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1.
J Biol Chem ; 299(6): 104782, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37146970

RESUMO

PKA is a downstream effector of many inflammatory mediators that induce pain hypersensitivity by increasing the mechanosensitivity of nociceptive sensory afferent. Here, we examine the molecular mechanism underlying PKA-dependent modulation of the mechanically activated ion channel PIEZO2, which confers mechanosensitivity to many nociceptors. Using phosphorylation site prediction algorithms, we identified multiple putative and highly conserved PKA phosphorylation sites located on intracellular intrinsically disordered regions of PIEZO2. Site-directed mutagenesis and patch-clamp recordings showed that substitution of one or multiple putative PKA sites within a single intracellular domain does not alter PKA-induced PIEZO2 sensitization, whereas mutation of a combination of nine putative sites located on four different intracellular regions completely abolishes PKA-dependent PIEZO2 modulation, though it remains unclear whether all or just some of these nine sites are required. By demonstrating that PIEZO1 is not modulated by PKA, our data also reveal a previously unrecognized functional difference between PIEZO1 and PIEZO2. Moreover, by demonstrating that PKA only modulates PIEZO2 currents evoked by focal mechanical indentation of the cell, but not currents evoked by pressure-induced membrane stretch, we provide evidence suggesting that PIEZO2 is a polymodal mechanosensor that engages different protein domains for detecting different types of mechanical stimuli.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico , Canais Iônicos , Mecanotransdução Celular , Humanos , Canais Iônicos/genética , Canais Iônicos/metabolismo , Mecanotransdução Celular/genética , Dor/fisiopatologia , Domínios Proteicos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Transporte Proteico/genética
2.
Neurosci Lett ; 806: 137228, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-37031944

RESUMO

Pain facilitation contributes to chronic pain conditions. Transcutaneous electrical nerve stimulation (TENS) is used to alleviate pain. The effects of conventional TENS on chronic pain have been limited, and its effects on pain facilitation are controversial. Because the analgesic effects of TENS depend on the setting parameters (e.g., pulse intensities or treatment time), the optimal TENS settings to maximize analgesic effects under various pain conditions have been investigated. High-intensity TENS (HI-TENS), which involves tolerable-level pulse intensities for a short duration, is another conventional TENS method that used to alleviate pain. However, the effects of HI-TENS on pain facilitation remain unclear. The temporal summation of pain is widely used to evaluate pain facilitation, and the temporal summation-nociceptive flexion reflex (TS-NFR) is a neuropsychological parameter that can be used to evaluate pain facilitation. We aimed to investigate the effects of HI-TENS on the TS-NFR in healthy participants. Participants were randomly allocated into HI-TENS (n = 15) and control groups (n = 16). HI-TENS was administered at the left lateral lower leg for 1 min. The TS-NFR elicited by three noxious stimuluses at the left sural nerve was obtained from electromyography of the left biceps femoris. The nociceptive flexion reflex (NFR) was obtained by a single noxious stimulus. We measured the thresholds of the NFR and the TS-NFR at baseline and post-intervention. The application of HI-TENS significantly increased the NFR threshold (p = 0.013) but not the TS-NFR threshold (p > 0.05). These results suggest that HI-TENS does not inhibit pain facilitation.


Assuntos
Nociceptividade , Dor , Reflexo , Estimulação Elétrica Nervosa Transcutânea , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Análise de Variância , Voluntários Saudáveis , Nociceptividade/fisiologia , Dor/fisiopatologia , Limiar da Dor/fisiologia , Reflexo/fisiologia , Resultado do Tratamento
4.
Curr Med Res Opin ; 39(3): 451-466, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36772818

