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INTRODUCTION: Endometriosis is a chronic inflammatory disease that affects â¼10 % of women. A significant fraction of patients experience limited or no efficacy with current therapies. Tissue adjacent to endometriosis lesions often exhibits increased neurite and vascular density, suggesting that disease pathology involves neurotrophic activity and angiogenesis. OBJECTIVES: We aim to evaluate the potential for key tyrosine-kinase-receptor-coupled neurotrophic molecules to contribute to endometriosis-associated pain in mice. METHODS: Peritoneal fluid was collected from endometriosis patients undergoing surgery and the levels of NGF and VEGFR1 regulators (VEGFA, VEGFB, PLGF, and sVEGFR1) were quantified by ELISA. VEGFR1 regulator concentrations were used to calculate VEGFR1 occupancy. We used genetic depletion, neutralizing antibodies, and pharmacological approaches to specifically block neurotrophic ligands (NGF or BDNF) or receptors (VEGFR1, TRKs) in a murine model of endometriosis-associated pain. Endometriosis-associated pain was measured using von Frey filaments, quantification of spontaneous abdominal pain-related behavior, and thermal discomfort. Disease parameters were evaluated by lesion size and prevalence. To evaluate potential toxicity, we measured the effect of entrectinib dose and schedule on body weight, liver and kidney function, and bone structure (via micro-CT). RESULTS: We found that entrectinib (pan-Trk inhibitor) or anti-NGF treatments reduced evoked pain, spontaneous pain, and thermal discomfort. In contrast, even though calculated receptor occupancy revealed that VEGFR1 agonist levels are sufficient to support signaling, blocking VEGFR1 via antibody or tamoxifen-induced knockout did not reduce pain or lesion size in mice. Targeting BDNF-TrkB with an anti-BDNF antibody also proved ineffective. Notably, changing dosing schedule to once weekly eliminated entrectinib-induced bone-loss without decreasing efficacy against pain. CONCLUSIONS: This suggests NGF-TrkA signaling, but not BDNF-TrkB or VEGF-VEGFR1, mediates endometriosis-associated pain. Moreover, entrectinib blocks endometriosis-associated pain and reduces lesion sizes. Our results also indicated that entrectinib-like molecules are promising candidates for endometriosis treatment.
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BACKGROUND: Visceral pain (VP) following laparoscopic sleeve gastrectomy remains a substantial problem. VP is associated with autonomic symptoms, especially nausea and vomiting, and is unresponsive to traditional pain management algorithms aimed at alleviating somatic (incisional) pain. The present study was performed to evaluate the safety and effectiveness of laparoscopic paragastric autonomic neural blockade (PG-ANB) in managing the symptoms associated with VP following sleeve gastrectomy. STUDY DESIGN: This prospective, double-blinded, randomized clinical trial involved patients undergoing laparoscopic sleeve gastrectomy at two high-volume institutions. The patients were randomized to laparoscopic transversus abdominis plane block with or without PG-ANB. The primary outcome was patient-reported pain scores assessed at 1, 8, and 24 h postoperatively. The secondary outcome measures were analgesic requirements, nausea, vomiting, hiccups, and hemodynamic changes immediately after PG-ANB and postoperatively. RESULTS: In total, 145 patients (block group, n = 72; control group, n = 73) were included in the study. The heart rate and mean arterial pressure significantly decreased 10 min after PG-ANB. The visual analog scale score for pain was significantly lower in the PG-ANB than in the control group at 1 h postoperatively (p < 0.001) and 8 h postoperatively (p < 0.001). Vomiting, nausea, sialorrhea, and hiccups were significantly less prevalent in the PG-ANB group. Patients in the PG-ANB group received fewer cumulative doses of analgesics at 1 h postoperatively (p = 0.003) and 8 h postoperatively (p < 0.001). No differences between the groups were detected at 24 h (p = 0.298). No complications related to PG-ANB occurred. CONCLUSION: PG-ANB safely and effectively reduces early VP, associated autonomic symptoms, and analgesic requirements after laparoscopic sleeve gastrectomy.
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Soluço , Laparoscopia , Obesidade Mórbida , Dor Visceral , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Músculos Abdominais , Dor Visceral/complicações , Dor Visceral/cirurgia , Estudos Prospectivos , Soluço/complicações , Soluço/cirurgia , Obesidade Mórbida/cirurgia , Método Duplo-Cego , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos , Analgésicos , Vômito/etiologia , Náusea/etiologia , Analgésicos Opioides , Anestésicos LocaisRESUMO
Purpose: To analyze the effect and mechanism of dexmedetomidine (DEX) analgesia pretreatment on functional chronic visceral pain in rats. Methods: Rats were divided into six groups: W1, W2, W3, W4, W5, and W6. The behavioral changes and electrophysiological indexes of rats in each group before and after DEX treatment were detected. Results: The levels of abdominal withdrawal reflex (AWR) in W5 and W6 groups were significantly lower than those in group W3, while the levels of thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were significantly higher than those in group W3 (p < 0.05). The electromyographic signals of W1, W5, and W6 groups showed little fluctuation, while those of groups W2, W3, and W4 showed obvious fluctuation. TLR4 mRNA expression, IRF3, P65, and phosphorylation levels in W4, W5, and W6 groups were significantly lower than those in group W2 (p < 0.05). Conclusions: Dexmedetomidine epidural anesthesia pretreatment could significantly inhibit visceral pain response in rats with functional chronic visceral pain, and its mechanism was related to the activation of TLR4 in spinal dorsal horn tissue of rats and the activation inhibition of IRF3 and P65 in the downstream key signals.
