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1.
Nat Commun ; 15(1): 6017, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019888

RESUMO

Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study (N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.


Assuntos
Encéfalo , Cognição , Imageamento por Ressonância Magnética , Dor Nociceptiva , Efeito Placebo , Humanos , Masculino , Feminino , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/psicologia , Adulto Jovem , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Teorema de Bayes , Analgesia/métodos , Afeto/fisiologia , Afeto/efeitos dos fármacos , Analgésicos/uso terapêutico , Analgésicos/farmacologia
2.
bioRxiv ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38979212

RESUMO

Cognitive neuroscience has advanced significantly due to the availability of openly shared datasets. Large sample sizes, large amounts of data per person, and diversity in tasks and data types are all desirable, but are difficult to achieve in a single dataset. Here, we present an open dataset with N = 101 participants and 6 hours of scanning per participant, with 6 multifaceted cognitive tasks including 2 hours of naturalistic movie viewing. This datasets' combination of ample sample size, extensive data per participant, more than 600 hours worth of data, and a wide range of experimental conditions - including cognitive, affective, social, and somatic/interoceptive tasks - positions it uniquely for probing important questions in cognitive neuroscience.

3.
bioRxiv ; 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37790543

RESUMO

Placebo analgesia is a replicable and well-studied phenomenon, yet it remains unclear to what degree it includes modulation of nociceptive processes. Some studies find effects consistent with nociceptive effects, but meta-analyses show that these effects are often small. We analyzed placebo analgesia in a large fMRI study (N = 392), including placebo effects on brain responses to noxious stimuli. Placebo treatment caused robust analgesia in both conditioned thermal and unconditioned mechanical pain. Placebo did not decrease fMRI activity in nociceptive pain regions, including the Neurologic Pain Signature (NPS) and pre-registered spinothalamic pathway regions, with strong support from Bayes Factor analyses. However, placebo treatment affected activity in pre-registered analyses of a second neuromarker, the Stimulus Intensity Independent Pain Signature (SIIPS), and several associated a priori brain regions related to motivation and value, in both thermal and mechanical pain. Individual differences in behavioral analgesia were correlated with neural changes in both thermal and mechanical pain. Our results indicate that processes related to affective and cognitive aspects of pain primarily drive placebo analgesia.

4.
Transl Psychiatry ; 13(1): 285, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37604880

RESUMO

Functional somatic syndromes (FSS) include fibromyalgia, irritable bowel syndrome (IBS), and others. In FSS patients, merely viewing negative affective pictures can elicit increased physical symptoms. Our aim was to investigate the neural mechanisms underlying such negative affect-induced physical symptoms in FSS patients. Thirty patients with fibromyalgia and/or IBS and 30 healthy controls (all women) watched neutral, positive and negative affective picture blocks during functional MRI scanning and rated negative affect and physical symptoms after every block. We compared brain-wide activation during negative versus neutral picture viewing in FSS patients versus controls using robust general linear model analysis. Further, we compared neurologic pain signature (NPS), stimulus intensity-independent pain signature (SIIPS) and picture-induced negative emotion signature (PINES) responses to the negative versus neutral affect contrast and investigated whether they mediated between-group differences in affective picture-induced physical symptom reporting. More physical symptoms were reported after viewing negative compared to neutral pictures, and this effect was larger in patients than controls (p = 0.025). Accordingly, patients showed stronger activation in somatosensory regions during negative versus neutral picture viewing. NPS, but not SIIPS nor PINES, responses were higher in patients than controls during negative versus neutral pictures (p = 0.026). These differential NPS responses partially mediated between-group differences in physical symptoms. In conclusion, picture-induced negative affect elicits physical symptoms in FSS patients as a result of activation of somatosensory and nociceptive brain patterns, supporting the idea that affect-driven alterations in processing of somatic signals is a critical mechanism underlying FSS.


