Deficient modulation of pain by a positive emotional context in fibromyalgia patients

This study aimed to investigate the modulating effects of emotional context on pain perception in 16 patients with fibromyalgia syndrome (FMS) and 16 healthy control (HC) subjects. An infrared laser was used to apply individually adapted painful stimuli to the dorsum of the left hand. The emotional background of the painful stimuli was modulated by concurrent presentations of negative, neutral, and positive picture stimuli selected from the International Affective Picture System. As control conditions, painful stimuli and the pictures were also presented by themselves. During each of the 5 laser-picture trials, subjects received 10 painful stimuli and were asked to rate the average intensity and unpleasantness of the experienced pain. Functional magnetic resonance images were obtained, using a T2^∗ sensitive echo planar sequence. HC subjects showed a linear increase in pain intensity and unpleasantness ratings when painful stimuli were presented during positive, neutral, and negative pictures. In contrast, FMS patients showed a quadratic trend for pain intensity ratings indicating a lack of pain reduction by the positive pictures. In addition, the FMS patients showed less activation in secondary somatosensory cortex, insula, orbitofrontal cortex, and anterior cingulate cortex during the positive picture pain trials. Our results suggest that fibromyalgia patients are less efficient in modulating pain by positive affect and may benefit less from appetitive events than healthy control subjects.     

广泛性焦虑障碍发病机制的静息态功能磁共振成像

目的 应用静息态功能磁共振成像(rs-fMRI)观察广泛性焦虑障碍(GAD)患者全脑活动及网络连接的变化,探索其与临床焦虑症状的相关性。方法 对28例GAD患者(GAD组)、28名健康对照(HC)组进行fMRI扫描。逐体素对比分析两组低频振幅(ALFF)和种子点静息态功能连接(FC)的差异,采用Pearson相关分析研究其与焦虑自评量表、汉密尔顿焦虑量表(HAM-A)、GAD-7项量表和汉密尔顿抑郁量表等评分的相关性。结果 GAD组双侧背内侧前额叶、左楔前叶/后扣带回和双侧背外侧前额叶ALFF值明显高于HC组(P均<0.05)。GAD组右侧眶额叶/岛叶-背内侧前额叶、左侧眶额叶/岛叶-背内侧前额叶、左侧背外侧前额叶皮层-右侧海马的功能连接与HAM-A评分和GAD-7评分均有相关性。结论 背侧前额叶皮层及楔前叶/后扣带回脑活动、前额叶-边缘组织回路异常可能是GAD重要的发病机制。     

Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case

Parietal, insular and anterior cingulate cortices are involved in the processing of noxious inputs and genesis of pain sensation. Parietal lesions may generate central pain by mechanisms generally assumed to involve the 'medial' pain system (i.e. medial thalamic nuclei and anterior cingulate cortex (ACC)). We report here PET and fMRI data in a patient who developed central pain and allodynia in her left side after a bifocal infarct involving both the right parietal cortex (SI and SII) and the right ACC (Brodmann areas 24 and 32), thus questioning the schematic representation of cortical pain processing. No rCBF increase was found in any part of the residual cingulate cortices, neither in the basal state (which included spontaneous pain and extended hypoperfusion around the infarct), nor during left allodynic pain. Thus, as previously observed in patients with lateral medullary infarct, neither spontaneous pain nor allodynia reproduce the cingulate activation observed after noxious pain in normal subjects. Conversely, both PET and fMRI data argue in favour of plastic changes in the 'lateral discriminative' pain system. Particularly, allodynia was associated with increased activity anteriorly to the infarct in the right insula/SII cortex. This response is likely to be responsible for the strange and very unpleasant allodynic sensation elicited on the left side by a non-noxious stimulation.     