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Animais , Ratos , Dexmedetomidina/administração & dosagem , Receptor 4 Toll-Like/análise , Dor Visceral/tratamento farmacológico , Analgesia/métodos , Fenômenos EletrofisiológicosAssuntos
Humanos , Dor Pós-Operatória , Cirurgia Bariátrica , Manejo da Dor , Dor Visceral , Gastrectomia , Bloqueio NervosoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Minthostachys verticillata (Griseb.) Epling (Lamiaceae), known as Peperina is a medicinal native plant, with a traditional use as a digestive, antispasmodic and antidiarrheic. AIM OF THE STUDY: Despite its folkloric use, no scientific evaluation of this plant related to the gastrointestinal inflammatory process has been carried out to date. The present study aims to assess the effects of M. verticillata on gastrointestinal system in experimental models. MATERIALS AND METHODS: M. verticillata (250 and 500 mg/kg) was orally tested in a colitis model induced by acetic acid. Colon weight/length ratio, oxidative stress (oxidized and reduced glutathione), histological changes using Alcian blue and hematoxylin & eosin staining and expression of IL1ß, TNFα, iNOS, COX-2 were evaluated. The effect of the extract in three additional in vivo models were studied: intestinal motility and diarrhea induced by ricin oil, and visceral pain induced by intracolonic administration of capsaicin. Finally, the activity on concentration response curves of acetylcholine, calcium chloride, potassium and serotonin were achieved in isolated rat jejunum. RESULTS: In the colitis model, M. verticillata induced a significant reduction in the colon weight/length ratio, oxidative stress and expression levels of IL-1ß, iNOS and COX-2. Also, the extract diminished the severity of microscopic tissue damage and showed protective effect on goblet cells. Intestinal motility, diarrhea, visceral pain-related behaviors and referred hyperalgesia were significantly reduced when the animals were treated with the extract. Furthermore, in isolated jejunum, M. verticillata significantly reduced the contraction induced by serotonin and acetylcholine. Likewise, the extract non-competitively inhibited the response-concentration induced by CaCl2 and inhibited both low and high K+-induced contractions. CONCLUSIONS: This is the first study to validate traditional use of M. verticillata for digestive disorders and demonstrated that its aqueous extract could represent a promising strategy in targeting the multifactorial pathophysiology of inflammatory bowel disease.
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Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Lamiaceae/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Ácido Acético/toxicidade , Animais , Anti-Inflamatórios/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Capsaicina/toxicidade , Óleo de Rícino/toxicidade , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Camundongos , Extratos Vegetais/uso terapêutico , Ratos Sprague-Dawley , Dor Visceral/induzido quimicamente , Dor Visceral/tratamento farmacológicoRESUMO
Cardiovascular disease (CVD) is the main cause of death worldwide, including in Brazil. Angina pectoris is a challenging disease because its clinical manifestation is not always related to the degree of obstruction. Visceral pain fromany source can be totally disabling. It influences all aspects of the life of a patient and it can be one of the main causes of absence from work and of family disruption. Spinal cord electrical stimulation (SCES) has been traditionally applied for the treatment of neuropathic pain, with good to excellent results. Visceral pain syndrome can be as debilitating and disabling as somatic or neuropathic pain; however, there seems to be a lack of consensus on the appropriate treatment and strategies for these disorders. Themajor difference of SCES for visceral pain, compared to postlaminectomy syndrome or to regional complex syndrome, is the number of stimulated dermatomes. In most viscera, the somatotopic arrangement has two to four medullar levels, sometimes requiring laterality. After reviewing the literature, we have concluded that SCES is now a viable, low-risk option with satisfactory results for the treatment of neuropathic and visceral pain; therefore, it can be used in refractory angina after the failure of standard therapy. However, further studies are required to increase the application and efficacy of this procedure in the clinical practice.