RESUMO

OBJECTIVES: The term "mixed pain" has been established when a mixture of different pain components (e.g. nociceptive, neuropathic, and nociplastic) are present. It has gained more and more acceptance amongst pain experts worldwide, but many questions around the concept of mixed pain are still unsolved. The sensation of pain is very personal. Cultural, social, personal experiences, idiomatic, and taxonomic differences should be taken into account during pain assessment. Therefore, a Latin American consensus committee was formed to further elaborate the essentials of mixed pain, focusing on the specific characteristics of the Latin American population. METHODS: The current approach was based on a systematic literature search and review carried out in Medline. Eight topics about the definition, diagnosis, and treatment of mixed pain were discussed and voted for by a Latin American consensus committee and recommendations were expressed. RESULTS: At the end of the meeting a total of 14 voting sheets were collected. The full consensus was obtained for 21 of 25 recommendations (15 strong agreement and 6 unanimous agreement) formulated for the above described 8 topics (7 of the 8 topics had for all questions at least a strong agreement - 1 topic had no agreement for all 4 questions). CONCLUSION: In a subject as complex as mixed pain, a consensus has been reached among Latin American specialists on points related to the definition and essence of this pain, its diagnosis and treatment. Recommendations for diagnosis and treatment of mixed pain in Latin America were raised.


Assuntos
Dor , Humanos , Consenso , América Latina/epidemiologia , Dor/diagnóstico , Dor/etiologia , Dor/fisiopatologia , Medição da Dor , Analgesia/métodos
5.
Acta Neurol Belg ; 123(2): 385-390, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35303287

RESUMO

The aim of this study was to compare structural changes of corpus callosum (CC), which is the largest collection of white matter in the brain, among migraineurs and healthy controls (HC). Diffusion tensor imaging (DTI) method which provides information about microscopic organization of the cell, especially white matter was used for this purpose. Fifty-one patients who were diagnosed with migraine and 44 age- and sex-matched HC were included in the study. Socio-demographic and clinical characteristics of the patients were noted. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measurements of CC genu, splenium, and body were performed for all participants. A significant difference was determined between migraine patients and HC regarding the FA values in the genu of CC (p < 0.001). When the clinical data of migraine patients and FA values in the genu of CC were analyzed via linear regression analysis, no significant finding was detected (p > 0.05). In conclusion, it can be suggested that there are microstructural changes in the CC of migraneurs; however, the clinical variable associated with this structural deterioration could not be determined.


Assuntos
Corpo Caloso , Imagem de Tensor de Difusão , Transtornos de Enxaqueca , Humanos , Corpo Caloso/anatomia & histologia , Corpo Caloso/diagnóstico por imagem , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/fisiopatologia , Masculino , Feminino , Anisotropia , Modelos Lineares , Dor/etiologia , Dor/fisiopatologia , Estudos Transversais , Adulto , Estudos Prospectivos
6.
Rev. esp. podol ; 34(2): 99-103, 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-229377

RESUMO

Objetivos: Conocer la percepción de los pacientes sobre el dolor y localización en los pies debido al lupus eritematoso sistémico (LES). Identificar los consejos y cuidados recibidos sobre los problemas de sus pies y calzado, y qué profesional los proporcionó. Conocer si los pacientes usaban ortesis plantares o calzado ortopédico. Pacientes y métodos: Estudio observacional, descriptivo, transversal, realizado entre marzo y mayo de 2021 sobre 47 personas con LES. Cinco participantes se excluyeron por no completar el cuestionario, siendo 42 los participantes después de obtener su consentimiento informado. Se confeccionó una hoja de recogida de datos para alcanzar los objetivos. Resultados: El 47.6 % de los pacientes presentaba dolor en los pies atribuido al LES durante la entrevista, con un promedio de dolor de 4.4 (DE = 2.97). El dolor se localizó principalmente en el antepié y los dedos. El 31 % y el 21.4 % recibieron cuidados o consejos para sus problemas en los pies respectivamente, siendo podólogos y reumatólogos los principales prescriptores. El 31 % recibió consejos sobre el calzado adecuado, proporcionados principalmente por podólogos y reumatólogos. El 33.33 % utilizaba ortesis plantares, siendo mayormente prescritas por reumatólogos y podólogos. Solo un 4.8 % utilizaba calzado ortopédico o hecho a medida. Conclusiones: Se encontró una prevalencia significativa de dolor en los pies atribuido al LES, siendo el antepié y los dedos las áreas más afectadas. Un porcentaje limitado de pacientes recibió cuidados y consejos para sus problemas en los pies, y el uso de ortesis plantares y calzado ortopédico fue poco común (AU)


