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2.
PLoS One ; 15(7): e0235346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32667951

RESUMO

Several studies have recently suggested that an abnormal processing of respiratory interoceptive and nociceptive (painful) stimuli may contribute to eating disorder (ED) pathophysiology. Mood and anxiety disorders (MA) are also characterized by abnormal respiratory symptoms, and show substantial comorbidity with ED. However, no studies have examined both respiratory and pain processing simultaneously within ED and MA. The present study systematically evaluated responses to perturbations of respiratory and nociceptive signals across the levels of physiology, behavior, and symptom report in a transdiagnostic ED sample (n = 51) that was individually matched to MA individuals (n = 51) and healthy comparisons (HC; n = 51). Participants underwent an inspiratory breath-holding challenge as a probe of respiratory interoception and a cold pressor challenge as a probe of pain processing. We expected both clinical groups to report greater stress and fear in response to respiratory and nociceptive perturbation than HCs, in the absence of differential physiological and behavioral responses. During breath-holding, both the ED and MA groups reported significantly more stress, feelings of suffocation, and suffocation fear than HC, with the ED group reporting the most severe symptoms. Moreover, anxiety sensitivity was related to suffocation fear only in the ED group. The heightened affective responses in the current study occurred in the absence of group differences in behavioral (breath hold duration, cold pressor duration) and physiological (end-tidal carbon dioxide, end-tidal oxygen, heart rate, skin conductance) responses. Against our expectations, there were no group differences in the response to cold pain stimulation. A matched-subgroup analysis focusing on individuals with anorexia nervosa (n = 30) produced similar results. These findings underscore the presence of abnormal respiratory interoception in MA and suggest that hyperreactivity to respiratory signals may be a potentially overlooked clinical feature of ED.


Assuntos
Anorexia Nervosa/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Dor Nociceptiva/fisiopatologia , Adolescente , Adulto , Afeto/fisiologia , Anorexia Nervosa/complicações , Anorexia Nervosa/epidemiologia , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/epidemiologia , Asfixia/fisiopatologia , Asfixia/terapia , Comorbidade , Medo/fisiologia , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Masculino , Transtornos do Humor/complicações , Transtornos do Humor/epidemiologia , Transtornos do Humor/fisiopatologia , Dor Nociceptiva/complicações , Dor Nociceptiva/epidemiologia , Dor/complicações , Dor/epidemiologia , Dor/fisiopatologia , Sistema Respiratório/fisiopatologia
3.
Am J Physiol Regul Integr Comp Physiol ; 319(3): R366-R375, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726157

RESUMO

We have tested the feasibility of thermal grills, a harmless method to induce pain. The thermal grills consist of interlaced tubes that are set at cool or warm temperatures, creating a painful "illusion" (no tissue injury is caused) in the brain when the cool and warm stimuli are presented collectively. Advancement in objective pain assessment research is limited because the gold standard, the self-reporting pain scale, is highly subjective and only works for alert and cooperative patients. However, the main difficulty for pain studies is the potential harm caused to participants. We have recruited 23 subjects in whom we induced electric pulses and thermal grill (TG) stimulation. The TG effectively induced three different levels of pain, as evidenced by the visual analog scale (VAS) provided by the subjects after each stimulus. Furthermore, objective physiological measurements based on electrodermal activity showed a significant increase in levels as stimulation level increased. We found that VAS was highly correlated with the TG stimulation level. The TG stimulation safely elicited pain levels up to 9 out of 10. The TG stimulation allows for extending studies of pain to ranges of pain in which other stimuli are harmful.