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Humanos , Masculino , Pessoa de Meia-Idade , Medula Espinal , Estimulação Elétrica Nervosa Transcutânea/métodos , Dor Visceral/terapia , Angina Pectoris/terapia , Resultado do Tratamento , Dor Visceral/etiologia , Angina Pectoris/diagnóstico por imagemRESUMO
Nonsteroidal anti-inflammatory drugs (NSAIDs) possess as primary action mechanism the inhibition of cyclooxygenases (COX-1, COX-2, and COX-3), thus producing a decreasing prostaglandin synthesis. This study was designed to evaluate whether the antinociception induced by NSAIDs could be modulated by clomipramine or risperidone using a chemical model of inflammatory acute visceral pain, the abdominal acetic acid induced a writhing test in mice. Dose-response curves, intraperitoneal, or intrathecal for the antinociceptive activity displayed by ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol were analyzed in order to obtain the ED50 of each drug. Pretreatment of mice with either clomipramine or risperidone, increased antinociceptive potency of ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol, expressed by a decrease in the values of antinociceptive ED50. The results that were obtained are in line with those where the inhibition of COXs provides a justification for most of the pharmacological actions. Nevertheless, several findings suggest other molecular mechanisms, among which may be mentioned, L-selecting shedding; inhibition of i-NOS; inhibition of NF-Kappa B; suppression metaloproteinasas; inhibition of ß2 integrin activation; activation of α2 -adrenoceptor; increase of IL-1ß; upregulation IL-6. In conclusion, the data generated in this study demonstrated that risperidone and clomipramine, separately, increase antinociceptive potency of NSAIDs in a chemical model of inflammatory acute visceral tonic pain.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Clomipramina/uso terapêutico , Risperidona/uso terapêutico , Dor Visceral/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Clomipramina/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Injeções Intraperitoneais , Injeções Espinhais , Masculino , Camundongos Endogâmicos , Medição da Dor , Risperidona/administração & dosagemRESUMO
OBJECTIVE: This study aimed to evaluate the effects of the methanol extract of Synadenium grantii Hook f. stems and its main isolated compound Query3,4,12,13-tetraacetylforbol-20-phenylacetate (1) on experimental dysmenorrhea in mice. METHODS: Female Swiss mice (n = 6-15) of 6-8 weeks old were used, selected according to the period of the estrous cycle. Animals in proestrus were treated intraperitoneally (i.p.) for 3 days with estradiol. They orally received, on the 4th day, S. grantii extract, the compound 1, ibuprofen or hyoscine butylbromide (Buscopan compound®). Then they were injected (i.p.) with oxytocin 1 h later and individually observed regarding the abdominal writhing for 45 min. The uterus was weighed, photographed and fixed in paraffin for histological analysis. KEY FINDINGS: The extract inhibited the abdominal writhing and similar results were obtained with compound 1 and the positive control drugs Ibuprofen and hyoscine butylbromide. Reduction of uterus volume and histological inflammatory parameters, such as oedema and leukocyte infiltrate, were observed in animals treated with the extract and compound 1. CONCLUSIONS: Our data show promising activity of the extract against dysmenorrhea, indicating important anti-inflammatory activity. Compound 1 appears to be, at least in part, the main responsible for this promising biological effect.
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Dismenorreia/tratamento farmacológico , Euphorbia/química , Extratos Vegetais/farmacologia , Animais , Brometo de Butilescopolamônio/farmacologia , Modelos Animais de Doenças , Edema/tratamento farmacológico , Feminino , Ibuprofeno/farmacologia , Camundongos , Fitoterapia/métodosRESUMO
ABSTRACT BACKGROUND AND OBJECTIVES: Visceral pain is induced by abnormalities of organs such as stomach, kidneys, bladder, gallbladder, intestines and others and includes distension, ischemia, inflammation and mesenteric traction. It is responsible for physical and psychic incapacity, absenteeism and poor quality of life. This study aimed at discussing major aspects of visceral pain with regard to prevalence, etiology and diagnosis. CONTENTS: According to Evidence-Based Medicine concepts, visceral pain etiology, diagnosis and prognosis were reviewed in LILACS, EMBASE and Pubmed databases. Therapeutic studies were not selected. The following terms were used as search strategy: ("visceral pain"[MeSH Terms] OR ("visceral"[All Fields] AND "pain"[All Fields]) OR "visceral pain"[All Fields]). Only studies published in Portuguese, English or Spanish were included. Narrative reviews with opinionated content and specific therapeutic procedures of medical specialties were excluded. Studies on visceral pain related to heart, cancer and musculoskeletal diseases and pregnancy were also excluded. CONCLUSION: Visceral pain is a heterogeneous condition where most frequent presentation is abdominal pain in the course of irritable bowel syndrome. Other diseases induce visceral pain and adequate diagnosis is critical for effective treatment.
