Thermal stimulus task fMRI in the cervical spinal cord at 7 Tesla.

Although functional magnetic resonance imaging (fMRI) is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0 . Increasing field strength enables higher spatial resolution and improved sensitivity to blood oxygenation level-dependent (BOLD) signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D echo-planar imaging (EPI) protocols, which differ in sensitivity to spatial and temporal B0 inhomogeneity. The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. All protocols used 3 mm slice thickness. For each protocol, the BOLD response to 13 10-s noxious thermal stimuli applied to the right thumb was acquired in a 10-min fMRI run. Image quality, temporal signal to noise ratio (SNR), and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment. PRACTITIONER POINTS: First stimulus task fMRI results in the spinal cord at 7 T. Single-shot 0.75 mm 2D EPI produced the highest mean z-statistic. Multi-shot 0.60 mm 2D EPI provided the best-localized activation and least distortion.

The dual facilitatory and inhibitory effects of social pain on physical pain perception.

Pain is a multi-dimensional phenomenon that encompasses both physical pain experienced physiologically and social pain experienced emotionally. The interactions between them are thought to lead to increased pain load. However, the effect of social pain on physical pain perception during interactions remains unclear. Four experiments were conducted merging physical and social pains to examine the behavioral pattern and neural mechanism of the effect of social pain on physical pain perception. Seemingly paradoxical effects of social pain were observed, which both facilitated and inhibited physical pain perception under different attention orientations. Brain imaging revealed that the posterior insula encoded the facilitatory effect, whereas the frontal pole engaged in the inhibitory effect. At a higher level, the thalamus further modulated both processes, playing a switch-like role under different concern statuses of social pain. These results provide direct evidence for the dual-pathway mechanism of the effect of social pain on physical pain.

Enhanced neural synchrony associated with long-term ballroom dance training.

Long-term dance training offers numerous benefits, including improvements in physical health, posture, body coordination, and mental health and well-being. Since dance is an art form of body-to-body communication, professional dancers may share feelings and thoughts on dance with their partners, owing to their shared training experiences. Considering this perspective, one may expect that professional dancers would demonstrate pronounced neural similarities when viewing dancing videos, which could be associated with their training duration. To test these hypotheses, we collected functional magnetic resonance imaging (fMRI) data while presenting ballroom dancing and neutral video clips with long durations (∼100 s each) to 41 professional ballroom dancers (19 pairs of dance partners) and 39 age- and sex-matched nondancers. Our findings revealed that dancers exhibited broader and stronger neural similarities across the whole brain when watching dancing video clips, as compared to the control group. These increased neural similarities could be interpreted in at least two distinct ways. First, neural similarities in certain brain regions within the motor control circuit (i.e., frontal cortical-basal ganglia-thalamic circuit) were significantly correlated with dance-related information (e.g., dance partners' cooperation duration), which reinforced the impact of long-term dance training on neural synchronization. Second, neural similarities in other brain regions (e.g., memory-related brain regions) were significantly correlated with subjects' impression of the viewed videos (i.e., whether they have watched before, familiarity, and liking), which may not necessarily be directly linked to long-term dance training. Altogether, our study provided solid evidence for synchronized neural mechanisms in professional dancers due to long-term dance training.

Thermal Stimulus Task fMRI in the Cervical Spinal Cord at 7 Tesla.

PURPOSE: Although functional MRI is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0. Increasing field strength enables higher spatial resolution and improved sensitivity to BOLD signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first stimulus task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D EPI protocols, as they differ in sensitivity to spatial and temporal B0 inhomogeneity. METHODS: The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. For each protocol, the BOLD response to thirteen 10-second noxious thermal stimuli applied to the right thumb was acquired in a 10-minute fMRI run. Image quality, temporal SNR, and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. RESULTS: Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. CONCLUSION: Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment.

Stigmatized experience is associated with exacerbated pain perception in depressed patients.