Assuntos
Resposta Galvânica da Pele/fisiologia , Temperatura Alta , Limiar da Dor/fisiologia , Dor/fisiopatologia , Sensação Térmica/fisiologia , Adulto , Temperatura Baixa , Feminino , Voluntários Saudáveis , Humanos , Medição da Dor/métodos
5.
Nat Commun ; 11(1): 2716, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483118

RESUMO

How do brain mechanisms create maladaptive attractions? Here intense maladaptive attractions are created in laboratory rats by pairing optogenetic channelrhodopsin (ChR2) stimulation of central nucleus of amygdala (CeA) in rats with encountering either sucrose, cocaine, or a painful shock-delivering object. We find that pairings make the respective rats pursue either sucrose exclusively, or cocaine exclusively, or repeatedly self-inflict shocks. CeA-induced maladaptive attractions, even to the painful shock-rod, recruit mesocorticolimbic incentive-related circuitry. Shock-associated cues also gain positive incentive value and are pursued. Yet the motivational effects of paired CeA stimulation can be reversed to negative valence in a Pavlovian fear learning situation, where CeA ChR2 pairing increases defensive reactions. Finally, CeA ChR2 valence can be switched to neutral by pairing with innocuous stimuli. These results reveal valence plasticity and multiple modes for motivation via mesocorticolimbic circuitry under the control of CeA activation.


Assuntos
Encéfalo/fisiologia , Núcleo Central da Amígdala/fisiologia , Channelrhodopsins/fisiologia , Dor/fisiopatologia , Recompensa , Animais , Núcleo Central da Amígdala/metabolismo , Channelrhodopsins/metabolismo , Cocaína/administração & dosagem , Sinais (Psicologia) , Feminino , Aprendizagem/efeitos dos fármacos , Aprendizagem/fisiologia , Masculino , Motivação/fisiologia , Optogenética/métodos , Ratos Sprague-Dawley , Sacarose/administração & dosagem
6.
Neuron ; 107(3): 538-551.e7, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502461

RESUMO

Pain is a source of substantial discomfort. Abnormal activity in both the zona incerta (ZI) and posterior complex of the thalamus (Po) are implicated in neuropathic pain, but their exact roles remain unclear. In particular, the precise cell types and molecular mechanisms of the ZI-Po circuit that regulate nociception are largely uncharacterized. Here, we found that parvalbumin (PV)-positive neuronal projections from the ventral ZI (ZIv) to the Po (ZIv-Po) are critical for promoting nocifensive behaviors, whereas selectively inhibiting ZIv-Po activity reduces nocifensive withdrawal responses. Furthermore, cannabinoid type 1 receptors (CB1Rs) are expressed specifically at ZIv-Po axon terminals in this circuit, and cannabinoids attenuate nocifensive responses through presynaptic inhibition. Selective inhibition of the ZIv-Po circuit or administration of cannabinoids into the Po are sufficient to ameliorate pathological pain. These findings identify the critical role of the ZIv-Po circuit and its modulation by endocannabinoids in controlling nocifensive behaviors.


Assuntos
Neurônios/fisiologia , Nociceptividade/fisiologia , Dor/fisiopatologia , Núcleos Posteriores do Tálamo/fisiologia , Receptor CB1 de Canabinoide/metabolismo , Zona Incerta/fisiologia , Animais , Comportamento Animal , Endocanabinoides , Camundongos , Inibição Neural , Vias Neurais , Neurônios/metabolismo , Dor/metabolismo , Parvalbuminas , Núcleos Posteriores do Tálamo/citologia , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , Zona Incerta/citologia
8.
PLoS One ; 15(5): e0232108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379766

