ABSTRACT
BACKGROUND: Although patients with chronic pain show behavioral signs of impaired endogenous pain modulation, responsible cerebral networks have yet to be anatomically delineated. We used diffusion tensor imaging (DTI) to examine the white-matter alterations in patients with chronic pain compared with healthy subjects. We further measured thermal pain modulatory responses using the offset analgesia (OA) paradigm. We tested whether the white-matter indices be associated with psychophysical parameters reflecting morbidity and modulatory responses of pain in patients, and whether they could serve as diagnostic biomarkers of chronic pain. METHODS: Twenty-six patients with chronic pain and 18 age- and gender-matched healthy controls were enrolled. After completing psychophysical questionnaires, they underwent OA measurement and whole-brain DTI in a 3 Tesla magnetic resonance imaging scanner. Fractional anisotropy (FA) and radial diffusivity (RD) of the white-matter were computed and compared between the groups with tract-based spatial statistics using the FMRIB Software Library (FSL) software. Correlations were sought among white-matter indices, thermal pain responses, and psychophysical parameters. The white-matter indices and OA-related parameters were tested whether they distinguish patients from controls by receiver operating characteristic analysis. RESULTS: During OA, patients showed a shorter latency to the maximum (maximum visual analog scale [VAS] latency, 16.0 ± 3.7 vs 18.9 ± 3.1 second [mean ± standard deviation, SD]; P = .032) but a longer latency to the minimum pain (OA latency, 15.6 ± 3.5 vs 11.1 ± 4.2 seconds; P = .004) than controls. They showed a smaller mean FA (0.44 ± 0.12 vs 0.45 ± 0.11; P = .012) and a larger mean RD of the global white-matter (0.00057 ± 0.00002 vs 0.00056 ± 0.00002; P = .038) than controls, at specific areas including the corpus callosum, anterior thalamic radiation, and forceps major. FA of the splenium of the corpus callosum was associated with maximum VAS latency (r = 0.493) and OA latency (r = -0.552). The Pain Catastrophizing Scale scores showed strong negative correlations with FA across those specific areas (r = -0.405). Those latencies during OA and white-matter metrics distinguished patients from controls (P < .05). CONCLUSIONS: Patients with chronic pain showed dysfunction of the white matter concerned with interhemispheric communication of sensorimotor information as well as descending corticothalamic modulation of pain in association with affective morbidity and altered temporal dynamics of pain perception. We suggest that an impaired interhemispheric modulation of pain, through the corpus callosum, might be a novel cerebral mechanism in chronification of pain.
ABSTRACT
Background Offset analgesia is a disproportionate decrease of pain perception following a slight decrease of noxious thermal stimulus and attenuated in patients with neuropathic pain. We examined offset analgesia in patients with heterogeneous chronic pain disorders and used functional magnetic resonance imaging to explore modification of cerebral analgesic responses in comparison with healthy controls. Results We recruited seventeen patients with chronic pain and seventeen age-, sex-matched healthy controls. We gave a noxious thermal stimulation paradigm including offset analgesia and control stimuli on the left volar forearm, while we obtained a real-time continuous pain rating and a whole-brain functional magnetic resonance imaging. Baseline, first plateau (5 s), increment (5 s), and second plateau (20 s) temperatures of offset analgesia stimulus were set at 32°C, 46°C, 47°C, and 46°C, respectively. Control stimulus included 30-s 46°C stimulus or only the first 10 s of offset analgesia stimulus. We evaluated magnitude of offset analgesia, analyzed cerebral activation by thermal stimulation, and further compared offset analgesia-related activation between the groups. Magnitude of offset analgesia was larger in controls than in patients (median: 28.9% (interquartile range: 11.0-56.0%) vs. 19.0% (4.2-48.7%), p = 0.047). During the second plateau, controls showed a larger blood oxygenation level-dependent activation than patients at the putamen, anterior cingulate, dorsolateral prefrontal cortices, nucleus accumbens, brainstem, and medial prefrontal cortex ( p < 0.05), which are known to mediate either of descending pain modulation or reward responses. Offset analgesia-related activity at the anterior cingulate cortex was negatively correlated with neuropathic component of pain in patients with chronic pain ( p = 0.004). Conclusions Attenuation of offset analgesia was associated with suppressed activation of the descending pain modulatory and reward systems in patients with chronic pain, at least in the studied cohort. The present findings might implicate both behavioral and cerebral plastic alterations contributing to chronification of pain. Clinical trial registry: The Japanese clinical trials registry (UMIN-CTR, No. UMIN000011253; http://www.umin.ac.jp/ctr /).
