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1.
J Oral Rehabil ; 50(2): 99-112, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36373958

RESUMO

BACKGROUND: The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) are used worldwide in adults. Until now, no adaptation for use in children has been proposed. OBJECTIVE: The aim of this study was to present comprehensive and short-form adaptations of Axis I and Axis II of the DC/TMD for adults that are appropriate for use with children in clinical and research settings. METHODS: Global Delphi studies with experts in TMDs and in pain psychology identified ways of adapting the DC/TMD for children. RESULTS: The proposed adaptation is suitable for children aged 6-9 years. Proposed changes in Axis I include (i) adapting the language of the Demographics and the Symptom Questionnaires to be developmentally appropriate for children, (ii) adding a general health questionnaire for children and one for their parents, (iii) replacing the TMD Pain Screener with the 3Q/TMD questionnaire and (iv) modifying the clinical examination protocol. Proposed changes in Axis II include (i) for the Graded Chronic Pain Scale, to be developmentally appropriate for children, (ii) adding anxiety and depression assessments that have been validated in children and (iii) adding three constructs (stress, catastrophising and sleep disorders) to assess psychosocial functioning in children. CONCLUSION: The recommended DC/TMD, including Axis I and Axis II, for children aged 6-9 years, is appropriate for use in clinical and research settings. This adapted the first version for children includes changes in Axis I and Axis II changes requiring reliability and validity testing in international settings. Official translations to different languages according to INfORM requirements will enable a worldwide dissemination and implementation.


Assuntos
Dor Crônica , Transtornos da Articulação Temporomandibular , Adulto , Criança , Humanos , Dor Facial/diagnóstico , Reprodutibilidade dos Testes , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/psicologia , Medição da Dor
2.
J Oral Rehabil ; 50(11): 1167-1180, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37144484

RESUMO

BACKGROUND: The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for use in adults is in use worldwide. Until now, no version of this instrument for use in adolescents has been proposed. OBJECTIVE: To present comprehensive and short-form adaptations of the adult version of DC/TMD that are appropriate for use with adolescents in clinical and research settings. METHODS: International experts in TMDs and experts in pain psychology participated in a Delphi process to identify ways of adapting the DC/TMD protocol for physical and psychosocial assessment of adolescents. RESULTS: The proposed adaptation defines adolescence as ages 10-19 years. Changes in the physical diagnosis (Axis I) include (i) adapting the language of the Demographics and the Symptom Questionnaires to be developmentally appropriate for adolescents, (ii) adding two general health questionnaires, one for the adolescent patient and one for their caregivers and (iii) replacing the TMD Pain Screener with the 3Q/TMD questionnaire. Changes in the psychosocial assessment (Axis II) include (i) adapting the language of the Graded Chronic Pain Scale to be developmentally appropriate for adolescents, (ii) adding anxiety and depression assessment that have been validated for adolescents and (iii) adding three constructs (stress, catastrophizing and sleep disorders) to assess psychosocial functioning in adolescents. CONCLUSION: The recommended DC/TMD, including Axis I and Axis II for adolescents, is appropriate to use in clinical and research settings. This adapted first version for adolescents includes changes in Axis I and Axis II requiring reliability and validity testing in international settings. Official translations of the comprehensive and short-form to different languages according to INfORM requirements will enable a worldwide dissemination and implementation.


Assuntos
Dor Crônica , Transtornos da Articulação Temporomandibular , Adulto , Adolescente , Humanos , Reprodutibilidade dos Testes , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/psicologia , Medição da Dor/métodos , Idioma , Dor Facial/diagnóstico
3.
Headache ; 62(6): 668-680, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35467018

RESUMO

OBJECTIVE: This case-control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents. BACKGROUND: Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity. METHODS: Twenty adolescents with migraine and 20 healthy controls were recruited from Cincinnati Children's Hospital. Participants completed surveys about their headaches and overall sleep quality, sleep hygiene, and perceived sleep difficulties (Insomnia Severity Scale [ISI]); completed wrist-worn actigraphy; and underwent a magnetic resonance imaging scan. RESULTS: Adolescents with migraine differed from healthy controls only in perceived difficulty in sleep initiation and maintenance (ISI: 8.5 ± 4.7 and 4.5 ± 3.7 [mean ± standard deviation], -4.00 [95% confidence: -6.7 to -1.3], p = 0.005) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. The differences in functional connectivity of the amygdala were not mediated by the subjective/objective sleep measures (ISI/wake minutes after sleep onset). CONCLUSIONS: Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.