Assuntos
Fibromialgia , Síndrome do Intestino Irritável , Humanos , Feminino , Fibromialgia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Dor , Afeto
5.
PLoS Biol ; 20(5): e3001620, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35500023

RESUMO

Information is coded in the brain at multiple anatomical scales: locally, distributed across regions and networks, and globally. For pain, the scale of representation has not been formally tested, and quantitative comparisons of pain representations across regions and networks are lacking. In this multistudy analysis of 376 participants across 11 studies, we compared multivariate predictive models to investigate the spatial scale and location of evoked heat pain intensity representation. We compared models based on (a) a single most pain-predictive region or resting-state network; (b) pain-associated cortical-subcortical systems developed from prior literature ("multisystem models"); and (c) a model spanning the full brain. We estimated model accuracy using leave-one-study-out cross-validation (CV; 7 studies) and subsequently validated in 4 independent holdout studies. All spatial scales conveyed information about pain intensity, but distributed, multisystem models predicted pain 20% more accurately than any individual region or network and were more generalizable to multimodal pain (thermal, visceral, and mechanical) and specific to pain. Full brain models showed no predictive advantage over multisystem models. These findings show that multiple cortical and subcortical systems are needed to decode pain intensity, especially heat pain, and that representation of pain experience may not be circumscribed by any elementary region or canonical network. Finally, the learner generalization methods we employ provide a blueprint for evaluating the spatial scale of information in other domains.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Dor , Medição da Dor
6.
Neuroimage ; 247: 118844, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34942367

RESUMO

Identifying biomarkers that predict mental states with large effect sizes and high test-retest reliability is a growing priority for fMRI research. We examined a well-established multivariate brain measure that tracks pain induced by nociceptive input, the Neurologic Pain Signature (NPS). In N = 295 participants across eight studies, NPS responses showed a very large effect size in predicting within-person single-trial pain reports (d = 1.45) and medium effect size in predicting individual differences in pain reports (d = 0.49). The NPS showed excellent short-term (within-day) test-retest reliability (ICC = 0.84, with average 69.5 trials/person). Reliability scaled with the number of trials within-person, with ≥60 trials required for excellent test-retest reliability. Reliability was tested in two additional studies across 5-day (N = 29, ICC = 0.74, 30 trials/person) and 1-month (N = 40, ICC = 0.46, 5 trials/person) test-retest intervals. The combination of strong within-person correlations and only modest between-person correlations between the NPS and pain reports indicate that the two measures have different sources of between-person variance. The NPS is not a surrogate for individual differences in pain reports but can serve as a reliable measure of pain-related physiology and mechanistic target for interventions.


Assuntos
Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Nociceptividade/fisiologia , Dor/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
7.
Pain Ther ; 10(2): 1375-1400, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34374961

RESUMO

BACKGROUND: Preventing transition to chronic back pain (CBP) is a long-sought strategy that could rescue patients from prolonged suffering. Recent rodent and human brain imaging studies suggest involvement of sexually dimorphic, dopaminergic-motivational, mesolimbic circuits in the transition to chronic pain (tCBP), and hint that the combination of carbidopa/levodopa and naproxen (LDP + NPX) may block tCBP. Here we evaluated, in people with recent-onset back pain, whether a 3-month treatment with LDP + NPX is safe, blocks tCBP, and whether its efficacy is sex-dependent. METHODS: A total of 72 participants were enrolled and stratified by risk for tCBP using brain-imaging biomarkers. Low-risk participants entered a no-treatment arm. Others were randomized to placebo + naproxen or LDP + NPX for 3 months. RESULTS: Both treatments resulted in more than 50% pain relief for approximately 75% of participants. A strong sex by treatment interaction was observed for daily pain intensity (phone NRS, P = 0.007), replicated on 4-week average pain (Pain/4w, P = 0.00001), and in intent-to-treat analysis (Pain/4w, P = 0.000004). Nucleus accumbens functional connectivity with medial prefrontal cortex, a predefined objective biomarker, showed sex dependence at baseline (P = 0.03) and sex-by-treatment interaction effect 3 months after treatment cessation (P = 0.031). Treatment modified the psychological profile of participants, and disrupted brain modeling-based predicted back pain intensity trajectories. Forty participants were queried 3.3 years from trial start; back pain ratings were similar between end of treatment and at 3.3 years (P = 0.62), indicating persistence of relief for this duration. CONCLUSIONS: These results provide the first evidence for preventing transition to chronic back pain using sex-specific pharmacotherapy. These provocative observations require confirmation in a larger study. ClinicalTrials.gov identifier: NCT01951105.

8.
Pain ; 160 Suppl 1: S37-S48, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31008848

RESUMO

This review expounds on types and properties of biomarkers for chronic pain, given a mechanistic model of processes underlying development of chronic pain. It covers advances in the field of developing biomarkers for chronic pain, while outlining the general principles of categorizing types of biomarkers driven by specific hypotheses regarding underlying mechanisms. Within this theoretical construct, example biomarkers are described and their properties expounded. We conclude that the field is advancing in important directions and the developed biomarkers have the potential of impacting both the science and the clinical practice regarding chronic pain.


