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1.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360719

RESUMO

Agonists of the Gi protein-coupled A3 adenosine receptor (A3AR) have shown important pain-relieving properties in preclinical settings of several pain models. Active as a monotherapy against chronic pain, A3AR agonists can also be used in combination with classic opioid analgesics. Their safe pharmacological profile, as shown by clinical trials for other pathologies, i.e., rheumatoid arthritis, psoriasis and fatty liver diseases, confers a realistic translational potential, thus encouraging research studies on the molecular mechanisms underpinning their antinociceptive actions. A number of pathways, involving central and peripheral mechanisms, have been proposed. Recent evidence showed that the prototypical A3AR agonist Cl-IB-MECA and the new, highly selective, A3AR agonist MRS5980 inhibit neuronal (N-type) voltage-dependent Ca2+ currents in dorsal root ganglia, a known pain-related mechanism. Other proposed pathways involve reduced cytokine production, immune cell-mediated responses, as well as reduced microglia and astrocyte activation in the spinal cord. The aim of this review is to summarize up-to-date information on A3AR in the context of pain, including cellular and molecular mechanisms underlying this effect. Based on their safety profile shown in clinical trials for other pathologies, A3AR agonists are proposed as novel, promising non-narcotic agents for pain control.


Assuntos
Agonistas do Receptor A3 de Adenosina/uso terapêutico , Sinalização do Cálcio/efeitos dos fármacos , Gânglios Espinais , Dor , Receptor A3 de Adenosina/metabolismo , Animais , Astrócitos/metabolismo , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiopatologia , Humanos , Microglia/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Dor/fisiopatologia
2.
Medicine (Baltimore) ; 100(31): e26511, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397794

RESUMO

ABSTRACT: Pain sensitization leading to polyalgia can be observed during infectious diseases. The blood pressure cuff-evoked pain threshold (BPCEPT) has been used in previous studies as a screening tool for fibromyalgia.We aimed to use the BPCEPT as a screening test for detecting pain sensitization in patients suffering from infectious diseases. We also investigated whether specific factors were associated with pain sensitization.We performed a prospective comparative study including all patients of our infectious diseases center in a 1-year period. We created a positive control group of patients suffering from fibromyalgia and a negative control group of "apparently healthy" patients consulting for vaccination.The blood pressure (BP) cuff was inflated until the patient signaled that they experienced pain, and this pressure value was noted.A total of 2355 patients were included. The positive control group had significantly lower values of the BPCEPT than all other groups. Among hospitalized patients with infectious diseases, a low BPCEPT was significantly associated with high temperature (P < .0001), older age (P = .002), being a woman (P = .004), high serum glutamic-oxaloacetic transaminase (P = .007), and high C reactive protein levels (P = .02). Moreover, in multivariate analysis, respiratory infection, meningitis, urinary tract infection, febrile neutropenia, and Q fever were independently associated with a low BPCEPT. A significant negative dynamic correlation between the BPCEPT and temperature was also observed (P < .001).We demonstrated for the first time in a large sample of patients that the BPCEPT method can be used to detect pain susceptibility. We observed a significant dynamic correlation between pain sensitization and temperature. Additionally, pain sensitization was associated with some diseases, suggesting that they trigger pain sensitivity.


Assuntos
Determinação da Pressão Arterial , Temperatura Corporal , Infecções/complicações , Dor/etiologia , Fatores Etários , Aspartato Aminotransferases/sangue , Determinação da Pressão Arterial/efeitos adversos , Proteína C-Reativa/metabolismo , Suscetibilidade a Doenças/diagnóstico , Suscetibilidade a Doenças/microbiologia , Suscetibilidade a Doenças/fisiopatologia , Feminino , Fibromialgia/complicações , Humanos , Infecções/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Limiar da Dor , Pressão/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
3.
Am J Phys Anthropol ; 176(2): 308-320, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34397101