Assuntos
Transtornos de Enxaqueca , Distúrbios do Início e da Manutenção do Sono , Adolescente , Tonsila do Cerebelo/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Humanos , Imageamento por Ressonância Magnética/métodos , Transtornos de Enxaqueca/diagnóstico por imagem , Sono
4.
J Oral Rehabil ; 49(5): 541-552, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34951729

RESUMO

BACKGROUND: Unlike the psychosocial assessment established for adults in the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), a standardised psychosocial assessment for children and adolescents with TMD complaints has not yet been established. OBJECTIVES: To develop a new standardised instrument set to assess the psychosocial functioning in children and adolescents by adapting the psychosocial status and pain-related disability (Axis II) of the adult DC/TMD and by including new instruments. METHODS: A modified Delphi method was used to survey 23 international TMD experts and four international experts in pain-related psychological factors for consensus regarding assessment tools for psychosocial functioning and pain-related disability in children and adolescents. The TMD experts reviewed 29 Axis II statements at round 1, 13 at round 2 and 2 at round 3. Agreement was set at 80% for first-round consensus level and 70% for each of the second and third rounds. The psychological experts completed a complementary Delphi survey to reach a consensus on tools to use to assess more complex psychological domains in children and adolescents. For the psychological experts, the first round included 10 open-ended questions on preferred screening tools for depression, anxiety, catastrophising, sleep problems and stress in children (ages 6-9 years old) and adolescents (ages 10-19 years old) as well as on other domains suggested for investigation. In the second round, the psychological experts received a 9-item questionnaire to prioritise the suggested instruments from most to least recommended. RESULTS: The TMD experts, after three Delphi rounds, reached consensus on the changes of DC/TMD to create a form to evaluate Axis II in children and adolescents with TMD complaints. The psychological experts added tools to assess depression and anxiety, sleep disorders, catastrophising, stress and resilience. CONCLUSION: Through international expert consensus, this study adapted Axis II of the adult DC/TMD to assess psychosocial functioning and pain-related disability in children and adolescents. The adapted Axis II protocols will be validated in the target populations.


Assuntos
Transtornos do Sono-Vigília , Transtornos da Articulação Temporomandibular , Adolescente , Adulto , Ansiedade/diagnóstico , Ansiedade/psicologia , Criança , Técnica Delphi , Humanos , Dor , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/psicologia , Adulto Jovem
5.
Headache ; 61(3): 485-492, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33231888

RESUMO

OBJECTIVE: To compare spatial pain modulation capabilities between adolescents with and without migraine. BACKGROUND: Conditioned pain modulation (CPM) responses at the leg are similar in adolescents with versus without migraine. However, the anatomical region of testing may affect spatial pain modulation capabilities as differences in nociceptive processing between patients with migraine and healthy controls are found in local areas that are near the site of clinical pain but not in nonlocal areas. This study aimed to examine spatial pain modulation capabilities tested by the CPM paradigm using test stimulus applied to a local body area. METHODS: Nineteen adolescents with migraine (age 14.9 ± 2.3, mean ± SD; 16 female) and 20 healthy adolescents (age 13.8 ± 2.5, mean ± SD; 16 female) completed this case-control study at Cincinnati Children's Hospital Medical Center. Pressure pain thresholds (PPT) were assessed at the trapezius before and during immersion of the foot in a cold water bath (8°C). RESULTS: In the migraine group (146.0 ± 79.1, mean ± SD), compared to healthy controls (248.0 ± 145.5, mean ± SD), significantly lower PPT (kilopascal) values were found (estimate = 124.28, 95% CI: 58.98, 189.59, p < 0.001; effect size: d = 1.40). No differences between the groups were found for pain intensity and unpleasantness ratings of cold-water immersion nor the CPM response. CONCLUSIONS: This study found altered ascending nociceptive processing of mechanical stimuli at the neck in adolescents with migraine. However, endogenous pain modulatory mechanisms were functional and not altered. In light of other studies, impairments in inhibitory control may not be involved in migraine pathophysiology in pediatric patients regardless of stimulus location.