Significant differences in central imaging of histamine-induced itch between atopic dermatitis and healthy subjects

Background/aim: This is the first investigation of the central processing of itch in the brain in 8 subjects with atopic dermatitis (AD) in comparison to 6 healthy controls (HC), comparing histamine‐induced itch related activations in the frontal, prefrontal, parietal, cingulate cortex, thalamus, basal ganglia and cerebellum. Methods: We employed 1% histamine‐dihydrochlorid‐iontophoresis of the left hand, recorded H₂ ¹⁵O‐PET‐scans and perception of itch intensity on a numeric rating scale. Results: There was no significant difference in perceived itch intensity between AD and HC. Significant increase in rCBF was found in HC in the contralateral somatosensory and motor cortex, midcingulate gyrus, and ipsilateral prefrontal cortex; in AD: in the contralateral thalamus, somatosensory, motor and prefrontal cortex and cerebellum, in the ipsilateral precentral, prefrontal, orbitofrontal cortex, insula, pallidum and cerebellum. More brain sites were activated in AD than in HC. Activation in AD was significantly higher in the contralateral thalamus, ipsilateral caudate and pallidum. Conclusions: We interpret our findings as possible central correlates of changes in the motor system in subjects with chronic itch, with activation of the basal ganglia possibly correlating to the vicious itch‐scratch‐circle in subjects with chronic itching skin diseases. However, further neuroimaging studies in healthy subjects and also in different skin diseases are needed to understand the complex mechanisms of the processing of itch.     

Gender differences in patterns of cerebral activation during equal experience of painful laser stimulation.

A previous functional imaging study demonstrated greater female response in the anterior insula and thalamus and left prefrontal activation in men and right prefrontal activation in women during equal heat intensity but unequal pain experience. For the current study, subjective intensities of noxious heat delivered to the back of the right hand were equalized across subjects, and regional cerebral blood flow was recorded by using positron emission tomography. The female subjects required less laser energy before reporting pain, but the difference was not significant. Correlation of regional cerebral blood flow with subjective pain experience in the whole group showed significant bilateral responses in the parietal, lateral premotor, prefrontal, secondary somatosensory, anterior cingulate and insula cortices, as well as the thalamus. There was significantly greater activation in the left, contralateral, prefrontal, primary and secondary somatosensory, parietal, and insula cortices in the male subjects compared with the female subjects and greater response in the perigenual cingulate cortex in the female subjects. Our study is the first to associate consistent pain experience with gender differences in central response. These differences may relate to differential processing of acute pain with implications for clinical disorders that show a female dominance. The subtle behavioral differences and inconsistent findings across studies, however, suggest the need for caution and further experimentation before speculating further.     

Chronic pain is associated with less grey matter volume in the anterior cingulum,anterior and posterior insula and hippocampus across three different chronic pain conditions

Background

Chronic pain of different aetiologies and localization has been associated with less grey matter volume (GMV) in several cortical and subcortical brain areas. Recent meta-analyses reported low reproducibility of GMV alterations between studies and pain syndromes.

Methods

To investigate GMV in common chronic pain conditions defined by body location (chronic back pain, n = 174; migraine, n = 92; craniomandibular disorder, n = 39) compared to controls (n = 296), we conducted voxel-based morphometry and determined GMV from high-resolution cranial MRIs obtained in an epidemiologic survey. Mediation analyses were performed between the presence of chronic pain and GMV testing the mediators stress and mild depression. The predictability of chronic pain was investigated with binomial logistic regression.

Results

Whole-brain analyses yielded reduced GMV within the left anterior insula and the anterior cingulate cortex, for a ROI approach additionally the left posterior insula and left hippocampus showing less GMV across all patients with chronic pain. The relationship of pain with GMV in the left hippocampus was mediated by self-reported stressors in the last 12 months. Binomial logistic regression revealed a predictive effect for GMV in the left hippocampus and left anterior insula/temporal pole for the presence of chronic pain.

Conclusions

Chronic pain across three different pain conditions was characterized by less GMV in brain regions consistently described for different chronic pain conditions before. Less GMV in the left hippocampus mediated by experienced stress during the last year might be related to altered pain learning mechanisms in chronic pain patients.

