RESUMO
Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal diseases. In this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1 (GATA1) in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation (NCI). The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay, chromatin immunoprecipitation, patch clamp, and interference in vitro and in vivo. In addition, a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG island. We showed that NCI caused the induction of GATA1, Ten-eleven translocation 3 (TET3), and purinergic receptors (P2X7Rs) in astrocytes of the spinal dorsal horn, and demonstrated that inhibiting these molecules markedly increased the pain threshold, inhibited the activation of astrocytes, and decreased the spinal sEPSC frequency. NCI also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1-TET3 physical interaction and GATA1 binding at the p2x7r promoter. Importantly, we showed that demethylation of the p2x7r locus (and the attendant increase in P2X7R expression) was reversed upon knockdown of GATA1 or TET3 expression, and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r promoter. These results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r transcription in spinal dorsal horn astrocytes, and provide a potential therapeutic strategy by targeting GATA1 and p2x7r locus binding.
Assuntos
Animais , Ratos , Astrócitos/metabolismo , Desmetilação do DNA , Epigênese Genética , Fator de Transcrição GATA1/metabolismo , Inflamação/metabolismo , Oligodesoxirribonucleotídeos/metabolismo , Ratos Sprague-Dawley , Receptores Purinérgicos P2X7/metabolismo , Dor Visceral/metabolismoRESUMO
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
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.
Assuntos
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
The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β adrenergic signaling in DRGs.
Assuntos
Animais , Masculino , Adrenérgicos , Farmacologia , Gânglios Espinais , Hiperalgesia , Tratamento Farmacológico , Hipersensibilidade , Tratamento Farmacológico , Privação Materna , Neurônios , Técnicas de Patch-Clamp , Métodos , Ratos Sprague-Dawley , Transdução de Sinais , Estresse Fisiológico , Fisiologia , Dor Visceral , MetabolismoRESUMO
It is commonly accepted that females and males differ in their experience of pain. Gender differences have been found in the prevalence and severity of pain in both clinical and animal studies. Sex-related hormones are found to be involved in pain transmission and have critical effects on visceral pain sensitivity. Studies have pointed out the idea that serum estrogen is closely related to visceral nociceptive sensitivity. This review aims to summarize the literature relating to the role of estrogen in modulating visceral pain with emphasis on deciphering the potential central and peripheral mechanisms.
Assuntos
Animais , Feminino , Humanos , Masculino , Estrogênios/metabolismo , Hiperalgesia/terapia , Sistema Imunitário , Nociceptores , Ovariectomia , Manejo da Dor , Limiar da Dor , Fatores Sexuais , Dor Visceral/terapiaRESUMO
BACKGROUND/AIMS: Abdominal pain can be evoked or exacerbated after gastrointestinal cold stimulation in some patients with diarrhea-predominant irritable bowel syndrome (IBS-D), indicating a low temperature-induced sensitization of visceral perception. We investigated the role of vagal transient receptor potential ankyrin 1 (TRPA1, a cold-sensing ion channel) in cold-aggravated visceral mechanonociception in a stress-induced IBS animal model. METHODS: TRPA1 expression was examined in antral biopsies of healthy controls and IBS-D patients. Abdominal symptoms were assessed before and after warm or cold water intake. The visceromotor response (VMR) to colorectal distention (CRD) following intra-antral infusion of cold saline was measured in animals undergoing sham or chronic water avoidance stress. TRPA1 expression, extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation, and neuronal calcium influx in vagal afferents were assessed. RESULTS: Compared to healthy controls, IBS-D patients displayed elevated antral TRPA1 expression, which was associated with symptom scores after cold (4°C) water intake. Intra-antral infusion of cold saline increased VMR to CRD in naive rats, an effect dependent on vagal afferents. In stressed rats, this effect was greatly enhanced. Functional blockade and gene deletion of TRPA1 abolished the cold effect on visceral nociception. TRPA1 expression in vagal (but not spinal) afferents increased after stress. Moreover, the cold-induced, TRPA1-dependent ERK1/2 activation and calcium influx in nodose neurons were more robust in stressed rats. CONCLUSIONS: Stress-exaggerated visceral mechanonociception after antral cold exposure may involve up-regulation of TRPA1 expression and function on vagal afferents. Our findings reveal a novel mechanism for abnormal gastrointestinal cold sensing in IBS.