Patients with depression not only have to cope with depressive and physical symptoms but also face stigmatization due to mental illness. Pain is a clinical symptom of many patients with depression. However, it is unclear whether stigmatized experience associated with mental illness directly affects depressed patients' pain perception. Here, using the event reflection task, Study 1 (N = 95) examined whether stigmatized experiences due to depression would affect patients' self-reported pain assessment. Study 2 (N = 43) further employed thermal stimuli at different intensities to examine whether stigmatization would affect patients' evoked pain. We found that patients with depression who experienced stigmatization based on mental illness reported higher pain catastrophizing and performed increased pain perception for noxious stimuli than those who did not. Our studies provide first-hand experimental evidence of the effect of stigmatized experiences on depressed patients' pain perception. The findings contribute insights for improving clinical treatment, suggesting that interventions should minimize stigmatization associated with mental illness to help patients maintain healthier physical and psychological states.

The association between ballroom dance training and empathic concern: Behavioral and brain evidence.

Dance is unique in that it is a sport and an art simultaneously. Beyond improving sensorimotor functions, dance training could benefit high-level emotional and cognitive functions. Duo dances also confer the possibility for dancers to develop the abilities to recognize, understand, and share the thoughts and feelings of their dance partners during the long-term dance training. To test this possibility, we collected high-resolution structural and resting-state functional magnetic resonance imaging (MRI) data from 43 expert-level ballroom dancers (a model of long-term exposure to duo dance training) and 40 age-matched and sex-matched nondancers, and measured their empathic ability using a self-report trait empathy scale. We found that ballroom dancers showed higher scores of empathic concern (EC) than controls. The EC scores were positively correlated with years with dance partners but negatively correlated with the number of dance partners for ballroom dancers. These behavioral results were supported by the structural and functional MRI data. Structurally, we observed that the gray matter volumes in the subgenual anterior cingulate cortex (ACC) and EC scores were positively correlated. Functionally, the connectivity between ACC and occipital gyrus was positively correlated with both EC scores and years with dance partners. In addition, the relationship between years with dance partners and EC scores was indirect-only mediated by the ACC-occipital gyrus functional connectivity. Therefore, our findings provided solid evidence for the close link between long-term ballroom dance training and empathy, which deepens our understanding of the neural mechanisms underlying this phenomenon.

Sex difference in trait empathy is encoded in the human anterior insula.

Females are considered the more empathic sex. This conventional view, however, has been challenged in the past few decades with mixed findings. These heterogeneous findings could be caused by the fact that empathy is a complex and multifaceted construct. To clarify whether sex differences exist in certain dimensions of empathy and whether they are associated with specific neural bases, this study measured trait empathy using the interpersonal reactivity index (IRI) and collected brain structural and functional magnetic resonance imaging data in a large sample of healthy participants (206 males vs. 302 females). We found that females scored higher in the personal distress (PD) subscale than males, but they were comparable to males in other IRI subscales. Sex difference in PD was encoded by brain structural (e.g. gray matter volume in left anterior insula [AI]) and functional (e.g. resting-state functional connectivity between left AI and temporoparietal junction/inferior frontal gyrus) characteristics. Notably, the relationship between sex and PD was indirect-only and serially mediated by AI-associated structural and functional characteristics. Altogether, our results suggested that sex difference existed in self-oriented affective empathy (i.e. PD) and highlighted the importance of the AI, both structurally and functionally, in mediating the sex difference in trait empathy.

Selective and replicable neuroimaging-based indicators of pain discriminability.

Neural indicators of pain discriminability have far-reaching theoretical and clinical implications but have been largely overlooked previously. Here, to directly identify the neural basis of pain discriminability, we apply signal detection theory to three EEG (Datasets 1-3, total N = 366) and two fMRI (Datasets 4-5, total N = 399) datasets where participants receive transient stimuli of four sensory modalities (pain, touch, audition, and vision) and two intensities (high and low) and report perceptual ratings. Datasets 1 and 4 are used for exploration and others for validation. We find that most pain-evoked EEG and fMRI brain responses robustly encode pain discriminability, which is well replicated in validation datasets. The neural indicators are also pain selective since they cannot track tactile, auditory, or visual discriminability, even though perceptual ratings and sensory discriminability are well matched between modalities. Overall, we provide compelling evidence that pain-evoked brain responses can serve as replicable and selective neural indicators of pain discriminability.