Objectives: To know the perception of patients about pain and location in the feet due to Systemic Lupus Erythematosus (SLE). Identify the advice and care received about the problems of your feet and footwear, and which professional provided it. To know if patients wore plantar orthoses or orthopedic shoes. Patients and methods: Observational, descriptive, cross-sectional study, conducted between March and May 2021 on 47 people with SLE. Five participants were excluded for not completing the questionnaire, with 42 participants after obtaining their informed consent. A data collection sheet was prepared to achieve the objectives. Results: A total of 47.6 % of patients had foot pain attributed to SLE during the interview, with an average pain of 4.4 (SD = 2.97). The pain was mainly localized to the forefoot and fingers. Thirtyone (31 %) and 21.4 % received care or advice for their foot problems respectively, with podiatrists and rheumatologists being the main prescribers. Also, 31 % received advice on proper footwear, provided mainly by podiatrists and rheumatologists. One third (33,33 %) used plantar orthoses, being mostly prescribed by rheumatologists and podiatrists. Only 4.8 % used orthopedic or custom-made shoes.Conclusions: A significant prevalence of foot pain attributed to SLE was found, with the forefoot and toes being the most affected areas. A limited percentage of patients received care and advice for their foot problems, and the use of plantar orthotics and orthopedic footwear was uncommon (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Dor/fisiopatologia , Aparelhos Ortopédicos , Órtoses do Pé , Lúpus Eritematoso Sistêmico/fisiopatologia , Estudos Transversais
7.
Proc Natl Acad Sci U S A ; 119(33): e2118501119, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35943985

RESUMO

Pain and itch are distinct sensations arousing evasion and compulsive desire for scratching, respectively. It's unclear whether they could invoke different neural networks in the brain. Here, we use the type 1 herpes simplex virus H129 strain to trace the neural networks derived from two types of dorsal root ganglia (DRG) neurons: one kind of polymodal nociceptors containing galanin (Gal) and one type of pruriceptors expressing neurotensin (Nts). The DRG microinjection and immunosuppression were performed in transgenic mice to achieve a successful tracing from specific types of DRG neurons to the primary sensory cortex. About one-third of nuclei in the brain were labeled. More than half of them were differentially labeled in two networks. For the ascending pathways, the spinothalamic tract was absent in the network derived from Nts-expressing pruriceptors, and the two networks shared the spinobulbar projections but occupied different subnuclei. As to the motor systems, more neurons in the primary motor cortex and red nucleus of the somatic motor system participated in the Gal-containing nociceptor-derived network, while more neurons in the nucleus of the solitary tract (NST) and the dorsal motor nucleus of vagus nerve (DMX) of the emotional motor system was found in the Nts-expressing pruriceptor-derived network. Functional validation of differentially labeled nuclei by c-Fos test and chemogenetic inhibition suggested the red nucleus in facilitating the response to noxious heat and the NST/DMX in regulating the histamine-induced scratching. Thus, we reveal the organization of neural networks in a DRG neuron type-dependent manner for processing pain and itch.


Assuntos
Galanina , Gânglios Espinais , Rede Nervosa , Neurotensina , Nociceptores , Dor , Prurido , Animais , Galanina/metabolismo , Gânglios Espinais/ultraestrutura , Herpesvirus Humano 1 , Camundongos , Camundongos Transgênicos , Rede Nervosa/ultraestrutura , Neurotensina/metabolismo , Nociceptores/metabolismo , Dor/fisiopatologia , Prurido/fisiopatologia , Núcleo Solitário/ultraestrutura
8.
J Integr Complement Med ; 28(11): 862-869, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35895503