RESUMO

Influential theoretical accounts take the position that classical conditioning can induce placebo effects through conscious expectancies. In the current study two different conditioning procedures (hidden and open) were used to separate expectancy from conditioning in order to reveal the role of expectancy in the formation of nocebo hyperalgesia. Eighty-seven healthy females were randomly assigned to three groups (hidden conditioning, open conditioning, and control). Participants were selected according to the Fear of Pain Questionnaire scores and assigned to two subgroups: high and low level of fear of pain (trait). They received electrocutaneous pain stimuli preceded by either an orange or blue color. During the conditioning phase, one color was paired with pain stimuli of moderate intensity (control stimuli) and the other color was paired with pain stimuli of high intensity (nocebo stimuli) in both hidden and open conditioning groups. Only participants in the open conditioning group were informed about this association, however just before the testing phase the expectancy of hyperalgesia induced in this way was withdrawn. In the control group, both colors were followed by control pain stimuli. During the testing phase all participants received a series of stimuli of the same intensity, regardless of the preceding color. Participants rated pain intensity, expectancy of pain intensity and fear (state). We found that nocebo hyperalgesia was induced by hidden rather than open conditioning. The hidden conditioning procedure did not produce conscious expectancies related to pain. Nocebo hyperalgesia was induced in participants with low and high fear of pain and there was no difference in the magnitude of the nocebo effect between both groups. Nocebo hyperalgesia was not predicted by the fear of upcoming painful stimuli.


Assuntos
Condicionamento Clássico/fisiologia , Hiperalgesia/fisiopatologia , Efeito Nocebo , Adulto , Medo/fisiologia , Medo/psicologia , Feminino , Humanos , Motivação/fisiologia , Dor/fisiopatologia , Dor/psicologia , Medição da Dor/métodos , Medição da Dor/psicologia , Limiar da Dor/fisiologia , Limiar da Dor/psicologia
9.
Int J Rehabil Res ; 43(3): 240-246, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32459670

RESUMO

Total knee replacement (TKR) is continuously increasing with significantly faster recovery times. Soft tissue pain and edema of operated limbs play an important role in early functional recovery. The present study aims to evaluate the effectiveness of the combination of Kinesiotaping and Lymphatic drainage for the containment of pain and edema as well as the improvement of the range of motion of the knee as integration with standard postoperative rehabilitation. Ninety-nine TKR patients were included in the randomized clinical trial and divided into three groups: Kinesiotaping and Lymphatic drainage Group, Lymphatic drainage Group, and Kinesiotaping Group. The assessment was carried out on days 2-4-6 postoperation. All the patients had also standard reeducation sessions. It was observed that both Kinesiotaping and Lymphatic drainage was useful in reducing pain and edema. A significantly higher improvement was observed in the group in which Lymphatic drainage was associated with Kinesiotaping with respect to the individual treatments, for pain and leg circumference over and under the knee, and at the ankle. Range of motion of the knee did not show any difference since the flexion degree was similar in all the three groups. No difference was found between Kinesiotaping and Lymphatic drainage. In conclusion, the treatment with a combination Kinesiotaping and Lymphatic drainage provided better results on pain and edema observed as early as the first days after the intervention, thus may be considered a valid support for standard rehabilitation and pharmacological intervention.


Assuntos
Edema/terapia , Drenagem Linfática Manual , Manejo da Dor , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho , Fita Atlética , Edema/fisiopatologia , Edema/cirurgia , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Medição da Dor , Período Pós-Operatório , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Resultado do Tratamento
10.
Nat Commun ; 11(1): 2293, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385249

RESUMO

The sodium channels Nav1.7, Nav1.8 and Nav1.9 are critical for pain perception in peripheral nociceptors. Loss of function of Nav1.7 leads to congenital insensitivity to pain in humans. Here we show that the spider peptide toxin called HpTx1, first identified as an inhibitor of Kv4.2, restores nociception in Nav1.7 knockout (Nav1.7-KO) mice by enhancing the excitability of dorsal root ganglion neurons. HpTx1 inhibits Nav1.7 and activates Nav1.9 but does not affect Nav1.8. This toxin produces pain in wild-type (WT) and Nav1.7-KO mice, and attenuates nociception in Nav1.9-KO mice, but has no effect in Nav1.8-KO mice. These data indicate that HpTx1-induced hypersensitivity is mediated by Nav1.9 activation and offers pharmacological insight into the relationship of the three Nav channels in pain signalling.