RESUMO

OBJECTIVES: Foot and ankle dysfunction in barefoot/minimally shod populations remains understudied. Although factors affecting musculoskeletal pain in Western populations are well-studied, little is known about how types of work, gender, and body shape influence bone and joint health in non-Western and minimally shod communities. This study examines the effect of human variation on locomotor disability in an agrarian community in Madagascar. MATERIALS AND METHODS: Foot measurements were collected along with height, weight, age, and self-report data on daily activity and foot and ankle pain from 41 male and 48 female adults. A short form revised foot function index (FFI-R), that measures functional disability related to foot pain, was calculated. Raw and normalized foot measurements were compared by gender and used in a multiple linear regression model to determine predictors of FFI-R. RESULTS: Compared to men, women reported higher FFI-R scores (p = 0.014), spent more time on their feet (p = 0.019), and had higher BMIs (p = 0.0001). For their weight, women had significantly smaller and narrower feet than men. Bimalleolar breadth (p = 0.0005) and foot length (p = 0.0223) standardized by height, time spent on feet (p = 0.0102), ankle circumference standardized by weight (p = 0.0316), and age (p = 0.0090) were significant predictors of FFI-R score. DISCUSSION: Our findings suggest that human variation in anatomical and behavioral patterns serve as significant explanations for increased foot and ankle pain in women in this non-Western rural population. Foot and ankle pain were prevalent at similar levels to those in industrialized populations, indicating that research should continue to examine its effect on similar barefoot/minimally shod communities.


Assuntos
Tornozelo , , Dor , População Rural/estatística & dados numéricos , Adolescente , Adulto , Tornozelo/anatomia & histologia , Tornozelo/patologia , Antropologia Física , Feminino , Pé/anatomia & histologia , Pé/patologia , Humanos , Madagáscar/epidemiologia , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/patologia , Dor/fisiopatologia , Sapatos/estatística & dados numéricos , Caminhada , Adulto Jovem
4.
Nat Neurosci ; 24(10): 1402-1413, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34373644

RESUMO

Pain decreases the activity of many ventral tegmental area (VTA) dopamine (DA) neurons, yet the underlying neural circuitry connecting nociception and the DA system is not understood. Here we show that a subpopulation of lateral parabrachial (LPB) neurons is critical for relaying nociceptive signals from the spinal cord to the substantia nigra pars reticulata (SNR). SNR-projecting LPB neurons are activated by noxious stimuli and silencing them blocks pain responses in two different models of pain. LPB-targeted and nociception-recipient SNR neurons regulate VTA DA activity directly through feed-forward inhibition and indirectly by inhibiting a distinct subpopulation of VTA-projecting LPB neurons thereby reducing excitatory drive onto VTA DA neurons. Correspondingly, ablation of SNR-projecting LPB neurons is sufficient to reduce pain-mediated inhibition of DA release in vivo. The identification of a neural circuit conveying nociceptive input to DA neurons is critical to our understanding of how pain influences learning and behavior.


Assuntos
Neurônios Dopaminérgicos , Mesencéfalo/fisiopatologia , Vias Neurais/fisiopatologia , Dor/fisiopatologia , Núcleos Parabraquiais/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Comportamento Animal , Mapeamento Encefálico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios , Nociceptividade , Optogenética , Dor/psicologia , Manejo da Dor , Substância Negra/fisiopatologia , Área Tegmentar Ventral/fisiopatologia
5.
Biomolecules ; 11(8)2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34439823

RESUMO

Alveolar osteitis (AO) is a common complication following the extraction of the teeth, particularly the lower third molars. It starts within a few days after the extraction and manifests mainly as pain in the extraction site. Several strategies of treatment are available in order to relieve pain and heal the extraction wound. Recently, a novel medical device combining hyaluronic acid (HA) and octenidine (OCT) was introduced for the treatment of AO. This series of case reports aims to summarize the initial clinical experiences with this new device and to highlight factors possibly interfering with this treatment. The medical documentation of five patients with similar initial situations treated for AO with HA + OCT device was analyzed in detail. Smoking and previous treatment with Alveogyl (Septodont, Saint-Maur-des-Fossés, France) were identified as factors interfering with the AO treatment with the HA + OCT device. In three patients without these risk factors, the treatment led to recovery within two or three days. The patient pretreated with Alveogyl and the smoker required six and seven applications of the HA + OCT device, respectively. According to these initial observations, it seems smoking and previous treatment with Alveogyl prolong the treatment of AO using the HA + OCT device that, in turn, shows a rapid effect if these risk factors are not present.