Assuntos
Transtornos de Enxaqueca/fisiopatologia , Nociceptividade/fisiologia , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Perna (Membro)/fisiologia , Masculino , Pescoço/fisiologia , Medição da Dor , Índice de Gravidade de Doença , Músculos Superficiais do Dorso/fisiologia
6.
Pain Med ; 22(11): 2426-2435, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34175959

RESUMO

OBJECTIVE: Virtual reality is a promising method to manage pain. Distraction-based virtual reality (VR-D) is thought to reduce pain by redirecting attention. Although VR-D can reduce pain associated with acutely painful procedures, it is unclear whether VR-D can reduce pain after surgery. We assessed the ability of a single VR-D session to decrease postoperative pain and anxiety and explored whether pain catastrophizing and anxiety sensitivity influenced these outcomes in children after surgery. DESIGN: Single-center, prospective, pilot study. SETTING: Cincinnati Children's Hospital Medical Center (CCHMC). SUBJECTS: Fifty children (7-21 years of age) with postoperative pain followed by the Acute Pain Service. METHODS: Patients received one VR-D session after surgery. Before the session, patients completed pain catastrophizing (Pain Catastrophizing Scale for Children) and anxiety sensitivity (Child Anxiety Sensitivity Index) questionnaires. The primary outcome consisted of changes in pain intensity after VR-D (immediately, 15 minutes, and 30 minutes). Secondary outcomes included changes in pain unpleasantness and anxiety. RESULTS: VR-D use was associated with a decrease in pain intensity immediately and 15 minutes after VR-D. Reductions in pain unpleasantness were observed up to 30 minutes after VR-D. VR-D was also associated with a reduction in anxiety immediately and at 15 minutes. Although patients with higher pain catastrophizing had higher baseline pain intensity and unpleasantness, they did not show larger pain reductions after VR-D than those with lower pain catastrophizing. CONCLUSIONS: VR-D may be beneficial in transiently reducing pain intensity, unpleasantness, and anxiety in children with postoperative pain. This study informs the design of a larger, randomized, controlled study assessing VR-D for acute postoperative pain and anxiety management.


Assuntos
Dor Pós-Operatória , Realidade Virtual , Ansiedade , Criança , Humanos , Projetos Piloto , Estudos Prospectivos
7.
J Med Internet Res ; 23(7): e26328, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34048358

RESUMO

BACKGROUND: Distraction-based therapies, such as virtual reality (VR), have been used to reduce pain during acutely painful procedures. However, distraction alone cannot produce prolonged pain reduction to manage sustained postoperative pain. Therefore, the integration of VR with other pain-reducing therapies, like guided relaxation, may enhance its clinical impact. OBJECTIVE: The goal of this pilot study was to assess the impact of a single guided relaxation-based VR (VR-GR) session on postoperative pain and anxiety reduction in children. We also explored the influence of pain catastrophizing and anxiety sensitivity on this association. METHODS: A total of 51 children and adolescents (7-21 years) with postoperative pain and followed by the Acute Pain Service at Cincinnati Children's Hospital were recruited over an 8-month period to undergo a single VR-GR session. Prior to VR, the patients completed 2 questionnaires: Pain Catastrophizing Scale for Children (PCS-C) and the Child Anxiety Sensitivity Index (CASI). The primary outcome was a change in pain intensity following the VR-GR session (immediately, 15 minutes, and 30 minutes). The secondary outcomes included changes in pain unpleasantness and anxiety. RESULTS: The VR-GR decreased pain intensity immediately (P<.001) and at 30 minutes (P=.04) after the VR session, but not at 15 minutes (P=.16) postsession. Reductions in pain unpleasantness were observed at all time intervals (P<.001 at all intervals). Anxiety was reduced immediately (P=.02) but not at 15 minutes (P=.08) or 30 minutes (P=.30) following VR-GR. Patients with higher CASI scores reported greater reductions in pain intensity (P=.04) and unpleasantness (P=.01) following VR-GR. Pain catastrophizing was not associated with changes in pain and anxiety. CONCLUSIONS: A single, short VR-GR session showed transient reductions in pain intensity, pain unpleasantness, and anxiety in children and adolescents with acute postoperative pain. The results call for a future randomized controlled trial to assess the efficacy of VR-GR. TRIAL REGISTRATION: ClinicalTrials.gov NCT04556747; https://clinicaltrials.gov/ct2/show/NCT04556747.