Neurological mechanism and treatment effects prediction of acupuncture on migraine without aura: Study protocol for a randomized controlled trial.

Introduction: Acupuncture is an effective treatment in migraine without aura (MWoA), but the neurological mechanism has not been investigated using multimodal magnetic resonance imaging (MRI). This trial will combine functional MRI, structural MRI, and diffusion tensor imaging to explore the potential neural mechanism of acupuncture on MWoA, and will use machine learning approach to predict acupuncture treatment effects. Methods: In this multimodal neuroimaging randomized controlled trial, a total of 60 MWoA participants will be randomly allocated to two groups: the real acupuncture treatment group and the sham acupuncture control group. This trial will include a 4-week baseline phase, a 4-week treatment phase, and a 12-week follow-up phase. Participants will undergo 12 acupuncture or sham acupuncture sessions during the treatment phase. The Headache Diary, Migraine-Specific Quality of Life Questionnaire, Headache Impact Test, Beck Depression Inventory-II, and Beck Anxiety Inventory will be utilized to evaluate the clinical efficacy. Multimodal MRI scans will be employed to investigate the mechanism of acupuncture at baseline, at the end of treatment, and after follow-up. Multimodal MRI data will be used to predict acupuncture treatment effects using machine learning technology. Discussion: This study hypothesized that acupuncture therapy may treat MWoA by restoring the neuropathological alterations in brain activity. Our finding should provide valuable scientific proof for the effects of acupuncture and demonstrate the usefulness of acupuncture in the treatment of MWoA. Moreover, acupuncture response prediction might decrease healthcare expenses and time lags for patients. Trial registration number: [ChiCTR2100044251].

Changes in brain connectivity linked to multisensory processing of pain modulation in migraine with acupuncture treatment.

Migraine without aura (MWoA) is a major neurological disorder with unsatisfactory adherence to current medications. Acupuncture has emerged as a promising method for treating MWoA. However, the brain mechanism underlying acupuncture is yet unclear. The present study aimed to examine the effects of acupuncture in regulating brain connectivity of the key regions in pain modulation. In this study, MWoA patients were recruited and randomly assigned to 4 weeks of real or sham acupuncture. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. A modern neuroimaging literature meta-analysis of 515 fMRI studies was conducted to identify pain modulation-related key regions as regions of interest (ROIs). Seed-to-voxel resting state-functional connectivity (rsFC) method and repeated-measures two-way analysis of variance were conducted to determine the interaction effects between the two groups and time (baseline and post-treatment). The changes in rsFC were evaluated between baseline and post-treatment in real and sham acupuncture groups, respectively. Clinical data at baseline and post-treatment were also recorded in order to determine between-group differences in clinical outcomes as well as correlations between rsFC changes and clinical effects. 40 subjects were involved in the final analysis. The current study demonstrated significant improvement in real acupuncture vs sham acupuncture on headache severity (monthly migraine days), headache impact (6-item Headache Impact Test), and health-related quality of life (Migraine-Specific Quality of Life Questionnaire). Five pain modulation-related key regions, including the right amygdala (AMYG), left insula (INS), left medial orbital superior frontal gyrus (PFCventmed), left middle occipital gyrus (MOG), and right middle cingulate cortex (MCC), were selected based on the meta-analysis on brain imaging studies. This study found that 1) after acupuncture treatment, migraine patients of the real acupuncture group showed significantly enhanced connectivity in the right AMYG/MCC-left MTG and the right MCC-right superior temporal gyrus (STG) compared to that of the sham acupuncture group; 2) negative correlations were established between clinical effects and increased rsFC in the right AMYG/MCC-left MTG; 3) baseline right AMYG-left MTG rsFC predicts monthly migraine days reduction after treatment. The current results suggested that acupuncture may concurrently regulate the rsFC of two pain modulation regions in the AMYG and MCC. MTG and STG may be the key nodes linked to multisensory processing of pain modulation in migraine with acupuncture treatment. These findings highlighted the potential of acupuncture for migraine management and the mechanisms underlying the modulation effects.