RESUMO JUSTIFICATIVA E OBJETIVOS: A dor visceral é causada por anormalidades de órgãos como o estômago, rim, bexiga, vesícula biliar, intestinos ou outros e inclui distensão, isquemia, inflamação e tração do mesentério. É responsável por incapacidade física e psíquica, absenteísmo do trabalho e má qualidade de vida. O objetivo deste estudo foi discutir os principais aspectos da dor visceral relacionados a prevalência, etiologia e diagnóstico. CONTEÚDO: Foram revisados segundo os preceitos da Medicina Baseada em Evidência os enfoques etiológicos, diagnóstico e prognóstico da dor visceral nas bases de indexações biomédicas, LILACS, EMBASE e Pubmed. Não foram selecionados os estudos terapêuticos. Utilizou-se como estratégia de busca os termos: ("visceral pain"[MeSH Terms] OR ("visceral"[All Fields] AND "pain"[All Fields]) OR "visceral pain"[All Fields]). Somente foram incluídos os estudos publicados em português, inglês ou espanhol. Foram excluídas as revisões narrativas de conteúdo opinativo e procedimentos terapêuticos específicos das especialidades médicas. Também foram excluídos os estudos sobre dor visceral relacionada às doenças do coração, neoplásicas, musculoesqueléticas e a gestação. CONCLUSÃO: A dor visceral é uma condição heterogênea, cuja apresentação mais frequente é de dor abdominal no curso de síndrome do intestino irritável. Outras doenças cursam com dor visceral e o diagnóstico adequado é fundamental para o tratamento eficaz.
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ABSTRACT Purpose: The aim of this study was to evaluate the relationship between tumor size and grade with visceral adipose index (VAI) levels in patients with renal cell carcinoma. Materials and methods: We retrospectively reviewed the records of 310 consecutive patients with RCC who underwent radical nephrectomy at our institution between January 2007 and May 2014. VAI was calculates for males and females seperately as this formula like previous study. The relationship between tumor size and nuclear grade with VAI levels were evaluated statisticaly. Analyses were completed using Chi-square tests and Logistic regression analysis. Results: Among the 310 total patients analyzed in our study, there were 176 males (56.8%) and 134 females (43.2%). VAI levels were statistically higher in men and women with high tumor size (p<0.001). VAI levels were statistically higher in men and women with high fuhrman grade (p<0.001). Conclusions: The components of VAI may have effect on tumor carcinogenesis in similar pathways. In our study patients with high VAI levels were found to have statistically significant higher nuclear grade and tumor size. VAI can be a useful index for the evaluation and calculation of renal cell cancer aggressiviness. Further studies with more patients are needed to confirm our study.
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Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Medição de Risco/métodos , Carga Tumoral , Gordura Intra-Abdominal/patologia , Neoplasias Renais/patologia , Índice de Massa Corporal , Modelos Logísticos , Fatores Sexuais , Estudos Retrospectivos , Fatores de Risco , Circunferência da Cintura , Gradação de Tumores , Pessoa de Meia-IdadeRESUMO
PURPOSE: The aim of this study was to evaluate the relationship between tumor size and grade with visceral adipose index (VAI) levels in patients with renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 310 consecutive patients with RCC who underwent radical nephrectomy at our institution between January 2007 and May 2014. VAI was calculates for males and females seperately as this formula like previous study. The relationship between tumor size and nuclear grade with VAI levels were evaluated statisticaly. Analyses were completed using Chi-square tests and Logistic regression analysis. RESULTS: Among the 310 total patients analyzed in our study, there were 176 males (56.8%) and 134 females (43.2%). VAI levels were statistically higher in men and women with high tumor size (p < 0,001). VAI levels were statistically higher in men and women with high fuhrman grade (p < 0,001). CONCLUSIONS: The components of VAI may have effect on tumor carcinogenesis in similar pathways. In our study patients with high VAI levels were found to have statistically significant higher nuclear grade and tumor size. VAI can be a useful index for the evaluation and calculation of renal cell cancer aggressiviness. Further studies with more patients are needed to confirm our study.
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Carcinoma de Células Renais/patologia , Gordura Intra-Abdominal/patologia , Neoplasias Renais/patologia , Medição de Risco/métodos , Carga Tumoral , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Circunferência da CinturaRESUMO
Using immunohistochemical techniques, we characterized changes in the expression of several neurochemical markers in lumbar 4-sacral 2 (L4-S2) dorsal root ganglion (DRG) neuron profiles (NPs) and the spinal cord of BALB/c mice after axotomy of the L6 and S1 spinal nerves, major tributaries of the pelvic (targeting pelvic visceral organs) and pudendal (targeting perineum and genitalia) nerves. Sham animals were included. Expression of cyclic AMP-dependent transcription factor 3 (ATF3), calcitonin gene-related peptide (CGRP), transient receptor potential cation channel subfamily V, member 1 (TRPV1), tyrosine hydroxylase (TH) and vesicular glutamate transporters (VGLUT) types 1 and -2 was analysed seven days after injury. L6-S1 axotomy induced dramatic de novo expression of ATF3 in many L6-S1 DRG NPs, and parallel significant downregulations in the percentage of CGRP-, TRPV1-, TH- and VGLUT2-immunoreactive (IR) DRG NPs, as compared to their expression in uninjured DRGs (contralateral L6-S1-AXO; sham mice); VGLUT1 expression remained unaltered. Sham L6-S1 DRGs only showed a small ipsilateral increase in ATF3-IR NPs (other markers were unchanged). L6-S1-AXO induced de novo expression of ATF3 in several lumbosacral spinal cord motoneurons and parasympathetic preganglionic neurons; in sham mice the effect was limited to a few motoneurons. Finally, a moderate decrease in CGRP- and TRPV1-like-immunoreactivities was observed in the ipsilateral superficial dorsal horn neuropil. In conclusion, injury of a mixed visceral/non-visceral nerve leads to considerable neurochemical alterations in DRGs matched, to some extent, in the spinal cord. Changes in these and potentially other nociception-related molecules could contribute to pain due to injury of nerves in the abdominopelvic cavity.
