scholarly journals Researching New Therapeutic Approaches for Abdominal Visceral Pain Treatment: Preclinical Effects of an Assembled System of Molecules of Vegetal Origin

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 22 ◽  
Author(s):  
Carmen Parisio ◽  
Elena Lucarini ◽  
Laura Micheli ◽  
Alessandra Toti ◽  
Lorenzo Di Cesare Mannelli ◽  
...  
Keyword(s):  
Visceral Pain ◽  
Pain Treatment ◽  
Therapeutic Option ◽  
Aloe Vera ◽  
Intestinal Damage ◽  
Boswellia Serrata ◽  
Rectal Balloon ◽  
Natural Origin ◽  
Eu Directive ◽  
Bowel Diseases

Abdominal pain is a frequent symptom of irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBDs). Although the knowledge of these pathologies is progressing, new therapeutic strategies continue to be investigated. In the present study, the effect of a system of molecules of natural origin (a medical device according to EU Directive 93/42/EC, engineered starting from Boswellia serrata resins, Aloe vera polysaccharides and Matricaria chamomilla and Melissa officinalis polyphenols) was evaluated against the intestinal damage and visceral pain development in DNBS-induced colitis model in rats. The system (250 and 500 mg kg−1) was orally administered once daily, starting three days before the injection of 2,4-dinitrobenzenesulfonic acid (DNBS) and for 14 days thereafter. The viscero-motor response (VMR) to colon-rectal balloon distension (CRD) was used as measure of visceral sensitivity. The product significantly reduced the VMR of DNBS-treated animals. Its effect on pain threshold was better than dexamethasone and mesalazine, and not lower than amitriptyline and otilonium bromide. At microscopic and macroscopic level, the tested system was more effective in protecting the intestinal mucosa than dexamethasone and mesalazine, promoting the healing of tissue lesions. Therefore, we suggest that the described system of molecules of natural origin may represent a therapeutic option to manage painful bowel diseases.

scholarly journals Novel Therapeutic Approaches to the Treatment of Chronic Abdominal Visceral Pain

2006 ◽  
Vol 6 ◽  
pp. 472-490 ◽  
Author(s):  
Franca Patrizi ◽  
Steven D. Freedman ◽  
Alvaro Pascual-Leone ◽  
Felipe Fregni
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Visceral Pain ◽  
Pain Treatment ◽  
Therapeutic Option ◽  
Therapeutic Options ◽  
Central Nervous System Stimulation ◽  
Chronic Pain Treatment ◽  
Novel Therapeutic

Chronic abdominal visceral pain (CAVP) has a significant clinical impact and represents one of the most frequent and debilitating disorders in the general population. It also leads to a significant economic burden due to workdays lost, reduced productivity, and long-term use of medications with their associated side effects. Despite the availability of several therapeutic options, the management of patients with CAVP is often inadequate, resulting in frustration for both patients and physicians. This may in part be explained by the lack of understanding of the mechanisms underlying chronic pain; in contrast with acute pain in which the pathophysiology is relatively well known and has several satisfactory therapeutic options. Recently, the development of tools for brain investigation, such as functional magnetic resonance imaging, has provided new insights on the pathophysiology of chronic pain. These new data have shown that plastic changes in the central and peripheral nervous system might play an important role in the maintenance of chronic pain. Therefore, approaches aimed at the modulation of the nervous system, rather than the ones interfering with the inflammatory pathways, may be more effective for chronic pain treatment. We propose that noninvasive central nervous system stimulation, with transcranial magnetic stimulation (TMS), might be a novel therapeutic option for CAVP. This paper will present an overview of the pathophysiology and the available therapies for CAVP, focusing on the recent advances in the treatment of this pathology.