The analgesic effect of nostalgia elicited by idiographic and nomothetic approaches on thermal stimulus.

Nostalgia is shown to relieve an individual's perception of pain evoked by cold water, pressure, and thermal stimuli. However, there is no direct evidence to show the analgesic effects of different nostalgia-inducing methods on various stimulus intensities. We conducted two studies to examine the analgesic effect, at different pain intensities, after inducing nostalgia either idiographically or nomothetically. Study 1 (N = 118) induced nostalgia through an idiographic approach (i.e., event reflection task) and found that nostalgia relieved both high and low thermal pain. Study 2 (N = 66) induced nostalgia through a nomothetic approach (i.e., viewing nostalgic pictures) and found that nostalgia relieved low but not high thermal pain. The findings verify the analgesic effect of nostalgia on thermal pain and suggest the potential moderating role of the nostalgia induction approach and pain intensity. Practically, these findings have implications for using nostalgia as a nonpharmacological treatment for pain.

Relapsing antibody-negative patients with features of neuromyelitis optica spectrum disorders: Differences in N-acetylaspartate level in the cervical spinal cord indicate distinct underlying processes.

BACKGROUND: Due to lack of biomarkers, antibody-negative patients with features of neuromyelitis optica spectrum disorders (NMOSD) are among the most challenging to diagnose and treat. Using unsupervised clustering, we recently identified 'MS-like', 'spinal MS-like', 'classic NMOSD-like' and 'NMOSD-like with brain involvement' subgroups in this cohort. OBJECTIVE: We used magnetic resonance spectroscopy (MRS) to examine differences in the level of key metabolites in the spinal cord between the four identified subgroups. METHODS: Twenty-five relapsing antibody-negative patients with NMOSD features classified by the unsupervised algorithm to one of the subgroups underwent a prospective cervical spinal cord MRS. Spectra from 16 patients fulfilled quality criteria and were included in the analysis. RESULTS: Total N-acetylaspartate (tNAA), but not total choline (tCho) or myo-inositol (Ins), was significantly different between the four subgroups (p = 0.03). In particular, tNAA was 47.8% lower in the 'MS-like' subgroup as compared with the 'classic NMOSD-like' subgroup (p = 0.02). While we found a negative overall correlation between tNAA and disability score (r = -0.514, p = 0.04) in the whole cohort, the disability score did not differ significantly between the subgroups to explain subgroup differences in tNAA level. CONCLUSIONS: Significant differences in the cervical spinal cord tNAA measurements confirm that the previously identified clinico-radiologic subgroups contain patients with distinct underlying disease processes.

Cerebral mechanism of Tuina analgesia in management of knee osteoarthritis using multimodal MRI: study protocol for a randomised controlled trial.

BACKGROUND: The chronic pain of patients with knee osteoarthritis (KOA) seriously affects their quality of life and leads to heavy social and economic burden. As a nondrug therapy in Traditional Chinese Medicine (TCM), Tuina is generally recognised as safe and effective for reducing the chronic pain of KOA. However, the underlying central mechanisms of Tuina for improving the pain of KOA are not fully understood. METHODS/DESIGN: This study will be a randomised controlled trial with a parallel-group design. A total of 60 eligible participants will be assigned to the Tuina group or healthcare education group (Education group) at 1:1 ratio using stratified randomisation with gender and age as factors. The interventions of both groups will last for 30 min per session and be conducted twice each week for 12 weeks. This study will primarily focus on pain evaluation assessed by detecting the changes in brain grey matter (GM) structure, white matter (WM) structure, and the cerebral functional connectivity (FC) elicited by Tuina treatment, e.g., thalamus, hippocampus, anterior cingulate gyrus, S1, insula, and periaqueductal grey subregions (PAG). The two groups of patients will be evaluated by clinical assessments and multimodal magnetic resonance imaging (MRI) to observe the alterations in the GM, WM, and FC of participants at the baseline and the end of 6 and 12 weeks' treatment and still be evaluated by clinical assessments but not MRI for 48 weeks of follow-up. The visual analogue scale of current pain is the primary outcome. The Short-Form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, 36-Item Short Form Health Survey, Hamilton Depression Scale, and Hamilton Anxiety Scale will be used to evaluate the pain intensity, pain feeling, pain emotion, clinical symptoms, and quality of life, respectively. MRI assessments, clinical data evaluators, data managers, and statisticians will be blinded to the group allocation in the outcome evaluation procedure and data analysis to reduce the risk of bias. The repeated measures analysis of variance (2 groups × 6 time points ANOVA) will be used to analyse numerical variables of the clinical and neuroimaging data obtained in the study. P<0.05 will be the statistical significance level. DISCUSSION: The results of this randomised controlled trial with clinical assessments and multimodal MRI will help reveal the influence of Tuina treatment on the potential morphological changes in cortical and subcortical brain structures, the white matter integrity, and the functional activities and connectivity of brain regions of patients with KOA, which may provide scientific evidence for the clinical application of Tuina in the management of KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000037966 . Registered on Sep. 8, 2020. DISSEMINATION: The results will be published in peer-reviewed journals and disseminated through the study's website, and conferences.