Subject(s)
Analgesia , Chronic Pain/drug therapy , Reward , Adult , Aged , Brain Mapping , Chronic Pain/psychology , Demography , Female , Humans , Male , Middle Aged , Oxygen/blood , Temperature , Time Factors , Young AdultABSTRACT
One feels a disproportionately large decrease of pain sensation on a slight decrease of thermal pain stimulus. Such phenomenon is termed offset analgesia and considered mediated by endogenous analgesic mechanisms. Offset analgesia was found attenuated in patients with neuropathic pain. We further found that such attenuation occurred in a more heterogeneous population of patients with chronic pain. By functional magnetic resonance imaging, we also found negative blood oxygenation level-dependent signals at those areas concerned with descending pain modulatory and reward systems during offset analgesia in the same cohort of patients. We propose that dysfunction of those systems, as revealed by attenuation of offset analgesia, might well be part of neural mechanisms of pain chronification.
Subject(s)
Analgesia , Chronic Pain/physiopathology , Nervous System/physiopathology , Humans , Magnetic Resonance Imaging , Pain MeasurementABSTRACT
PURPOSE: Although cerebral structural and functional changes were uncovered by neuroimaging in patients with chronic low back pain (CLBP), their associations remain to be clarified. We co-analyzed anatomical and functional magnetic resonance imaging data in those patients and tested whether cortical gray matter volume changes are associated with altered pain modulatory networks underlying chronification of pain. METHODS: In 16 patients with CLBP and 16 heathy controls, we performed functional magnetic resonance imaging during mechanical pain stimulation on the lower back followed by anatomical imaging. We performed voxel-based morphometry and functional connectivity analysis from the seeds with altered gray matter volume, and examined correlations between imaging and psychophysical parameters. RESULTS: Patients showed decreases in gray matter volume at the right dorsolateral prefrontal cortex, middle occipital gyrus, and cerebellum, and showed increases at the bilateral primary sensorimotor cortices, left fusiform gyrus, and right cerebellum compared with controls (P < 0.001). Dorsolateral prefrontal and fusiform volumes showed negative associations with affective comorbidity, whereas motor cortex volume with impaired daily activity (P < 0.05). Connectivity was decreased between the cerebellar and limbic, and increased between the bilateral sensorimotor regions (PFDR < 0.05). Higher pain intensity and unpleasantness correlated with enhanced bilateral sensorimotor and dorsolateral-medial prefrontal networks, respectively (P < 0.05). CONCLUSION: Patients showed a decreased volume of cortical center for descending pain modulation and an increased volume of sensorimotor network, in association with suppressed descending pain modulatory and cerebellum-limbic networks and enhanced sensorimotor network during pain. Such structural and functional alterations might be part of cerebral pathophysiology of CLBP.
Subject(s)
Low Back Pain/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Case-Control Studies , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Inadvertently, the Fig. 7 was published incorrectly in the original publication of the article. The correct figure should be as below.