Assuntos
Alvéolo Seco/tratamento farmacológico , Ácido Hialurônico/uso terapêutico , Iminas/uso terapêutico , Dor/tratamento farmacológico , Piridinas/uso terapêutico , Cicatrização/efeitos dos fármacos , Adolescente , Adulto , Creosoto/efeitos adversos , Combinação de Medicamentos , Alvéolo Seco/etiologia , Alvéolo Seco/fisiopatologia , Alvéolo Seco/cirurgia , Equipamentos e Provisões , Feminino , Humanos , Hidrocarbonetos Iodados/efeitos adversos , Pessoa de Meia-Idade , Dente Molar/cirurgia , Dor/etiologia , Dor/fisiopatologia , Dor/cirurgia , Fatores de Risco , Fumar/efeitos adversos , Timol/efeitos adversos , Extração Dentária/efeitos adversos , Resultado do Tratamento , Cicatrização/fisiologia
6.
BMC Neurol ; 21(1): 272, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243742

RESUMO

BACKGROUND: Human hairy (not glabrous skin) is equipped with a subgroup of C-fibers, the C-tactile (CT) fibers. Those do not mediate pain but affective aspects of touch. CT-fiber-activation reduces experimental pain if they are intact. In this pilot study we investigated pain modulating capacities of CT-afferents in CRPS. METHODS: 10 CRPS-patients (mean age 33 years, SEM 3.3) and 11 healthy controls (mean age 43.2 years, SEM 3.9) participated. CT-targeted-touch (brush stroking, velocity: 3 cm/s) was applied on hairy and glabrous skin on the affected and contralateral limb. Patients rated pleasantness of CT-targeted-touch (anchors: 1 "not pleasant"-4 "very pleasant") twice daily on 10 days. Pain intensity (NRS: 0 "no pain" - 10 "worst pain imaginable") was assessed before, 0, 30, 60 and 120 min after each CT-stimulation. To assess sensory changes, quantitative-sensory-testing was performed at the beginning and the end of the trial period. RESULTS: CT-targeted-touch was felt more pleasant on the healthy compared to the affected limb on hairy (p < 0.001) and glabrous skin (p 0.002), independent of allodynia. In contrast to healthy controls patients felt no difference between stimulating glabrous and hairy skin on the affected limb. Thermal pain thresholds increased after CT-stimulation on the affected limb (cold-pain-threshold: p 0.016; heat-pain-threshold: p 0.033). CONCLUSIONS: CT-stimulation normalizes thermal pain thresholds but has no effect on the overall pain in CRPS. Therefore, pain modulating properties of CT-fibers might be too weak to alter chronic pain in CRPS. Moreover, CT-fibers appear to lose their ability to mediate pleasant aspects of touch in CRPS.


Assuntos
Síndromes da Dor Regional Complexa/fisiopatologia , Fibras Nervosas Amielínicas/fisiologia , Dor/fisiopatologia , Adulto , Humanos , Limiar da Dor/fisiologia , Projetos Piloto , Percepção do Tato/fisiologia
7.
Molecules ; 26(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299631

RESUMO

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague-Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.


Assuntos
Analgésicos Opioides/farmacologia , Comportamento Animal/efeitos dos fármacos , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Masculino , Dor/tratamento farmacológico , Dor/fisiopatologia , Ratos , Ratos Sprague-Dawley
8.
Worldviews Evid Based Nurs ; 18(4): 299-307, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34302432

RESUMO

BACKGROUND: Pressure ulcer (PU) development begins with an inflammatory response, arising due to pressure and shear forces causing changes to the cytoskeletal structure of cells. Thus, pain, synonymous with inflammation, may be an indicator of PU development. AIM: To explore the role of pain as an indicator of PU development and to determine how this pain was measured. METHOD: We searched PUBMED, CINAHL, SCOPUS, Cochrane, and EMBASE databases. A total of 879 records were returned, with eight satisfying the inclusion criteria. Narrative data synthesis was undertaken. The quality of studies was assessed using the evidence-based librarianship (EBL) checklist. RESULTS: The studies were conducted between 2000 and 2019, and 75% (n = 6) employed a cross-sectional design. The mean sample size was 760 participants (SD = 703). Of the included studies, 87.5% (n = 7) identified that pain was associated with PU development. The most frequent pain assessment tool was the numeric rating scale (37.5%; n = 3). Using the EBL checklist, 62.5% (n = 5) of the studies scored ≥75%, reflecting validity. LINKING EVIDENCE TO ACTION: Pain is associated with PU development; however, further research is required to validate these findings and assess the characteristics associated with pain as a symptom preceding PU development.