Coupling cognitive and brainstem dysfunction in multiple sclerosis-related chronic neuropathic limb pain.

Chronic pain in multiple sclerosis is common and difficult to treat. Its mechanisms remain incompletely understood. Dysfunction of the descending pain modulatory system is known to contribute to human chronic pain conditions. However, it is not clear how alterations in executive function influence this network, despite healthy volunteer studies linking function of the descending pain modulatory system, to cognition. In adults with multiple sclerosis-associated chronic neuropathic limb pain, compared to those without pain, we hypothesized altered functional connectivity of the descending pain modulatory system, coupled to executive dysfunction. Specifically we hypothesized reduced mental flexibility, because of potential importance in stimulus reappraisal. To investigate these hypotheses, we conducted a case-control cross-sectional study of 47 adults with relapsing remitting multiple sclerosis (31 with chronic neuropathic limb pain, 16 without pain), employing clinical, neuropsychological, structural, and functional MRI measures. We measured brain lesions and atrophy affecting descending pain modulatory system structures. Both cognitive and affective dysfunctions were confirmed in the chronic neuropathic limb pain group, including reduced mental flexibility (Delis Kaplan Executive Function System card sorting tests P < 0.001). Functional connectivity of rostral anterior cingulate and ventrolateral periaqueductal gray, key structures of the descending pain modulatory system, was significantly lower in the group experiencing chronic neuropathic pain. There was no significant between-group difference in whole-brain grey matter or lesion volumes, nor lesion volume affecting white matter tracts between rostral anterior cingulate and periaqueductal gray. Brainstem-specific lesion volume was higher in the chronic neuropathic limb pain group (P = 0.0017). Differential functional connectivity remained after correction for brainstem-specific lesion volume. Gabapentinoid medications were more frequently used in the chronic pain group. We describe executive dysfunction in people with multiple sclerosis affected by chronic neuropathic pain, along with functional and structural MRI evidence compatible with dysfunction of the descending pain modulatory system. These findings extend understanding of close inter-relationships between cognition, function of the descending pain modulatory system, and chronic pain, both in multiple sclerosis and more generally in human chronic pain conditions. These findings could support application of pharmacological and cognitive interventions in chronic neuropathic pain associated with multiple sclerosis.

Pain-related reorganization in the primary somatosensory cortex of patients with postherpetic neuralgia.