Significance

Grey matter reorganization could serve as a diagnostic biomarker for chronic pain. In a large cohort, we here replicated findings of less grey matter volume across three pain conditions in the left anterior and posterior insula, anterior cingulate and left hippocampus. Less hippocampal grey matter was mediated by experienced stress.     

Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain

Differences in brain activation in experimentally induced and chronic neuropathic pain conditions are useful for understanding central mechanisms leading to chronic neuropathic pain. Many mapping studies investigating both pain conditions are now available, and the latest tools for coordinate-based meta-analysis offer the possibility of random effects statistics. We performed a meta-analysis based on a literature search of published functional magnetic resonance imaging group studies to compare patterns of activity during experimentally induced and chronic neuropathic pain, for the later including four fibromyalgia studies. Stimulus-dependent activation in experimental pain was further divided into "thermal" and "non thermal" stimuli. A conjunction of experimentally induced and chronic neuropathic pain revealed activation of the bilateral secondary somatosensory cortex, right middle cingulate cortex, right inferior parietal lobe, supplementary motor area, right caudal anterior insula, and bilateral thalamus. Primary somatosensory activation was only observed during experimental non-thermal stimulation. Chronic neuropathic pain studies showed increased activation in the left secondary somatosensory cortex, anterior cingulate cortex, and right caudal anterior insula when compared to experimentally induced pain. Activation clusters in the anterior cingulate cortex and caudal anterior insula suggest a strong emotional contribution to the processing of chronic neuropathic pain.     

Chronic low-back pain modulation is enhanced by hypnotic analgesic suggestion by recruiting an emotional network: a PET imaging study

This study aimed to characterize the neural networks involved in patients with chronic low-back pain during hypnoanalgesia. PET was performed in 2 states of consciousness, normal alertness and hypnosis. Two groups of patients received direct or indirect analgesic suggestion. The normal alertness state showed activations in a cognitive-sensory pain modulation network, including frontotemporal cortex, insula, somatosensory cortex, and cerebellum. The hypnotic state activated an emotional pain modulation network, including frontotemporal cortex, insula, caudate, accumbens, lenticular nuclei, and anterior cingulate cortex (ACC). Direct suggestion activated cognitive processes via frontal, prefrontal, and orbitofrontal cortices, while indirect suggestion activated a widespread and more emotional network including frontal cortex, anterior insula, inferior parietal lobule, lenticular nucleus, and ACC. Confirmed by visual analog scale data, these results suggest that chronic pain modulation is greater with hypnosis, which enhances both activated networks.     

膝骨关节炎和腰痛患者的脑低频振幅影像学特征比较北大核心CSCD

目的基于静息态功能磁共振成像低频振幅(ALFF)分析方法探讨膝骨关节炎(KOA)和腰痛两种慢性疼痛患者脑影像学特征的异同。方法2015年8月至2021年9月在福建福州市各社区招募KOA患者16例及年龄、性别相似的健康人16例(对照组1);从Openpain数据库获得27例腰痛患者和年龄、性别相似的健康人32例(对照组2)。比较受试者的ALFF。采用简明疼痛量表(BPI)对KOA患者进行疼痛评分,采用视觉模拟量表(VAS)对腰痛患者进行疼痛评分,并与ALFF进行相关性分析。结果与各自对照组相比,KOA和腰痛患者左前脑岛ALFF降低,KOA患者海马和后扣带回ALFF降低,腰痛患者升高;KOA患者左楔前叶、左中扣带回、右中脑导水管周围灰质区域ALFF降低,右中央前回、中央后回ALFF升高;腰痛患者双前扣带回、双眶部额前回、左背外侧前额叶、右内侧前额叶ALFF降低,右海马旁回、右杏仁核ALFF升高;KOA患者左中扣带回ALFF与BPI评分负相关(r=-0.73,P=0.003),腰痛患者右海马/杏仁核ALFF与VAS评分正相关(r=0.73,P=0.003)。结论不同类型慢性疼痛有共同和特异的脑影像学特征。前脑岛、海马和后扣带回ALFF改变可能是KOA和腰痛的共同病理机制。     

