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1.
Vet J ; 250: 71-78, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383423

RESUMO

In the face of increasing recognition and interest in treating chronic pain in companion animals, we struggle with a lack of therapeutic options. A significant barrier to the development of new therapeutics, or the critical evaluation of current therapies, is our inability to accurately measure chronic pain and its impact on companion animals. Over the last 20 years, much progress has been made in developing methods to measure chronic pain via subjective and objective methods - particularly in owner assessment tools and measurements of limb use and activity. Most work has been focused on chronic joint pain conditions, but there has been relatively little work in other areas of chronic pain, such as neuropathic and cancer pain. Although progress has been made, there is a considerable interest in improving our assessment of chronic pain, as evidenced by the multiple disciplines across industry, academia, and clinical practice from the veterinary and human medical fields that participated in the Pain in Animals Workshop held at the National Institutes of Health in 2017. This review is one product of that meeting and summarizes the current state of knowledge surrounding the measurement of chronic pain (musculoskeletal, cancer, neuropathic), and its impact, in cats and dogs.


Assuntos
Doenças do Gato/patologia , Dor Crônica/veterinária , Doenças do Cão/patologia , Medição da Dor/veterinária , Animais , Gatos , Dor Crônica/patologia , Cães
2.
Nat Neurosci ; 22(10): 1649-1658, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31451801

RESUMO

Comorbid depressive symptoms (CDS) in chronic pain are a common health problem, but the neural circuit mechanisms underlying these symptoms remain unclear. Here we identify a novel pathway involving 5-hydroxytryptamine (5-HT) projections from the dorsal raphe nucleus (5-HTDRN) to somatostatin (SOM)-expressing and non-SOM interneurons in the central nucleus of the amygdala (CeA). The SOMCeA neurons project directly to the lateral habenula, an area known involved in depression. Inhibition of the 5-HTDRN→SOMCeA pathway produced depression-like behavior in a male mouse model of chronic pain. Activation of this pathway using pharmacological or optogenetic approaches reduced depression-like behavior in these mice. Human functional magnetic resonance imaging data showed that compared to healthy controls, functional connectivity between the CeA-containing centromedial amygdala and the DRN was reduced in patients with CDS but not in patients in chronic pain without depression. These findings indicate that a novel 5-HTDRN→SOMCeA→lateral habenula pathway may mediate at least some aspects of CDS.


Assuntos
Dor Crônica/patologia , Depressão/patologia , Vias Neurais/patologia , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/patologia , Animais , Comportamento Animal , Dor Crônica/complicações , Dor Crônica/diagnóstico por imagem , Depressão/complicações , Depressão/diagnóstico por imagem , Núcleo Dorsal da Rafe/diagnóstico por imagem , Núcleo Dorsal da Rafe/patologia , Feminino , Habenula/diagnóstico por imagem , Habenula/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/diagnóstico por imagem , Neuralgia/diagnóstico por imagem , Neuralgia/patologia , Optogenética , Serotonina/metabolismo , Somatostatina/metabolismo
4.
Andrologia ; 51(9): e13361, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31264247

RESUMO

We aimed to evaluate whether pelvic magnetic resonance imaging (MRI) could play a role in better assessing chronic pelvic pain syndrome. We evaluated 44 male patients (median 41 aged) with a clinical history of painful pelvic symptoms, lasting for at least three of the previous 6 months, associated with urinary, anorectal and sexual disorders in the absence of bacterial prostate infection. All these patients underwent ultrasound (US) and MRI evaluation of the pelvis. Prostate imaging findings, such as gland morphology evaluated by US and prostatic signal intensity on MRI, appeared normal in the majority of patients (38/44; 82%). Extraparenchymal alterations were found in 28 patients (63.6%); the most frequent was the dilatation of periprostatic vein plexus (20/28; 71.4%), significantly correlated to chronic pelvic pain syndrome (p = 0.0013), regardless of different clinical presentations. This finding was tested in a control group of 90 patients, demonstrating an excellent specificity (97%), good positive predictive value (87%) and diagnostic accuracy (80%). MRI confirmed its high capability in evaluating prostatic and extraprostatic structures. Periprostatic vein dilatation, which identified approximately two-thirds of the patients with chronic pelvic pain syndrome using pelvic MRI, significantly correlated to chronic pelvic pain syndrome, independently of patient age, symptoms and prostatic volume.