Assuntos
Realidade Virtual , Adolescente , Ansiedade/prevenção & controle , Transtornos de Ansiedade , Criança , Humanos , Dor Pós-Operatória/terapia , Projetos Piloto
8.
J Med Internet Res ; 23(4): e25916, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33667177

RESUMO

BACKGROUND: Virtual reality (VR) and augmented reality (AR) interventions are emerging as promising tools in the treatment of pediatric chronic pain conditions. However, in this young field, there is little consensus to guide the process of engaging in the development and evaluation of targeted VR-based interventions. OBJECTIVE: The INOVATE-Pain (Interdisciplinary Network on Virtual and Augmented Technologies for Pain management) consortium aims to advance the field of VR for pediatric chronic pain rehabilitation by providing guidance for best practices in the design, evaluation, and dissemination of VR-based interventions targeting this population. METHODS: An interdisciplinary meeting of 16 academics, clinicians, industry partners, and philanthropy partners was held in January 2020. RESULTS: Reviewing the state of the field, the consortium identified important directions for research-driven innovation in VR and AR clinical care, highlighted key opportunities and challenges facing the field, and established a consensus on best methodological practices to adopt in future efforts to advance the research and practice of VR and AR in pediatric pain. The consortium also identified important next steps to undertake to continue to advance the work in this promising new area of digital health pain interventions. CONCLUSIONS: To realize the promise of this realm of innovation, key ingredients for success include productive partnerships among industry, academic, and clinical stakeholders; a uniform set of outcome domains and measures for standardized evaluation; and widespread access to the latest opportunities, tools, and resources. The INOVATE-Pain collaborative hopes to promote the creation, rigorous yet efficient evaluation, and dissemination of innovative VR-based interventions to reduce pain and improve quality of life for children.


Assuntos
Realidade Aumentada , Dor Crônica , Realidade Virtual , Adolescente , Criança , Dor Crônica/terapia , Humanos , Manejo da Dor , Qualidade de Vida
9.
Headache ; 60(6): 1165-1182, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32323877

RESUMO

OBJECTIVES: This basic mechanistic study examined the changes in brain activation and resting-state connectivity after 8 weeks of CBT in youth with migraine. BACKGROUND: Cognitive behavioral therapy (CBT) is a psychological intervention that is effective in reducing pain in migraine patients. However, the neural mechanisms underlying CBT in adolescents with migraine are not yet known. METHODS: Eighteen adolescents with migraine (15 females, age 15.1 ± 2.1 years [mean ± SD]) completed 8 weekly CBT sessions. Before the first and after the final CBT session, participants underwent structural and resting-state blood-oxygen-level-dependent contrast MRI scans. Arterial spin labeling was also used to examine brain activation during the resting state. For connectivity analyses, the right and left amygdala were chosen as seed regions. Relationships of the time courses within these seeds with voxels across the whole brain were evaluated. RESULTS: Headache frequency decreased from 15 ± 7.4 headaches per month before CBT to 10 ± 7.4 after CBT (P < .001). After CBT, greater brain activations in frontal regions involved in cognitive regulation of pain were found. In addition, after CBT increased connectivity between the amygdala and frontal regions was observed. Associations between brain activation and amygdalar connectivity with a reduction in headache frequency were also observed. CONCLUSIONS: Alterations in brain function and amygdalar connectivity with areas involved in nociceptive processing, cognitive function, and emotional regulation may underlie the ability of CBT to aid in the prevention of headaches in migraine patients.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Terapia Cognitivo-Comportamental , Conectoma , Lobo Frontal/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Transtornos de Enxaqueca/terapia , Adolescente , Tonsila do Cerebelo/diagnóstico por imagem , Criança , Seguimentos , Lobo Frontal/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos de Enxaqueca/diagnóstico por imagem , Resultado do Tratamento
10.
Pain Med ; 21(9): 1961-1970, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32337554