Assuntos
Encéfalo/diagnóstico por imagem , Dor Crônica/sangue , Dor Crônica/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Animais , Biomarcadores/sangue , Encéfalo/metabolismo , Eletroencefalografia/métodos , Eletroencefalografia/tendências , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/tendências , Rede Nervosa/metabolismo , Medula Espinal/metabolismo
9.
Pain ; 158(6): 1069-1082, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28328579

RESUMO

Chronic pain symptoms often change over time, even in individuals who have had symptoms for years. Studying biological factors that predict trends in symptom change in chronic pain may uncover novel pathophysiological mechanisms and potential therapeutic targets. In this study, we investigated whether brain functional connectivity measures obtained from resting-state functional magnetic resonance imaging at baseline can predict longitudinal symptom change (3, 6, and 12 months after scan) in urologic chronic pelvic pain syndrome. We studied 52 individuals with urologic chronic pelvic pain syndrome (34 women, 18 men) who had baseline neuroimaging followed by symptom tracking every 2 weeks for 1 year as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We found that brain functional connectivity can make a significant prediction of short-term (3 month) pain reduction with 73.1% accuracy (69.2% sensitivity and 75.0% precision). In addition, we found that the brain regions with greatest contribution to the classification were preferentially aligned with the left frontoparietal network. Resting-state functional magnetic resonance imaging measures seemed to be less informative about 6- or 12-month symptom change. Our study provides the first evidence that future trends in symptom change in patients in a state of chronic pain may be linked to functional connectivity within specific brain networks.


Assuntos
Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Conectoma , Progressão da Doença , Rede Nervosa/fisiopatologia , Dor Pélvica/prevenção & controle , Doenças Urológicas/fisiopatologia , Adulto , Dor Crônica/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Dor Pélvica/diagnóstico , Serviços Postais , Reprodutibilidade dos Testes , Descanso , Sensibilidade e Especificidade , Síndrome , Doenças Urológicas/diagnóstico
10.
Brain ; 139(Pt 7): 1958-70, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27190016

RESUMO

SEE TRACEY DOI101093/BRAIN/AWW147 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Mechanisms of chronic pain remain poorly understood. We tracked brain properties in subacute back pain patients longitudinally for 3 years as they either recovered from or transitioned to chronic pain. Whole-brain comparisons indicated corticolimbic, but not pain-related circuitry, white matter connections predisposed patients to chronic pain. Intra-corticolimbic white matter connectivity analysis identified three segregated communities: dorsal medial prefrontal cortex-amygdala-accumbens, ventral medial prefrontal cortex-amygdala, and orbitofrontal cortex-amygdala-hippocampus. Higher incidence of white matter and functional connections within the dorsal medial prefrontal cortex-amygdala-accumbens circuit, as well as smaller amygdala volume, represented independent risk factors, together accounting for 60% of the variance for pain persistence. Opioid gene polymorphisms and negative mood contributed indirectly through corticolimbic anatomical factors, to risk for chronic pain. Our results imply that persistence of chronic pain is predetermined by corticolimbic neuroanatomical factors.


Assuntos
Tonsila do Cerebelo , Dor nas Costas , Dor Crônica , Hipocampo , Imageamento por Ressonância Magnética/métodos , Rede Nervosa , Córtex Pré-Frontal , Substância Branca , Adulto , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiopatologia , Dor nas Costas/diagnóstico por imagem , Dor nas Costas/fisiopatologia , Dor Crônica/diagnóstico por imagem , Dor Crônica/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Neuroimagem Funcional/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Fatores de Risco , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia
11.
Pain ; 157(2): 508-509, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26797510
12.
Hum Brain Mapp ; 36(2): 683-94, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25307796