Assuntos
Dor Crônica/diagnóstico , Imagem por Ressonância Magnética , Dor Pélvica/diagnóstico , Próstata/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Dor Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pélvica/patologia , Valor Preditivo dos Testes , Próstata/irrigação sanguínea , Próstata/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia
5.
Artigo em Chinês | MEDLINE | ID: mdl-31327215

RESUMO

Exosomes are nanovesicles secreted by a variety of living cells, which are involved in biological processes such as inflammation,antigen presentation,tumor invasion, and cell differentiation.They are a new mechanism of intercellular communication in the body.Airway chronic inflammatory diseases such as chronic rhinosinusitis,allergic rhinitis, chronic obstructive pulmonary disease,bronchial asthma,etc.are non-specifically involved in airway intrinsic cells,inflammatory cells and inflammatory factors under various internal and external stimuli.Heterotropic inflammatory disease.Exosomes contain a variety of protein,RNA,lipid and other signal transmission media, the are important to chronic inflammation of the airways,and chronic rhinosinusitis,nasal polyps,bronchial asthma,and chronic obstructive pulmonary disease.The occurrence and development of chronic inflammation of the airway is closely related. This article summarizes the current research progress of exosomes and discusses their role in chronic inflammatory diseases of the airways.


Assuntos
Asma/patologia , Dor Crônica/patologia , Exossomos , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia , Humanos
6.
Expert Opin Pharmacother ; 20(16): 1961-1970, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31355689

RESUMO

Introduction: Given our improved understanding of the role of central sensitization (CS) in many patients with chronic pain, it seems rational to account for CS during treatment. Areas covered: First, the treatment rationale based on the complex mechanisms underlying CS in patients having chronic pain is presented. Second, emphasis is given to explaining the concept of CS when providing treatment, as well as why patients and clinicians should focus on long-term rather than short-term treatment effects. Third, possible pharmacological and non-pharmacological treatment options are discussed. Expert opinion: Centrally acting drugs such as tricyclic compounds, serotonin-norepinephrine reuptake inhibitors, and α2δ ligands each target mechanisms that are often dysfunctional in patients having chronic pain and CS, but decades of clinical practice and clinical trials have not resulted in satisfactory outcomes. This comes as no surprise; CS comprises complex psycho-neuro-immunological interactions, while each of the tested drugs targets one or two of those mechanisms from a purely biomedical viewpoint. Clinicians willing to take CS into account should design an individually tailored multimodal treatment plan comprising pain neuroscience education, cognition-targeted exercise therapy, sleep management, stress management, and/or dietary intervention.


Assuntos
Dor Crônica/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Analgésicos Opioides/farmacologia , Analgésicos Opioides/uso terapêutico , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sensibilização do Sistema Nervoso Central/efeitos dos fármacos , Dor Crônica/metabolismo , Dor Crônica/patologia , Humanos , Inibidores de Captação de Serotonina/farmacologia
7.
Curr Opin Anaesthesiol ; 32(5): 623-628, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31356363

RESUMO

PURPOSE OF REVIEW: The medicinal use of cannabis has recently become the focus of much medical, as well as political, attention. This reality of growing use but limited evidence creates unique dilemmas for the prescribing clinician. The purpose of this review is to explore current evidence and gaps in knowledge and offer some practical considerations. RECENT FINDINGS: There is robust preclinical data regarding the relevance of the endocannabinoid system to many pain-relevant processes. However, evidence to support cannabis-based medicines clinical use is still lacking. The best evidence to date is in managing neuropathic pain, although whether effects are clinically significant remains undetermined. However, the safety profile of cannabinoids seems favorable, especially by comparison to other medications used for pain control. SUMMARY: The endocannabinoid system is undoubtedly a new and exciting pharmaceutical target for chronic pain management, but transition from preclinical to clinical studies has so far proved difficult. Although it is reasonable to consider cannabinoids for otherwise unresponsive pain, care should be taken in frail clinical populations. As this has become a socioeconomic and political issue in which agendas often take precedence over due diligence, there is a pressing need for unbiased empirical data and high quality evidence to better inform prescribers and patients.