Cerebral responses to pain in patients suffering acute post-dental extraction pain measured by positron emission tomography (PET)

Previous studies with normal volunteers have demonstrated distributed cortical responses to experimental heat pain within a network of structures. The network includes the insula, anterior cingulate, prefrontal, inferior parietal and somatosensory cortices. Patients suffering from chronic nociceptive pain following rheumatoid arthritis (RA) have shown damped central responses to experimental heat pain applied to the back of the right hand. In this study of patients with acute, left-sided, post-molar-extraction (surgical) pain, we assessed the cortical responses to experimental heat pain, applied to the back of the right hand, using positron emission tomography (PET), and compared the responses with a previously reported control group and the RA group. In response to the experimental heat pain, the surgical group indicated significantly increased regional cerebral blood flow in the prefrontal cortex [Brodman's area (BA) 44] ipsilateral to the heat stimulus. Contralateral increases were detected in the putamen and transverse temporal gyrus (BA 40/41/42) with bilateral increases in the insular cortex. Compared to the control and RA group, there were significantly reduced responses in the anterior cingulate (BA 24), pre-frontal medial, and orbito-frontal (BA 9/10/32/47) cortices. These results suggest that relatively discrete regions of the cerebral cortex are responsible for acute nociceptive processing during an acute inflammatory episode. The reduced frontal and anterior cingulate responses to the experimental heat pain (applied to the right hand) during acute inflammatory pain (left jaw) illustrates cortical modulation of nociceptive processing that may be related to non-somatotopic, bilateral, nociceptive inputs to these areas.     

Differential coding of hyperalgesia in the human brain: a functional MRI study

Neuropathic pain can be both ongoing or stimulus-induced. Stimulus-induced pain, also known as hyperalgesia, can be differentiated into primary and secondary hyperalgesia. The former results from sensitization of peripheral nociceptive structures, the latter involves sensitization processes within the central nervous system (CNS). Hypersensitivity towards heat stimuli, i.e. thermal hyperalgesia, is a key feature of primary hyperalgesia, whereas secondary hyperalgesia is characterized by hypersensitivity towards mechanical (e.g. pin-prick) stimulation. Using functional magnetic resonance imaging (fMRI), we investigated if brain activation patterns associated with primary and secondary hyperalgesia might differ. Thermal and pin-prick hyperalgesia were induced on the left forearm in 12 healthy subjects by topical capsaicin (2.5%, 30 min) application. Equal pain intensities of both hyperalgesia types were applied during fMRI experiments, based on previous quantitative sensory testing. Simultaneously, subjects had to rate the unpleasantness of stimulus-related pain. Pin-prick hyperalgesia (i.e. subtraction of brain activations during pin-prick stimulation before and after capsaicin exposure) led to activations of primary and secondary somatosensory cortices (S1 and S2), associative-somatosensory cortices, insula and superior and inferior frontal cortices (SFC, IFC). Brain areas activated during thermal hyperalgesia (i.e. subtraction of brain activations during thermal stimulation before and after capsaicin exposure) were S1 and S2, insula, associative-somatosensory cortices, cingulate cortex (GC), SFC, middle frontal cortex (MFC) and IFC. When compared to pin-prick hyperalgesia, thermal hyperalgesia led to an increased activation of bilateral anterior insular cortices, MFC, GC (Brodmann area 24' and 32') and contralateral SFC and IFC, despite equal pain intensities. Interestingly, stronger activations of GC, contralateral MFC and anterior insula significantly correlated to higher ratings of the stimulus-related unpleasantness. We conclude that thermal and mechanical hyperalgesia produce substantially different brain activation patterns. This is linked to different psychophysical properties.     

Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study.