RESUMO

OBJECTIVE: Mental, emotional, physical, and general fatigue, as well as vigor, have each been associated with pain interference-defined as pain-related disruption of social, recreational, and work-related activities-in patients with chronic orofacial pain (COFP). The objectives of the current study were to compare levels of these fatigue subtypes across younger, middle-aged, and older patients with COFP and test the associations between fatigue subtypes and pain interference in these age groups. DESIGN: A cross-sectional cohort design was used. SETTING: Participants self-reported fatigue subtypes (Multidimensional Fatigue Symptom Inventory-Short Form), pain interference (West Haven-Yale Multidimensional Pain Inventory), pain intensity (visual analog scale), pain duration (months), depression (Symptom Checklist 90-Revised), and sleep quality (Pittsburgh Sleep Quality Index) at their initial appointment at a tertiary orofacial pain clinic. SUBJECTS: Sixty younger (age 18-39), 134 middle-aged (age 40-59), and 51 older (age 60-79) COFP patients provided data for the study. METHODS: Analysis of variance was used to compare levels of fatigue subtypes between the age groups. Regression with dummy-coding was used to test if the relationship between fatigue subtypes and pain interference varied by age. RESULTS: Older COFP patients reported less general fatigue and more vigor than younger or middle-aged adults. Fatigue subtypes were each associated with greater pain interference, but associations became nonsignificant after controlling for depression, sleep, and pain intensity/duration. Age group-by-fatigue subtype interactions were not observed. CONCLUSIONS: Managing fatigue may be important to reduce pain interference in COFP populations and may be accomplished in part by improving depression and sleep.


Assuntos
Dor Crônica , Transtornos do Sono-Vigília , Adolescente , Adulto , Idoso , Dor Crônica/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Dor Facial/epidemiologia , Fadiga/epidemiologia , Humanos , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Adulto Jovem
11.
Int J Behav Med ; 26(2): 217-229, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30809770

RESUMO

BACKGROUND: The current studies investigated associations between pain intensity and pain frequency with loneliness, hostility, and social functioning using cross-sectional, longitudinal, and within-person data from community-dwelling adults with varying levels of pain. METHOD: Secondary analysis of preexisting data was conducted. Study 1 investigated cross-sectional (baseline data: n = 741) and longitudinal (follow-up data: n = 549, observed range between baseline and follow-up: 6-53 months) associations. Study 2 tested within-person associations using daily diaries across 30 days from a subset of the participants in Study 1 (n = 69). RESULTS: Cross-sectionally, pain intensity and frequency were associated with higher loneliness (ßintensity = 0.16, ßfrequency = 0.17) and worse social functioning (ßintensity = - 0.40, ßfrequency = - 0.34). Intensity was also associated with higher hostility (ß = 0.11). Longitudinally, pain intensity at baseline predicted hostility (ß = 0.19) and social functioning (ß = - 0.20) at follow-up, whereas pain frequency only predicted social functioning (ß = - 0.21). Within people, participants reported higher hostility (γ = 0.002) and worse social functioning (γ = - 0.013) on days with higher pain, and a significant average pain by daily pain interaction was found for loneliness. Pain intensity did not predict social well-being variables on the following day. CONCLUSION: Pain intensity and frequency were associated with social well-being, although the effects were dependent on the social well-being outcome and the time course being examined.