Assuntos
Dor Crônica/tratamento farmacológico , Maconha Medicinal/administração & dosagem , Neuralgia/tratamento farmacológico , Manejo da Dor/métodos , Dor Crônica/patologia , Endocanabinoides/metabolismo , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/tendências , Humanos , Maconha Medicinal/efeitos adversos , Maconha Medicinal/economia , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Manejo da Dor/efeitos adversos , Manejo da Dor/tendências , Política , Fatores Socioeconômicos , Resultado do Tratamento
8.
Pain Physician ; 22(3): E191-E203, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31151342

RESUMO

BACKGROUND: Although the association of gray matter morphology alterations and pain-related psychosocial characteristics with pain intensity and chronification in people with chronic spinal pain is evident, research on their mutual interaction is scarce and does not account for possible gender differences. Gender-based differences are, however, of utmost importance to consider when examining pain neurobiology. OBJECTIVES: To look for gender differences in the association between magnetic resonance imaging- (MRI) derived brain gray matter morphology and self-reported psychosocial characteristics. STUDY DESIGN: An explorative, observational study. SETTING: University Hospitals Ghent and Brussels, Belgium. METHODS: Brain gray matter morphology (using MRI) and self-reported psychosocial characteristics were examined in women and men with nonspecific chronic spinal pain. Statistical analyses were performed in SPSS and R to identify differences between men and women regarding brain gray matter, self-reported psychosocial characteristics, as well as gender differences in the association between those outcome measures. RESULTS: A total of 94 people with chronic spinal pain were studied, including 32 men (15 suffering from neck pain, 17 suffering from low back pain; demographics [mean ± SD] age: 45.00 ± 12.02 years; pain duration: 128.37 ± 110.45 months), and 62 women (36 suffering from neck pain, 26 suffering from low back pain; demographics [mean ± SD] age: 38.78 ± 12.69 years; pain duration: 114.27 ± 92.45 months). Woman showed larger (positive) associations of several central brain areas (paracentral, precentral, postcentral, etc.) with perceived consequences (P < 0.001), emotional representations (P < 0.001), chronicity (P < 0.001), and pain catastrophizing (P< 0.001). Men showed larger (both positive and negative) associations of the precuneus cortex, the precentral gyrus, and the insula with perceived personal control (P < 0.001) and kinesiophobia (P < 0.001). LIMITATIONS: Other factors, such as menstrual cycle and medication can have a certain influence, and were only partly taken into consideration in the present investigation to obtain sufficient power. Another limitation is the observational study design, which hampers the possibility to look for causal or temporal interactions. CONCLUSIONS: Gray matter morphology relates differently to psychosocial characteristics in women and men. These explorative findings provide ideas for further research to investigate if targeting perceived negative consequences of the illness, perceived emotional representations, perceived chronicity, and pain catastrophizing in women, and perceived personal control of the illness and kinesiophobia in men, could contribute to the normalization of brain alterations in people with nonspecific chronic spinal pain. KEY WORDS: Gray matter, brain morphology, central nervous system, illness perceptions, central sensitization.


Assuntos
Encéfalo/patologia , Dor Crônica/patologia , Dor Crônica/psicologia , Substância Cinzenta/patologia , Caracteres Sexuais , Adulto , Sensibilização do Sistema Nervoso Central/fisiologia , Dor Crônica/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Health Psychol ; 38(5): 422-430, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045425

RESUMO

OBJECTIVE: Children of mothers with chronic pain are at increased risk for poor health, but few studies have examined what characteristics of maternal chronic pain may be associated with children's risk. This study identified subgroups of mothers based on patterns of pain, physical function, and emotional function on the 29-item Patient-Reported Outcomes Measurement Information System® (PROMIS-29®) and evaluated associations between maternal subgroups and children's pain and emotional functioning. METHODS: Mothers with chronic pain (n = 334) completed the PROMIS-29® and reported on pain intensity, pain interference, physical functioning, anxiety, depression, fatigue, sleep disturbance, and participation in social activities. Mothers and their school-age children also completed measures of child pain and emotional functioning. RESULTS: Latent profile analysis of PROMIS® domains indicated a 4-class solution (Group 1: 13.5%, Group 2: 9.9%, Group 3: 43.5%, and Group 4: 32.9%). Group 4 reported the most severe pain, psychological distress, and sleep disturbances and the lowest functioning. Group 1 reported the lowest pain, psychological distress, and sleep disturbances and the highest functioning, while Groups 2 and 3 represented moderate symptoms. Groups significantly differed on maternal reports of children's pain frequency, but not intensity, and children's self-reported somatic symptoms. Further, child depressive symptoms (mother-proxy and self-reported), anxiety (mother-proxy reported), and pain catastrophizing (self-reported) differed by maternal group. CONCLUSIONS: Patterns of maternal symptoms and functioning were associated with pain frequency and emotional symptoms in children. Further examination of individual differences in mothers with chronic pain that may confer risk for chronic pain and psychological disorders in children is warranted. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Dor Crônica/epidemiologia , Mães/psicologia , Medidas de Resultados Relatados pelo Paciente , Adulto , Dor Crônica/patologia , Feminino , Humanos , Masculino
10.
Breast Cancer ; 26(6): 758-765, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31127501