RESUMO

Objective: The nociceptive system has been implicated in acupuncture analgesia, although acupuncture's precise mechanism of action remains unknown. Electric pain-related evoked potentials (PREPs) have emerged as an effective and reliable electrophysiologic method for evaluation of the human nociceptive system by electric stimulation of nociceptive Aδ and C fibers. This pilot mechanistic study aims to assess the feasibility of using advanced PREP techniques together with electroacupuncture and to use PREPs to characterize acupuncture's effect on nociception. Methods: Seven healthy volunteers underwent a previously designed electroacupuncture protocol using acupoints in the legs bilaterally, which has been demonstrated to induce systemic analgesia. Advanced PREP techniques involving tripolar stimulating electrode, varying interstimulus interval, and incorporating a cognitive task during PREPs were used. PREPs were assessed before electroacupuncture, during electroacupuncture, and 30 min after electroacupuncture. Subjective pain perception in response to the PREP-related electric pain stimuli delivered to the nondominant hand was assessed on the visual analog scale (VAS) at baseline, during electroacupuncture, and 30 min postelectroacupuncture. Results: Reliable PREP N1, P1, and N2 waves were obtained from all subjects at the following average latencies: N1 = 131.5 msec, P1 = 189.4 msec, and N2 = 231.1 msec. Electroacupuncture caused a significant reduction in PREP N1P1 wave amplitudes from 25.6 to 15.4 µV (p = 0.006) and electric pain perception on the VAS-from 2.86 to 2.14 (p = 0.008), compared to baseline. These effects were sustained at 30 min postacupuncture with N1P1 wave amplitude 17.2 µV (p = 0.030) and VAS 2.28 (p = 0.030), compared to baseline. Conclusions: Electroacupuncture causes significant changes in objective nociception, measured by PREP N1P1 wave amplitudes, and in subjective nociception, measured by the VAS, and these effects are sustained for 30 min after electroacupuncture. Planned future studies will involve chronic pain populations and will aim to assess acupuncture's longer term analgesic effects.


Assuntos
Eletroacupuntura , Nociceptividade , Humanos , Eletroacupuntura/efeitos adversos , Potenciais Evocados/fisiologia , Nociceptividade/fisiologia , Dor/fisiopatologia , Projetos Piloto
10.
Proc Natl Acad Sci U S A ; 119(30): e2114094119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35858441

RESUMO

Clinical evidence suggests that pain hypersensitivity develops in patients with attention-deficit/hyperactivity disorder (ADHD). However, the mechanisms and neural circuits involved in these interactions remain unknown because of the paucity of studies in animal models. We previously validated a mouse model of ADHD obtained by neonatal 6-hydroxydopamine (6-OHDA) injection. Here, we have demonstrated that 6-OHDA mice exhibit a marked sensitization to thermal and mechanical stimuli, suggesting that phenotypes associated with ADHD include increased nociception. Moreover, sensitization to pathological inflammatory stimulus is amplified in 6-OHDA mice as compared to shams. In this ADHD model, spinal dorsal horn neuron hyperexcitability was observed. Furthermore, ADHD-related hyperactivity and anxiety, but not inattention and impulsivity, are worsened in persistent inflammatory conditions. By combining in vivo electrophysiology, optogenetics, and behavioral analyses, we demonstrated that anterior cingulate cortex (ACC) hyperactivity alters the ACC-posterior insula circuit and triggers changes in spinal networks that underlie nociceptive sensitization. Altogether, our results point to shared mechanisms underlying the comorbidity between ADHD and nociceptive sensitization. This interaction reinforces nociceptive sensitization and hyperactivity, suggesting that overlapping ACC circuits may be targeted to develop better treatments.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Hiperalgesia , Dor , Animais , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Modelos Animais de Doenças , Giro do Cíngulo/fisiopatologia , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Comportamento Impulsivo , Camundongos , Optogenética , Oxidopamina/farmacologia , Dor/induzido quimicamente , Dor/fisiopatologia , Simpatolíticos/farmacologia
11.
Science ; 377(6601): 80-86, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35617374

RESUMO

Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to the development of pain hypersensitivity. How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that after peripheral nerve injury, microglia degrade extracellular matrix structures, perineuronal nets (PNNs), in lamina I of the spinal cord dorsal horn. Lamina I PNNs selectively enwrap spinoparabrachial projection neurons, which integrate nociceptive information in the spinal cord and convey it to supraspinal brain regions to induce pain sensation. Degradation of PNNs by microglia enhances the activity of projection neurons and induces pain-related behaviors. Thus, nerve injury-induced degradation of PNNs is a mechanism by which microglia selectively augment the output of spinal nociceptive circuits and cause pain hypersensitivity.