Assuntos
Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Ativação do Canal Iônico , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.9/metabolismo , Peptídeos/efeitos adversos , Venenos de Aranha/efeitos adversos , Sequência de Aminoácidos , Animais , Feminino , Gânglios Espinais/patologia , Humanos , Hiperalgesia/complicações , Masculino , Camundongos Knockout , Canal de Sódio Disparado por Voltagem NAV1.7/química , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.9/química , Neurônios/efeitos dos fármacos , Neurônios/patologia , Dor/complicações , Dor/fisiopatologia , Ratos
11.
J Headache Pain ; 21(1): 47, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375638

RESUMO

BACKGROUND: Migraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation. METHODS: Forty-eight migraineurs without aura during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized seed-based functional connectivity analysis to investigate whether patients exhibited abnormal functional connectivity between sub-regions of sensorimotor brain areas and cortex regions. RESULTS: We found that patients with migraineurs without aura exhibited disrupted functional connectivities between the sensorimotor areas and the visual cortex, temporal cortex, posterior parietal lobule, prefrontal areas, precuneus, cingulate gyrus, sensorimotor areas proper and cerebellum areas compared with healthy controls. In addition, the clinical data of the patients, such as disease duration, pain intensity and HIT-6 score, were negatively correlated with these impaired functional connectivities. CONCLUSION: In patients with migraineurs without aura, the functional connectivities between the sensorimotor brain areas and other brain regions was reduced. These disrupted functional connectivities might contribute to abnormalities in visual processing, multisensory integration, nociception processing, spatial attention and intention and dysfunction in cognitive evaluation and modulation of pain. Recurrent headache attacks might lead to the disrupted network between primary motor cortex and temporal regions and between primary somatosensory cortex and temporal regions. Pain sensitivity and patient quality of life are closely tied to the abnormal functional connectivity between sensorimotor regions and other brain areas.


Assuntos
Imagem por Ressonância Magnética/métodos , Enxaqueca sem Aura/diagnóstico por imagem , Córtex Motor/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Córtex Somatossensorial/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca sem Aura/fisiopatologia , Córtex Motor/fisiopatologia , Rede Nervosa/fisiopatologia , Dor/diagnóstico por imagem , Dor/fisiopatologia , Qualidade de Vida , Córtex Somatossensorial/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto Jovem
12.
J Headache Pain ; 21(1): 48, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375649

RESUMO

OBJECTIVE: To evaluate the relationship between pain catastrophizing level, sensory processing patterns, and headache severity among adolescents with episodic migraine. BACKGROUND: Catastrophizing about pain is a critical variable in how we understand adjustment to pain and has a unique contribution in predicting pain intensity. Recent reports found that migraine is also related to enhanced sensory sensitivity. However, the relationship between pain severity, pain catastrophizing level and sensory sensitivity requires greater study especially among adolescents. METHODS: Participants were 92 adolescents aged 13-18 years, 40 with episodic migraine and 52 healthy controls. The migraine patients were prospectively recruited from outpatient pediatric neurology clinics. All participants completed the Adolescent/Adult Sensory Profile (AASP), and the Pain Catastrophizing Scale for children (PCS-ch). The migraine groups also completed the PedMIDAS, which measures Headache related disability. RESULTS: Adolescents with migraine had significantly lower tendency to seek sensory input than healthy controls. Elevated rumination and helplessness correlated with higher migraine pain severity. Tendency to avoid sensory input predicted the migraine related disability level. They also significantly higher pain catastrophizing level than healthy controls, as seen in enhanced rumination (p ≤ 0.001) and helplessness (p ≤ 0.05). CONCLUSIONS: Sensory processing difficulties are common among adolescents with episodic migraine. Sensory avoidance may be related to pain experience, and pain catastrophizing and disability level. TRIAL REGISTRATION: ISRCTN ISRCTN73824458. Registered 28 September 2014. retrospectively registered.