RESUMO

BACKGROUND: In breast cancer survivors, multiple risk factors for health-related quality of life (HRQoL) and chronic pain, including cancer treatment-related factors, psychosocial factors, and central sensitization (CS), have been suggested; however, there has been no comparative study between breast cancer survivors with and without pain. This study aimed to compare the demographic characteristics, psychological factors, and CS-related symptoms between breast cancer survivors with pain, those without pain, and healthy controls, and to investigate the relationships of these factors with HRQoL. METHODS: We conducted a cross-sectional survey of 218 women, including patients who underwent breast cancer surgery and adjuvant therapy and healthy women. RESULTS: Patients were divided into the pain group (n = 42), without-pain group (n = 51), and healthy group (n = 47); thus, among breast cancer survivors, 45% reported chronic pain. The proportion of participants who received breast cancer treatments, such as axillary lymph node dissection and chemotherapy, was higher in the pain group than in the without-pain group (p < 0.05). The Central Sensitization Inventory (CSI) and psychosocial factors in the pain group were higher than those in the without-pain group and healthy group (p < 0.01). The CSI and PCS showed larger effect sizes than treatment-related factors. Moreover, HRQoL was significantly correlated with CSI, PCS, Patient Health Questionnaire-2, and Generalized Anxiety Disorder-2 scale (all, p < 0.01). On multiple linear regression analysis, CSI accounted for 43% of the variance in HRQoL. CONCLUSIONS: CS and pain catastrophizing may be more associated with the development and/or maintenance of persistent pain than treatment-related factors.


Assuntos
Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Sobreviventes de Câncer , Sensibilização do Sistema Nervoso Central , Dor Crônica/patologia , Qualidade de Vida , Adulto , Idoso , Ansiedade , Estudos de Coortes , Estudos Transversais , Depressão , Feminino , Humanos , Japão , Modelos Lineares , Pessoa de Meia-Idade , Autorrelato
11.
Urol Int ; 103(2): 211-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31129663

RESUMO

The objective is to observe if it could be possible to use the apoptosis test to distinguish different aetiologies in chronic pelvic pain syndrome (CPPS). A prospective study was done, 106 patients, 57 had previously been diagnosed with urological chronic pelvic pain (UCPP)/interstitial cystitis (IC) and 49 patients with gynaecological chronic pelvic pain (GCPP). Neoplastic cells cultures were exposed to the urine of patients with UCPP/IC and patients with GCPP. The urine ability to provoque apoptosis on them was analysed. The apoptosis degree was measured by quantifying the percentage of cells in phase subG0, determined by a flow cytometry analysis. It is observed that the cell cultures exposed to urine of patients with UCPP had a significantly higher sub-G1 peak and G2 phase than those of the cells exposed to urine from patient's GCPP. The average values of apoptosis in patients with UCPP were significantly higher to that obtained in -patients having GCPP. With the apoptosis tests having a value >10%, it is considered as positive as well. This means that when we are faced with a patient who has UCPP or non-bladder chronic pelvic pain, the probability of having an UCPP increases by 45% when the apoptosis test is positive for a value >10%. Urine from patients with UCPP has significantly higher apoptotic effect over than the effect produced by urine from patients with GCPP. The apoptosis test could be useful as an illness biomarker.


Assuntos
Apoptose , Dor Crônica/etiologia , Doenças dos Genitais Femininos/etiologia , Dor Pélvica/etiologia , Doenças Urológicas/etiologia , Adulto , Dor Crônica/patologia , Feminino , Doenças dos Genitais Femininos/complicações , Doenças dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Dor Pélvica/patologia , Estudos Prospectivos , Autorrelato , Doenças Urológicas/complicações , Doenças Urológicas/patologia , Adulto Jovem
12.
Women Birth ; 32(2): e272-e278, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31007208