Assuntos
Hiperalgesia , Microglia , Dor , Traumatismos dos Nervos Periféricos , Corno Dorsal da Medula Espinal , Animais , Matriz Extracelular/patologia , Hiperalgesia/etiologia , Hiperalgesia/patologia , Hiperalgesia/fisiopatologia , Microglia/patologia , Dor/patologia , Dor/fisiopatologia , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/patologia , Ratos , Ratos Sprague-Dawley , Corno Dorsal da Medula Espinal/patologia , Corno Dorsal da Medula Espinal/fisiopatologia
12.
Proc Natl Acad Sci U S A ; 119(21): e2118847119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35594393

RESUMO

G protein­coupled receptors (GPCRs) are involved in regulation of manifold physiological processes through coupling to heterotrimeric G proteins upon ligand stimulation. Classical therapeutically active drugs simultaneously initiate several downstream signaling pathways, whereas biased ligands, which stabilize subsets of receptor conformations, elicit more selective signaling. This concept of functional selectivity of a ligand has emerged as an interesting property for the development of new therapeutic molecules. Biased ligands are expected to have superior efficacy and/or reduced side effects by regulating biological functions of GPCRs in a more precise way. In the last decade, 5-HT7 receptor (5-HT7R) has become a promising target for the treatment of neuropsychiatric disorders, sleep and circadian rhythm disorders, and pathological pain. In this study, we showed that Serodolin is unique among a number of agonists and antagonists tested: it behaves as an antagonist/inverse agonist on Gs signaling while inducing ERK activation through a ß-arrestin­dependent signaling mechanism that requires c-SRC activation. Moreover, we showed that Serodolin clearly decreases hyperalgesia and pain sensation in response to inflammatory, thermal, and mechanical stimulation. This antinociceptive effect could not be observed in 5-HT7R knockout (KO) mice and was fully blocked by administration of SB269-970, a specific 5-HT7R antagonist, demonstrating the specificity of action of Serodolin. Physiological effects of 5-HT7R stimulation have been classically shown to result from Gs-dependent adenylyl cyclase activation. In this study, using a ß-arrestin­biased agonist, we provided insight into the molecular mechanism triggered by 5-HT7R and revealed its therapeutic potential in the modulation of pain response.


Assuntos
Arrestina , Dor , Serotonina , Arrestina/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Humanos , Ligantes , Dor/tratamento farmacológico , Dor/fisiopatologia , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , beta-Arrestina 1/metabolismo , beta-Arrestinas/metabolismo
13.
Brain ; 145(7): 2586-2601, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35598161

RESUMO

In perilous and stressful situations, the ability to suppress pain can be critical for survival. The rostral ventromedial medulla contains neurons that robustly inhibit nocioception at the level of the spinal cord through a top-down modulatory pathway. Although much is known about the role of the rostral ventromedial medulla in the inhibition of pain, the precise ability to directly manipulate pain-inhibitory neurons in the rostral ventromedial medulla has never been achieved. We now expose a cellular circuit that inhibits nocioception and itch in mice. Through a combination of molecular, tracing and behavioural approaches, we found that rostral ventromedial medulla neurons containing the kappa-opioid receptor inhibit itch and nocioception. With chemogenetic inhibition, we uncovered that these neurons are required for stress-induced analgesia. Using intersectional chemogenetic and pharmacological approaches, we determined that rostral ventromedial medulla kappa-opioid receptor neurons inhibit nocioception and itch through a descending circuit. Lastly, we identified a dynorphinergic pathway arising from the periaqueductal grey that modulates nociception within the rostral ventromedial medulla. These discoveries highlight a distinct population of rostral ventromedial medulla neurons capable of broadly and robustly inhibiting itch and nocioception.