Assuntos
Diagnóstico Precoce , Dor/diagnóstico , Dor/fisiopatologia , Lesão por Pressão/diagnóstico , Lesão por Pressão/fisiopatologia , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Molecules ; 26(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34299443

RESUMO

Although persistent pain is estimated to affect about 20% of the adult population, current treatments have poor results. Polypharmacology, which is the administration of more than one drug targeting on two or more different sites of action, represents a prominent therapeutic approach for the clinical management of persistent pain. Thus, in the drug discovery process the "one-molecule-multiple targets" strategy nowadays is highly recognized. Indeed, multitarget ligands displaying a better antinociceptive activity with fewer side effects, combined with favorable pharmacokinetic and pharmacodynamic characteristics, have already been shown. Multitarget ligands possessing non-opioid/opioid and opioid/opioid mechanisms of action are considered as potential drug candidates for the management of various pain conditions. In particular, dual-target MOPr (mu opioid peptide receptor)/DOPr (delta opioid peptide receptor) ligands exhibit an improved antinociceptive profile associated with a reduced tolerance-inducing capability. The benzomorphan-based compounds LP1 and LP2 belong to this class of dual-target MOPr/DOPr ligands. In the present manuscript, the structure-activity relationships and the pharmacological fingerprint of LP1 and LP2 compounds as suitable drug candidates for persistent pain relief is described.


Assuntos
Benzomorfanos/farmacologia , Dor/tratamento farmacológico , Receptores Opioides delta/efeitos dos fármacos , Receptores Opioides mu/efeitos dos fármacos , Analgésicos/farmacologia , Analgésicos Opioides/farmacologia , Animais , Benzomorfanos/química , Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Humanos , Ligantes , Dor/fisiopatologia , Manejo da Dor/métodos , Receptores Opioides delta/metabolismo , Receptores Opioides mu/metabolismo , Relação Estrutura-Atividade
10.
J Clin Invest ; 131(13)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196305

RESUMO

Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons. Mice treated with IgG from FMS patients displayed increased sensitivity to noxious mechanical and cold stimulation, and nociceptive fibers in skin-nerve preparations from mice treated with FMS IgG displayed an increased responsiveness to cold and mechanical stimulation. These mice also displayed reduced locomotor activity, reduced paw grip strength, and a loss of intraepidermal innervation. In contrast, transfer of IgG-depleted serum from FMS patients or IgG from healthy control subjects had no effect. Patient IgG did not activate naive sensory neurons directly. IgG from FMS patients labeled satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia (DRG), but no cells in the spinal cord. Furthermore, FMS IgG bound to human DRG. Our results demonstrate that IgG from FMS patients produces painful sensory hypersensitivities by sensitizing peripheral nociceptive afferents and suggest that therapies reducing patient IgG titers may be effective for fibromyalgia.


Assuntos
Fibromialgia/imunologia , Fibromialgia/fisiopatologia , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Fibromialgia/etiologia , Gânglios Espinais/fisiopatologia , Humanos , Imunização Passiva , Imunoglobulina G/administração & dosagem , Imunoglobulina G/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nociceptores/imunologia , Nociceptores/fisiologia , Dor/fisiopatologia , Limiar da Dor/fisiologia
11.
Life Sci ; 280: 119724, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34144059