RESUMO

BACKGROUND: The increasing prevalence and adverse outcomes associated with opioid analgesia use in women of reproductive age have become a significant public health issue internationally, with use during pregnancy potentially affecting maternal and infant health outcomes. OBJECTIVE: This study aims to provide national estimates of chronic pain, pain severity and analgesia use in Australian women of reproductive age by pregnancy status. METHOD: Data were obtained from the Australian Bureau of Statistics 2011-12 National Health Survey (n=20,426). Weighting was applied to sample data to obtain population estimates. For this study data were analysed for pregnant (n=166, N=192,617) and non-pregnant women (n=4710, N=5,256,154) of reproductive age (15-49 years). RESULTS: Chronic or reoccurring pain was reported in 5.1% of pregnant women and 9.7% of non-pregnant women, and 0.7% and 2.6% of pregnant and non-pregnant women reported recent opioid analgesia use respectively. Moderate-to-very severe pain was more common in pregnant than non-pregnant women taking opioid analgesics, and no pain and very mild-to-mild pain in non-pregnant women. CONCLUSION: Approximately 1 in 20 pregnant Australian women have chronic or reoccurring pain. Opioid analgesia was used by around 1% of Australian pregnant women during a two-week period, with use associated with moderate-to-very severe pain. Given that the safety of many analgesic medications in pregnancy remains unknown, pregnant women and health professionals require accurate, up-to-date information on the risks and benefits of analgesic use during pregnancy. Further evidence on the decision-making processes of pregnant women with pain should assist health professionals maximise outcomes for mothers and infants.


Assuntos
Analgesia/estatística & dados numéricos , Analgésicos Opioides/uso terapêutico , Dor Crônica/epidemiologia , Complicações na Gravidez/epidemiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Austrália/epidemiologia , Dor Crônica/tratamento farmacológico , Dor Crônica/patologia , Feminino , Humanos , Medição da Dor , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/patologia , Prevalência , Adulto Jovem
13.
Biomed Res Int ; 2019: 2193436, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001552

RESUMO

Background: Percutaneous DiscoGel® (Gelscom SAS, France), introduced in 2007 as a promising new minimal invasive technique, showed efficacy and safety in lumbar spine surgery, with limited use and scientific reports with regard to the cervical spine. Since the first publication of its use on the cervical spine (2010), less than 100 cases have been published. We introduce an initial experience with this relatively new procedure. We hypothesized that percutaneous DiscoGel® is a safe and effective option for chronic neck pain of cervical discogenic origin. Method: This was a clinical study on 10 patients with chronic discogenic pain operated on for 18 cervical discs with percutaneous DiscoGel®. Inclusion criteria were patients with chronic axial or referred neck pain with MRI showing a cervical disc that is consistent with patient symptoms and failed conservative treatment. Exclusion criteria were clinical myelopathy, motor deficit, severe stenosis or reduced disc height by more than 50%, or previous cervical spine surgery. Results: A total of 10 cases consisting of 6 females and 4 males underwent treatment with percutaneous DiscoGel® for 18 cervical discs. C5/C6 was the most affected level. The mean preoperative VAS score was 8; the postoperative VAS scores at 6 weeks and 3 months were 2.2 and 2.9, respectively. There were no postoperative complications or neurological deficits. Conclusion: The present study has the limitation of the small number of cases; however, with the limited number of studies and less than 100 published cases in the literature, this initial work shows that cervical percutaneous DiscoGel® is an effective minimally invasive bridging option between conservative and open surgical treatment for cervical discogenic pain, with a high success rate. The differentiation of pain types (nociceptive, referred, radicular, and trapezius myalgia) that can coexist is crucial for procedure selection and improving treatment outcome.


Assuntos
Dor Crônica/tratamento farmacológico , Etanol/administração & dosagem , Cervicalgia/tratamento farmacológico , Adolescente , Adulto , Vértebras Cervicais/patologia , Vértebras Cervicais/fisiopatologia , Dor Crônica/patologia , Dor Crônica/fisiopatologia , Feminino , Humanos , Disco Intervertebral/patologia , Disco Intervertebral/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cervicalgia/patologia , Cervicalgia/fisiopatologia
14.
Br J Anaesth ; 123(2): e303-e311, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30948036

