Neural Mechanisms of Antinociceptive Effects of Hypnosis

Background: The neural mechanisms underlying the modulation of pain perception by hypnosis remain obscure. In this study, we used positron emission tomography in 11 healthy volunteers to identify the brain areas in which hypnosis modulates cerebral responses to a noxious stimulus.

Methods: The protocol used a factorial design with two factors: state (hypnotic state, resting state, mental imagery) and stimulation (warm non-noxious vs. hot noxious stimuli applied to right thenar eminence). Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. After each scan, the subject was asked to rate pain sensation and unpleasantness. Statistical parametric mapping was used to determine the main effects of noxious stimulation and hypnotic state as well as state-by-stimulation interactions (i.e., brain areas that would be more or less activated in hypnosis than in control conditions, under noxious stimulation).

Results: Hypnosis decreased both pain sensation and the unpleasantness of noxious stimuli. Noxious stimulation caused an increase in regional cerebral blood flow in the thalamic nuclei and anterior cingulate and insular cortices. The hypnotic state induced a significant activation of a right-sided extrastriate area and the anterior cingulate cortex. The interaction analysis showed that the activity in the anterior (mid-)cingulate cortex was related to pain perception and unpleasantness differently in the hypnotic state than in control situations.     

Clinical hypnosis modulates functional magnetic resonance imaging signal intensities and pain perception in a thermal stimulation paradigm

OBJECTIVE: This study was designed to describe regional changes in blood oxygenation level dependent signals in functional magnetic resonance images (fMRI) elicited by thermal pain in hypnotized subjects. These signals approximately identify the neural correlates of the applied stimulation to identify neuroanatomic structures involved in the putative effects of clinical hypnosis on pain perception. METHODS: After determination of the heat pain threshold of 12 healthy volunteers, fMRI scans were performed at 1.5 Tesla by using echoplanar imaging technique during repeated painful heat stimuli. Activation of brain regions in response to thermal pain during hypnosis (using a fixation and command technique of hypnosis) was compared with responses without hypnosis. RESULTS: With hypnosis, less activation in the primary sensory cortex, the middle cingulate gyrus, precuneus, and the visual cortex was found. An increased activation was seen in the anterior basal ganglia and the left anterior cingulate cortex. There was no difference in activation within the right anterior cingulate gyrus in our fMRI studies. No activation was seen within the brainstem and thalamus under either condition. CONCLUSION: Our observations indicate that clinical hypnosis may prevent nociceptive inputs from reaching the higher cortical structures responsible for pain perception. Whether the effects of hypnosis can be explained by increased activation of the left anterior cingulate cortex and the basal ganglia as part of a possible inhibitory pathway on pain perception remains speculative given the limitations of our study design.     

Imaging human cerebral pain modulation by dose-dependent opioid analgesia: a positron emission tomography activation study using remifentanil

BACKGROUND: Previous imaging studies have demonstrated a number of cortical and subcortical brain structures to be activated during noxious stimulation and infusion of narcotic analgesics. This study used O-water and positron emission tomography to investigate dose-dependent effects of the short-acting mu-selective opioid agonist remifentanil on regional cerebral blood flow during experimentally induced painful heat stimulation in healthy male volunteers. METHODS: Positron emission tomography measurements were performed with injection of 7 mCi O-water during nonpainful heat and painful heat stimulation of the volar forearm. Three experimental conditions were used during both sensory stimuli: saline, 0.05 microg x kg x min remifentanil, and 0.15 microg x kg x min remifentanil. Cardiovascular and respiratory parameters were monitored noninvasively. Across the three conditions, dose-dependent effects of remifentanil on regional cerebral blood flow were analyzed on a pixel-wise basis using a statistical parametric mapping approach. RESULTS: During saline infusion, regional cerebral blood flow increased in response to noxious thermal stimulation in a number of brain regions as previously reported. There was a reduction in pain-related activations with increasing doses of remifentanil in the thalamus, insula, and anterior and posterior cingulate cortex. Increasing activation occurred in the cingulofrontal cortex (including the perigenual anterior cingulate cortex) and the periaqueductal gray. CONCLUSIONS: Remifentanil induced regional cerebral blood flow increases in the cingulofrontal cortex and periaqueductal gray during pain stimulation, indicating that mu-opioidergic activation modulates activity in pain inhibitory circuitries. This provides direct evidence that opioidergic analgesia is mediated by activation of established descending antinociceptive pathways.     