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Gânglios Espinais/metabolismo , Neurônios/metabolismo , Nervo Pudendo/metabolismo , Medula Espinal/metabolismo , Fator 3 Ativador da Transcrição/metabolismo , Animais , Axotomia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Regulação para Baixo , Genitália/inervação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neurônios Motores/metabolismo , Pelve/inervação , Períneo/inervação , Canais de Cátion TRPV/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Regulação para Cima , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/metabolismoRESUMO
Orofacial pain conditions can be classified into somatic, visceral or neuropathic pain. Somatic pain is triggered by a noxious stimulus generally inducted by peripheral traumas, such as dental implants surgeries (IMP). Visceral pain initiates within internal body tissues and is normally triggered by inflammation, as in inflammatory toothaches (IT). The third condition is neuropathic pain, which results from persistent injury to the peripheral nerve as in Atypical Odontalgia (AO). The aims of this study were: 1- to investigate somatosensory abnormalities, using mechanical, painful, and electrical quantitative sensory testing (QST), in somatic (IMP patients), visceral (IT) and neuropathic pain (AO); 2- to quantify how accurately QST discriminates an IT or AO diagnosis; and 3- to investigate the influence implant surgeries or pulpectomy may have on somatosensory system and sensory nerve fibers. Sixty subjects were divided in three groups: IMP (n = 20), IT (n = 20) and AO group (n = 20). A sequence of five QSTs and the Conditioned Pain Modulation Test (CPM) were performed one month and three months after dental implant surgery (IMP group) or pulpectomy (IT group). AO group was evaluated only at baseline. QST comprehended Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Dynamical Mechanical Allodynia (DMA), Current Perception Threshold (CPT) for A-beta (frequency of 2000Hz), A-delta (250Hz) and C fibers (5Hz) and Temporal Summation Test (TS). "Z" score transformation were applied to the data, and within and between groups were statistically analyzed using two-way ANOVA. In addition, the receiver operating characteristic curve analysis, diagnostic accuracy, sensitivity, specificity, likelihood ratios, and diagnostic odds ratio of QSTs were calculated (α = 5%). The findings of this study proved that: 1- loss of function for touch threshold and electrical threshold of C fibers is present in inflammatory toothache; 2- allodynia, hyperalgesia, gain of function for touch and pain thresholds and impaired pain modulation is detected in atypical odontalgia; 3- some QSTs may be used as complementary tests in the differential diagnosis of atypical odontalgia and inflammatory toothache with strong accuracy; 4- the most accurate QSTs for differential diagnosis between subjects with AO and IT were MDT, MPT and DMA where touch threshold forces > 1 g/mm2 and pain threshold forces > 10g/mm2 can be used to accurately discriminate AO from IT; and 5- no somatosensory modification is found after implant surgery and reduced electrical threshold in C fiber is found for patients with inflammatory toothache after 3 months of pulpectomy.(AU)
As dores orofaciais podem ser classificadas em dores somáticas, viscerais ou neuropáticas. A dor somática está relacionada a um estímulo nocivo evidente, geralmente associada a um trauma periférico, como por exemplo, nas cirurgias de implantes (IMP). As dores viscerais têm origem dentro dos órgãos e cavidades internas do corpo e são ativadas pela inflamação, como no exemplo da dor de dente do tipo Pulpite Aguda (PA). A terceira condição é a dor neuropática, que resulta de uma lesão persistente ao nervo periférico, como ocorre na Odontalgia Atípica (OA). Os objetivos deste estudo foram: 1- avaliar as alterações somatossensoriais, por meio do uso de Testes Sensoriais Quantitativos (TSQ) mecânicos, dolorosos e elétricos em dores somáticas (pacientes IMP), viscerais (PA) e neuropáticas (OA); 2- quantificar a acurácia dos TSQs na descriminação diagnóstica de uma PA ou OA; e 3- investigar alterações somatossensoriais e nas fibras nervosas sensoriais após cirurgia de instalação de implantes dentários ou pulpectomia. Sessenta sujeitos foram divididos em três grupos: IMP (n = 20), PA (n = 20) e OA (n = 20). Uma sequência de cinco TSQs e o teste de Controle da Modulação da Dor (CMD) foram realizados um mês e três meses após cirurgia de implantes (grupo IMP) ou pulpectomia (grupo PA). No grupo OA, os testes foram realizados somente uma vez no início do estudo. Os TSQs englobaram o Limiar de Detecção Mecânica (LDM), Limiar de Dor Mecânica (LDoM), Alodinia Mecânica Dinâmica (AMD), Limiar de Percepção de Corrente (LPC) para fibras A-beta (frequência de 2000Hz), A-delta (250Hz) e C (5 Hz), e o teste de Somação Temporal (ST). A transformação em escores de "Z" foi aplicada aos dados, e diferenças intra e inter-grupos foram analisadas usando ANOVA de medidas repetidas. Ainda, a acurácia diagnóstica dos TSQs foi medida por meio da sensibilidade, especificidade, razão de verossimilhança e razão de chances para diagnóstico (α = 5%). Os resultados deste estudo mostraram que: 1- perda da função em limiar táctil e limiar elétrico de fibras C está presente na Pulpite Aguda; 2- alodinia, hiperalgesia, ganho de função nos limiares de tato e de dor, e modulação da dor prejudicada são encontrados em pacientes com odontalgia atípica; 3- alguns TSQs podem ser usados como testes diagnósticos complementares ao diagnóstico diferencial entre PA e OA; 4- os TSQs com maior acurácia para o diagnóstico diferencial entre indivíduos com PA e OA foram LDM LDoM e AMD, onde uma força maior que 1 g/mm2 para limiar de tato e maior que 10 g/mm2 para limiar de dor podem ser usados com precisão; e 5- nenhuma alteração somatossensorial é encontrada após cirurgia de implantes e uma redução no limiar elétrico em fibras C é encontrado em pacientes com PA após 3 meses da pulpectomia.(AU)
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neuralgia Facial/fisiopatologia , Dor Facial/diagnóstico , Dor Facial/etiologia , Dor Facial/fisiopatologia , Hiperalgesia/fisiopatologia , Medição da Dor/métodos , Dor Visceral/fisiopatologia , Análise de Variância , Estudos de Casos e Controles , Diagnóstico Diferencial , Limiar da Dor/fisiologia , Valores de Referência , Curva ROCRESUMO
Labor pain has been reported as a severe pain and can be considered as a model of acute visceral pain. It is well known that extracellular purines have an important role in pain signaling in the central nervous system. This study analyzes the relationship between extracellular purines and pain perception during active labor. A prospective observational study was performed. Cerebrospinal fluid (CSF) levels of the purines and their metabolites were compared between women at term pregnancy with labor pain (n = 49) and without labor pain (Caesarian section; n = 47). Control groups (healthy men and women without chronic or acute pain-n = 40 and 32, respectively) were also investigated. The CSF levels of adenosine were significantly lower in the labor pain group (P = 0.026) and negatively correlated with pain intensity measured by a visual analogue scale (r = -0.48, P = 0.0005). Interestingly, CSF levels of uric acid were significantly higher in healthy men as compared to women. Additionally, pregnant women showed increased CSF levels of ADP, GDP, adenosine and guanosine and reduced CSF levels of AMP, GTP, and uric acid as compared to non-pregnant women (P < 0.05). These findings suggest that purines, in special the nucleoside adenosine, are associated with pregnancy and labor pain.
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Dor do Parto/líquido cefalorraquidiano , Trabalho de Parto/líquido cefalorraquidiano , Purinas/líquido cefalorraquidiano , Adenosina/líquido cefalorraquidiano , Difosfato de Adenosina/líquido cefalorraquidiano , Adulto , Cesárea , Feminino , Guanosina/líquido cefalorraquidiano , Guanosina Difosfato/líquido cefalorraquidiano , Humanos , Masculino , Medição da Dor , Percepção da Dor , Gravidez , Estudos ProspectivosRESUMO
When an organ disease is ruled out as the origin of pelvic pain, the superior hypogastric plexus (SHP) injury and consequent dysfunction could be the mechanism of visceral chronic pain perpetuation. As much as a dorsal discus herniation may harm the dorsal or ventral roots, a ventral discus herniation at L4-L5 or L5-S1 may result in direct physical trauma to the SHP, maintaining chronic visceral pain mediated by sympathetic dysfunction, conceivably also afferent fibers dysfunction. We propose that similarly to nociceptive somatic dysfunction named complex regional pain syndrome, the maintained sympathetic pelvic pain secondary to straight physical damage to the SHP characterize in fact the same disease, but in nociceptive visceral tissue, named visceral complex regional pain syndrome, a concept constructed based on the International Association for the Study of Pain criteria (1994).