Assuntos
Comportamento do Adolescente/psicologia , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/psicologia , Medição da Dor/psicologia , Índice de Gravidade de Doença , Adolescente , Comportamento do Adolescente/fisiologia , Catastrofização/diagnóstico , Catastrofização/fisiopatologia , Catastrofização/psicologia , Cognição/fisiologia , Emoções/fisiologia , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/fisiopatologia , Dor/diagnóstico , Dor/fisiopatologia , Dor/psicologia , Medição da Dor/métodos , Estudos Prospectivos
13.
J Headache Pain ; 21(1): 45, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375641

RESUMO

BACKGROUND: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people, and with increasing trends in general populations. Different risk factors for pain have been identified, but generally from studies with limited samples and a limited number of candidate predictors. The aim of this study is to evaluate the predictors of pain from a large set of variables and respondents. METHODS: We used part of the harmonized dataset of ATHLOS project, selecting studies and waves with a longitudinal course, and in which pain was absent at baseline and with no missing at follow-up. Predictors were selected based on missing distribution and univariable association with pain, and were selected from the following domains: Socio-demographic and economic characteristics, Lifestyle and health behaviours, Health status and functional limitations, Diseases, Physical measures, Cognition, personality and other psychological measures, and Social environment. Hierarchical logistic regression models were then applied to identify significant predictors. RESULTS: A total of 13,545 subjects were included of whom 5348 (39.5%) developed pain between baseline and the average 5.2 years' follow-up. Baseline risk factors for pain were female gender (OR 1.34), engaging in vigorous exercise (OR 2.51), being obese (OR 1.36) and suffering from the loss of a close person (OR 1.88) whereas follow-up risk factors were low energy levels/fatigue (1.93), difficulties with walking (1.69), self-rated health referred as poor (OR 2.20) or average to moderate (OR 1.57) and presence of sleep problems (1.80). CONCLUSIONS: Our results showed that 39.5% of respondents developed pain over a five-year follow-up period, that there are proximal and distal risk factors for pain, and that part of them are directly modifiable. Actions aimed at improving sleep, reducing weight among obese people and treating fatigue would positively impact on pain onset, and avoiding vigorous exercise should be advised to people aged 60 or over, in particular if female or obese.


Assuntos
Envelhecimento/fisiologia , Bases de Dados Factuais/tendências , Dor/diagnóstico , Dor/epidemiologia , Vigilância da População , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Peso Corporal/fisiologia , China/epidemiologia , Cognição/fisiologia , Europa (Continente)/epidemiologia , Exercício Físico/fisiologia , Feminino , Seguimentos , Nível de Saúde , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Dor/fisiopatologia , Vigilância da População/métodos , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Adulto Jovem
14.
J Vasc Interv Radiol ; 31(6): 912-916.e1, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32376178

RESUMO

Eight patients who underwent percutaneous cryoablation of mixed and/or motor nerves over a period of 5 years were identified. Distances from the ablation sites to origins of distal musculature were measured, and times to initial clinical recovery were collected. Strength progression over time following muscle activation was also collected and analyzed. All patients demonstrated activation of all muscles distal to the ablation, and the calculated mean rate of nerve regeneration based on distance to the origin of the assessed musculature and time to muscle activation for the group was 1.5 mm/day ± 1.1.


Assuntos
Criocirurgia , Denervação Muscular/métodos , Força Muscular , Músculo Esquelético/inervação , Regeneração Nervosa , Dor/cirurgia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Criocirurgia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/patologia , Denervação Muscular/efeitos adversos , Dor/diagnóstico , Dor/fisiopatologia , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/patologia , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Nat Neurosci ; 23(7): 854-868, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32424286

RESUMO

General anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in part by activating supraspinal analgesic circuits. We discovered a distinct population of GABAergic neurons activated by GA in the mouse central amygdala (CeAGA neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeAGA neurons. CeAGA neurons also possess basal activity that mostly reflects animals' internal state rather than external stimuli. Optogenetic activation of CeAGA potently suppressed both pain-elicited reflexive and self-recuperating behaviors across sensory modalities and abolished neuropathic pain-induced mechanical (hyper-)sensitivity. Conversely, inhibition of CeAGA activity exacerbated pain, produced strong aversion and canceled the analgesic effect of low-dose ketamine. CeAGA neurons have widespread inhibitory projections to many affective pain-processing centers. Our study points to CeAGA as a potential powerful therapeutic target for alleviating chronic pain.