Pain Attenuation through Mindfulness is Associated with Decreased Cognitive Control and Increased Sensory Processing in the Brain

Pain can be modulated by several cognitive techniques, typically involving increased cognitive control and decreased sensory processing. Recently, it has been demonstrated that pain can also be attenuated by mindfulness. Here, we investigate the underlying brain mechanisms by which the state of mindfulness reduces pain. Mindfulness practitioners and controls received unpleasant electric stimuli in the functional magnetic resonance imaging scanner during a mindfulness and a control condition. Mindfulness practitioners, but not controls, were able to reduce pain unpleasantness by 22% and anticipatory anxiety by 29% during a mindful state. In the brain, this reduction was associated with decreased activation in the lateral prefrontal cortex and increased activation in the right posterior insula during stimulation and increased rostral anterior cingulate cortex activation during the anticipation of pain. These findings reveal a unique mechanism of pain modulation, comprising increased sensory processing and decreased cognitive control, and are in sharp contrast to established pain modulation mechanisms.     

Imaging pain modulation by subanesthetic S-(+)-ketamine

Little is known about the effects of low-dose S-(+)-ketamine on the cerebral processing of pain. We investigated the effects of subanesthetic IV S-(+)-ketamine doses on the perception of experimental painful heat stimuli. Healthy volunteers were evaluated with functional magnetic resonance imaging (fMRI) while receiving the painful stimuli in conjunction with placebo and increasing doses (0.05, 0.1, 0.15 mg x kg(-1) x h(-1)) of ketamine infusion. Vital variables were monitored and all subjects rated pain intensity and unpleasantness on a numerical rating scale. Alterations in consciousness were measured using a psycho-behavioral questionnaire. Pain unpleasantness declined as ketamine dosage was increased (55.1% decrease, placebo versus 0.15 mg x kg(-1) x h(-1) ketamine). Pain intensity ratings also decreased with increasing ketamine dosage but to a lesser extent (23.1% decrease). During placebo administration, a typical pain activation network (thalamus, insula, cingulate, and prefrontal cortex) was found, whereas decreased pain perception with ketamine was associated with a dose-dependent reduction of pain-induced cerebral activations. Analysis of the dose-dependent ketamine effects on pain processing showed a decreasing activation of the secondary somatosensory cortex (S2), insula and anterior cingulate cortex. This part of the anterior cingulate cortex (midcingulate cortex) has been linked with the affective pain component that underlines the potency of ketamine in modulating affective pain processing.     

Imaging Human Cerebral Pain Modulation by Dose-dependent Opioid Analgesia: A Positron Emission Tomography Activation Study Using Remifentanil

Background: Previous imaging studies have demonstrated a number of cortical and subcortical brain structures to be activated during noxious stimulation and infusion of narcotic analgesics. This study used 15O-water and positron emission tomography to investigate dose-dependent effects of the short-acting [mu]-selective opioid agonist remifentanil on regional cerebral blood flow during experimentally induced painful heat stimulation in healthy male volunteers.

Methods: Positron emission tomography measurements were performed with injection of 7 mCi 15O-water during nonpainful heat and painful heat stimulation of the volar forearm. Three experimental conditions were used during both sensory stimuli: saline, 0.05 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil, and 0.15 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil. Cardiovascular and respiratory parameters were monitored noninvasively. Across the three conditions, dose-dependent effects of remifentanil on regional cerebral blood flow were analyzed on a pixel-wise basis using a statistical parametric mapping approach.

Results: During saline infusion, regional cerebral blood flow increased in response to noxious thermal stimulation in a number of brain regions as previously reported. There was a reduction in pain-related activations with increasing doses of remifentanil in the thalamus, insula, and anterior and posterior cingulate cortex. Increasing activation occurred in the cingulofrontal cortex (including the perigenual anterior cingulate cortex) and the periaqueductal gray.     

The contribution of neuroimaging techniques to the understanding of supraspinal pain circuits: implications for orofacial pain.