RESUMO

BACKGROUND: Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes. METHODS: We compared ALFF differences by MRI between cLBP subjects (90) and HCs (74), conducted a discriminative analysis to validate the results, and explored structural changes in key brain regions of cLBP. We also compared ALFF changes in cLBP patients after pain-exacerbating manoeuvres. RESULTS: ALFF was increased in the post-/precentral gyrus (PoG/PrG), paracentral lobule (PCL)/supplementary motor area (SMA), and anterior cingulate cortex (ACC), and grey matter volume was increased in the left ACC in cLBP patients. PCL/SMA ALFF reliably discriminated cLBP patients from HCs in an independent cohort. cLBP patients showed increased ALFF in the insula, amygdala, hippocampal/parahippocampal gyrus, and thalamus and decreased ALFF in the default mode network (DMN) when their spontaneous low back pain intensity increased after the pain-exacerbating manoeuvre. CONCLUSIONS: Brain low-frequency oscillations in the PCL, SMA, PoG, PrG, and ACC may be associated with the neuropathology of cLBP. Low-frequency oscillations in the insula, amygdala, hippocampal/parahippocampal gyrus, thalamus, and DMN are sensitive to manoeuvre-induced spontaneous back pain intensity changes.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Dor Crônica/patologia , Dor Lombar/patologia , Imagem por Ressonância Magnética/métodos , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuropatologia , Descanso , Adulto Jovem
15.
Cell Mol Gastroenterol Hepatol ; 7(2): 433-445, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30739868

RESUMO

Chronic abdominal pain is the most common gastrointestinal issue and contributes to the pathophysiology of functional bowel disorders and inflammatory bowel disease. Current theories suggest that neuronal plasticity and broad alterations along the brain-gut axis contribute to the development of chronic abdominal pain, but the specific mechanisms involved in chronic abdominal pain remain incompletely understood. Accumulating evidence implicates glial cells in the development and maintenance of chronic pain. Astrocytes and microglia in the central nervous system and satellite glia in dorsal root ganglia contribute to chronic pain states through reactive gliosis, the modification of glial networks, and the synthesis and release of neuromodulators. In addition, new data suggest that enteric glia, a unique type of peripheral glia found within the enteric nervous system, have the potential to modify visceral perception through interactions with neurons and immune cells. Understanding these emerging roles of enteric glia is important to fully understand the mechanisms that drive chronic pain and to identify novel therapeutic targets. In this review, we discuss enteric glial cell signaling mechanisms that have the potential to influence chronic abdominal pain.


Assuntos
Dor Abdominal/patologia , Sistema Nervoso Entérico/patologia , Neuroglia/patologia , Animais , Dor Crônica/patologia , Humanos , Hiperalgesia/patologia , Nociceptores/metabolismo
16.
Eur J Obstet Gynecol Reprod Biol ; 234: 171-178, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30708269

RESUMO

OBJECTIVE: Evaluate whether symptoms and/or transvaginal ultrasound (TVS) 'soft markers' (ovarian immobility and/or site-specific tenderness (SST)) are associated with endometriosis type/location. STUDY DESIGN: Multicenter prospective observational study (January 2009 to February 2013) in tertiary centers for women with chronic pelvic pain who underwent detailed history, specialized TVS, and laparoscopy. Chart findings were collated into a study database. Outcome measures included correlation between symptoms, ovarian immobility or SST on TVS and endometriosis type and/or location. The performance of ovarian immobility to predict ipsilateral SE was evaluated in terms of accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 189 participants were included. Ovarian immobility on TVS was significantly associated with: ipsilateral pelvic pain, uterosacral ligament (USL) and pelvic sidewall superficial endometriosis (SE), endometrioma, posterior compartment deep endometriosis (DE), pouch of Douglas (POD) obliteration, and need for bowel surgery (all p < 0.05). For women with isolated SE (i.e.no endometrioma, DE, or POD obliteration), left ovarian immobility was significantly associated with left USL SE (p = 0.01) and left adnexal SST corresponded to left pelvic sidewall SE (p = 0.03). The accuracy, sensitivity, specificity, PPV and NPV for ovarian immobility at TVS and the presence of ipsilateral pelvic sidewall SE for the left ovary was: 71%, 16%, 87%, 27% and 78%, respectively; and for the right ovary was: 82%, 7.0%, 94%, 14% and 87%, respectively. CONCLUSION: Ovarian immobility on TVS was significantly associated with ipsilateral pelvic pain, USL/pelvic sidewall SE, endometrioma, posterior compartment DE, and POD obliteration. The diagnostic accuracy of ovarian immobility for disease location in women with isolated SE showed a high specificity and NPV, but poor sensitivity and PPV, suggesting that ipsilateral pelvic sidewall SE is less likely to be present in women with a mobile ovary (in the absence of endometrioma or DE). Larger studies are required to further evaluate the usefulness of soft markers for the localization of isolated SE.