Assuntos
Hostilidade , Relações Interpessoais , Solidão/psicologia , Dor/psicologia , Adulto , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
13.
Adm Policy Ment Health ; 46(6): 807-820, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31584109

RESUMO

Adolescent psychiatric rehospitalizations are common, cause patients and their families severe psychological distress, and use tremendous healthcare resources. This study sought to identify predictors of rehospitalization in 783 adolescents in the 2 year period following psychiatric hospitalization at a major treatment facility in a large urban area. A current diagnosis of posttraumatic stress disorder, greater severity of lifetime suicidal ideation (SI) and stronger treatment alliance prior to hospitalization were associated with a greater likelihood of rehospitalization. Overall, severe lifetime SI was the strongest predictor of rehospitalization; although, within the first 4 months post-discharge, moderate lifetime SI was the strongest predictor. Future research should continue to identify additional factors that may influence rehospitalization, such as the intensity of post-discharge services.


Assuntos
Hospitalização , Transtornos Mentais , Readmissão do Paciente/tendências , Adolescente , Boston , Criança , Registros Eletrônicos de Saúde , Feminino , Previsões , Humanos , Masculino , Alta do Paciente , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos , Ideação Suicida
14.
Mol Pain ; 13: 1744806917724259, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28741447

RESUMO

Abstract: Pain is one of the most prominent symptoms of osteoarthritis. However, there is often discordance between the pain experienced by individuals with osteoarthritis and the degree of articular pathology. This suggests that individual differences, including genetic variability in the central processing of nociceptive stimuli, may impact the presentation of osteoarthritis. Here, we show that the single nucleotide polymorphism rs16868943 in the collagen gene COL11A2 is significantly associated with lowered heat pain tolerance on the arm in participants with knee osteoarthritis (P = 1.21 × 10−6, P = 0.0053 after Bonferroni correction, beta = −3.42). A total of 161 knee osteoarthritis participants were included and evaluated for heat, punctate and pressure pain sensitivity of the affected knee and the ipsilateral arm. Each participant was genotyped for 4392 single nucleotide polymorphisms in genes implicated in pain perception, inflammation and mood and tested for association with pain sensitivity. The minor A allele of single nucleotide polymorphism rs16868943 was significantly associated with lower arm heat pain tolerance after correction for age, gender, race, and study site. This single nucleotide polymorphism was also nominally associated with other measures of heat pain sensitivity, including lowered knee heat pain tolerance (P = 1.14 × 10−5, P = 0.05 after Bonferroni correction), lowered arm heat pain threshold (P = 0.0039, uncorrected) and lowered knee heat pain threshold (P = 0.003, uncorrected). Addition of genotypes from 91 participants without knee pain produced a significant interaction between knee osteoarthritis status and the rs16868943 single nucleotide polymorphism in heat pain tolerance (P = 1.71 × 10−5), such that rs16868943 was not associated with heat pain tolerance in participants without knee pain (P = 0.12, beta = 1.3). This is the first study to show genetic association with heat pain tolerance in individuals with osteoarthritis. The association is specific to participants who have already developed knee osteoarthritis, suggesting that the COL11A2 gene, which has previously been associated with familial osteoarthritis, may play a role in pain sensitization after the development of osteoarthritis.


Assuntos
Colágeno Tipo XI/genética , Osteoartrite do Joelho/genética , Percepção da Dor/efeitos dos fármacos , Dor/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Feminino , Genótipo , Temperatura Alta , Humanos , Articulação do Joelho/metabolismo , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Medição da Dor/métodos
15.
J Pharmacol Exp Ther ; 360(1): 1-13, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27754931

