Cortical processing of noxious somatosensory stimuli in the persistent vegetative state

The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. We used positron emission tomography to assess the central processing of noxious somatosensory stimuli in the PVS. Changes in regional cerebral blood flow were measured during high-intensity electrical stimulation of the median nerve compared with rest in 15 nonsedated patients and in 15 healthy controls. Evoked potentials were recorded simultaneously. The stimuli were experienced as highly unpleasant to painful in controls. Brain glucose metabolism was also studied with [(18)F]fluorodeoxyglucose in resting conditions. In PVS patients, overall cerebral metabolism was 40% of normal values. Nevertheless, noxious somatosensory stimulation-activated midbrain, contralateral thalamus, and primary somatosensory cortex in each and every PVS patient, even in the absence of detectable cortical evoked potentials. Secondary somatosensory, bilateral insular, posterior parietal, and anterior cingulate cortices did not show activation in any patient. Moreover, in PVS patients, the activated primary somatosensory cortex was functionally disconnected from secondary somatosensory, bilateral posterior parietal, premotor, polysensory superior temporal, and prefrontal cortices. In conclusion, somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices.     

Altered central sensorimotor processing in patients with complex regional pain syndrome

Alterations in tactile sensitivity are common in patients with chronic pain. Recent brain imaging studies have indicated that brain areas activated by acute experimental pain partly overlap with areas processing innocuous tactile stimuli. However, the possible effect of chronic pain on central tactile processing has remained unclear. We have examined, both clinically and with whole-head magnetoencephalography, six patients suffering from complex regional pain syndrome (CRPS) of the upper limb. The cortical somatosensory responses were elicited by tactile stimuli applied to the fingertips and the reactivity of spontaneous brain oscillations was monitored as well. Tactile stimulation of the index finger elicited an initial activation at 65 ms in the contralateral SI cortex, followed by activation of the ipsi- and contralateral SII cortices at about 130 ms. The SI responses were 25-55% stronger to stimulation of the painful than the healthy side. The distance between SI representations of thumb and little finger was significantly shorter in the hemisphere contralateral than ipsilateral to the painful upper limb. In addition, reactivity of the 20-Hz motor cortex rhythm to tactile stimuli was altered in the CRPS patients, suggesting modified inhibition of the motor cortex. These results imply that chronic pain may alter central tactile and motor processing.     

Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study

Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory, motor and autonomic dysfunctions of still unknown origin. Pain and mechanical hyperalgesia are hallmarks of CRPS. There are several lines of evidence that central nervous system (CNS) changes are crucial for the development and maintenance of mechanical hyperalgesia. However, little is known about the cortical structures associated with the processing of hyperalgesia in pain patients. This study describes the use of functional magnetic resonance imaging (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS. Twelve patients, in whom previous quantitative sensory testing revealed the presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by von-Frey filaments at the affected limb. For control, the identical stimulation was performed on the unaffected limb. fMRI was used to explore the corresponding cortical activations. Mechanical stimulation at the unaffected limb was non-painful and mainly led to an activation of the contralateral primary somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia) and led to a significantly increased activation of the S1 cortex (contralateral), S2 (bilateral), insula (bilateral), associative-somatosensory cortices (contralateral), frontal cortices and parts of the anterior cingulate cortex. The results of our study indicate a complex cortical network activated during pin-prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not only involved in nociceptive, but also in cognitive and motor processing.     

植物状态,闭锁综合征和脑死亡的经颅多普勒超声检查

目的：比较植物状态（ＰＶＳ）、闭锁综合征和脑死亡患者脑血流的特点。方法：用经颅多普勒超声（ＴＣＤ）检测ＰＶＳ、闭锁综合征和脑死亡患者双侧大脑中动脉（ＭＣＡ）和基底动脉（ＢＡ）的血流情况。结果：持续植物状态ＭＣＡ和ＢＡ的平均血流速分别为２９．０ｃｍ／ｓ和２３．３ｃｍ／ｓ，较正常下降４７％和２２．３％。闭锁综合征ＭＣＡ和ＢＡ的平均血流速分别为４８．０ｃｍ／ｓ和１０．３ｃｍ／ｓ，分别较正常下降８．２％和６０．０％。提示ＰＶＳ的血流速减慢以前循环为主，而闭锁综合征的血流速减慢以后循环为主。脑死亡则为特殊的双向血流、收缩期短小尖波或无血流信号，与ＰＶＳ或闭锁综合征患者的ＴＣＤ完全不同。结论：根据前后循环血流速减慢的不同及特殊的脑血流频谱，ＴＣＤ能帮助医师鉴别上述三种临床上有时易混淆的状态     