Assuntos
Anestésicos Gerais/farmacologia , Núcleo Central da Amígdala/efeitos dos fármacos , Neurônios GABAérgicos/efeitos dos fármacos , Dor/fisiopatologia , Animais , Feminino , Masculino , Camundongos , Vias Neurais/efeitos dos fármacos , Percepção da Dor/efeitos dos fármacos , Percepção da Dor/fisiologia
16.
PLoS One ; 15(4): e0231077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32282836

RESUMO

INTRODUCTION: This study aimed to investigate the differences in the Injustice Experience Questionnaire (IEQ) scores during the early period after the diagnosis of Whiplash-associated disorder (WAD) between Japanese and Canadian samples, and the associations between the IEQ scores and treatment terms in Japanese patients with acute WAD. METHODS: We used secondary data for the IEQ scores of Canadian patients with acute WAD. In Japan, we collected data from 85 consecutively enrolled patients with acute WAD, and their treatment terms were collected; these referred to the number of days between the date of injury and the closure date of the insurance claim and the number of treatment visits. Before treatment, the Numeric Rating Scale, Neck Disability Index, Hospital Anxiety and Depression Scale, IEQ, and Euro Quality of Life five-dimensional questionnaire were administered. The variables were subjected to multivariate analysis with each treatment term. RESULTS: The IEQ scores were higher in Japan than in Canada. Through multiple regression analysis, IEQ scores were independently correlated with treatment terms. The optimal cutoff point of the IEQ scores for a prolonged treatment term was 21 and 22 points, respectively. CONCLUSIONS: The IEQ scores were associated with treatment terms in patients with acute WAD in Japan.


Assuntos
Depressão/epidemiologia , Mialgia/epidemiologia , Dor/epidemiologia , Traumatismos em Chicotada/epidemiologia , Canadá/epidemiologia , Depressão/fisiopatologia , Depressão/psicologia , Depressão/terapia , Feminino , Humanos , Seguro , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mialgia/fisiopatologia , Mialgia/psicologia , Mialgia/terapia , Dor/fisiopatologia , Dor/psicologia , Manejo da Dor , Análise de Regressão , Inquéritos e Questionários , Traumatismos em Chicotada/fisiopatologia , Traumatismos em Chicotada/psicologia , Traumatismos em Chicotada/terapia
17.
PLoS Biol ; 18(4): e3000491, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32282798

RESUMO

Nervous systems exploit regularities in the sensory environment to predict sensory input, adjust behavior, and thereby maximize fitness. Entrainment of neural oscillations allows retaining temporal regularities of sensory information, a prerequisite for prediction. Entrainment has been extensively described at the frequencies of periodic inputs most commonly present in visual and auditory landscapes (e.g., >0.5 Hz). An open question is whether neural entrainment also occurs for regularities at much longer timescales. Here, we exploited the fact that the temporal dynamics of thermal stimuli in natural environment can unfold very slowly. We show that ultralow-frequency neural oscillations preserved a long-lasting trace of sensory information through neural entrainment to periodic thermo-nociceptive input as low as 0.1 Hz. Importantly, revealing the functional significance of this phenomenon, both power and phase of the entrainment predicted individual pain sensitivity. In contrast, periodic auditory input at the same ultralow frequency did not entrain ultralow-frequency oscillations. These results demonstrate that a functionally significant neural entrainment can occur at temporal scales far longer than those commonly explored. The non-supramodal nature of our results suggests that ultralow-frequency entrainment might be tuned to the temporal scale of the statistical regularities characteristic of different sensory modalities.