RESUMO

AIMS: Gulf War Illness (GWI) is manifested as multiple chronic symptoms, including chronic pain, chronic fatigue, sleep problems, neuropsychiatric disorders, respiratory, gastrointestinal, and skin problems. No single target tissue or unifying pathogenic process has been identified that accounts for this variety of symptoms. The brainstem has been suspected to contribute to this multiple symptomatology. The aim of this study was to assess the role of the brainstem in chronic sleep problems and pain in GWI veterans. MATERIALS AND METHODS: We enrolled 90 veterans (Age = 50 ± 5, 87% Male) who were deployed to the 1990-91 Gulf War and presented with GWI symptoms. Sleep quality was evaluated using the global Pittsburgh Sleep Quality Index. Pain intensities were obtained with the Brief Pain Inventory sum score. Volumes in cortical, subcortical, brainstem, and brainstem subregions and diffusion tensor metrics in 10 bilateral brainstem tracts were tested for correlations with symptom measures. KEY FINDINGS: Poorer sleep quality was significantly correlated with atrophy of the whole brainstem and brainstem subregions (including midbrain, pons, medulla). Poorer sleep quality also significantly correlated with lower fractional anisotropy in the nigrostriatal tract, medial forebrain tract, and the dorsal longitudinal fasciculus. There was a significant correlation between increased pain intensity and decreased fractional anisotropy in the dorsal longitudinal fasciculus. These correlations were not altered after controlling for age, sex, total intracranial volumes, or additional factors, e.g., depression and neurological conditions. SIGNIFICANCE: These findings suggest that the brainstem plays an important role in the aberrant neuromodulation of sleep and pain symptoms in GWI.


Assuntos
Tronco Encefálico/fisiopatologia , Dor/etiologia , Síndrome do Golfo Pérsico/complicações , Síndrome do Golfo Pérsico/fisiopatologia , Transtornos do Sono-Vigília/etiologia , Tronco Encefálico/patologia , Doença Crônica , Feminino , Guerra do Golfo , Humanos , Masculino , Pessoa de Meia-Idade , Dor/patologia , Dor/fisiopatologia , Síndrome do Golfo Pérsico/patologia , Sono , Transtornos do Sono-Vigília/patologia , Transtornos do Sono-Vigília/fisiopatologia , Veteranos
12.
J Ayub Med Coll Abbottabad ; 33(2): 344-346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34137559

RESUMO

Synovial sarcoma (SS) is a rare and aggressive mesenchymal tumour accounting for around 5-10% soft tissue neoplasms usually found in joints of upper and lower extremities. A 35years old healthy looking male patient from Afghanistan presented with swelling on palmar side of base of thumb from last one year. Seven months back excisional biopsy was taken report of which showed neurofibroma/dermatofibroma with. No evidence of malignancy seen. From last 5months mass reappeared and gradually increased in size with itching sensation and mild pain. On local examination there was 5×4×5 cm reddish mass on palmar surface of base of thumb with extension into mid thenar eminence with diffuse margins. X-ray showed soft tissue density mass with spikes of calcification. Ultrasound showed 4.2×4×4.5 cm heterogeneous solid lesion on anteromedial surface of root of right thumb without any remarkable intralesional calcification and remarkable intralesional vasculature. MRI reported lobulated well defined soft tissue mass eliciting low to intermediate signal on T1 and WIs and bright signal on T2and STIR Vividly enhancing mass. Case was operated mass was excised and biopsy sent. Post op status was unremarkable. Biopsy reported poorly differentiated biphasic synovial sarcoma. No recurrence seen till 3months.


Assuntos
Sarcoma Sinovial/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Polegar/patologia , Adulto , Afeganistão , Biópsia , Humanos , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia , Dor/fisiopatologia , Prurido/fisiopatologia , Sarcoma Sinovial/diagnóstico por imagem , Sarcoma Sinovial/patologia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia
13.
FASEB J ; 35(7): e21747, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34151467

RESUMO

We tested the hypothesis that the cognitive impairment associated with inflammatory pain may result from dysregulation of the top-down control of locus ceruleus's (LC) activity by the medial prefrontal cortex (mPFC). Injection of complete Freund's adjuvant (CFA) served as a model for inflammatory pain. The CFA injection decreased the thermal thresholds in both sexes but only the male mice showed increased anxiety-like behavior and diminished cognition, while the females were not affected. Increased calcium fluorescence, a marker for neuronal activity, was detected by photometry in the mPFC of males but not in females with CFA. Next, while chemogenetic inhibition of the projections from the mPFC to the LC improved the object recognition memory of males with pain, the inhibition of the mPFC to LC pathway in female mice produced anxiolysis and spatial memory deficits. The behavior results prompted us to compare the reciprocal innervation of mPFC and LC between the sexes. We used an anterograde transsynaptic tagging technique, which relies on postsynaptic cre transfer, to assess the innervation of LC by mPFC efferents. The males showed a higher rate of postsynaptic cre transfer into LC neurons from mPFC efferents than the females. And vice versa, a retrograde tracing experiment demonstrated that LC to mPFC projection neurons were more numerous in females when compared to males. In conclusion, we provide evidence that subtle differences in the reciprocal neuronal circuit between the LC and mPFC may contribute to sex differences associated with the adverse cognitive effects of inflammatory pain.