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BACKGROUNDS AND OBJECTIVES: Visceral pain shows many pathophysiological properties that make this form of pain unique, not only because of the clinical properties of the sensation but also because the neurobiological mechanisms that mediate the sensory process. This study aimed at reviewing the pathophysiology of visceral pain. CONTENTS: The activation and sensitization of visceral nociceptors are heavily influenced by the secretory and motor properties of the microenvironment where the sensory receptors are located. In some cases, epithelial cells can play a direct role in the activation of primary sensory neurons. Subclinical alterations of the visceral epithelium can contribute to enhanced visceral sensitivity. Central hypersensitivity induced by visceral activation can be caused by mobilization of AMPA receptors from the cytosol to the membrane of nociceptive neurons. In addition, functional pain syndromes, such as the Irritable Bowel Syndrome, could be triggered or maintained by hormonal alterations, particularly those involving sex hormones such as estrogen. CONCLUSION: The neurobiological mechanisms that mediate visceral pain are sufficiently unique to preclude interpreting visceral pain conditions purely as a direct extrapolation of what we know about somatic pain. The functional properties of visceral nociceptors are different from those of their somatic counterparts and the microenvironment where visceral nociceptors are located, and especially the motor and secretory functions of organs like the gut, play a key role in the activation and sensitization of visceral sensory receptors. .
JUSTIFICATIVA E OBJETIVOS: A dor visceral apresenta muitas propriedades fisiopatológicas que fazem dela única, não apenas devido às propriedades clínicas da sensação, mas também devido aos mecanismos neurobiológicos que mediam o processo sensorial. O objetivo deste estudo foi rever a fisiopatologia da dor visceral. CONTEÚDO: A ativação e a sensibilização dos nociceptores viscerais são altamente influenciadas pelas propriedades secretórias e motoras do microambiente onde os receptores sensoriais estão localizados. Em alguns casos, as células epiteliais podem ter uma função direta na ativação de neurônios sensoriais primários. Alterações subclínicas do epitélio visceral podem contribuir para o aumento da sensibilidade visceral. A hipersensibilidade central induzida pela ativação visceral pode ser causada pela mobilização de receptores AMPA do citosol para a membrana de neurônios nociceptivos. Além disso, síndromes dolorosas funcionais, como a Síndrome do Intestino Irritável, podem ser provocadas ou mantidas por alterações hormonais, especialmente aquelas envolvendo hormônios sexuais, como o estrógeno. CONCLUSÃO: Os mecanismos neurobiológicos que mediam a dor visceral são suficientemente únicos para excluir a possibilidade de interpretar condições de dor visceral puramente como a extrapolação direta do que sabemos sobre dor somática. As propriedades funcionais dos nociceptores viscerais são diferentes das dos nociceptores somáticos e o microambiente onde os nociceptores viscerais estão localizados, e principalmente as funções motoras e secretórias de órgãos como o intestino, têm função importante na ativação e sensibi...
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Henry Head, neurólogo británico, ha pasado a la historia de la medicina occidental por su contribución a la creación de los mapas de dermatomas. Una modalidad terapéutica dentro de la medicina neuralterapéutica es la terapia de segmento y, dentro del estudio del marco de sustentación teórica y experimental de su utilidad se encuentra este artículo. Las hipótesis planteadas por Head en cuanto a la asociación e interrelación de sensibilidad cutánea y visceral, pueden constituirse en un aporte para las bases neuroanatómicas y fisiológicas de la neuralterapia y la medicina en general. Se realiza una revisión histórica de una parte de su trabajo menos difundida, dedicada al dolor referido en la enfermedad visceral y en los cambios mentales asociados a la misma...
Henry Head, a British neurologist, carved a name for himself in the Western Medicine Annals for his contribution to the creation of dermatome maps. Segment therapy stands as one of the therapeutic modalities making up neural-therapeutic medicine, and this paper is within the theoretical and experimental support frame of the study of its utilization. The hypotheses proposed by Head in terms of association and interrelation of cutaneous and visceral sensitivity can be deemed as a contribution to the neural-anatomic physiologic grounds for not only neural-therapy, but also general medicine. This paper constitutes a historic review of one of the least known parts of his work, devoted to visceral-disease-referred pain and visceral-disease-associated mental changes...
Assuntos
Terapias Complementares , História da Medicina , Dor Referida , Dor VisceralRESUMO
BACKGROUND AND OBJECTIVES: Abdomen is the most frequent site for acute or chronic painful syndromes, for referred pain from distant structures or for pain caused by systemic injuries. Abdominal visceral pain is induced by hollow viscera or parenchymal viscera walls stretching or by peritoneal stretching. Complex diagnosis and treatment have motivated this study. Patients with chronic abdominal pain are usually undertreated and underdiagnosed. The interdisciplinary treatment aims at minimizing patients' distress, relieving pain and improving their quality of life. CONTENTS: Since visceral diseases may determine pain of different types and, usually, challenge physicians with regard to their diagnosis and treatment, the authors have described in a practical way painful characteristics and associations with more common diseases. CONCLUSION: The interdisciplinary treatment, with the association of pharmacological measures to physical medicine and rehabilitation procedure and to psychological follow up, decreases distress and inabilities and improves quality of life.