Assuntos
Animais , Humanos , Ratos , Dor Abdominal , Anquirinas , Biópsia , Cálcio , Temperatura Baixa , Ingestão de Líquidos , Deleção de Genes , Síndrome do Intestino Irritável , Modelos Animais , Neurônios , Nociceptividade , Fosforilação , Proteínas Quinases , Estresse Psicológico , Regulação para Cima , Nervo Vago , Dor Visceral , ÁguaRESUMO
BACKGROUND: The use of aroma oils dates back to at least 3000 B.C., where it was applied to mummify corpses and treat the wounds of soldiers. Since the 1920s, the term “aromatherapy” has been used for fragrance therapy with essential oils. The purpose of this study was to determine whether the essential oil of Eucalyptus (EOE) affects pain pathways in various pain conditions and motor coordination. METHODS: Mice were subjected to inhalation or intraperitoneal injection of EOE, and its analgesic effects were assessed by conducting formalin, thermal plantar, and acetic acid tests; the effects of EOE on motor coordination were evaluated using a rotarod test. To determine the analgesic mechanism, 5′-guanidinonaltrindole (κ-opioid antagonist, 0.3 mg/kg), naltrindole (δ-opioid antagonist, 5 mg/kg), glibenclamide (δ-opioid antagonist, 2 mg/kg), and naloxone (μ-opioid antagonist, 4, 8, 12 mg/kg) were injected intraperitoneally. RESULTS: EOE showed an analgesic effect against visceral pain caused by acetic acid (EOE, 45 mg/kg); however, no analgesic effect was observed against thermal nociceptive pain. Moreover, it was demonstrated that EOE did not have an effect on motor coordination. In addition, an anti-inflammatory effect was observed during the formalin test. CONCLUSIONS: EOE, which is associated with the μ-opioid pain pathway, showed potential effects against somatic, inflammatory, and visceral pain and could be a potential therapeutic agent for pain.
Assuntos
Animais , Humanos , Camundongos , Ácido Acético , Analgésicos , Aromaterapia , Cadáver , Eucalyptus , Formaldeído , Glibureto , Inalação , Injeções Intraperitoneais , Militares , Naloxona , Antagonistas de Entorpecentes , Dor Nociceptiva , Óleos , Óleos Voláteis , Medição da Dor , Teste de Desempenho do Rota-Rod , Dor Visceral , Ferimentos e LesõesRESUMO
BACKGROUND/AIMS: Visceral pain and hypothalamic-pituitary-adrenal axis (HPA) dysregulation is a common characteristic in irritable bowel syndrome (IBS) patients. Previously, we reported that a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) prevents chronic stress-mediated brain function abnormalities by attenuating the HPA axis response. Here, we compared the effect between different probiotic treatments on the perception of visceral pain during colorectal distension (CRD) following a chronic stress and the consequences to the activity of the HPA axis. METHODS: After a 2-week treatment with a combined probiotic formulation, or L. helveticus or B. longum alone in stressed mice, the visceral pain in response to CRD was recorded. The expression of glucocorticoid receptors was determined in the different brain areas involved in the stress response (hypothalamus, hippocampus, and prefrontal cortex). The plasma levels of stress hormones were also measured. RESULTS: A pretreatment using the combination of probiotic formulation significantly reduces the chronic stress-induced visceral hypersensitivity respectively at 0.06, 0.08, and 0.10 mL CRD volume. However, a single probiotic (B. longum or L. helveticus) administration is less effective in reducing visceral pain in stressed mice. Moreover, the expression of the glucocorticoid receptor mRNA was consistently up-regulated in several brain areas after pretreatment with a combined probiotic, which correlated with the normalization of stress response compared to the inconsistent effects of a single probiotic. CONCLUSION: The combination of L. helveticus and B. longum is more effective in regulating glucocorticoid negative feedback on the HPA axis than probiotic alone and subsequently in treating stress-induced visceral pain.
Assuntos
Animais , Humanos , Camundongos , Bifidobacterium , Encéfalo , Hipocampo , Hipersensibilidade , Síndrome do Intestino Irritável , Lactobacillus helveticus , Lactobacillus , Plasma , Probióticos , Receptores de Glucocorticoides , RNA Mensageiro , Sulfaleno , Dor VisceralRESUMO
BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.
Assuntos
Humanos , Encéfalo , Área de Broca , Núcleo Caudado , Classificação , Dispepsia , Neuroimagem Funcional , Voluntários Saudáveis , Imageamento por Ressonância Magnética , Giro Para-Hipocampal , Lobo Parietal , Perfusão , Córtex Pré-Frontal , Sensação , Córtex Somatossensorial , Dor Visceral , ÁguaRESUMO
BACKGROUND/AIMS: Post-operative ileus (POI) is a common complication of abdominal surgery. DA-9701, an extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that also alleviates visceral pain. The aim of this study was to investigate whether DA-9701 can ameliorate POI in rats. METHODS: A total of 32 rats were divided into 4 groups: no surgery/no medication (NSNM), no surgery/medication (NSM), surgery/no medication (SNM), and surgery/medication (SM). Gastrointestinal transit (GIT), which is assessed by migration of charcoal, and cumulative stool weight were measured at 24 hours after surgery. RESULTS: GIT was significantly more delayed in the SNM group than in the other groups (SNM vs NSNM, P < 0.001; SNM vs NSM, P < 0.001; SNM vs SM, P = 0.005). Cumulative stool weight in that group was also lower than in the no surgery groups (SNM vs NSNM, P = 0.007; SNM vs NSM, P = 0.033), and there was no significant difference between the SM group and the no surgery groups (SM vs NSM, P = 0.703; SM vs NSNM, P = 0.347). CONCLUSION: DA-9701 can ameliorate POI by reducing delayed GIT and improving defecation in a rat model of POI.