Assuntos
Inflamação/fisiopatologia , Locus Cerúleo/fisiopatologia , Dor/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Feminino , Masculino , Transtornos da Memória/fisiopatologia , Camundongos , Neurônios/fisiologia , Caracteres Sexuais , Memória Espacial/fisiologia
14.
Nat Rev Neurosci ; 22(8): 458-471, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34127843

RESUMO

The sensory, associative and limbic neocortical structures play a critical role in shaping incoming noxious inputs to generate variable pain perceptions. Technological advances in tracing circuitry and interrogation of pathways and complex behaviours are now yielding critical knowledge of neocortical circuits, cellular contributions and causal relationships between pain perception and its abnormalities in chronic pain. Emerging insights into neocortical pain processing suggest the existence of neocortical causality and specificity for pain at the level of subdomains, circuits and cellular entities and the activity patterns they encode. These mechanisms provide opportunities for therapeutic intervention for improved pain management.


Assuntos
Analgesia , Neocórtex/fisiopatologia , Percepção da Dor/fisiologia , Dor/fisiopatologia , Animais , Humanos , Vias Neurais/fisiopatologia , Manejo da Dor
15.
Am J Physiol Regul Integr Comp Physiol ; 321(2): R186-R196, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34133246

RESUMO

An objective measure of pain remains an unmet need of people with chronic pain, estimated to be 1/3 of the adult population in the United States. The current gold standard to quantify pain is highly subjective, based upon self-reporting with numerical or visual analog scale (VAS). This subjectivity complicates pain management and exacerbates the epidemic of opioid abuse. We have tested classification and regression machine learning models to objectively estimate pain sensation in healthy subjects using electrodermal activity (EDA). Twenty-three volunteers underwent pain stimulation using thermal grills. Three different "pain stimulation intensities" were induced for each subject, who reported the "pain sensation" right after each stimulus using a VAS (0-10). EDA data were collected throughout the experiment. For machine learning, we computed validated features of EDA based on time-domain decomposition, spectral analysis, and differential features. Models for estimation of pain stimulation intensity and pain sensation achieved maximum macroaveraged geometric mean scores of 69.7% and 69.2%, respectively, when three classes were considered ("No," "Low," and "High"). Regression of levels of stimulation intensity and pain sensation achieved R2 values of 0.357 and 0.47, respectively. Overall, the high variance and inconsistency of VAS scores led to lower performance of pain sensation classification, but regression was better for pain sensation than stimulation intensity. Our results provide that three levels of pain can be quantified with good accuracy and physiological evidence that sympathetic responses recorded by EDA are more correlated to the applied stimuli's intensity than to the pain sensation reported by the subject.


Assuntos
Eletrodiagnóstico , Aprendizado de Máquina , Medição da Dor , Percepção da Dor , Limiar da Dor , Dor/diagnóstico , Processamento de Sinais Assistido por Computador , Pele/inervação , Sistema Nervoso Simpático/fisiopatologia , Adulto , Estudos de Viabilidade , Feminino , Resposta Galvânica da Pele , Temperatura Alta , Humanos , Masculino , Dor/etiologia , Dor/fisiopatologia , Dor/psicologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Adulto Jovem
16.
Neuroimage ; 238: 118249, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34116146