The aim of this article was to give an overview of the current knowledge of supraspinal pain mechanisms derived from neuroimaging studies, and to present data related to chronic orofacial pain disorders. The available studies implied that the anterior cingulate cortex plays a role in the emotional-affective component of pain, as well as in pain-related attention and anxiety. The somatosensory cortices may be involved in encoding spatial, temporal, and intensity aspects of noxious input. The insula may mediate both affective and sensory-discriminative aspects of the pain experience. The thalamus appears to be a multifunctional relay system. The prefrontal cortex has been implied in the pain-related attention processing; it does not have intensity encoding properties. Chronic pain conditions were associated with increased activity in the somatosensory cortices, anterior cingulate cortex, and the prefrontal cortex, and with decreased activity in the thalamus. Few neuroimaging studies used experimental stimuli to the trigeminal system or included orofacial pain patients. However, the available studies appeared to be in agreement with those using stimuli to other body parts and those concerning other chronic pain conditions. Overall, the available data suggest that chronic (orofacial) pain states may be related to a dysfunctional brain network and may involve a compromised descending inhibitory control system. The somatosensory cortices, anterior cingulate cortex, thalamus, and prefrontal cortex may play a vital role in the pathophysiology of chronic pain and should be the main focus of future neuroimaging studies in chronic pain patients.     

The anatomy of pain

Pain is a sensory and emotional experience that is personal and unique to an individual. Nociception is different from pain and considers the neural process of encoding and processing noxious stimuli. Anatomically noxious stimuli are transduced by nociceptors to an electrical signal carried by first-order neurons to the dorsal horn of the spinal cord. From the spinal cord second-order neurons project in tracts to the thalamus, where third-order neurons continue to higher cerebral centres. There is no known primary pain processing centre in the brain, instead multiple different areas activate and interact in response to noxious stimuli. The brain centres associated with pain perception overlap with those involved in depression. The brain regulates the nociceptive information it receives and can exert both anti- and pro-nociceptive influence. Pathology in the peripheral and central nervous systems can contribute to nociception and pain, as can changes in the interaction of higher cerebral centres. Appreciating the anatomical structures involved in pain and nociception affords an understanding of where different therapies may be applied to alleviate pain.     

Functional neuroimaging of gastric distention

This study aimed to measure brain activation during gastric distention as a way to investigate short-term satiety. We estimated regional cerebral blood flow with positron emission tomography (¹⁵O-water) during gastric balloon inflation and deflation in 18 healthy young women. The contrast between inflated minus deflated conditions showed activation in the following four key regions that were identified a priori: dorsal brain stem; left inferior frontal gyrus; bilateral insula; and right subgenual, anterior cingulate cortex. Extant neuroimaging literature provides context for these areas as follows: the brain stem represents vagal projection zones for visceral afferent processing; the inferior frontal gyrus serves as a convergence zone for processing food-related stimuli; and both the insula and subgenual anterior cingulate cortex respond to emotional stimulation. The identification of neural correlates of gastric distention is a key step in the discovery of new treatments for obesity. New therapies could intervene by modifying the perception of gastric distention, an important contributor to meal termination and short-term satiety. This first study of brain activation during nonpainful, proximal gastric distention provides the groundwork for future research to discover novel treatments for obesity. Presented in part at the annual meeting of the Minnesota Surgical Society, Minneapolis, Minnesota, April 19, 2002. Supported by the Mark A. Nugent Foundation, NIDDK (5P30 DK50456-08) and ORWH (R01-DK52291), NARSAD, and the Department of Veterans Affairs.     

Interactions of pain intensity and cognitive load: the brain stays on task

Pain naturally draws one's attention. However, humans are capable of engaging in cognitive tasks while in pain, although it is not known how the brain represents these processes concurrently. There is some evidence for a cortical interaction between pain- and cognitive-related brain activity, but the outcome of this interaction may depend on the relative load imposed by the pain versus the task. Therefore, we used 3 levels of cognitive load (multisource interference task) and 2 levels of pain intensity (median nerve stimulation) to examine how functional magnetic resonance imaging activity in regions identified as pain-related or cognitive-related responds to different combinations of pain intensity and cognitive load. Overall, most pain-related or cognitive-related brain areas showed robust responses with little modulation. However, during the more intense pain, activity in primary sensorimotor cortex, secondary somatosensory cortex/posterior insula, anterior insula, paracentral lobule, caudal anterior cingulate cortex, cerebellum, and supplementary motor area was modestly attenuated by the easy task and in some cases the difficult task. Conversely, cognitive-related activity was not modulated by pain, except when cognitive load was minimal during the control task. These findings support the notion that brain networks supporting pain perception and cognition can be simultaneously active.     