Studies on functional and structural changes in the primary somatosensory cortex (S1) have provided important insights into neural mechanisms underlying several chronic pain conditions. However, the role of S1 plasticity in postherpetic neuralgia (PHN) remains elusive. Combining psychophysics and magnetic resonance imaging (MRI), we investigated whether pain in PHN patients is linked to S1 reorganization as compared with healthy controls. Results from voxel-based morphometry showed no structural differences between groups. To characterize functional plasticity, we compared S1 responses to noxious laser stimuli of a fixed intensity between both groups and assessed the relationship between S1 activation and spontaneous pain in PHN patients. Although the intensity of evoked pain was comparable in both groups, PHN patients exhibited greater activation in S1 ipsilateral to the stimulated hand. Pain-related activity was identified in contralateral superior S1 (SS1) in controls as expected, but in bilateral inferior S1 (IS1) in PHN patients with no overlap between SS1 and IS1. Contralateral SS1 engaged during evoked pain in controls encoded spontaneous pain in patients, suggesting functional S1 reorganization in PHN. Resting-state fMRI data showed decreased functional connectivity between left and right SS1 in PHN patients, which scaled with the intensity of spontaneous pain. Finally, multivariate pattern analyses (MVPA) demonstrated that BOLD activity and resting-state functional connectivity of S1 predicted within-subject variations of evoked and spontaneous pain intensities across groups. In summary, functional reorganization in S1 might play a key role in chronic pain related to PHN and could be a potential treatment target in this patient group.

Thalamocortical Mechanisms for Nostalgia-Induced Analgesia.

As a predominately positive emotion, nostalgia serves various adaptive functions, including a recently revealed analgesic effect. The current fMRI study aimed to explore the neural mechanisms underlying the nostalgia-induced analgesic effect on noxious thermal stimuli of different intensities. Human participants' (males and females) behavior results showed that the nostalgia paradigm significantly reduced participants' perception of pain, particularly at low pain intensities. fMRI analysis revealed that analgesia was related to decreased brain activity in pain-related brain regions, including the lingual and parahippocampal gyrus. Notably, anterior thalamic activation during the nostalgia stage predicted posterior parietal thalamus activation during the pain stage, suggesting that the thalamus might play a key role as a central functional linkage in the analgesic effect. Moreover, while thalamus-PAG functional connectivity was found to be related to nostalgic strength, periaqueductal gray-dorsolateral prefrontal cortex (PAG-dlPFC) functional connectivity was found to be associated with pain perception, suggesting possible analgesic modulatory pathways. These findings demonstrate the analgesic effect of nostalgia and, more importantly, shed light on its neural mechanism.SIGNIFICANCE STATEMENT Nostalgia is known to reduce individuals' perception of physical pain. The underlying brain mechanisms, however, are unclear. Our study found that the thalamus plays a key role as a functional linkage between nostalgia and pain, suggesting a possible analgesic modulatory mechanism of nostalgia. These findings have implications for the underlying brain mechanisms of psychological analgesia.

Elucidating distinct clinico-radiologic signatures in the borderland between neuromyelitis optica and multiple sclerosis.

BACKGROUND: Separating antibody-negative neuromyelitis optica spectrum disorders (NMOSD) from multiple sclerosis (MS) in borderline cases is extremely challenging due to lack of biomarkers. Elucidating different pathologies within the likely heterogenous antibody-negative NMOSD/MS overlap syndrome is, therefore, a major unmet need which would help avoid disability from inappropriate treatment. OBJECTIVE: In this study we aimed to identify distinct subgroups within the antibody-negative NMOSD/MS overlap syndrome. METHODS: Twenty-five relapsing antibody-negative patients with NMOSD features underwent a prospective brain and spinal cord MRI. Subgroups were identified by an unsupervised algorithm based on pre-selected NMOSD/MS discriminators. RESULTS: Four subgroups were identified. Patients from Group 1 termed "MS-like" (n = 6) often had central vein sign and cortical lesions (83% and 67%, respectively). All patients from Group 2 ("spinal MS-like", 8) had short-segment myelitis and no MS-like brain lesions. Group 3 ("classic NMO-like", 6) had high percentage of bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM, 80% and 60%, respectively) and normal brain appearance (100%). Group 4 ("NMO-like with brain involvement", 5) typically had a history of NMOSD-like brain lesions and LETM. When compared with other groups, Group 4 had significantly decreased fractional anisotropy in non-lesioned tracts (0.46 vs. 0.49, p = 0.003) and decreased thalamus volume (0.84 vs. 0.98, p = 0.04). CONCLUSIONS: NMOSD/MS cohort contains distinct subgroups likely corresponding to different pathologies and requiring tailored treatment. We propose that non-conventional MRI might help optimise diagnosis in these challenging patients.