RESUMO

Previous behavioral studies have shown that sharing painful experiences can strengthen social bonds and promote mutual prosociality, yet the neural mechanisms underlying this phenomenon remain unclear. We hypothesized that sharing a painful experience induces brain-to-brain synchronization and mutual empathy for each other's pain between pain-takers and pain-observers, which then leads to enhanced social bonding. To test this hypothesis, we adopted an electroencephalographic (EEG) hyper-scanning technique to assess neuronal and behavioral activity during a Pain-Sharing task in which high- or low-intensity pain stimulation was randomly delivered to one participant of a dyad on different experimental trials. Single-brain analysis showed that sensorimotor α-oscillation power was suppressed more when expecting high-intensity pain than when expecting low-intensity pain similarly for self-directed or partner-directed pain. Dual-brain analysis revealed that expecting high-intensity pain induced greater brain-to-brain synchronization of sensorimotor α-oscillation phases between pain-takers and pain-observers than did expecting low-intensity pain. Mediation analysis further revealed that brain-to-brain synchronization of sensorimotor α-oscillations mediated the effects of pain-stimulation intensity on mutual affective sharing for partner-directed pain. This mutual affective empathy during the task predicted the social bonding, as indexed by prosocial inclinations measured after the task. These results support the hypothesis that sharing a painful experience triggers emotional resonance between pairs of individuals through brain-to-brain synchronization of neuronal α-oscillations recorded over the sensorimotor cortex, and this emotional resonance further strengthens social bonds and motivates prosocial behavior within pairs of individuals.


Assuntos
Encéfalo/fisiopatologia , Empatia/fisiologia , Dor/fisiopatologia , Adolescente , Eletroencefalografia , Emoções , Feminino , Humanos , Masculino , Dor/psicologia , Comportamento Social , Adulto Jovem
17.
PLoS Comput Biol ; 17(6): e1009097, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34101729

RESUMO

The amygdala is a brain area involved in emotional regulation and pain. Over the course of the last 20 years, multiple researchers have studied sensory and motor connections within the amygdala in trying to understand the ultimate role of this structure in pain perception and descending control of pain. A number of investigators have been using cell-type specific manipulations to probe the underlying circuitry of the amygdala. As data have accumulated in this research space, we recognized a critical need for a single framework to integrate these data and evaluate emergent system-level responses. In this manuscript, we present an agent-based computational model of two distinct inhibitory neuron populations in the amygdala, those that express protein kinase C delta (PKCδ) and those that express somatostatin (SOM). We utilized a network of neural links to simulate connectivity and the transmission of inhibitory signals between neurons. Type-specific parameters describing the response of these neurons to noxious stimuli were estimated from published physiological and immunological data as well as our own wet-lab experiments. The model outputs an abstract measure of pain, which is calculated in terms of the cumulative pro-nociceptive and anti-nociceptive activity across neurons in both hemispheres of the amygdala. Results demonstrate the ability of the model to produce changes in pain that are consistent with published studies and highlight the importance of several model parameters. In particular, we found that the relative proportion of PKCδ and SOM neurons within each hemisphere is a key parameter in predicting pain and we explored model predictions for three possible values of this parameter. We compared model predictions of pain to data from our earlier behavioral studies and found areas of similarity as well as distinctions between the data sets. These differences, in particular, suggest a number of wet-lab experiments that could be done in the future.


Assuntos
Núcleo Central da Amígdala/fisiologia , Modelos Neurológicos , Dor/fisiopatologia , Animais , Núcleo Central da Amígdala/lesões , Núcleo Central da Amígdala/fisiopatologia , Biologia Computacional , Modelos Animais de Doenças , Dominância Cerebral/fisiologia , Fenômenos Eletrofisiológicos , Humanos , Técnicas In Vitro , Masculino , Camundongos , Rede Nervosa/fisiologia , Rede Nervosa/fisiopatologia , Neuralgia/fisiopatologia , Neurônios/classificação , Neurônios/fisiologia , Proteína Quinase C-delta/metabolismo , Somatostatina/metabolismo , Análise de Sistemas
18.
Commun Biol ; 4(1): 553, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976383

RESUMO

The formation and persistence of negative pain-related expectations by classical conditioning remain incompletely understood. We elucidated behavioural and neural correlates involved in the acquisition and extinction of negative expectations towards different threats across sensory modalities. In two complementary functional magnetic resonance imaging studies in healthy humans, differential conditioning paradigms combined interoceptive visceral pain with somatic pain (study 1) and aversive tone (study 2) as exteroceptive threats. Conditioned responses to interoceptive threat predictors were enhanced in both studies, consistently involving the insula and cingulate cortex. Interoceptive threats had a greater impact on extinction efficacy, resulting in disruption of ongoing extinction (study 1), and selective resurgence of interoceptive CS-US associations after complete extinction (study 2). In the face of multiple threats, we preferentially learn, store, and remember interoceptive danger signals. As key mediators of nocebo effects, conditioned responses may be particularly relevant to clinical conditions involving disturbed interoception and chronic visceral pain.