Dissociable brain activation responses to 5-Hz electrical pain stimulation: a high-field functional magnetic resonance imaging study

BACKGROUND: To elucidate neural correlates associated with processing of tonic aching pain, the authors used high-field (3-T) functional magnetic resonance imaging with a blocked parametric study design and characterized regional brain responses to electrical stimulation according to stimulus intensity-response functions. METHODS: Pain was induced in six male volunteers using a 5-Hz electrical stimulus applied to the right index finger. Scanning sequences involved different levels of stimulation corresponding to tingling sensation (P1), mild pain (P2), or high pain (P3). Common effects across subjects were sought using a conjunction analyses approach, as implemented in statistical parametric mapping (SPM-99). RESULTS: The contralateral posterior/mid insula and contralateral primary somatosensory cortex were most associated with encoding stimulus intensity because they showed a positive linear relation between blood oxygenation level-dependent signal responses and increasing stimulation intensity (P1 < P2 < P3). The contralateral secondary somatosensory cortex demonstrated a response function most consistent with a role in pain intensity encoding because it had no significant response during the innocuous condition (P1) but proportionally increased activity with increasingly painful stimulus intensities (0 < P2 < P3). Finally, a portion of the anterior cingulate cortex (area 24) and supplementary motor area 6 demonstrated a high pain-specific response (P3). CONCLUSIONS: The use of response function modeling, conjunction analysis, and high-field imaging reveals dissociable regional responses to a tonic aching electrical pain. Most specifically, the primary somatosensory cortex and insula seem to encode stimulus intensity information, whereas the secondary somatosensory cortex encodes pain intensity information. The cingulate findings are consistent with its proposed role in processing affective-motivational aspects of pain.     

Neural mechanisms underlying deafferentation pain: a hypothesis from a neuroimaging perspective

Deafferentation pain following nerve injury annoys patients, and its management is a challenge in clinical practice. Although the mechanisms underlying deafferentation pain remain poorly understood, progress in the development of multidimensional neuroimaging techniques is casting some light on these issues. Deafferentation pain likely results from reorganization of the nervous system after nerve injury via processes that interact with the substrates for pain perception (the pain matrix). Therapeutic effects of motor cortex stimulation on deafferentation pain suggest that the core mechanisms underlying deafferentation pain also interact with the motor system. Therefore, simultaneous neuroimaging and brain stimulation, an emerging neuroimaging technique, was developed to investigate complicated interactions among motor, somatosensory, and pain systems. In healthy participants, parts of the pain matrix (the anterior cingulate cortex, parietal operculum, and thalamus) show activity during both somatosensory stimulation and brain stimulation to the motor cortex. This finding indicates that motor, somatosensory, and pain systems communicate among each other via the neural network. A better understanding of the plastic mechanisms influencing such cross-talk among these systems will help develop therapeutic interventions using brain stimulation and neurofeedback.     

Isoflurane depresses electroencephalographic and medial thalamic responses to noxious stimulation via an indirect spinal action

Anesthetics such as isoflurane act in the spinal cord to suppress movement in response to noxious stimulation. Spinal anesthesia decreases hypnotic/sedative requirements, possibly by decreasing afferent transmission of stimuli. We hypothesized that isoflurane action in the spinal cord would similarly depress the ascending transmission of noxious input to the thalamus and cerebral cortex. In six isoflurane-anesthetized goats, we measured electroencephalographic (EEG) and thalamic single-unit responses to a clamp applied to the forelimb. Cranial bypass permitted differential isoflurane delivery to the torso and cranial circulations. When the cranial-torso isoflurane combination was 1.3% +/- 0.2%-1.0% +/- 0.4% the noxious stimulus did not evoke significant changes in the EEG or thalamic activity: 389 (153-544) to 581 (172-726) impulses/min, (median, 25th-75th percentile range, P: > 0.05). When the cranial-torso isoflurane combination was 1.3% +/- 0.2%-0.3% +/- 0.2%, noxious stimulation increased thalamic activity: 804 (366-1162) to 1124 (766-1865) impulses/min (P: < 0.05), and the EEG "desynchronized": total EEG power decreased from 25 +/- 20 microV(2) to 12 +/- 8 microV(2) (P: < 0.05). When the cranial-torso isoflurane was 1.7% +/- 0.1%-0.3% +/- 0.2%, the noxious stimulus did not significantly affect thalamic: 576 (187-738) to 1031 (340-1442) impulses/min (P: > 0.05), or EEG activity. The indirect torso effect of isoflurane on evoked EEG total power (12.6 +/- 2.7 microV(2)/vol%, mean +/- SE) was quantitatively similar to the direct cranial effect (17.7 +/- 3.0 microV(2)/vol%; P: > 0.05). These data suggest that isoflurane acts in the spinal cord to blunt the transmission of noxious inputs to the thalamus and cerebral cortex, and thus might indirectly contribute to anesthetic endpoints such as amnesia and unconsciousness. Implications: Isoflurane action in the spinal cord diminished the transmission of noxious input to the brain. Because memory and consciousness are likely dependent on the "arousal" state of the brain, this indirect action of isoflurane could contribute to anesthetic-induced amnesia and unconsciousness.     