Assuntos
Dor Crônica/diagnóstico por imagem , Endometriose/diagnóstico por imagem , Dor Pélvica/diagnóstico por imagem , Ultrassonografia/estatística & dados numéricos , Adulto , Biomarcadores/análise , Dor Crônica/patologia , Escavação Retouterina/diagnóstico por imagem , Endometriose/etiologia , Endometriose/patologia , Feminino , Humanos , Ovário/diagnóstico por imagem , Dor Pélvica/complicações , Dor Pélvica/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia/métodos , Útero/diagnóstico por imagem , Vagina/diagnóstico por imagem , Adulto Jovem
17.
J Med Internet Res ; 21(2): e11398, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30720437

RESUMO

BACKGROUND: Ecological momentary assessment (EMA) involves repeated sampling of people's current experiences in real time in their natural environments, which offers a granular perspective on patients' experience of pain and other symptoms. However, EMA can be burdensome to patients, and its benefits depend upon patients' engagement in the assessments. OBJECTIVE: The goal of this study was to investigate factors affecting EMA-completion rates among patients with chronic pain. METHODS: This individual patient data meta-analysis was based on 12 EMA datasets that examined patients with chronic noncancer-related pain (n=701). The EMA-completion rates were calculated on a daily basis for each patient. Multilevel models were used to test the following predictors of completion rates at different levels: within-patient factors (days into the study and daily pain level), between-patient factors (age, sex, pain diagnosis, and average pain level per person), and between-study EMA design factors (study duration, sampling density, and survey length). RESULTS: Across datasets, an EMA-completion rate of 85% was observed. The strongest results were found for the between-patient factor age: Younger respondents reported lower completion rates than older respondents (P=.002). One within-patient factor, study day, was associated with completion rates (P<.001): over the course of the studies, the completion rates declined. The two abovementioned factors interacted with each other (P=.02) in that younger participants showed a more rapid decline in EMA completion over time. In addition, none of the other hypothesized factors including gender, chronic pain diagnoses, pain intensity levels, or measures of study burden showed any significant effects. CONCLUSION: Many factors thought to influence the EMA-completion rates in chronic pain studies were not confirmed. However, future EMA research in chronic pain should note that study length and young age can impact the quality of the momentary data and devise strategies to maximize completion rates across different age groups and study days.


Assuntos
Dor Crônica/patologia , Avaliação Momentânea Ecológica/normas , Adulto , Feminino , Humanos , Masculino , Projetos de Pesquisa , Inquéritos e Questionários
18.
Mol Pain ; 15: 1744806918825044, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30799685

RESUMO

BACKGROUND: The glutamate type 1 transporter (GLT1) plays a major role in glutamate homeostasis in the brain. Although alterations of GLT1 activity have been linked to persistent pain, the significance of these changes is poorly understood. Focusing on the rostral ventromedial medulla, a key site in pain modulation, we examined the expression and function of GLT1 and related transcription factor kappa B-motif binding phosphoprotein (KBBP) in rats after adjuvant-induced hind paw inflammation. RESULTS: After inflammation, GLT1 and KBBP showed an early upregulation and gradual transition to downregulation that lasted throughout the eight-week observation period. Nitration of GLT1 was reduced at 30 min and increased at eight weeks after inflammation, suggesting an initial increase and later decrease in transporter activity. Mechanical hyperalgesia and paw edema exhibited an initial developing phase with peak hyperalgesia at 4 to 24 h, a subsequent attenuating phase, followed by a late persistent phase that lasted for months. The downregulation of GLT1 occurred at a time when hyperalgesia transitioned into the persistent phase. In the rostral ventromedial medulla, pharmacological block with dihydrokainic acid and RNAi of GLT1 and KBBP increased nociception and overexpression of GLT1 reversed persistent hyperalgesia. Further, the initial upregulation of GLT1 and KBBP was blocked by local anesthetic block, and pretreatment with dihydrokainic acid facilitated the development of hyperalgesia. CONCLUSIONS: These results suggest that the initial increased GLT1 activity depends on injury input and serves to dampen the development of hyperalgesia. However, later downregulation of GLT1 fosters the net descending facilitation as injury persists, leading to the emergence of persistent pain.