Assuntos
Encéfalo/fisiologia , Percepção da Dor/fisiologia , Dor/fisiopatologia , Estimulação Acústica , Adulto , Eletroencefalografia , Feminino , Humanos , Lasers , Masculino , Dor/psicologia , Medição da Dor , Processamento de Sinais Assistido por Computador
18.
Proc Natl Acad Sci U S A ; 117(18): 10045-10054, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32312820

RESUMO

Although pain is a prevalent nonmotor symptom in Parkinson's disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that the STN might play a critical role in parkinsonian pain hypersensitivity. To test this hypothesis, we established a unilateral parkinsonian mouse model with moderate lesions of dopaminergic neurons in the substantia nigra. The mice displayed pain hypersensitivity and neuronal hyperactivity in the ipsilesional STN and in central pain-processing nuclei. Optogenetic inhibition of STN neurons reversed pain hypersensitivity phenotypes in parkinsonian mice, while hyperactivity in the STN was sufficient to induce pain hypersensitivity in control mice. We further demonstrated that the STN differentially regulates thermal and mechanical pain thresholds through its projections to the substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus (GPi)/ventral pallidum (VP), respectively. Interestingly, optogenetic inhibition of STN-GPi/STN-VP and STN-SNr projections differentially elevated mechanical and thermal pain thresholds in parkinsonian mice. In summary, our results support the hypothesis that the STN and its divergent projections play critical roles in modulating pain processing under both physiological and parkinsonian conditions, and suggest that inhibition of individual STN projections may be a therapeutic strategy to relieve distinct pain phenotypes in PD.


Assuntos
Neurônios/fisiologia , Dor/fisiopatologia , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Animais , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Dopamina/farmacologia , Globo Pálido/efeitos dos fármacos , Humanos , Hipersensibilidade , Camundongos , Neurônios/efeitos dos fármacos , Oxidopamina/farmacologia , Dor/complicações , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Doença de Parkinson/complicações , Substância Negra/fisiopatologia , Núcleo Subtalâmico/efeitos dos fármacos
19.
Anesthesiology ; 133(1): 165-184, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32349075

RESUMO

BACKGROUND: Brain-derived estrogen is implicated in pain-related aversion; however, which estrogen receptors mediate this effect remains unclear. This study hypothesized that the different estrogen receptors in the rostral anterior cingulate cortex play distinct roles in pain-related aversion. METHODS: Formalin-induced conditioned place avoidance and place escape/avoidance paradigms were used to evaluate pain-related aversion in rodents. Immunohistochemistry and Western blotting were used to detect estrogen receptor expression. Patch-clamp recordings were used to examine N-methyl-D-aspartate-mediated excitatory postsynaptic currents in rostral anterior cingulate cortex slices. RESULTS: The administration of the estrogen receptor-ß antagonist 4-(2-phenyl-5,7-bis [trifluoromethyl] pyrazolo [1,5-a] pyrimidin-3-yl) phenol (PHTPP) or the G protein-coupled estrogen receptor-1 antagonist (3aS*,4R*,9bR*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta [c] quinolone (G15) but not the estrogen receptor-α antagonist 1,3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride (MPP) into the rostral anterior cingulate cortex blocked pain-related aversion in rats (avoidance score, mean ± SD: 1,3-bis [4-hydroxyphenyl]-4-methyl-5-(4-[2-piperidinylethoxy] phenol)-1H-pyrazole dihydrochloride (MPP): 47.0 ± 18.9%, 4-(2-phenyl-5,7-bis [trifluoromethyl] pyrazolo [1,5-a] pyrimidin-3-yl) phenol (PHTPP): -7.4 ± 20.6%, and [3aS*,4R*,9bR*]-4-[6-bromo-1,3-benzodioxol-5-yl]-3a,4,5,9b-3H-cyclopenta [c] quinolone (G15): -4.6 ± 17.0% vs. vehicle: 46.5 ± 12.2%; n = 7 to 9; P < 0.0001). Consistently, estrogen receptor-ß knockdown but not estrogen receptor-α knockdown by short-hairpin RNA also inhibited pain-related aversion in mice (avoidance score, mean ± SD: estrogen receptor-α-short-hairpin RNA: 26.0 ± 7.1% and estrogen receptor-ß-short-hairpin RNA: 6.3 ± 13.4% vs. control short-hairpin RNA: 29.1 ± 9.1%; n = 7 to 10; P < 0.0001). Furthermore, the direct administration of the estrogen receptor-ß agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN) or the G protein-coupled estrogen receptor-1 agonist (±)-1-([3aR*,4S*,9bS*]-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl)-ethanone (G1) into the rostral anterior cingulate cortex resulted in conditioned place avoidance (avoidance score, mean ± SD: 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN): 35.3 ± 9.5% and (±)-1-([3aR*,4S*,9bS*]-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl)-ethanone (G1): 43.5 ± 22.8% vs. vehicle: 0.3 ± 14.9%; n = 8; P < 0.0001) but did not affect mechanical or thermal sensitivity. The activation of the estrogen receptor-ß/protein kinase A or G protein-coupled estrogen receptor-1/protein kinase B pathway elicited the long-term potentiation of N-methyl-D-aspartate-mediated excitatory postsynaptic currents. CONCLUSIONS: These findings indicate that estrogen receptor-ß and G protein-coupled estrogen receptor-1 but not estrogen receptor-α in the rostral anterior cingulate cortex contribute to pain-related aversion by modulating N-methyl-D-aspartate receptor-mediated excitatory synaptic transmission.