Exercise for Neuropathic Pain: A Systematic Review and Expert Consensus.

Background: Neuropathic pain (NP), a severe and disruptive symptom following many diseases, normally restricts patients' physical functions and leads to anxiety and depression. As an economical and effective therapy, exercise may be helpful in NP management. However, few guidelines and reviews focused on exercise therapy for NP associated with specific diseases. The study aimed to summarize the effectiveness and efficacy of exercise for various diseases with NP supported by evidence, describe expert recommendations for NP from different causes, and inform policymakers of the guidelines. Design: A systematic review and expert consensus. Methods: A systematic search was conducted in PubMed. We included systematic review and meta-analysis, randomized controlled trials (RCTs), which assessed patients with NP. Studies involved exercise intervention and outcome included pain intensity at least. Physiotherapy Evidence Database and the Assessment of Multiple Systematic reviews tool were used to grade the quality assessment of the included RCTs and systematic reviews, respectively. The final grades of recommendation were based on strength of evidence and a consensus discussion of results of Delphi rounds by the Delphi consensus panel including 21 experts from the Chinese Association of Rehabilitation Medicine. Results: Eight systematic reviews and 21 RCTs fulfilled all of the inclusion criteria and were included, which were used to create the 10 evidence-based consensus statements. The 10 expert recommendations regarding exercise for NP symptoms were relevant to the following 10 different diseases: spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, cervical radiculopathy, sciatica, diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV/AIDS, and surgery, respectively. The exercise recommended in the expert consensus involved but was not limited to muscle stretching, strengthening/resistance exercise, aerobic exercise, motor control/stabilization training and mind-body exercise (Tai Chi and yoga). Conclusions: Based on the available evidence, exercise is helpful to alleviate NP intensity. Therefore, these expert consensuses recommend that proper exercise programs can be considered as an effective alternative treatment or complementary therapy for most patients with NP. The expert consensus provided medical staff and policymakers with applicable recommendations for the formulation of exercise prescription for NP. This consensus statement will require regular updates after five-ten years.

[Central neural mechanism of increased pain sensitivity induced by nicotine abstinence].

Nicotine is the main addictive component in cigarettes that motivates dependence on tobacco use for smokers and makes it difficult to quit through regulating a variety of neurotransmitter release and receptor activations in the brain. Even though nicotine has an analgesic effect, clinical studies demonstrated that nicotine abstinence reduces pain threshold and increases pain sensitivity in smoking individuals. The demand for opioid analgesics in nicotine abstinent patients undergoing surgery has greatly increased, which results in many side effects, such as nausea, vomiting, and respiratory depression, etc. In addition, these side effects would hinder patients' physical and psychological recovery. Therefore, identifying the neural mechanism of the increase of pain sensitivity induced by nicotine abstinence and deriving a way to cope with the increased demand for postoperative analgesics would have enormous basic and clinical implications. In this review, we first discussed different experimental pain stimuli (e.g., cold, heat, and mechanical pain)-induced pain sensitivity changes after a period of nicotine dependence/abstinence from both animal and human studies. Then, we summarized the effects of the brain neurotransmitter release (e.g., serotonin, norepinephrine, endogenous opioids, dopamine, and γ-aminobutyric acid) and their corresponding receptor activation changes after nicotine abstinence on pain sensitivity. Finally, we discussed the limits in recent studies. We proposed that more attention should be paid to human studies, especially studies among chronic pain patients, and functional magnetic resonance imaging might be a useful tool to reveal the mechanisms of abstinence-induced pain sensitivity changes. Besides, considering the influence of duration of nicotine dependence/abstinence and gender on pain sensitivity, we proposed that the effects of nicotine abstinence and individual differences (e.g., duration of abstinence from smoking, chronic/acute abstinence, and gender) on abstinence-induced pain sensitivity should be fully considered in formulating pain treatment protocols. In summary, this paper could deepen our understanding of nicotine abstinence-induced pain sensitivity changes and its underlying neural mechanism, and could also provide effective scientific theories to guide clinical pain diagnosis and treatment, which has important clinical significance.