ABSTRACT
BACKGROUND: Low anterior resection syndrome (LARS) is a distressing condition that affects approximately 25-80% of patients following surgery for rectal cancer. LARS is characterized by debilitating bowel dysfunction symptoms, including fecal incontinence, urgent bowel movements, and increased frequency of bowel movements. Although biofeedback therapy has demonstrated effectiveness in improving postoperative rectal control, the research results have not fulfilled expectations. Recent research has highlighted that stimulating the pudendal perineal nerves has a superior impact on enhancing pelvic floor muscle function than biofeedback alone. Hence, this study aims to evaluate the efficacy of a combined approach integrating biofeedback with percutaneous electrical pudendal nerve stimulation (B-PEPNS) in patients with LARS through a randomized controlled trial (RCT). METHODS AND ANALYSIS: In this two-armed multicenter RCT, 242 participants with LARS after rectal surgery will be randomly assigned to undergo B-PEPNS (intervention group) or biofeedback (control group). Over 4 weeks, each participant will undergo 20 treatment sessions. The primary outcome will be the LARS score. The secondary outcomes will be anorectal manometry and pelvic floor muscle electromyography findings and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scores. Data will be collected at baseline, post-intervention (1 month), and follow-up (6 months). DISCUSSION: We anticipate that this study will contribute further evidence regarding the efficacy of B-PEPNS in alleviating LARS symptoms and enhancing the quality of life for patients following rectal cancer surgery. TRIAL REGISTRATION: Chinese Clincal Trials Register ChiCTR2300078101. Registered 28 November 2023.
Subject(s)
Biofeedback, Psychology , Fecal Incontinence , Multicenter Studies as Topic , Pudendal Nerve , Quality of Life , Randomized Controlled Trials as Topic , Rectal Neoplasms , Transcutaneous Electric Nerve Stimulation , Humans , Biofeedback, Psychology/methods , Treatment Outcome , Transcutaneous Electric Nerve Stimulation/methods , Fecal Incontinence/therapy , Fecal Incontinence/physiopathology , Fecal Incontinence/etiology , Rectal Neoplasms/surgery , Rectal Neoplasms/therapy , Female , Middle Aged , Syndrome , Male , Adult , Pelvic Floor/physiopathology , Pelvic Floor/innervation , Recovery of Function , China , Defecation , Aged , Proctectomy/adverse effects , Postoperative Complications/etiology , Postoperative Complications/therapy , Electromyography , ManometryABSTRACT
18F-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) is the most sensitive tool for studying brain metabolism in vivo. We investigated the image patterns of 18F-FDG PET during reperfusion injury and correlated changes of whole brain blood flow utilizing a rat myocardial ischemia/reperfusion injury (MIRI) model. The results assessed by echocardiography indicated resultant cardiac dysfunction after ischemia-reperfusion in the rat heart. It was found that the average standardized uptake value (SUVaverage) of the whole brain was significantly decreased in model rats, and the glucose uptake of different brain regions including accumbens core/shell (Acb), left caudate putamen (LCPu), hippocampus (HIP), left hypothalamus (LHYP), olfactory (OLF), superior colliculus (SC), right midbrain (RMID), ventral tegmental area (VTA), inferior colliculus (IC) and left thalamus whole (LTHA) was significantly decreased in MIRI rats whereas no significant difference was found in the SUVaverage of amygdala (AMY), right CPu, RHYP, right HYP, left MID, right THA, pons and medulla oblongata (MO). These 18F-FDG PET data provide a reliable identification method for brain metabolic changes in rats with MIRI.
Subject(s)
Brain/diagnostic imaging , Cerebrovascular Circulation , Myocardial Reperfusion Injury/diagnostic imaging , Positron-Emission Tomography , Animals , Brain/blood supply , Disease Models, Animal , Fluorodeoxyglucose F18/pharmacology , Humans , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/physiopathology , RatsABSTRACT
The rostral ventromedial medulla (RVM) is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor (MC4R) expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus (NRM) and nucleus gigantocellularis pars α (NGCα)]. Fluorescence immunohistochemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryptophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.
Subject(s)
Medulla Oblongata/metabolism , Neurons, Afferent/metabolism , Nociception/physiology , Receptor, Melanocortin, Type 4/metabolism , Serotonergic Neurons/metabolism , Tyrosine 3-Monooxygenase/metabolism , Animals , Female , Male , Medulla Oblongata/cytology , Mice , Mice, Transgenic , Neural Pathways/cytology , Neural Pathways/metabolism , Neurons, Afferent/cytology , Receptor, Melanocortin, Type 4/geneticsABSTRACT
Despite its clinical importance, the underlying central mechanisms of pruritic behaviors are poorly understood. To investigate the role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behaviors in mice, we tested the effect of arcuate nucleus neurons and interscapular brown adipose tissue (IBAT) on itch produced by intradermal injection of chloroquine in the nape of the neck. Our results provide several lines of evidence for an important role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behavior: (1) Intradermal microinjection of chloroquine resulted in a dramatic increase in itch behaviors accompanied by the activation of c-Fos positive neurons in arcuate nucleus; (2) Microinjection of chloroquine significantly increased IBAT temperature in the mice. These findings suggested that chloroquine-induced pruritic behaviors were associated with the activity of nociceptive arcuate nucleus neurons.
Subject(s)
Arcuate Nucleus of Hypothalamus/physiopathology , Chloroquine/adverse effects , Nociceptors/physiology , Pruritus/chemically induced , Pruritus/physiopathology , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Male , Mice , Mice, Inbred C57BL , Nociceptors/drug effectsABSTRACT
OBJECTIVE: To study the chemical constituents of hybridized Bulbus Fritillariae Ussuriensis. METHOD: The chemical constituents were isolated by silica column chromatography and their structures were identified by physical and chemical eveidences and spectral analysis (IR, 1H-NMR, 13C-NMR, 2D-NMR, MS). RESULT: Seven compounds were obtained and identified as (20S,25S)5alpha, 14alpha, 17beta-cevanine-6beta-hydroxy-3-one (hupehenirine, ZF1), (20S,25S)5alpha, 14alpha, 17beta-cevanine-3beta-hydroxy-6-one (hupehenizine, ZF2), (20R,25S)5alpha, 14alpha-cevanine-3beta,20beta-dihydroxy-6-one (peiminine, verticinone, ZF3), (20S,25S)5alpha, 14alpha, 17beta-cevanine-3beta, 6beta-dihydroxy (hupehenine, ZF4), (20R,25S)5alpha, 14alpha-cevanine-3beta, 6beta, 20beta-trihydroxy (isoverticine, ZF5), (20R,25S)5alpha, 14alpha-cevanine-3beta, 6alpha, 20beta-trihydroxy (peimine, verticine, ZF6), (20S,25S)5alpha, 14alpha, 17beta-evanine-6beta-hydroxy-3beta-O-beta-D-glucoside (hupeheninoside, ZF7). CONCLUSION: Compounds ZF1-7 were isolated from hybridized Bulbus Fritillariae Ussuriensis for the first time.