ABSTRACT
PURPOSE: A considerable portion of chronic low back pain (cLBP) patients lack anatomical abnormality, resist conventional therapeutic interventions, and their symptoms are often complicated with psychological and social factors. Such patients have been reported to show cerebral abnormalities both in anatomy and function by neuroimaging studies. Here we examined differences in cerebral reactivity to a simulated low back pain stimulus between cLBP patients and healthy controls by functional magnetic resonance imaging (fMRI), and their behavioral correlates from a psychophysical questionnaire. METHODS: Eleven cLBP patients and 13 healthy subjects (HS) were enrolled in this study. After psychophysical evaluation on-going pain with McGill Pain Questionnaire Short Form (MPQ), they underwent whole-brain fMRI in a 3-Tesla MRI scanner while receiving three blocks of 30-s mechanical pain stimuli at the left low back with a 30-s rest in between, followed by a three-dimensional anatomical imaging. Functional images were analyzed with a multi-subject general linear model for blood oxygenation level-dependent (BOLD) signal changes associated with pain. Individual BOLD signal amplitudes at activated clusters were examined for correlation with psychophysical variables. Two in the cLBP and five data sets in the HS groups were excluded from analysis because of deficient or artifactual data or mismatch in age. RESULTS: The HS group showed LBP-related activation at the right insular cortex, right dorsolateral prefrontal cortex (DLPFC), left anterior cingulate cortex (ACC), and left precuneus; and deactivation in a large area over the parietal and occipital cortices, including the bilateral superior parietal cortex. On the other hand, the cLBP group did not show any significant activation at those cortical areas, but showed similar deactivation at the bilateral superior parietal cortex and part of the premotor area. An HS > cLBP contrast revealed significantly less activity at the ACC and DLPFC in the cLBP group, which was negatively correlated with higher MPQ scores. CONCLUSIONS: The cLBP patients showed attenuated reactivity to pain at the ACC and DLPFC, known cortical areas mediating affective component, and top-down modulation, of pain. The present results might be associated with possible dysfunction of the descending pain inhibitory system in patients with chronic low back pain, which might possibly play a role in chronification of pain.
Subject(s)
Low Back Pain/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Aged , Case-Control Studies , Cerebral Cortex , Female , Humans , Male , Middle Aged , Pain Measurement/methods , Surveys and QuestionnairesABSTRACT
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal cardiovascular disease if left untreated. In patients with IPAH with psychiatric illness or other complications, careful attention is required when administering medical therapies that may affect their hemodynamics. Patients suffering from IPAH who undergo anesthesia and surgery have a high mortality and morbidity rate. We describe the treatment of intractable psychiatric symptoms with electroconvulsive therapy (ECT) in a patient with IPAH. CASE PRESENTATION: A 23-year-old woman with IPAH and type I diabetes mellitus (DM) presented with malignant catatonia. Her heart function was classified as New York Heart Association (NYHA) class III. She required a rapid cure and ECT due to various psychiatric symptoms resistant to conventional medications. Pulmonary hypertensive (PH) crisis is the most concerning complication that can be induced by the sympathetic stimulation of ECT. To avoid PH crisis, we administered oxygen using a laryngeal mask and administered remifentanil for anesthesia. We also prepared standby nitric oxide for possible PH crisis, although it was ultimately not needed. With 14 ECT sessions, her malignant catatonia was ameliorated without physical complications. CONCLUSION: ECT is an acceptable option for the treatment of medication-refractory psychiatric disturbances in patients with IPAH, provided careful management is assured to prevent or address complications.
Subject(s)
Catatonia/therapy , Electroconvulsive Therapy/methods , Familial Primary Pulmonary Hypertension/therapy , Catatonia/complications , Familial Primary Pulmonary Hypertension/complications , Female , Humans , Young AdultSubject(s)
Low Back Pain , Brain , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , NeuropathologyABSTRACT
Much evidence has been accumulated on the cerebral mechanisms of pain perception owing to rapid and diverse development in magnetic resonance imaging and its analysis techniques over the last decades. In addition to pain-evoked cerebral activities, our knowledge now extends into chronic pain-associated alterations in cerebral connectivity over networks and in gray matter density, which characterize cerebral steady-state pathological properties underlying chronic pain conditions. A dynamic cerebral model for chronification of pain is presented, in which a bottom-up nociception via the lateral system leads to a reactive, top-down hyperactivity of the medial system, and eventually to both functional and anatomical degeneration of pain modulatory mechanisms and reward systems. All such biomarkers of "chronic pain brain" revealed by neuroimaging will hopefully help us in diagnosis of chronic pain and evaluation of therapeutics for each patient on an outpatient basis.