Cortical Alpha Rhythms Are Related to the Anticipation of Sensorimotor Interaction Between Painful Stimuli and Movements: A High-Resolution EEG Study

We tested whether cortical activation anticipating painful stimuli is reduced more by integrative processes on somatosensory painful and motor information relative to the same hand than when that information refers to different hands. In 3 conditions, visual warning stimuli were followed by visual target stimuli associated with an electrical painful stimulation at left index finger. In the Pain (control) condition, no task was required after the target stimuli. In the “Pain + ipsilateral movement” condition, the subjects had to perform a movement of the left index finger. In the “Pain + contralateral movement” condition, they had to perform a movement of the right index finger. Meanwhile, electroencephalographic data were recorded (n = 18) from 128 scalp electrodes. Off line, these data were spatially enhanced by surface Laplacian transformation. Sensorimotor cortical activation before the painful stimulation was probed by the percentage power reduction of alpha rhythms at approximately 8 to 12 Hz (event-related desynchronization, ERD). Results showed that the subjects perceived a lower stimulus intensity in both “Pain + ipsilateral” and “Pain + contralateral” conditions compared with the control “Pain” condition. Furthermore, wide anticipatory alpha ERD (approximately 10–12 Hz) was lower in amplitude in the “Pain + ipsilateral” than in the “Pain + contralateral” condition. These results suggest that modulation of alpha rhythms is a putative physiological mechanism underlying anticipatory processes preceding the integration of painful and motor information at cortical level. Furthermore, these processes show a marked interference (“gating”) when the sensorimotor integration refer to the same hand as opposed to both hands.PerspectiveWe showed that cortical alpha rhythms preceding painful stimulation are influenced by the preparation of contralateral and ipsilateral finger movements. These results motivate further investigation for testing the hypothesis that chronic pain patients might exaggerate the anticipatory activation of sensorimotor cortex to negligible pain stimuli.     

The relation between catastrophizing and facial responsiveness to pain

Pain catastrophizing has recently been suggested to have a social function based on a positive association observed with facial responsiveness to noxious stimulation. However, this assumption is based on studies applying nociceptive stimuli of fixed intensity, such that high catastrophizers not only displayed increased pain behavior but also rated the stimulation as being more painful. The aim of this study was to investigate the relation between catastrophizing and facial responsiveness while controlling for individual differences in pain sensitivity. The facial expression of pain was investigated in 44 young and pain-free individuals in response to painful and non-painful phasic heat stimuli. Painful temperatures were tailored to the individual sensitivity to produce moderate pain. Facial responses were videotaped and objectively examined using the Facial Action Coding System. We also assessed skin conductance activity as an autonomic indicator of pain-related responses. Catastrophizing was assessed using the Pain Catastrophizing Scale (PCS). In accordance with previous findings, subjects scoring higher on pain catastrophizing required lower thermal intensities to induce a moderately painful sensation (r=-0.40, p=0.007). However, catastrophizing did not correlate with facial responsiveness to perceptually controlled painful stimulation (r=-0.02, p=0.88). Moreover, correlation analyses revealed no significant associations between catastrophizing and skin conductance responses. The present findings provide further support for the impact of pain catastophizing on pain sensitivity. However, our finding of no relation between catastrophizing and facial responsiveness when participants are experiencing comparable psychophysical pain intensities, challenges previous assumptions that high catastrophizers display amplified pain behavior; at least in young and pain-free individuals.     

脑外伤后持续性植物状态的研究现状

持续性植物状态 ( Persistent Vegetative State, PVS) 是指一种持续觉醒而无意识状态 , 目前各国间对 PVS的诊断标准尚未达到统一 . PVS以脑外伤最为多见 , 其主要病理表现为弥漫性轴索损害、脑皮层弥漫性坏死及选择性丘脑坏死 . 正电子发射型计算机断层显像是目前检查 PVS最有意义的方法 . PVS目前没有确切有效的治疗方法 , 脑外伤后 PVS较其他原因的 PVS预后好 .     