RESUMO

Autotaxin (ATX) is a secreted glycoprotein that converts lysophosphatidylcholine (LPC) to the bioactive phospholipid lysophosphatidic acid (LPA) and is the major enzyme generating circulating LPA. Inhibition of LPA signaling has profound antifibrotic effects in multiple organ systems, including lung, kidney, skin, and peritoneum. However, other LPA-generating pathways exist, and the role of ATX in localized tissue LPA production and fibrosis remains unclear and controversial. In this study, we describe the preclinical pharmacologic, pharmacokinetic, and pharmacodynamic properties of a novel small-molecule ATX inhibitor, PAT-505 [3-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl) thio)-2-fluorobenzoic acid sodium salt]. PAT-505 is a potent, selective, noncompetitive inhibitor that displays significant inhibition of ATX activity in plasma and liver tissue after oral administration. When dosed therapeutically in a Stelic Mouse Animal Model of nonalcoholic steatohepatitis (NASH), PAT-505 treatment resulted in a small but significant improvement in fibrosis with only minor improvements in hepatocellular ballooning and hepatic inflammation. In a choline-deficient, high-fat diet model of NASH, therapeutic treatment with PAT-505 robustly reduced liver fibrosis with no significant effect on steatosis, hepatocellular ballooning, or inflammation. These data demonstrate that inhibiting autotaxin is antifibrotic and may represent a novel therapeutic approach for the treatment of multiple fibrotic liver diseases, including NASH.


Assuntos
Inibidores Enzimáticos/farmacologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/enzimologia , Diester Fosfórico Hidrolases/metabolismo , Piperazinas/farmacologia , Animais , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Masculino , Camundongos , Piperazinas/farmacocinética , Piperazinas/uso terapêutico
17.
Psychosom Med ; 76(4): 302-10, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24804882

RESUMO

OBJECTIVE: Enhanced pain facilitation is reportedly an important contributor to the clinical pain experiences of individuals with knee osteoarthritis (OA). Ethnic differences in the prevalence and severity of knee OA in addition to associated pain are also well documented. Temporal summation (TS) of pain is a widely applicable quantitative sensory testing method that invokes neural mechanisms related to pain facilitatory processes. This study tested whether TS of pain, an index of pain facilitation, differentially predicts the clinical pain experiences of African Americans and non-Hispanic whites with symptomatic knee OA. METHODS: A total of 225 study participants underwent assessment of TS of mechanical and heat pain stimuli applied to their most symptomatic knee and their ipsilateral hand (mechanical) or forearm (heat). Using telephone-based surveys, participants subsequently reported their average and worst clinical pain severity across four consecutive weeks after the assessment of TS. RESULTS: In predicting future clinical pain, ethnicity interacted with TS of mechanical pain (but not heat pain), such that TS of mechanical pain at the knee significantly predicted greater clinical ratings of average (b = 0.02, p = .016) and worst (b = 0.02, p = .044) clinical pain for non-Hispanic whites but not African Americans (p values > .30). CONCLUSIONS: These results reveal the importance of considering ethnicity when examining pain facilitation and the clinical pain of individuals with symptomatic knee OA. The results of this study are discussed in terms of ethnic differences in the predictors of clinical pain experiences among African Americans and non-Hispanic whites with knee OA.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Osteoartrite do Joelho/etnologia , Limiar da Dor/fisiologia , Dor/etnologia , População Branca/estatística & dados numéricos , Negro ou Afro-Americano/psicologia , Índice de Massa Corporal , Feminino , Temperatura Alta/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Medição da Dor/métodos , Estimulação Física/métodos , Prevalência , Estudos Prospectivos , Análise de Regressão , Índice de Gravidade de Doença , Fatores de Tempo , População Branca/psicologia
18.
Ann Behav Med ; 48(1): 50-60, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24352850

RESUMO

BACKGROUND: Pain hypervigilance is an important aspect of the fear-avoidance model of pain that may help explain individual differences in pain sensitivity among persons with knee osteoarthritis (OA). PURPOSE: The purpose of this study was to examine the contribution of pain hypervigilance to clinical pain severity and experimental pain sensitivity in persons with symptomatic knee OA. METHODS: We analyzed cross-sectional data from 168 adults with symptomatic knee OA. Quantitative sensory testing was used to measure sensitivity to heat pain, pressure pain, and cold pain, as well as temporal summation of heat pain, a marker of central sensitization. RESULTS: Pain hypervigilance was associated with greater clinical pain severity, as well as greater pressure pain. Pain hypervigilance was also a significant predictor of temporal summation of heat pain. CONCLUSIONS: Pain hypervigilance may be an important contributor to pain reports and experimental pain sensitivity among persons with knee OA.