功能磁共振成像和正电子发射断层摄影技术在麻醉学研究中的应用

背景 功能影像学的发展,特别是功能磁共振成像(functional magnetic resonance imaging,fMRI)和正电子发射断层摄影技术(positron emission tomography,PET)的不断发展,为我们在全麻药物作用机制及疼痛等的研究中提供了新的技术方法.目的 现就近年来这两种技...     

功能磁共振成像和正电子发射断层摄影技术在麻醉学研究中的应用

背景 功能影像学的发展,特别是功能磁共振成像(functional magnetic resonance imaging,fMRI)和正电子发射断层摄影技术(positron emission tomography,PET)的不断发展,为我们在全麻药物作用机制及疼痛等的研究中提供了新的技术方法.目的 现就近年来这两种技术在麻醉学研究中的主要应用作一综述.内容 研究发现,全麻药可使丘脑等区神经元活性降低,扣带前回和岛叶等区神经元活性增强.对大脑受体系统的研究,证实了大脑的GABAA受体参与介导全麻药在人体内发挥作用的机制.对疼痛的研究表明,阿片类镇痛药能使痛觉感受相关区域活性降低,同时使参与痛觉调节相关区域活性增强.趋向 功能影像学技术的逐渐成熟和广泛应用必定会促使麻醉学研究不断前进和发展.     

Dose-dependent Effects of Propofol on the Central Processing of Thermal Pain

Background: Anatomic and physiologic data show that multiple regions of the forebrain are activated by pain. However, the effect of anesthetic level on nociceptive input to these regions is not well understood.

Methods: The authors used positron emission tomography to measure the effect of various concentrations of propofol on pain-evoked changes in regional cerebral blood flow. Fifteen volunteers were scanned while warm and painful heat stimuli were presented to the volar forearm using a contact thermode during administration of target propofol concentrations of 0.0 [mu]g/ml (alert control), 0.5 [mu]g/ml (mild sedation), 1.5 [mu]g/ml (moderate sedation), and 3.5 [mu]g/ml (unconsciousness).

Results: During the 0.5-[mu]g/ml target propofol concentration (mild sedation), the subjects' pain ratings increased relative to the alert control condition; correspondingly, pain-evoked regional cerebral blood flow increased in the thalamus and the anterior cingulate cortex. In contrast, when subjects lost consciousness (3.5 [mu]g/ml), pain-evoked responses in the thalamus and the anterior cingulate cortex were no longer observed, whereas significant pain-evoked activation remained in the insular cortex.     

Inner experience of pain: imagination of pain while viewing images showing painful events forms subjective pain representation in human brain

Pain is an unpleasant sensation, and at the same time, it is always subjective and affective. Ten healthy subjects viewed 3 counterbalanced blocks of images from the International Affective Picture System: images showing painful events and those evoking emotions of fear and rest. They were instructed to imagine pain in their own body while viewing each image showing a painful event (the imagination of pain). Using functional magnetic resonance imaging, we compared cerebral hemodynamic responses during the imagination of pain with those to emotions of fear and rest. The results show that the imagination of pain is associated with increased activity in several brain regions involved in the pain-related neural network, notably the anterior cingulate cortex (ACC), right anterior insula, cerebellum, posterior parietal cortex, and secondary somatosensory cortex region, whereas increased activity in the ACC and amygdala is associated with the viewing of images evoking fear. Our results indicate that the imagination of pain even without physical injury engages the cortical representations of the pain-related neural network more specifically than emotions of fear and rest; it also engages the common representation (i.e., in ACC) between the imagination of pain and the emotion of fear.     