JUSTIFICATIVA E OBJETIVOS: O abdômen é o local mais frequente das síndromes dolorosas agudas ou crônicas, de dor referida de origem em estruturas distantes ou de dor decorrente de lesões sistêmicas. A dor visceral abdominal ocorre por tensão ou estiramento da parede das vísceras ocas ou da cápsula das vísceras parenquimatosas e pela tração ou estiramento peritoneal. O diagnóstico e o tratamento complexos motivaram este estudo. Os pacientes com dor abdominal crônica usualmente são subtratados e subdiagnosticados. O tratamento interdisciplinar visa minimizar o sofrimento do paciente, aliviar a dor e melhorar sua qualidade de vida. CONTEÚDO: Como as doenças viscerais podem determinar dores de vários tipos e, habitualmente, desafiam os médicos no seu diagnóstico e tratamento, os autores descreveram de forma prática, as características dolorosas e as associações com as doenças mais incidentes. CONCLUSÃO: O tratamento interdisciplinar com a associação das medidas farmacológicas aos procedimentos de medicina física e reabilitação e ao acompanhamento psicológico diminui o sofrimento e as incapacidades e melhora a qualidade de vida.
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JUSTIFICATIVA E OBJETIVOS: Os pacientes que sofrem de dor visceral podem apresentá-la em diferentes áreas do corpo. Este tipo de dor é percebido de forma difusa, diferente da dor por estimulação dolorosa cutânea, no que concerne a localização e intervalo de aparecimento. O objetivo deste estudo foi demonstrar um caso de dor visceral em paciente submetido a procedimento urológico seguido de complicação no pós-operatório RELATO DO CASO: Paciente do gênero masculino, 60 anos, em uso de varfarina, deu entrada no pronto-socorro apresentando quadro de dor abdominal com predominância em flanco esquerdo, 48 horas após procedimento urológico transuretral. Na investigação complementar foi identificada a presença de hematoma retroperitonial em loja renal esquerda. Inicialmente o paciente recebeu tratamento conservador, e foi iniciada analgesia com morfina por via endovenosa através de bomba de analgesia controlada pelo paciente. Com o aumento do hematoma, optou-se por intervenção cirúrgica para realização de nefrectomia esquerda. CONCLUSÃO: A convergência neurofisiológica dos aferentes somáticos e viscerais que adentram o sistema nervoso central parece explicar a dor visceral referida, onde estímulos nóxicos sobre as vísceras provocam dor referida em áreas somáticas. Este caso ilustra o manuseio de um caso de dor visceral aguda onde a utilização de analgesia venosa controlada por paciente com morfina associada à dipirona foi empregada como estratégia para o controle de dor, para o qual se mostrou eficiente.
BACKGROUND AND OBJECTIVES: Patients may have visceral pain in different parts of the body. This pain is perceived as diffuse, differently from painful skin stimulation pain, with regard to location and interval of presentation. This study aimed at showing a case of visceral pain in a patient submitted to urological procedure followed by postoperative complication. CASE REPORT: Male patient, 60 years old, using warfarin, entered the first-aid unit with abdominal pain predominantly in the left flank, 48 hours after transuretral urological procedure. Investigation has identified the presence of retroperitoneal hematoma in left renal lobe. Initially patient was conservatively treated with intravenous morphine by patient-controlled analgesia pump. Since hematoma has increased, we decided for left nephrectomy surgical procedure. CONCLUSION: The neurophysiologic convergence of somatic and visceral afferents entering the central nervous system seems to explain referred visceral pain, where noxious viscera stimuli induce referred pain in somatic areas. This report illustrates a case of acute visceral pain management where venous patient-controlled analgesia with morphine associated to dipirone was used to control pain, for which it was effective.
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El dolor visceral crónico se produce por la distención de los receptores neuronales localizados en las mucosas de los distintos órganos del aparato digestivo, presentándose clínicamente como un dolor con una localización difusa, con intensidad moderada a severa, que se describe generalmente de tipo cólico. Presentamos un caso clínico de una paciente con que consultó por un dolor crónico no oncológico de tipo visceral con componente neuropático, cuya causa etiológica correspondió a sobrecrecimieno bacteriano intestinal. Por lo que debemos considerar esta patología como etiología de un dolor visceral crónico...
Chronic Visceral pain is caused by the distension of neuronal receptors located in the lining the digestive organs, clinically presenting as pain with a diffuse localization and moderate to severe intensity, usually is described colicky. We present a case report a patient who presented with chronic noncancer visceral pain with neuropathic component, which accounted etiology Small intestinal bacterial overgrowth. We must consider this disease as a cause of chronic visceral pain...