers, based on estimates of conduction velocity and on the observation that the freezing pain took on a burning quality of slower onset during an A-fiber pressure block of nerve fibers. We also investigated changes in skin sensation following the freezing stimulus, and found that freezing led to (a) an immediate, significant decrease in the cold pain threshold (to higher temperatures), which recovered to baseline in <16 min, (b) a concomitant change in the quality of cold pain from dull to burning, (c) a significant, parallel increase in the threshold for the perception of cooling (to lower temperatures) which frequently manifested as a complete loss of cold sensation, and (d) a mild heat pain hyperalgesia which was still present 24 h later. The changes in thermal sensitivity were not accompanied by consistent changes in mechanical sensitivity. These results indicate that a characteristic sharp, stinging pain is reliably evoked abruptly at the phase transition of supercooled skin water to ice The ensuing brief decrease in cold pain threshold with burning quality, coupled with decreased sensitivity to cold, are speculated to reflect a central disinhibition of C-fiber nociceptor input due to reduced cold fiber activity. These effects may be relevant to frostbite, and distinguish themselves from the more pronounced thermal and mechanical hyperalgesia seen following intense freeze lesion of the skin.     

How efficient is the orienting of spatial attention to pain? An experimental investigation

This study investigated how efficient spatial attention was oriented to pain in 2 experiments. Participants detected whether painful (pain group) or nonpainful (control group) somatosensory stimuli were delivered to the left or right hand. Each stimulus was preceded by a visual cue presented near to the stimulated hand (valid trial), the opposite hand (invalid trial), or centrally between hands. To examine both exogenous and endogenous orienting of attention, the spatial predictability of somatosensory targets was manipulated. In the first experiment, visual cues were nonpredictive for the location of the pain stimulus, as a result of which, orienting was purely exogenous, i.e., resulting from the occurrence of the visual cue at the location of somatosensory input. In the second experiment, visual cues were spatially predictive, as a result of which, endogenous control was added, i.e., attention driven by expectations of where the somatosensory target will occur. The results showed that only in experiment 1 was spatial attention oriented more efficiently to painful compared with nonpainful somatosensory stimulation. This effect was due to faster responses on valid relative to baseline trials (engagement), rather than slower responses on invalid relative to baseline trials (disengagement), and was significantly correlated with self-reported bodily threat. In experiment 2, prioritization of the pain location was probably overridden by task strategies because it was advantageous for participants' task performance to attend to the cued location irrespective of whether stimulation was painful or not. Implications of these findings for theories of hypervigilance and attentional management of pain are discussed.     

Comparison of human pain sensation and flexion withdrawal evoked by noxious radiant heat

The purpose of this study was to determine the reliability of flexion withdrawal magnitude as an indicator of pain sensation. In 10 healthy human volunteers, we compared the magnitude and latency of integrated biceps EMG with the subjects' rating of pain, using a visual analog scale, elicited by noxious radiant heat stimuli applied to the dorsal forearm. The magnitude and inverse latency of withdrawal, although variable, increased exponentially as a functions of stimulus temperature. The stimulus response functions for mean withdrawal magnitude and mean pain intensity were similar for lower stimulus temperatures, but at higher temperatures the withdrawal continued to increase exponentially whereas pain intensity reached a plateau. The pain intensity and withdrawal magnitude for each stimulus were poorly correlated. Under the conditions of this experiment, mean pain intensity and mean withdrawal magnitude were both well correlated with stimulus temperature, but the magnitude of withdrawal did not reliably reflect the intensity of pain sensation.     

Natural history of sensory function after herpes zoster

The natural history of sensory function in the first 6 months after herpes zoster (HZ) was determined in a cohort of 94 subjects at elevated risk for developing post-herpetic neuralgia (PHN). All four visits included ratings of pain and sensory symptoms, mapping areas of altered sensation and allodynia, and quantitative thermal and mechanical sensory testing. The last three visits included the capsaicin response test. Sensory thresholds in distant control skin were stable. Mirror-image skin was persistently hyperesthetic to warming and mechanical stimuli and hyperalgesic to heat compared to distant control skin. HZ skin showed deficits in all thermal modalities. Sensory recovery was limited and selective. Allodynia area and severity, hyperalgesia to von Frey hair, and cold detection threshold improved, but deficits to warmth and heat pain did not. Capsaicin on HZ skin significantly aggravated pain and allodynia in the majority of subjects at 6–8 weeks after HZ onset. At study entry, eventual PHN subjects had significantly more impairment in detecting warmth and cold, a larger area of altered sensation, a larger area of allodynia, and more severe allodynia. The results support the study hypothesis that severity of initial injury predicts PHN, especially impaired cold sensation in HZ skin. The hypothesis that PHN develops because of a failure to recover normal neural function was not supported. Sensory recovery proceeded at the same rate in eventual pain-free and eventual PHN subjects and is not a requirement for pain resolution. Early interventions that reduce neural injury or enhance recovery should be of benefit.     

Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia

Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.     

Disruption of thermal perception in a multiple sclerosis patient with central pain

OBJECTIVE: To investigate integrative thermal perception in a patient with multiple sclerosis. DESIGN: Quantitative thermosensory testing was used to evaluate pain and other sensations produced by heat, cold, and the thermal grill pain illusion. PATIENT: The authors report on a 43-year-old patient with central pain manifest most strongly in her left arm and hand, contralateral to an upper cervical spinothalamic lesion due to multiple sclerosis. OUTCOME MEASURES AND RESULTS: Quantitative thermosensory testing showed that the patient had heat hypalgesia (no pain with stimuli of 45-50 degrees C) and cold allodynia (pain with innocuous cool temperatures, 25-10 degrees C). Whereas healthy subjects rated 20 degrees and 40 degrees C as nonpainful, but the thermal grill (intermixed 20 and 40 degrees C stimuli) as painful, the patient rated the thermal grill as less painful than 20 degrees C. CONCLUSIONS: The absence of thermal grill-evoked pain is consistent with the hypothesis that in some cases of central pain the loss of the thermosensory pathway results in disruption of the normal cold inhibition of burning pain.