脑外伤后持续植物状态患者的促醒康复护理

对植物状态（ＰＶＳ）患者除了药物、运动康复手段外,还加强基础护理、营养调理、刺激性康复护理、家庭支持等,并对其苏醒程度和日常生活能力及时进行评估和记录。结果：１０ 例恢复意识,苏醒前后起ＡＤＬ评分均明显提高,８ 例生活基本能自理。在ＰＶＳ患者病情相对稳定时,预防并发症和保证患者足够营养是促醒康复的根本;有重点地进行刺激性康复护理,以改变大脑皮质的抑制状态;同时注重家庭参与是促醒康复的补充形式。根据患者的病情和家庭背景等情况探索一套适合ＰＶＳ的促醒康复护理,对其意识的恢复有着积极的临床指导意义。     

Speech motor program maintenance,but not switching,is enhanced by left-hemispheric deep brain stimulation in Parkinson's disease

Speech reaction time (SRT) was measured in a response priming protocol in 12 participants with Parkinson's disease (PD) and hypokinetic dysarthria “on” and “off” left-hemispheric deep brain stimulation (DBS). Speech preparation was measured during speech motor programming in two randomly ordered speech conditions: speech maintenance and switching. Double blind testing was completed in participants with DBS of globus pallidus pars interna (GPi) (n?=?5) or subthalamic nucleus (STN) (n?=?7). SRT was significantly faster in the maintenance vs switch task, regardless of DBS state. SRT was faster in the speech maintenance task “on” stimulation, while there was no difference in speech switching “on” and “off” DBS. These data suggest that left-hemispheric DBS may have differential effects on aspects of speech preparation in PD. It is hypothesized that speech maintenance improvements may result from DBS-induced cortical enhancements, while the lack of difference in switching may be related to inhibition deficits mediated by the right-hemisphere. Alternatively, DBS may have little influence on the higher level motor processes (i.e., motor planning) which it is believed the switch task engaged to a greater extent than the maintenance task.     

The antinociceptive effects of stimulating the pretectal nucleus of the rat

Changes in the tail-flick latency to noxious heat were studied following electrical stimulation of the dorso-medial thalamus of the rat. Brief (15 sec), low intensity (35 microA) stimulation of the anterior pretectal nucleus caused no escape behavior or motor deficits but increased tail-flick latency for more than 45 min. Responses to non-noxious stimuli were enhanced but the animals were not hyperactive. The anterior pretectal nucleus does not receive retinal or accessory visual inputs like other parts of the pretectal complex but is known to receive axons from somatosensory cortex and project to the perirubral mesencephalic reticular formation and the periaqueductal gray (PAG). The antinociceptive effects of anterior pretectal stimulation were much longer lasting than those of PAG, less disrupting to motor performance and the stimulation was not aversive.     

Touch or pain? Spatio-temporal patterns of cortical fMRI activity following brief mechanical stimuli

Most imaging studies on the human pain system have concentrated so far on the spatial distribution of pain-related activity. In the present study, we investigated similarities and differences between the spatial and temporal patterns of brain activity related to touch vs. pain perception. To this end, we adopted an event-related functional magnetic resonance imaging (fMRI) paradigm allowing us to separately assess the activity related to stimulus anticipation, perception, and coding. The fMRI signal increases following brief mechanical noxious or non-noxious stimulation of the hand dorsum were largely overlapping in the contralateral and ipsilateral hemispheres, including portions of the parietal, insular, frontal and cingulate cortices. Higher activity following noxious stimulation was found in the contralateral mid-anterior insular cortex, in the anterior mid-cingulate cortex (aMCC) and in the adjacent dorso-medial frontal cortex. Significant decreases in fMRI signals following both tactile and painful stimuli were found in perigenual cingulate (pACC)/medial prefrontal cortex (MPF) and in the posterior cingulate/precuneus/paracentral lobule; more intense decreases were found in the pACC/MPF following painful stimuli. fMRI signal increases in the contralateral insula and in aMCC, but not in the parietal cortex, were more prolonged following painful than tactile stimuli. Moreover, a second peak of signal increases (albeit of lower intensity) was found in anterior insula and aMCC during pain intensity rating. These results show specific spatio-temporal patterns of cortical activity related to processing noxious vs. non-noxious mechanical stimuli.     