Subject(s)
Brain/pathology , Chronic Pain/diagnosis , Magnetic Resonance Imaging/methods , HumansABSTRACT
Recent advancement in functional brain imaging techniques has revealed much of the global effects of general anesthetics on the human brain. General anesthetics preferentially suppress specific brain areas including the parietal association cortex and the thalamus, part of which appears to mirror the default mode network. Low-level sensory areas are relatively preserved and remain activated even under deep sedation by anesthetics. Functional connectivity analysis by resting-state functional magnetic resonance imaging has shown that general anesthetics moderately suppress functional connectivity of the default mode network. Midazolam-induced loss of consciousness is associated with remarkable suppression of cortico-cortical propagation of evoked currents. Overall, those results prompt us to hypothesize that general anesthetics induce loss of consciousness by disrupting the integrative properties of the cerebral cortex.
Subject(s)
Anesthesia, General , Brain/physiology , Diagnostic Imaging , Anesthetics, General/pharmacology , Brain/metabolism , Cerebral Cortex/physiology , Cerebrovascular Circulation/drug effects , Humans , Pain/physiopathologyABSTRACT
Functional neuroimaging techniques have revealed the cerebral substrates of pain perception (pain matrix) in humans, which include the thalamus, as well as primary, secondary somatosensory, insular, anterior cingulate, and prefrontal cortices. Functional magnetic resonance imaging (fMRI) could be the most suitable candidate for routine clinical use in the evaluation of pain because of its relatively low cost and the absence of irradiation. Here the author summarizes the practical aspects of fMRI studies on pain, and proposes the "bottom-up/top-down theory" of cerebral pain processing that explains possible interaction among discrete parts of pain matrix. Long-term, plastic changes induced by such interaction could play a pivotal role in the exaggerated brain activity of chronic pain patients. The top-down component of pain matrix also explains basic neuroimaging findings on the anticipation, empathy, and placebo effects of pain, and on the cortical trigger of the descending pain inhibitory system. Finally, the author summarizes his recent research on the cerebral substrates of chronic low back pain, and shows a case study on neuropathic pain using fMRI, which hopefully should help in planning clinical fMRI studies for a longitudinal follow-up of chronic pain patients.
Subject(s)
Magnetic Resonance Imaging , Pain/diagnosis , HumansABSTRACT
A 70-year-old woman, who had neither complication nor risk factors of ischemic heart disease, was scheduled for a partial resection of the left lung. After an epidural catheter was placed at the T7-8 interspace, general anesthesia was induced and maintained with propofol and fentanyl. Once stable vital signs had been confirmed, 3 ml of 0.5% ropivacaine was given through the epidural catheter. Bradycardia with hypotension progressively developed and continued despite the intravenous administration of phenylephrine, ephedrine, and atropine. Fourteen minutes after the injection of ropivacaine, the electrocardiogram showed an elevation of the ST segment. One minute later, the heart rhythm changed to a 2:1-type second degree block. Although a bolus of 1 mg epinephrine was injected intravenously, severe hypotension and bradycardia persisted, leading to the complete block and paroxysmal ventricular tachycardia. Continuous infusion of nitroglycerin as well as cardiopulmonary resuscitation was started. The sinus rhythm with normal ST segment was eventually restored with subsequent hemodynamic stability. Intraoperative transesophageal echocardiography indicated a satisfactory cardiac wall motion. Coronary spasm was suspected because of the transient ST segment elevation and the absence of wall motion abnormality after the recovery. The clinical course of the A-V block appearing shortly after ST segment elevation suggested that the right coronary artery, perfusing the A-V node areas, was involved.