An fMRI version of the Farnsworth-Munsell 100-Hue test reveals multiple color-selective areas in human ventral occipitotemporal cortex.

Studies of patients with cerebral achromatopsia have suggested that ventral occipitotemporal cortex is important for color perception. We created a functional magnetic resonance imaging (fMRI) version of a clinical test commonly used to assess achromatopsia, the Farnsworth-Munsell 100-Hue test. The test required normal subjects to use color information in the visual stimulus to perform a color sequencing task. A modification of the test requiring ordering by luminance was used as a control task. Subjects were also imaged as they passively viewed colored stimuli. A limited number of areas responded more to chromatic than achromatic stimulation, including primary visual cortex. Most color-selective activity was concentrated in ventral occipitotemporal cortex. Several areas in ventral cortex were identified. The most posterior, located in posterior fusiform gyrus, corresponded to the area activated by passive viewing of colored stimuli. More anterior and medial color-selective areas were located in the collateral sulcus and fusiform gyrus. These more anterior areas were not identified in previous imaging studies which used passive viewing of colored stimuli, and were most active in our study when visual color information was behaviorally relevant, suggesting that attention influences activity in color-selective areas. The fMRI version of the Farnsworth-Munsell test may be useful in the study of achromatopsia.     

Dissociable Brain Activation Responses to 5-Hz Electrical Pain Stimulation: A High-field Functional Magnetic Resonance Imaging Study

Background: To elucidate neural correlates associated with processing of tonic aching pain, the authors used high-field (3-T) functional magnetic resonance imaging with a blocked parametric study design and characterized regional brain responses to electrical stimulation according to stimulus intensity-response functions.

Methods: Pain was induced in six male volunteers using a 5-Hz electrical stimulus applied to the right index finger. Scanning sequences involved different levels of stimulation corresponding to tingling sensation (P1), mild pain (P2), or high pain (P3). Common effects across subjects were sought using a conjunction analyses approach, as implemented in statistical parametric mapping (SPM-99).

Results: The contralateral posterior/mid insula and contralateral primary somatosensory cortex were most associated with encoding stimulus intensity because they showed a positive linear relation between blood oxygenation level-dependent signal responses and increasing stimulation intensity (P1 < P2 < P3). The contralateral secondary somatosensory cortex demonstrated a response function most consistent with a role in pain intensity encoding because it had no significant response during the innocuous condition (P1) but proportionally increased activity with increasingly painful stimulus intensities (0 < P2 < P3). Finally, a portion of the anterior cingulate cortex (area 24) and supplementary motor area 6 demonstrated a high pain-specific response (P3).     

Functional magnetic resonance imaging studies of pain: an investigation of signal decay during and across sessions

BACKGROUND: Several investigations into brain activation caused by pain have suggested that the multiple painful stimulations used in typical block designs may cause attenuation over time of the signal within activated areas. The effect this may have on pain investigations using multiple tasks has not been investigated. The signal decay across a task of four repeating pain stimulations and between two serial pain tasks separated by a 4-min interval was examined to determine whether signal attenuation may significantly confound pain investigations. METHODS: The characteristics of the brain activation of six subjects were determined using whole brain blood oxygenation level-dependent functional magnetic resonance imaging on a 1.5-T scanner. Tasks included both tingling and pain induced by transcutaneous electrical stimulation of the median nerve. The average group maps were analyzed by general linear modeling with corrected cluster P values of less than 0.05. The time courses of individual voxels were further investigated by analysis of variance with P values of less than 0.05. RESULTS: Significant differences between pain and tingling were found in the ipsilateral cerebellum, contralateral thalamus, secondary somatosensory cortex, primary somatosensory cortex, and anterior cingulate cortex. Highly significant signal decay was found to exist across each single pain task, but the signal was found to be restored after a 4-min rest period. CONCLUSIONS: This work shows that serial pain tasks can be used for functional magnetic resonance imaging studies using electrical nerve stimulation as a stimulus, as long as sufficient time is allowed between the two tasks.