Deep Brain Stimulation and Motor Cortical Stimulation for Neuropathic Pain

Deep brain stimulation (DBS) is an important treatment option for neuropathic pain. DBS has a considerable history, and it can be used successfully for a wide number of pain syndromes. Epidural motor cortex stimulation (MCS) also is a treatment option for neuropathic pain. Less invasive than DBS, MCS has been rapidly adopted and studied since first described in 1991. A growing body of literature supports the use of MCS for facial pain, though further study to better define the mechanism of action and the most appropriate patient populations is ongoing.     

Cognitive modulation of pain-related brain responses depends on behavioral strategy

Interactions of pain and cognition have been studied in humans and animals previously, but the relationship between such behavioral interactions and brain activity is unknown. We aimed to show using functional MRI (fMRI) how a cognitively demanding task (Stroop) modulates pain-related brain activations and conversely, how pain modulates attention-related activity. Reaction time data indicated two types of pain responders: subjects in the A group had a faster Stroop reaction time when pain was concomitant to the attention task, while those in the P group had a slower Stroop performance during painful stimulation. fMRI data obtained during Stroop performance with and without noxious stimulation were subjected to region of interest analyses. We first tested whether brain activity during painful median nerve stimulation was modulated by cognitive load. We next tested whether brain activity during the high conflict cognitive task was modulated by pain. Pain-related activity in three regions, primary (S1), and secondary (S2) somatosensory cortices, and anterior insula, was attenuated by cognitive engagement, but this effect was specific to the A group. Pain-related activations in the caudal and rostral anterior cingulate cortex (ACC) and ventroposterior thalamus were not modulated by cognitive load. None of the areas showing attention-related responses, including bilateral dorsolateral prefrontal and posterior parietal cortices, were modulated by pain. These findings suggest that cortical regions associated with pain can be modulated by cognitive strategies. Furthermore, the distinction of behavioral subgroups may relate to cognitive coping strategies taken by patients with chronic pain.     

HM-PAO-SPECT in persistent vegetative state after head injury: Prognostic indicator of the likelihood of recovery?

Management of patients presenting with traumatic persistent vegetative state (PVS) calls for extensive resources. The ability to predict whether or not a patient is likely to recover is a critical issue. In 12 patients with PVS admitted consecutively for early rehabilitation after head injury, pattern of brain activity was measured by^99mTc-hexamethyl-propylenamineoxime (^99mTc-HM-PAO) brain SPECT (single photon emission computer tomography). All patients were re-investigated after a mean observation period of 3 years. A global reduction of cortical blood flow was a reliable predictor of poor longterm outcome, but the demonstration of only focal deficits did not reliably indicate a favourable outcome. Brain SPECT may help to improve outcome prediction in patients with traumatic PVS.     

Cortical representation of experimental tooth pain in humans

Cortical processing of electrically induced pain from the tooth pulp was studied in healthy volunteers with fMRI. In a first experiment, cortical representation of tooth pain was compared with that of painful mechanical stimulation to the hand. The contralateral S1 cortex was activated during painful mechanical stimulation of the hand, whereas tooth pain lead to bilateral activation of S1. The S2 and insular region were bilaterally activated by both stimuli. In S2, the center of gravity of the activation during painful mechanical stimulation was more medial/posterior compared to tooth pain. In the insular region, tooth pain induced a stronger activation of the anterior and medial parts. The posterior part of the anterior cingulate gyrus was more strongly activated by painful stimulation of the hand. Differential activations were also found in motor and frontal areas including the orbital frontal cortex where tooth pain lead to greater activations. In a second experiment, we compared the effect of weak with strong tooth pain. A significantly greater activation by more painful tooth stimuli was found in most of those areas in which tooth pain had induced more activation than hand pain. In the medial frontal and right superior frontal gyri, we found an inverse relationship between pain intensity and BOLD contrast. We concluded that tooth pain activates a cortical network which is in several respects different from that activated by painful mechanical stimulation of the hand, not only in the somatotopically organized somatosensory areas but also in parts of the 'medial' pain projection system.     