RESUMO

Smoking is associated with increased incidence of chronic pain. However, the evidence is cross-sectional in nature, and underlying mechanisms remain unclear. In a longitudinal observational study, we examined the relationship between smoking, transition to chronic pain, and brain physiology. In 160 subjects with subacute back pain (SBP: back pain lasting 4-12 weeks, and no prior back pain [BP] for at least 1 year) pain characteristics, smoking status, and brain functional properties were measured repeatedly over 1 year. Sixty-eight completed the study, subdivided into recovering (SBPr, n = 31) and persisting (SBPp, n = 37), based on >20% decrease in BP over the year. Thirty-two chronic back pain (CBP: duration > 5 years) and 35 healthy controls were similarly monitored. Smoking prevalence was higher in SBP and CBP but not related to intensity of BP. In SBP, smoking status at baseline was predictive of persistence of BP 1 year from symptom onset (differentiating SBPp and SBPr with 0.62 accuracy). Smoking status combined with affective properties of pain and medication use improved prediction accuracy (0.82). Mediation analysis indicated the prediction of BP persistence by smoking was largely due to synchrony of fMRI activity between two brain areas (nucleus accumbens and medial prefrontal cortex, NAc-mPFC). In SBP or CBP who ceased smoking strength of NAc-mPFC decreased from precessation to postcessation of smoking. We conclude that smoking increases risk of transitioning to CBP, an effect mediated by corticostriatal circuitry involved in addictive behavior and motivated learning.


Assuntos
Dor nas Costas/fisiopatologia , Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Fumar/fisiopatologia , Adulto , Dor nas Costas/complicações , Dor nas Costas/tratamento farmacológico , Mapeamento Encefálico , Dor Crônica/complicações , Dor Crônica/tratamento farmacológico , Progressão da Doença , Feminino , Seguimentos , Humanos , Modelos Logísticos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Fatores de Risco , Abandono do Hábito de Fumar , Inquéritos e Questionários
13.
J Neurophysiol ; 111(5): 1065-76, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24335219

RESUMO

The hippocampus has been shown to undergo significant changes in rodent models of neuropathic pain; however, the role of the hippocampus in human chronic pain and its contribution to pain chronification have remained unexplored. Here we examine hippocampal processing during a simple visual attention task. We used functional MRI to identify intrinsic and extrinsic hippocampal functional connectivity (synchronous neural activity), comparing subacute back pain (SBP, back pain 1-4 mo) and chronic back pain (CBP, back pain >10 yr) patients to control (CON) subjects. Both groups showed more extensive hippocampal connectivity than CON subjects. We then examined the evolution of hippocampal connectivity longitudinally in SBP patients who recovered (SBPr, back pain decreased >20% in 1 yr) and those with persistent pain (SBPp). We found that SBPp and SBPr subjects have distinct changes in hippocampal-cortical connectivity over 1 yr; specifically, SBPp subjects showed large decreases in hippocampal connectivity with medial prefrontal cortex (HG-mPFC). Furthermore, in SBP patients the strength of HG-mPFC reflected variations in back pain over the year. These relationships were replicated when examined in a different task performed by SBP patients (rating fluctuations of back pain), indicating that functional connectivity of the hippocampus changes robustly in subacute pain and the nature of these changes depends on whether or not patients recover from SBP. The observed reorganization of processing within the hippocampus and between the hippocampus and the cortex seems to contribute to the transition from subacute to chronic pain and may also underlie learning and emotional abnormalities associated with chronic pain.


Assuntos
Dor nas Costas/fisiopatologia , Dor Crônica/fisiopatologia , Hipocampo/fisiopatologia , Adulto , Atenção/fisiologia , Mapeamento Encefálico , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Percepção Visual/fisiologia
14.
Nat Neurosci ; 15(8): 1117-9, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22751038

RESUMO

The mechanism of brain reorganization in pain chronification is unknown. In a longitudinal brain imaging study, subacute back pain (SBP) patients were followed over the course of 1 year. When pain persisted (SBPp, in contrast to recovering SBP and healthy controls), brain gray matter density decreased. Initially greater functional connectivity of nucleus accumbens with prefrontal cortex predicted pain persistence, implying that corticostriatal circuitry is causally involved in the transition from acute to chronic pain.


Assuntos
Dor nas Costas/fisiopatologia , Encéfalo/fisiopatologia , Dor Aguda/fisiopatologia , Adulto , Biomarcadores , Encéfalo/patologia , Dor Crônica/fisiopatologia , Corpo Estriado/fisiopatologia , Feminino , Seguimentos , Previsões/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Vias Neurais/fisiopatologia , Núcleo Accumbens/fisiopatologia , Medição da Dor/instrumentação , Córtex Pré-Frontal/fisiopatologia
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