Subject(s)
Anesthesia, Epidural , Anesthesia, General , Coronary Vasospasm/etiology , Intraoperative Complications/etiology , Pneumonectomy , Aged , Coronary Vasospasm/diagnosis , Coronary Vasospasm/therapy , Echocardiography, Transesophageal , Electrocardiography , Female , Heart Block/diagnosis , Heart Block/etiology , Humans , Intraoperative Complications/diagnosis , Intraoperative Complications/therapy , Lung Neoplasms/secondary , Lung Neoplasms/surgeryABSTRACT
Offset analgesia (OA) represents a disproportionately large decrease of pain perception after a brief, temporary increment of thermal pain stimulus and was reported attenuated in patients with neuropathic pain. We examined whether OA depends on the increment duration before offset, and whether individual features of OA distinguish patients with chronic pain and healthy controls. We used a Peltier-type thermal stimulator and OA paradigms including 5-, 10-, or 15-s duration of 1°C-increment (T2) over 45°C. We first examined OA response, on the left volar forearm, at 3 different T2's in 40 healthy volunteers, and OA and constant stimulus responses in 12 patients with chronic pain and 12 matched healthy controls. We measured magnitude of OA ([INCREMENT]OA) and maximum visual analogue scale (VAS) latency (time to peak VAS) during constant stimulus for each individual. Pain perception kinetics were compared with analysis of variance and sought for correlations with psychophysical parameters with a significance threshold at P < 0.05. In healthy controls, longer T2 at 10 or 15 seconds resulted in larger [INCREMENT]OA compared with T2 at 5 seconds (P = 0.04). In patients, [INCREMENT]OA was significantly smaller than controls at T2 = 5 or 10 seconds (P < 0.05) but grew comparable at T2 = 15 seconds with controls. Maximum VAS latency was longer in patients than in controls and negatively correlated with [INCREMENT]OA in patients. An OA index ([INCREMENT]OA/[maximum VAS latency]) proved diagnostic of chronic pain with an area under the receiver operating characteristic curve at 0.897. Patients with chronic pain showed impairment of OA and reduced temporal sharpening of pain perception, which might imply possible disturbance of the endogenous pain modulatory system.
Subject(s)
Analgesia/methods , Chronic Pain/drug therapy , Pain Perception/physiology , Adult , Aged , Female , Humans , Hypesthesia/physiopathology , Male , Middle Aged , Pain Measurement , Pain Perception/drug effects , Physical Stimulation , Psychophysics , ROC Curve , Reaction Time/drug effects , Reaction Time/physiology , Young AdultABSTRACT
STUDY DESIGN: A cross-sectional study. OBJECTIVE: The aim of this study was to evaluate activity of the nucleus accumbens (NAc) in response to lumbar mechanical stimulation in patients with chronic low back pain (cLBP) using functional magnetic resonance imaging (fMRI). SUMMARY OF BACKGROUND DATA: Although a modified activity of the NAc was characterized in cLBP patients, its pathological significance has yet to be determined. We hypothesized that NAc activation in response to pain might differ depending on the extent of psychiatric problems, which might be associated with the affective/motivational background of chronic pain. METHODS: Twenty-one patients with cLBP (four men, 17 women) were recruited. Subjects were divided into two groups on the basis of scores on the patient version of the Brief Scale for Psychiatric problems in Orthopaedic Patients (BS-POP) scores: ≥17 (High Score, HiS group) and <17 (non-High Score, non-HiS group). Each subject was placed in the prone position on a 3-Tesla magnetic resonance imaging (MRI) scanner and stimulated by mechanical stimulation on the left lower back. Three blocks of 30-second pain stimulus calibrated at either 3 or 5 on an 11-grade numerical rating scale (NRS) were applied with intervening 30-second rest conditions during whole-brain echo-planar imaging. Functional images were analyzed using a multisubject general linear model with Bonferroni multiple comparisons. RESULTS: Subjects in the HiS group had more intense daily pain and lower quality of life than those in the non-HiS group (Pâ<â0.05). Catastrophic thinking in relation to pain experience did not differ between the groups. Activation at the NAc was smaller in the HiS group than in the non-HiS group (Pâ<â0.001). CONCLUSION: The presence of psychiatric problems was associated with attenuated activity of the NAc in cLBP patients. Dysfunction of the NAc might potentially be involved in the affective/motivational factors in the chronification of LBP. LEVEL OF EVIDENCE: N/A.