Although electrical stimulation of the precentral gyrus (MCS) is emerging as a promising technique for pain control, its mechanisms of action remain obscure, and its application largely empirical. Using positron emission tomography (PET) we studied regional changes in cerebral flood flow (rCBF) in 10 patients undergoing motor cortex stimulation for pain control, seven of whom also underwent somatosensory evoked potentials and nociceptive spinal reflex recordings. The most significant MCS-related increase in rCBF concerned the ventral-lateral thalamus, probably reflecting cortico-thalamic connections from motor areas. CBF increases were also observed in medial thalamus, anterior cingulate/orbitofrontal cortex, anterior insula and upper brainstem; conversely, no significant CBF changes appeared in motor areas beneath the stimulating electrode. Somatosensory evoked potentials from SI remained stable during MCS, and no rCBF changes were observed in somatosensory cortex during the procedure. Our results suggest that descending axons, rather than apical dendrites, are primarily activated by MCS, and highlight the thalamus as the key structure mediating functional MCS effects. A model of MCS action is proposed, whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in pain-related structures receiving afferents from these nuclei, including the medial thalamus, anterior cingulate and upper brainstem. MCS could influence the affective-emotional component of chronic pain by way of cingulate/orbitofrontal activation, and lead to descending inhibition of pain impulses by activation of the brainstem, also suggested by attenuation of spinal flexion reflexes. In contrast, the hypothesis of somatosensory cortex activation by MCS could not be confirmed by our results.     

Functional imaging of sensory decline and gain induced by differential noxious stimulation

It is increasingly recognized that pain-induced plasticity may provoke secondary sensory decline, i.e. centrally-mediated hypoesthesia and hypoalgesia. We investigated perceptual changes induced by conditioning electrical stimulation of C-nociceptors differing in stimulation frequencies and duty cycles provoking either sensory gain (i.e. mechanical hyperalgesia; Stim1) or sensory decline (i.e. hypoesthesia and hypoalgesia; Stim2). Underlying brain processing was investigated using functional magnetic resonance imaging. Before conditioning stimuli, tactile stimulation and pin-prick stimuli led to differential activations of primary and secondary somatosensory cortices (S1, S2), insula and prefrontal cortices (PFC). After induction of mechanical hyperalgesia (Stim1), increased activations were detected in somatosensory/pain-related areas (S1, S2, insula, cingulate cortex) and networks involved in attentional and cognitive processing (parieto-frontal, parieto-cingulate and frontal circuits). In contrast, after induction of hypoesthesia and hypoalgesia (Stim2) the degree of sensory decline for touch and mechanical pain was directly correlated with deactivations within S1, whereas networks associated with attentional and cognitive processing showed increased activation. Therefore, our results demonstrate that brain processing underlying pain-induced sensory gain substantially differs from pain-induced sensory decline. A potential neurobiological mechanism of secondary CNS-mediated hypoesthesia and hypoalgesia may involve modification of local inhibitory networks within somatosensory cortices.     

原发性三叉神经痛患者脑结构和功能连接改变

目的 探讨原发性三叉神经痛（PTN）患者脑结构和功能连接（FC）改变。方法 对38例PTN患者（PTN组）和38名健康志愿者（对照组）行3.0T MR扫描。先以基于体素的形态学分析法计算PTN组相对对照组的灰质体积（GMV）改变，以存在形态学差异的脑区为ROI，采用静息态功能磁共振成像（rs-fMRI）检测组间FC强度差异。结果 PTN组多个脑区存在广泛GMV萎缩，包括扣带回前部（ACC）和中部、右侧岛叶（Ins）、右侧第二躯体感觉区（S2）、左侧初级运动皮质、左侧运动前区及双侧颞叶，且右侧Ins/S2与ACC、前额叶内侧部、扣带回后部及双侧前额叶背外侧部FC普遍增强，右侧Ins/S2和ACC的FC强度与疼痛程度呈负相关（r=-0.552，P<0.01）。结论 PTN患者脑内存在多维度结构和功能改变。右侧Ins/S2和ACC的FC增强可能作为评估PTN程度的较有效的影像学指标。     