Assuntos
Giro do Cíngulo/fisiopatologia , Dor/fisiopatologia , Dor/psicologia , Receptores Estrogênicos , Animais , Aprendizagem da Esquiva , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/genética , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Antagonistas de Estrogênios/farmacologia , Receptor beta de Estrogênio/efeitos dos fármacos , Receptor beta de Estrogênio/genética , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley , Receptores Estrogênicos/efeitos dos fármacos , Receptores Estrogênicos/genética
20.
J Neurosci ; 40(17): 3478-3490, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32241836

RESUMO

Gamma-band oscillations (GBOs) elicited by transient nociceptive stimuli are one of the most promising biomarkers of pain across species. Still, whether these GBOs reflect stimulus encoding in the primary somatosensory cortex (S1) or nocifensive behavior in the primary motor cortex (M1) is debated. Here we recorded neural activity simultaneously from the brain surface as well as at different depths of the bilateral S1/M1 in freely-moving male rats receiving nociceptive stimulation. GBOs measured from superficial layers of S1 contralateral to the stimulated paw not only had the largest magnitude, but also showed the strongest temporal and phase coupling with epidural GBOs. Also, spiking of superficial S1 interneurons had the strongest phase coherence with epidural GBOs. These results provide the first direct demonstration that scalp GBOs, one of the most promising pain biomarkers, reflect neural activity strongly coupled with the fast spiking of interneurons in the superficial layers of the S1 contralateral to the stimulated side.SIGNIFICANCE STATEMENT Nociceptive-induced gamma-band oscillations (GBOs) measured at population level are one of the most promising biomarkers of pain perception. Our results provide the direct demonstration that these GBOs reflect neural activity coupled with the spike firing of interneurons in the superficial layers of the primary somatosensory cortex (S1) contralateral to the side of nociceptive stimulation. These results address the ongoing debate about whether nociceptive-induced GBOs recorded with scalp EEG or epidurally reflect stimulus encoding in the S1 or nocifensive behavior in the primary motor cortex (M1), and will therefore influence how experiments in pain neuroscience will be designed and interpreted.


Assuntos
Ritmo Gama/fisiologia , Córtex Motor/fisiopatologia , Nociceptividade/fisiologia , Dor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Potenciais Somatossensoriais Evocados/fisiologia , Interneurônios/fisiologia , Masculino , Percepção da Dor/fisiologia , Ratos
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