Assuntos
Animais , Ratos , Carvão Vegetal , Corydalis , Defecação , Trânsito Gastrointestinal , Grelina , Íleus , Modelos Animais , Sêmen , Dor VisceralRESUMO
BACKGROUND/AIMS: Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. METHODS: DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension. RESULTS: Incubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials induced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltage-gated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89. CONCLUSIONS: Our data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection.
Assuntos
Animais , Humanos , Ratos , Dor Abdominal , Potenciais de Ação , Corticosterona , Proteínas Quinases Dependentes de AMP Cíclico , Grupos Diagnósticos Relacionados , Dispepsia , Gânglios , Gânglios Espinais , Hipersensibilidade , Injeções Intraperitoneais , Músculos do Pescoço , Neurônios , Proteína Quinase C , Proteínas Quinases , Sódio , Canais de Sódio , Raízes Nervosas Espinhais , Estômago , Dor VisceralRESUMO
BACKGROUND/AIMS: Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins expression and visceral pain threshold. METHODS: Post-infectious IBS was induced in mice via a Trichinella spiralis infection. Visceral sensitivity was measured with abdominal withdrawal reflex to colorectal distention. Inflammation in the small intestine and colon was scored with H&E staining. Expression location of Piezo proteins was confirmed by immunohistochemistry. Abundance of Piezo proteins were measured with real-time reverse transcriptase polymerase chain reaction. RESULTS: Piezo1 and Piezo2 proteins were expressed in the intestinal epithelial cells. The expression levels of Piezo1 and Piezo2 were abundant in the colon than the small intestine (P < 0.001 for Piezo1, P = 0.003 for Piezo2). Expression of Piezo2 in the colon significantly correlated to the visceral sensitivity (r = −0.718, P = 0.001) rather than the mucosal inflammation. CONCLUSION: Piezo2 is a candidate biomarker for visceral hypersensitivity in IBS.
Assuntos
Animais , Humanos , Camundongos , Colo , Células Epiteliais , Hiperalgesia , Hipersensibilidade , Imuno-Histoquímica , Inflamação , Intestino Delgado , Canais Iônicos , Síndrome do Intestino Irritável , Reflexo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trichinella spiralis , Dor VisceralRESUMO
A 22-years-old female patient at 171 cm and 67 kg visited the Department of Breast Surgery of the hospital with a mass accompanied with pain on the left side breast as chief complaints. Since physical examination revealed a suspected huge mass, breast surgeon decided to perform surgical excision and requested anesthesia to our department. Surgery of breast tumor is often under local anesthesia. However, in case of big size tumor, surgery is usually performed under general anesthesia. The patient feared general anesthesia. Unlike abdominal surgery, there is no need to control visceral pain for breast and anterior thoracic wall surgery. Therefore, we decided to perform resection under regional anesthesia. Herein, we report a successful anesthetic and pain management of the patient undergoing excision of a huge breast fibroadenoma under regional anesthesia using Pecs II and internal intercostal plane block.
Assuntos
Feminino , Humanos , Anestesia , Anestesia por Condução , Anestesia Geral , Anestesia Local , Neoplasias da Mama , Mama , Fibroadenoma , Mastectomia Segmentar , Manejo da Dor , Exame Físico , Nervos Torácicos , Parede Torácica , Dor VisceralRESUMO
Bisthiourea derivatives were synthesized by the reaction of benzoylisothiocyanate and diamines to give 1,2-Bis [N'-benzoylthioureidobenzene [1], l,3-di[benzoylthioureido] benzene [2] and l,4-di [benzoylthioureido] benzene [3] in acetone. Acute toxicity study revealed that LD[50] of compound [1] and [3] is 120 mg/kg body weight. Visceral pain induced by injecting i.p acetic acid in mice were strongly inhibited by all the compounds. 94.65, 95.25 and 85.54% analgesic activity were observed in compounds [1], [2] and [3] at 15 mg/kg and [2] and [3] shows 97.63 and 96.42% at 30 mg/kg body weight respectively while [1] gives 100% analgesic activity. 100% cytotoxicity was observed in compounds [2] and [3] and 96% in compound [1] at 750 ppm. The results suggest that these compounds may have potential values for treatment of cancer and painful disorders
Assuntos
Animais de Laboratório , Testes de Toxicidade Aguda , Analgésicos , Dor Visceral , Técnicas In Vitro , CamundongosRESUMO
ABSTRACT Objective: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. Materials and Methods: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. Results: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. Conclusions: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.