Assuntos
Vias Aferentes/metabolismo , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Dor Crônica/patologia , Neuroglia/metabolismo , Sistema X-AG de Transporte de Aminoácidos/genética , Animais , Aprendizagem da Esquiva , Tronco Encefálico/fisiologia , Dor Crônica/induzido quimicamente , Modelos Animais de Doenças , Transportador 1 de Aminoácido Excitatório/genética , Transportador 1 de Aminoácido Excitatório/metabolismo , Adjuvante de Freund/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hiperalgesia/fisiopatologia , Imunoprecipitação , Masculino , Medição da Dor , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução Genética
19.
Mol Pain ; 15: 1744806919827469, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30638145

RESUMO

Chronic pain is a pathological manifestation of neuronal plasticity supported by altered gene transcription in spinal cord neurons that results in long-lasting hypersensitivity. Recently, the concept that epigenetic regulators might be important in pathological pain has emerged, but a clear understanding of the molecular players involved in the process is still lacking. In this study, we linked Dnmt3a2, a synaptic activity-regulated de novo DNA methyltransferase, to chronic inflammatory pain. We observed that Dnmt3a2 levels are increased in the spinal cord of adult mice following plantar injection of Complete Freund's Adjuvant, an in vivo model of chronic inflammatory pain. In vivo knockdown of Dnmt3a2 expression in dorsal horn neurons blunted the induction of genes triggered by Complete Freund's Adjuvant injection. Among the genes whose transcription was found to be influenced by Dnmt3a2 expression in the spinal cord is Ptgs2, encoding for Cox-2, a prime mediator of pain processing. Lowering the levels of Dnmt3a2 prevented the establishment of long-lasting inflammatory hypersensitivity. These results identify Dnmt3a2 as an important epigenetic regulator needed for the establishment of central sensitization. Targeting expression or function of Dnmt3a2 may be suitable for the treatment of chronic pain.


Assuntos
Dor Crônica/complicações , DNA (Citosina-5-)-Metiltransferases/metabolismo , Epigênese Genética , Hiperalgesia/metabolismo , Inflamação/complicações , Células do Corno Posterior/metabolismo , Regulação para Cima/fisiologia , Animais , Capsaicina/farmacologia , Células Cultivadas , Dor Crônica/induzido quimicamente , Dor Crônica/patologia , Ciclo-Oxigenase 1/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , Modelos Animais de Doenças , Proteínas de Escherichia coli/metabolismo , Adjuvante de Freund/toxicidade , Lateralidade Funcional , Masculino , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Medição da Dor , Fosfopiruvato Hidratase/metabolismo , Células do Corno Posterior/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Medula Espinal/patologia , Regulação para Cima/efeitos dos fármacos
20.
Glia ; 67(6): 1062-1075, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30648289

RESUMO

Chronic pain is one of the most prevalent chronic diseases in the world. The plastic changes of sensory neurons in dorsal root ganglia (DRG) have been extensively studied as the underlying periphery mechanism. Recent studies revealed that satellite cells, the major glial cells in DRG, also played important roles in the development/modulation of chronic pain. Whether DRG satellite glial cells generate new neurons as their counterparts in enteric nerve ganglia and carotid body do under pathological conditions remains poorly investigated. Here, we report that chronic pain induces proliferation and upregulation of progenitor markers in the sex-determining region Y-box 2 (Sox2)- and platelet-derived growth factor receptor alpha (PDGFRα)-positive satellite glial cells. BrdU incorporation assay revealed the generation of IB4- and CGRP-positive neurons, but not NF200-positive neurons in DRG ipsilateral to injury. Genetic fate tracings showed that PDGFRα-positive cells did not generate neurons, whereas Sox2-positive cells produced both IB4- and CGRP-positive neurons. Interestingly, glial fibrillary acidic protein-positive cells, a subpopulation of Sox2-positive satellites, only gave birth to IB4-positive neurons. Local persistent delivery of tetrodotoxin to the sciatic nerve trunk significantly reduced the pain-induced neurogenesis. Furthermore, patch-clamp studies demonstrated that these glia-derived new neurons could fire action potentials and respond to capsaicin. Taken together, our data demonstrated a chronic pain-induced nociceptive neurogenesis in DRG from Sox2-positive satellite cells, indicating a possible contribution of DRG neurogenesis to the pathology of chronic pain.


Assuntos
Dor Crônica/metabolismo , Gânglios Espinais/metabolismo , Neurogênese/fisiologia , Fatores de Transcrição SOXB1/biossíntese , Células Satélites Perineuronais/metabolismo , Animais , Dor Crônica/patologia , Gânglios Espinais/química , Gânglios Espinais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição SOXB1/análise , Células Satélites Perineuronais/química , Células Satélites Perineuronais/patologia
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