Assuntos
Ansiedade/psicologia , Osteoartrite do Joelho/psicologia , Limiar da Dor/psicologia , Dor/psicologia , Idoso , Idoso de 80 Anos ou mais , Ansiedade/complicações , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Dor/complicações , Medição da Dor , Índice de Gravidade de Doença
19.
J Psychopathol Clin Sci ; 133(4): 333-346, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38709616

RESUMO

Externalizing psychopathology has been found to have small to moderate associations with neighborhood and family sociodemographic characteristics. However, prior studies may have used suboptimal operationalizations of neighborhood sociodemographic characteristics and externalizing psychopathology, potentially misestimating relations between these constructs. To address these limitations, in the current study we test different measurement models of these constructs and assess the structural relations between them. Using a population-representative sample of 2,195 twins and siblings from the Georgia Twin Study and data from the National Neighborhood Data Archive and 2000 U.S. Census, we assessed the fit of competing measurement models for family sociodemographic, neighborhood sociodemographic, and neighborhood environment characteristics. In structural models, we regressed a general externalizing dimension on different operationalizations of these variables separately and then simultaneously in a final model. Latent variable operationalizations of family sociodemographic, neighborhood sociodemographic, and neighborhood environment characteristics explained no more variance in broad externalizing psychopathology than other operationalizations. In an omnibus model, family sociodemographic characteristics showed a small association with externalizing psychopathology, while neighborhood sociodemographic and environmental characteristics did not. Family sociodemographic characteristics showed small associations with neighborhood sociodemographic and environmental characteristics, and neighborhood sociodemographic characteristics were moderately associated with neighborhood environment. These findings suggest that family sociodemographic characteristics are more associated with the development of broad externalizing psychopathology in youth than neighborhood sociodemographic characteristics and neighborhood environment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Características de Residência , Humanos , Masculino , Feminino , Características de Residência/estatística & dados numéricos , Criança , Adolescente , Georgia/epidemiologia , Fatores Sociodemográficos , Características da Vizinhança , Família/psicologia , Psicopatologia , Gêmeos/psicologia , Irmãos/psicologia
20.
Pain Rep ; 9(2): e1146, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38505830

RESUMO

Introduction: Chronic pain may negatively affect social functioning, but no study to date has examined the specific social impact of different chronic pain conditions in young women, and whether living with multiple chronic overlapping pain conditions (COPCs) differently influences social domains. Objectives: This study aimed to assess social functioning (social isolation, hostility, informational support satisfaction, social roles, emotional support, friendships, and family relationships) among young women with chronic pain compared with pain-free controls and to test whether the number of COPCs influenced the extent of social burden. Methods: Participants aged 18 to 30 years with a physician-confirmed diagnoses of migraine, fibromyalgia, or temporomandibular disorder (TMD) and pain-free controls were invited to participate from across the United States. After confirming eligibility, participants completed a 1-hour REDCap online questionnaire assessing social functioning. Results: One hundred four participants (mean age 24.54 ± 3.35 years) were included (n = 26 with TMD, n = 25 with fibromyalgia, n = 25 with migraine, and n = 28 controls). All 3 chronic pain groups combined reported worse functioning than controls on friendship (P = 0.038), social isolation (P = 0.002), and social roles (P < 0.001). There were no differences on social variables between the 3 chronic pain groups (all P's > 0.05). Compared with those with 3 COPCs, participants with 1 condition reported better family relationships (P = 0.024). Conclusions: Experience of chronic pain-regardless of the specific pain condition-may negatively affect some areas of social functioning in young women.

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