Assuntos
Bulbo , Neurônios , Dor , Prurido , Receptores Opioides kappa , Animais , Bulbo/citologia , Camundongos , Neurônios/fisiologia , Dor/fisiopatologia , Prurido/fisiopatologia , Receptores Opioides kappa/metabolismo
15.
Arthroscopy ; 38(3): 783-785, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35248229

RESUMO

There is a well-established relationship between mental distress, mental health disorders, and the perception of pain and physical dysfunction. While determining the root cause is often challenging, increasing levels of mental distress are associated with increasingly disruptive manifestation of physical symptoms and vice versa. In femoroacetabular impingement syndrome, patients with preoperative mental distress exhibit more impactful levels of symptoms. Patients do show symptomatic improvement with appropriate surgical management, even in the presence of mental distress. Patients and surgeons should recognize both the physical and mental contributions to pain perception when developing a treatment plan for musculoskeletal pathologies and incorporate this as part of the postoperative rehabilitation process.


Assuntos
Artroscopia , Impacto Femoroacetabular , Impacto Femoroacetabular/fisiopatologia , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/fisiopatologia , Articulação do Quadril/cirurgia , Humanos , Dor/fisiopatologia , Percepção
16.
J Integr Neurosci ; 21(1): 34, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35164470

RESUMO

This research explored how the manipulation of interoceptive attentiveness (IA) can influence the frontal (dorsolateral prefrontal cortex (DLPFC) and somatosensory cortices) activity associated with the emotional regulation and sensory response of observing pain in others. 20 individuals were asked to observe face versus hand, painful/non-painful stimuli in an individual versus social condition while brain hemodynamic response (oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) components) was measured via functional Near-Infrared Spectroscopy (fNIRS). Images represented either a single person (individual condition) or two persons in social interaction (social condition) both for the pain and body part set of stimuli. The participants were split into experimental (EXP) and control (CNT) groups, with the EXP explicitly required to concentrate on its interoceptive correlates while observing the stimuli. Quantitative statistical analyses were applied to both oxy- and deoxy-Hb data. Firstly, significantly higher brain responsiveness was detected for pain in comparison to no-pain stimuli in the individual condition. Secondly, a left/right hemispheric lateralization was found for the individual and social condition, respectively, in both groups. Besides, both groups showed higher DLPFC activation for face stimuli presented in the individual condition compared to hand stimuli in the social condition. However, face stimuli activation prevailed for the EXP group, suggesting the IA phenomenon has certain features, namely it manifests itself in the individual condition and for pain stimuli. We can conclude that IA promoted the recruitment of internal adaptive regulatory strategies by engaging both DLPFC and somatosensory regions towards emotionally relevant stimuli.


Assuntos
Córtex Pré-Frontal Dorsolateral/fisiologia , Empatia/fisiologia , Face , Lateralidade Funcional/fisiologia , Mãos , Interocepção/fisiologia , Dor/fisiopatologia , Percepção Social , Córtex Somatossensorial/fisiologia , Adulto , Mapeamento Encefálico , Córtex Pré-Frontal Dorsolateral/diagnóstico por imagem , Feminino , Humanos , Masculino , Dor/diagnóstico por imagem , Córtex Somatossensorial/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho , Adulto Jovem
17.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35181604