Assuntos
Animais , Feminino , Vísceras/fisiopatologia , Modelos Animais de Doenças , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/fisiopatologia , Hipersensibilidade/complicações , Hipersensibilidade/fisiopatologia , Mastócitos/patologia , Pressão , Urodinâmica , Vísceras/patologia , Distribuição Aleatória , Reprodutibilidade dos Testes , Ratos Wistar , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/patologia , Bexiga Urinária Hiperativa/patologia , Dor Visceral/complicações , Dor Visceral/fisiopatologia , Dor Visceral/patologia , Hipersensibilidade/patologia , Intestinos/fisiopatologia , Intestinos/patologiaRESUMO
BACKGROUND/AIMS: Dai-kenchu-to (DKT), a traditional Japanese herbal medicine, is known to increase gastrointestinal motility and improve ileal function. We tested our hypotheses that (1) pretreatment with DKT would block the colorectal distention-induced visceromotor response in rats, and (2) pretreatment with DKT would attenuate colorectal distention-induced adrenocorticotropic hormone (ACTH) release and anxiety-related behavior. METHODS: Rats were pretreated with vehicle or DKT (300 mg/kg/5 mL, per os). Visceromotor responses were analyzed using electromyography in response to colorectal distention (10, 20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention. Plasma ACTH and serum corticosterone levels were measured after exposure to the elevated-plus maze. RESULTS: Colorectal distention produced robust contractions of the abdominal musculature, graded according to stimulus intensity, in vehicle-treated rats. At 40, 60, and 80 mmHg of colorectal distention, the visceromotor responses of DKT-treated rats was significantly lower than that of vehicle-treated rats. At 80 mmHg, the amplitude was suppressed to approximately one-third in DKT-treated rats, compared with that in vehicle-treated rats. Smooth muscle compliance and the velocity of accommodation to 60 mmHg of stretching did not significantly differ between the vehicle-treated and DKT-treated rats. Similarly, the DKT did not influence colorectal distention-induced ACTH release, corticosterone levels, or anxiety-related behavior in rats. CONCLUSIONS: Our results suggest that DKT attenuates the colorectal distention-induced visceromotor responses, without increasing smooth muscle compliance, ACTH release or anxiety-related behavior in rats.
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Animais , Humanos , Ratos , Hormônio Adrenocorticotrópico , Ansiedade , Povo Asiático , Complacência (Medida de Distensibilidade) , Corticosterona , Eletromiografia , Motilidade Gastrointestinal , Medicina Herbária , Músculo Liso , Plasma , Dor VisceralRESUMO
Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH.
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Humanos , Dor Abdominal , Sistema Nervoso Central , Hormônios Esteroides Gonadais , Hiperalgesia , Hipersensibilidade , Síndrome do Intestino Irritável , Ligantes , Percepção da Dor , Patologia , Fosfotransferases , Receptores Adrenérgicos , Receptores de Canabinoides , Receptores de Glutamato , Receptores Opioides , Receptores Ativados por Proteinase , Receptores de Serotonina , Taquicininas , Tirosina , Dor VisceralRESUMO
BACKGROUND: Total knee replacement is often accompanied by severe post-operative pain. Oxycodone has sufficient analgesic effects and somewhat greater, but tolerable side effects compared to fentanyl. However, most studies on the topic evaluate visceral pain relief. In this study, we determine the effectiveness of oxycodone for somatic pain and evaluate the incidence of side effects. METHODS: Sixty-nine patients were involved in a randomized control trial. Analgesic agents were administered to two experimental groups at a post anesthetic care unit (PACU) 15 min after PACU admission: a 50 µg fentanyl group (n = 40) and a 4 mg oxycodone group (n = 29), both with severe pain (numeric rating scale, NRS > 5). Changes in NRS at the PACU were measured. Additional analgesic agents were administered at 0–6, 6–12, 12–24, and 24–48 h after surgery. RESULTS: Total fentanyl consumption and the number of patients who required additional opioids were significantly lower in the oxycodone group than in the fentanyl group. Incidence of side effects was not significantly different between the two groups. CONCLUSIONS: Oxycodone shows a better analgesic effect than fentanyl in somatic pain in the acute phase of post-operative pain. The side effects of oxycodone are not significantly different from those of fentanyl.
Assuntos
Humanos , Analgésicos , Analgésicos Opioides , Artroplastia do Joelho , Fentanila , Incidência , Dor Nociceptiva , Oxicodona , Dor VisceralRESUMO
Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.