Temporal summation of heat pain in humans: Evidence supporting thalamocortical modulation

Noxious cutaneous contact heat stimuli (48 °C) are perceived as increasingly painful when the stimulus duration is extended from 5 to 10 s, reflecting the temporal summation of central neuronal activity mediating heat pain. However, the sensation of increasing heat pain disappears, reaching a plateau as stimulus duration increases from 10 to 20 s. We used functional magnetic resonance imaging (fMRI) in 10 healthy subjects to determine if active central mechanisms could contribute to this psychophysical plateau. During heat pain durations ranging from 5 to 20 s, activation intensities in the bilateral orbitofrontal cortices and the activation volume in the left primary (S1) somatosensory cortex correlated only with perceived stimulus intensity and not with stimulus duration. Activation volumes increased with both stimulus duration and perceived intensity in the left lateral thalamus, posterior insula, inferior parietal cortex, and hippocampus. In contrast, during the psychophysical plateau, both the intensity and volume of thalamic and cortical activations in the right medial thalamus, right posterior insula, and left secondary (S2) somatosensory cortex continued to increase with stimulus duration but not with perceived stimulus intensity. Activation volumes in the left medial and right lateral thalamus, and the bilateral mid-anterior cingulate, left orbitofrontal, and right S2 cortices also increased only with stimulus duration. The increased activity of specific thalamic and cortical structures as stimulus duration, but not perceived intensity, increases is consistent with the recruitment of a thalamocortical mechanism that participates in the modulation of pain-related cortical responses and the temporal summation of heat pain.     

Altered Resting State Connectivity of the Insular Cortex in Individuals With Fibromyalgia

The insular cortex (IC) and cingulate cortex (CC) are critically involved in pain perception. Previously we demonstrated that fibromyalgia (FM) patients have greater connectivity between the insula and default mode network at rest, and that changes in the degree of this connectivity were associated with changes in the intensity of ongoing clinical pain. In this study we more thoroughly evaluated the degree of resting-state connectivity to multiple regions of the IC in individuals with FM and healthy controls. We also investigated the relationship between connectivity, experimental pain, and current clinical chronic pain. Functional connectivity was assessed using resting-state functional magnetic resonance imaging in 18 FM patients and 18 age- and sex-matched healthy controls using predefined seed regions in the anterior, middle, and posterior IC. FM patients exhibited greater connectivity between 1) right mid IC and right mid/posterior CC and right mid IC, 2) right posterior IC and left CC, and 3) right anterior IC and left superior temporal gyrus. Healthy controls displayed greater connectivity between left anterior IC and bilateral medial frontal gyrus/anterior cingulate cortex; and left posterior IC and right superior frontal gyrus. Within the FM group, greater connectivity between the IC and CC was associated with decreased pressure-pain thresholds.PerspectiveThese data provide further support for altered resting-state connectivity between the IC and other brain regions known to participate in pain perception/modulation, which may play a pathogenic role in conditions such as FM. We speculate that altered IC connectivity is associated with the experience of chronic pain in individuals with FM.     

Cerebral mechanisms of experimental hyperalgesia in fibromyalgia

The present study examined the hyperresponsiveness of the central nervous system in patients with fibromyalgia syndrome (FMS) related to mechanical hyperalgesia. The goals were to differentiate between increased pain ratings and hyperalgesia related either to peripheral or to central sensitization and to correlate with cerebral activation pattern. Seventeen patients and 17 healthy controls were examined, placing an experimental incision in the right volar forearm and causing tonic pain. Experimental pain, primary and secondary hyperalgesia were assessed during the time course of the experimental pain, and the changes in hyperalgesia were correlated to brain activation (functional magnetic resonance imaging). Patients with FMS experienced the experimental pain during the time course as more painful than healthy controls (F_score = 3.93, p_score = 0.008). While they did not present a different course of primary hyperalgesia (F_score = 1.01, p_score = 0.40), they did show greater secondary hyperalgesia (F_score = 5.45, p_score = 0.004). In patients with FMS, the cerebral pattern corresponding to secondary hyperalgesia was altered. The activity in the dorsolateral prefrontal cortex was inversely correlated with secondary hyperalgesia in healthy controls (R = ?0.34 p = 0.005); in patients, this correlation was disrupted (R = 0.19 p = 0.12). These findings point to an alteration of pain transmission at the central level in FMS (e.g., loss of inhibition) and might be related to changes in cerebral‐midbrain‐spinal mechanisms of pain inhibition.     