Subject(s)
Chronic Pain/diagnostic imaging , Low Back Pain/diagnostic imaging , Mental Health , Nucleus Accumbens/diagnostic imaging , Quality of Life/psychology , Adult , Catastrophization/diagnostic imaging , Catastrophization/physiopathology , Catastrophization/psychology , Chronic Pain/physiopathology , Chronic Pain/psychology , Cross-Sectional Studies , Echo-Planar Imaging , Female , Health Surveys , Humans , Low Back Pain/physiopathology , Low Back Pain/psychology , Magnetic Resonance Imaging , Male , Middle Aged , Nucleus Accumbens/physiopathology , Pain Measurement , Severity of Illness Index , Young AdultABSTRACT
We report anesthetic management of a 5-year-old girl for corpus callosotomy indicated for the treatment of intractable epilepsy. The procedure mandated intraoperative monitoring of evoked potentials and electrocorticogram. During the first half of the surgery until the corpus callosum was exposed, anesthesia was maintained with continuous infusion of propofol. Motor and somatosensory evoked potentials were monitored and diagnosed as intact throughout the procedure, with no epileptic activity observed in 32-lead electrocorticogram. Then propofol infusion was replaced with the inhalation of sevoflurane, 2.0% in air/oxygen mixture, which induced epileptic spike-and-wave activities, synchronized between the hemispheres, in electrocorticogram. After the completion of corpus callosotomy, we observed interhemispheric desynchronization of epileptic activities indicating successful surgical intervention. The patient emerged from anesthesia uneventfully with no neurological deficits, and thereafter with decreased incidence of generalized epileptic episodes. We suggest that such switch of anesthetic agents between propofol and sevoflurane should be helpful in intraoperative electrophysiological monitoring for ascertaining both functional preservation and successful intervention during epileptic surgery.
Subject(s)
Anesthesia/methods , Corpus Callosum/surgery , Epilepsy/surgery , Methyl Ethers , Monitoring, Intraoperative/methods , Propofol , Anesthetics, Combined , Cerebral Cortex , Child, Preschool , Electrophysiology , Evoked Potentials, Motor , Evoked Potentials, Somatosensory , Female , Humans , SevofluraneSubject(s)
Anesthesia, General/mortality , Awareness/drug effects , Consciousness Monitors , Electroencephalography/instrumentation , Hypnotics and Sedatives/administration & dosage , Monitoring, Intraoperative/instrumentation , Anesthesia, General/adverse effects , Humans , Hypnotics and Sedatives/adverse effects , Monitoring, Intraoperative/methods , Myocardial Infarction/etiology , Myocardial Infarction/mortality , Risk Assessment , Risk Factors , Signal Processing, Computer-Assisted , Stroke/etiology , Stroke/mortality , Time FactorsABSTRACT
Difficult Airway Management (DAM) is one of the most important skills for medical practice, especially for anesthesiologists. A seminar of DAM was held in the 51 st annual meeting of Japan Society of Anesthesiologists. It consisted of a 60-minute lecture about ASA difficult airway management algorithm, and a 120-minute hands-on training session using a mid-fidelity human simulator. The lecture was held twice, and was opened to every JSA member without pre-registration. More than 100 participants attended each lecture. The hands-on training session, which required preregistration, was held three times. Each training session was limited to 8 participants, and a total of 23 participants attended the session. The training session was restricted to only participants and staffs so that their privacy was secured. The questionnaire about DAM was collected after the lectures or the training sessions. Most of the participants of lectures were certified anesthesiologists, and they agreed that the DAM seminar was useful. The questionnaire revealed that the most popular technique for DAM was insertion of laryngeal mask airway (ILMA). Otherwise the invasive techniques were difficult to be experienced in the clinical practice. We suspected that the DAM seminar was useful, especially for the invasive technique without substitute training methods under clinical situation.
Subject(s)
Anesthesiology/education , Education, Medical, Continuing/methods , Respiratory Physiological Phenomena , Airway Obstruction/therapyABSTRACT
To evaluate the effect of combined intravenous administration of the calcium antagonists, nicardipine and diltiazem, on the circulatory responses to tracheal intubation, the mean arterial pressure (MAP) and rate pressure product (RPP) in response to laryngoscopy following tracheal intubation were compared in patients receiving saline placebo or nicardipine 10 µg·kg-1 and diltiazem 0.1 mg·kg-1 60 s before the initiation of laryngoscopy. Each group was comprised of ten patients undergoing elective surgery. The patients receiving saline showed a significant increase in MAP and RPP associated with tracheal intubation. However, these increases were significantly attenuated (P<0.05) in the patients to whom nicardipine and diltiazem were administered concurrently.