颅脑损伤后持续植物状态的促醒康复治疗

目的探讨颅脑损伤后持续性植物状态患者的促醒康复方法。方法27例持续性植物状态患者分为不同年龄段,均采用药物、声光电刺激及运动训练等综合康复治疗2~5个月。按持续性植物状态评分标准进行疗效评定。结果患者的病程与年龄段与康复疗效有关,10~30岁年龄段及发病3个月内的治疗效果最显著。结论系统地综合康复治疗可明显提高持续性植物状态患者的促醒率,且年龄愈小发病时间越短,康复效果愈好,大部分植物状态患者有康复的可能性。     

高频rTMS、脑仿生电及其序贯治疗脑外伤持续植物状态患者的临床观察

目的:观察高频重复经颅磁刺激(rTMS)、脑仿生电刺激及其序贯治疗脑外伤持续植物状态(PVS)患者的临床疗效.方法:入组的脑外伤PVS患者予常规药物及康复治疗,并随机分为3组:rTMS组(24例),予高频rT-MS治疗;脑仿生电组(23例),予脑仿生电治疗;rTMS与脑仿生电联合组(简称联合组,26例),先高频rTMS...     

Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease

The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson's disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off-medication condition with the stimulator turned on or off (on- and off-stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age-matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P=.019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off-stimulation condition. In the on-stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber-mediated sensations.     

Functional topography of the secondary somatosensory cortex for nonpainful and painful stimulation of median and tibial nerve: an fMRI study

Functional magnetic resonance imaging (fMRI) was used to study the cortical activity of the bilateral secondary somatosensory cortex (SII) during nonpainful (motor threshold) and painful electrical stimulation of median and tibial nerves. fMRI recordings were performed in eight normal young adults. The aim was at evaluating the working hypothesis of a spatial segregation of nonpainful and painful populations not only in the "hand" representation of SII [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for nonpainful and painful stimuli: an fMRI study. NeuroImage 20, 1625-1638.] but also in its "foot" representation. Results showed that, in both "hand" and "foot" representations of bilateral SII, the activity elicited by the painful stimulation was localized more posteriorly with respect to that elicited by the nonpainful stimulation. A fine spatial analysis of the SII responses revealed a clear somatotopic organization in the bilateral SII subregion especially reactive to the nonpainful stimuli (i.e., segregation of the hand and foot representations). In contrast, it was not possible to disentangle the "hand" and "foot" representations of SII for painful stimuli. These results extended to the SII "foot" representation previous evidence of a spatial segregation in the SII "hand" representation of subregions for the painful and nonpainful stimuli. Furthermore, they suggest that noxious information is not somatotopically represented in human bilateral SII, at least as inferred from fMRI data at 1.5 T.     

Brain stimulation in the treatment of chronic neuropathic and non-cancerous pain

Chronic neuropathic pain is one of the most prevalent and debilitating disorders. Conventional medical management, however, remains frustrating for both patients and clinicians owing to poor specificity of pharmacotherapy, delayed onset of analgesia and extensive side effects. Neuromodulation presents as a promising alternative, or at least an adjunct, as it is more specific in inducing analgesia without associated risks of pharmacotherapy. Here, we discuss common clinical and investigational methods of neuromodulation. Compared to clinical spinal cord stimulation (SCS), investigational techniques of cerebral neuromodulation, both invasive (deep brain stimulation [DBS] and motor cortical stimulation [MCS]) and noninvasive (repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]), may be more advantageous. By adaptively targeting the multidimensional experience of pain, subtended by integrative pain circuitry in the brain, including somatosensory and thalamocortical, limbic and cognitive, cerebral methods may modulate the sensory-discriminative, affective-emotional and evaluative-cognitive spheres of the pain neuromatrix. Despite promise, the current state of results alludes to the possibility that cerebral neuromodulation has thus far not been effective in producing analgesia as intended in patients with chronic pain disorders. These techniques, thus, remain investigational and off-label. We discuss issues implicated in inadequate efficacy, variability of responsiveness, and poor retention of benefit, while recommending design and conceptual refinements for future trials of cerebral neuromodulation in management of chronic neuropathic pain. PERSPECTIVE: This critical review focuses on factors contributing to poor therapeutic utility of invasive and noninvasive brain stimulation in the treatment of chronic neuropathic and pain of noncancerous origin. Through key clinical trial design and conceptual refinements, retention and consistency of response may be improved, potentially facilitating the widespread clinical applicability of such approaches.