RESUMO

Acute stress leads to sequential activation of functional brain networks. A biologically relevant question is exactly which (single) cells belonging to brain networks are changed in activity over time after acute stress across the entire brain. We developed a preprocessing and analytical pipeline to chart whole-brain immediate early genes' expression-as proxy for cellular activity-after a single stressful foot shock in four dimensions: that is, from functional networks up to three-dimensional (3D) single-cell resolution and over time. The pipeline is available as an R package. Most brain areas (96%) showed increased numbers of c-fos+ cells after foot shock, yet hypothalamic areas stood out as being most active and prompt in their activation, followed by amygdalar, prefrontal, hippocampal, and finally, thalamic areas. At the cellular level, c-fos+ density clearly shifted over time across subareas, as illustrated for the basolateral amygdala. Moreover, some brain areas showed increased numbers of c-fos+ cells, while others-like the dentate gyrus-dramatically increased c-fos intensity in just a subset of cells, reminiscent of engrams; importantly, this "strategy" changed after foot shock in half of the brain areas. One of the strengths of our approach is that single-cell data were simultaneously examined across all of the 90 brain areas and can be visualized in 3D in our interactive web portal.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Dor/fisiopatologia , Animais , Eletrochoque/métodos , Pé/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Rede Nervosa/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Análise de Célula Única , Análise Espaço-Temporal , Estresse Fisiológico/fisiologia
18.
Neuron ; 110(4): 559-561, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35176237

RESUMO

Transfer between cells is an unexpected addition to the mitochondrial life cycle. In this issue of Neuron, Van der Vlist et al. now provide evidence that M2-macrophages infiltrating sensory ganglia resolve pain by transferring particles containing mitochondria to neurons-thus boosting nociceptors back to normal function.


Assuntos
Gânglios Espinais , Nociceptores , Gânglios Espinais/citologia , Humanos , Mitocôndrias , Neurônios , Nociceptores/metabolismo , Dor/fisiopatologia
19.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983852

RESUMO

The perception of pain is shaped by somatosensory information about threat. However, pain is also influenced by an individual's expectations. Such expectations can result in clinically relevant modulations and abnormalities of pain. In the brain, sensory information, expectations (predictions), and discrepancies thereof (prediction errors) are signaled by an extended network of brain areas which generate evoked potentials and oscillatory responses at different latencies and frequencies. However, a comprehensive picture of how evoked and oscillatory brain responses signal sensory information, predictions, and prediction errors in the processing of pain is lacking so far. Here, we therefore applied brief painful stimuli to 48 healthy human participants and independently modulated sensory information (stimulus intensity) and expectations of pain intensity while measuring brain activity using electroencephalography (EEG). Pain ratings confirmed that pain intensity was shaped by both sensory information and expectations. In contrast, Bayesian analyses revealed that stimulus-induced EEG responses at different latencies (the N1, N2, and P2 components) and frequencies (alpha, beta, and gamma oscillations) were shaped by sensory information but not by expectations. Expectations, however, shaped alpha and beta oscillations before the painful stimuli. These findings indicate that commonly analyzed EEG responses to painful stimuli are more involved in signaling sensory information than in signaling expectations or mismatches of sensory information and expectations. Moreover, they indicate that the effects of expectations on pain are served by brain mechanisms which differ from those conveying effects of sensory information on pain.


Assuntos
Encéfalo/fisiopatologia , Dor/fisiopatologia , Transdução de Sinais , Teorema de Bayes , Eletroencefalografia , Humanos , Medição da Dor
20.
PLoS One ; 17(1): e0263356, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35089966

RESUMO

OBJECTIVES: Chronic pain is a significant societal problem and pain complaints are one of the main causes of work absenteeism and emergency room visits. Physical activity has been associated with reduced risk of suffering from musculoskeletal pain complaints, but the exact relationship in an older adult sample is not known. METHODS: Participants self-reported their physical activity level and whether they were often troubled by bone, joint, or muscle pain. Logistic regression analyses revealed the nature of the relationship between musculoskeletal pain and physical activity cross-sectionally and longitudinally over the course of 10 years. Data were taken from the English Longitudinal Study of Ageing, comprising of 5802 individuals residing in England aged 50 or older. RESULTS: Only high levels of physical activity were associated with a reduced risk of suffering from musculoskeletal pain compared to a sedentary lifestyle longitudinally. In addition, having low wealth, being female, and being overweight or obese were found to be risk factors for suffering from musculoskeletal pain. CONCLUSIONS: The development of interventions aimed at alleviating and preventing musculoskeletal pain complaints might benefit from incorporating physical activity programs, weight loss, and aspects addressing wealth inequality to maximise their efficacy.


Assuntos
Exercício Físico/fisiologia , Dor/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/fisiopatologia
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