Assuntos
Extinção Psicológica/fisiologia , Aprendizagem/fisiologia , Dor/fisiopatologia , Adulto , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Dor Nociceptiva/fisiopatologia , Dor Visceral/fisiopatologia
19.
Phys Ther Sport ; 50: 139-144, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34020290

RESUMO

OBJECTIVES: Fear of movement may be a source of systemic bias in studies reporting functional deficits in patients with Achilles tendinopathy. The purpose of this study was to assess the effects of kinesiophobia on completion rate and performance on tests evaluating lower extremity function, while controlling for self-reported pain. DESIGN: Cross-sectional study; SETTING: Tendon research laboratory. PARTICIPANTS: Ninety-four participants with Achilles tendinopathy. MAIN OUTCOME MEASURES: Completion (yes/no) and performance (cm) on the counter-movement jump, hopping, and drop counter-movement jump. RESULTS: The models fit the data (R^2 = 0.81, both models). TSK score did not predict completion (beta = -0.01, 95% CI = -0.13 - 0.09, P = 0.74) but pain did (beta = -0.36, 95% CI = -0.53 to -0.19, P < 0.0001). TSK score did not predict performance (beta = -0.06, 95% CI = -0.14 - 0.003, P = 0.07), but pain did (beta = -0.15, 95% CI = -0.22 to -0.07, P < 0.0001). CONCLUSIONS: Kinesiophobia did not affect the physical performance tests in patients with Achilles tendinopathy. Measures of physical performance should be interpreted alongside self-reported pain.


Assuntos
Tendão do Calcâneo/lesões , Medo , Dor/fisiopatologia , Dor/psicologia , Tendinopatia/fisiopatologia , Tendinopatia/psicologia , Tendão do Calcâneo/fisiopatologia , Adulto , Estudos Transversais , Teste de Esforço/métodos , Feminino , Humanos , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Movimento , Medição da Dor , Desempenho Físico Funcional , Autorrelato
20.
J Athl Train ; 56(5): 473-483, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34000018

RESUMO

CONTEXT: Athletes are often exposed to pain due to injury and competition. Using preliminary evidence, researchers have shown that cardiovascular measures could be an objective measure of pain, but the cardiovascular response can be influenced by psychological factors, such as catastrophizing. OBJECTIVE: To use a painful cold-pressor test (CPT) to measure the relationship among catastrophizing, pain, and cardiovascular variables in athletes. DESIGN: Cohort study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 36 male rugby athletes (age = 24.0 ± 4.6 years, height = 180.0 ± 6.1 cm, mass = 90.5 ± 13.8 kg). MAIN OUTCOME MEASURE(S): We measured catastrophizing using the Pain Catastrophizing Scale and pain using a numeric pain rating scale. Cardiovascular measures were heart rate, systolic and diastolic blood pressure, and heart rate variability. RESULTS: During the CPT, participants experienced increases in pain (from 0 to 4.1 ± 2.2), systolic blood pressure (from 126.7 ± 16.5 to 149.7 ± 23.4 mm Hg), diastolic blood pressure (from 76.9 ± 8.3 to 91.9 ± 11.5 mm Hg), and heart rate variability (from 0.0164 ± 0.0121 to 0.0400 ± 0.0323 milliseconds; all P values < .001). In addition, we observed a decrease in heart rate after the CPT (P = .04). We found a correlation between athletes' pain catastrophizing and both pain intensity and change in heart rate during the CPT (P = .02 and P = .003, respectively). Linear regression indicated that pain and catastrophizing explained 29% of the variance in the change in heart rate (P = .003). CONCLUSIONS: Athletes who had catastrophizing thoughts were more likely to experience higher levels of pain and a greater cardiovascular response during a painful stimulus. The change in cardiovascular variables may be a good objective measure of pain in athletes in the future.


Assuntos
Atletas/psicologia , Pressão Sanguínea/fisiologia , Catastrofização , Frequência Cardíaca/fisiologia , Medição da Dor/métodos , Dor , Adulto , Catastrofização/fisiopatologia , Catastrofização/psicologia , Estudos de Coortes , Resposta ao Choque Frio , Feminino , Humanos , Masculino , Dor/fisiopatologia , Dor/psicologia
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