首发精神分裂症患者威斯康星卡片分类测验中的脑功能障碍研究

目的:探讨首发未服药精神分裂症患者进行威斯康星卡片分类测验(WCST)操作时的脑功能状态特点。方法:20名健康受试者(对照组)和20名首发未服药精神分裂症患者(患者组)操作WCST和颜色卡片分类测验(CCST)时进行脑功能磁共振成像(fMRI),比较2组激活脑区的激活体积。结果:对照组WCST和CCST功能图像相减获得的脑活动功能图像显示,激活主要分布在双侧前额叶,尤其是背外侧部以及顶叶后下部皮质和前扣带回。患者组WCST操作成绩较对照组差,有显著性差异(P<0.01)。与对照组相比,患者组的左侧前额叶背外侧部、左前扣带回皮质激活低下,左顶叶后下部皮质激活增加(P<0.01或0.05)。结论:双侧前额叶,尤其是背外侧部,以及顶叶后下部皮质和前扣带回皮质参与WCST操作的高级认知过程。精神分裂症患者在未治疗前就存在执行功能缺陷,其前额叶和扣带回功能低下,可能与患者执行功能障碍相关;后顶叶皮质功能亢进,可能对前额叶功能低下有补偿作用。     

An fMRI study of cerebral processing of brush-evoked allodynia in neuropathic pain patients

Previous human imaging studies have revealed a network of brain regions involved in the processing of allodynic pain; this includes prefrontal areas, insula, cingulate cortex, primary and secondary somatosensory cortices and parietal association areas. In this study, the neural correlates of the perceived intensity of allodynic pain in neuropathic pain patients were investigated. In eight patients, dynamic mechanical allodynia was provoked and brain responses recorded using functional magnetic resonance imaging (fMRI). Voxels in which the magnitude of fMRI signal correlated linearly with the ratings of allodynic pain across the group were determined in a whole brain analysis using a general linear model. To ensure that activation reflected only allodynic pain ratings, a nuisance variable containing ratings of ongoing pain was included in the analysis. We found that the magnitude of activation in the caudal anterior insula (cAI) correlates with the perceived intensity of allodynic pain across subjects, independent of the level of ongoing pain. However, the peak of activation in the allodynic condition was located in the rostral portion (rAI). This matches the representation of other clinical pain syndromes, confirmed by a literature review. In contrast, experimental pain in healthy volunteers resides predominantly in the cAI, as shown by the same literature review. Taken together, our data and the literature review suggest a functional segregation of anterior insular cortex.     

Gender differences in regional brain response to visceral pressure in IBS patients.

In two experiments including a total of 30 irritable bowel syndrome patients, symptom-mimicking rectal pressure stimuli elicited changes in regional neural activation as measured by positron electron tomography (PET) cerebral blood flow images. Although most stimuli were not rated as painful, rectal pressure increased regional cerebral blood flow (rCBF) in areas commonly associated with somatic pain, including the anterior cingulate, insula, prefrontal cortex, thalamus, and cerebellum. Despite similar stimulus ratings in male and female patients, regional activations were much stronger for males. In both experiments, rectal pressure activated the insula bilaterally in males but not in females. Insula activation was associated most strongly with objective visceral pressure, whereas anterior cingulate activation was associated more with correlated ratings of subjective discomfort. The insula is discussed as a visceral sensory cortex. Several possible reasons for the insula gender effect are proposed.