scholarly journals Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

2021 ◽  
Vol 10 (4) ◽  
pp. 853
Author(s):  
Giuseppe Privitera ◽  
Daniela Pugliese ◽  
Gian Ludovico Rapaccini ◽  
Antonio Gasbarrini ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Current Knowledge ◽  
Real Life ◽  
Response To Therapy ◽  
Significant Heterogeneity ◽  
Intestinal Damage ◽  
Biological Therapies ◽  
Early Markers ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

scholarly journals Role of Testosterone Levels on the Combinatorial Effect of Boswellia serrata Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells

2021 ◽  
Vol 20 ◽  
pp. 153473542199682
Author(s):  
Prathesha Pillai ◽  
Ginil Kumar Pooleri ◽  
Shantikumar V. Nair
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Early Stage ◽  
Therapeutic Option ◽  
Specific Antigen ◽  
Cell Killing ◽  
Receptor Expression ◽  
Lncap Cells ◽  
Boswellia Serrata ◽  
Physiological Serum

Co-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. However, the whole extract of the gum resin Boswellia serrata (BS) and anti-androgen enzalutamide has not been explored in prostate cancer to date. We hypothesized that the BS extract containing 30% (AKBA) with enzalutamide acted synergistically in the early phase of cancer, especially in LNCaP cells, by inhibiting androgen receptor (AR) and by reducing cell proliferation, and further, that the extract would be superior to the action of the active ingredient AKBA when used alone or in combination with enzalutamide. To test our hypothesis, we treated LNCaP cells with BS extract or AKBA and enzalutamide both individually and in combination to analyze cell viability under different levels of dihydrotestosterone (DHT). The inhibition of androgen receptor (AR) followed by the expression of prostate-specific antigen (PSA) and the efflux mechanism of the cells were analyzed to determine the effect of the combination on the cellular mechanism. Cells derived from prostate cancer patients were also tested with the combination. Only 6 µM enzalutamide along with BS in the range of 4.1 µg/ml to 16.4 µg/ml gave the best synergistic results with nearly 50% cell killing even though standard enzalutamide doses were as high as 48 µM. Cell killing was most effective at intermediate DHT concentrations of approximately 1 nM, which corresponds to normal physiological serum levels of DHT. The Pgp expression level and the androgen receptor expression levels were reduced under the combination treatment; the former helping to minimize drug efflux and the latter by reducing the sensitivity to hormonal changes. Furthermore, the combination reduced the PSA level secreted by the cells. In contrast, AKBA could not achieve the needed synergism for adequate cell killing at equivalent concentrations. The combination of enzalutamide and BS extract containing 30% AKBA because of their synergistic interaction is an attractive therapeutic option for treating early stage (hormone-dependent) prostate cancer and is superior to the use of AKBA alone.

scholarly journals Evaluation of the quality and safety of butter with an antioxidant complex of natural origin (birch bark extract and Aloe Vera)

2021 ◽  
Vol 640 (3) ◽  
pp. 032004
Author(s):  
A P Simonenkova ◽  
A V Mamaev ◽  
V N Masalov ◽  
O N Luneva ◽  
E N Demina ◽  
...  
Keyword(s):  
Aloe Vera ◽  
Bark Extract ◽  
Birch Bark ◽  
Quality And Safety ◽  
Natural Origin

Pain treatment and prevention in pediatric palliative care

2021 ◽  
pp. 292-311
Author(s):  
Stefan J. Friedrichsdorf
Keyword(s):  
Chronic Pain ◽  
Palliative Care ◽  
Visceral Pain ◽  
Pain Treatment ◽  
Symptom Control ◽  
Pediatric Palliative Care ◽  
Serious Illness ◽  
Psychological Therapies ◽  
Total Pain ◽  
The Usa

Annually, at least 21 million children could benefit from pediatric palliative care (PPC) and 8 million would need specialized PPC services. In the USA alone, more than 40,000 children aged 0–19 years die annually; 55% of them are infants younger than 1 year of age. Pain is common, under-recognized, and under-treated, especially in children with progressive neurodegenerative and chromosomal conditions with central nervous system impairment. Unrelieved pain is also common in children with advanced serious illness during the end-of-life period, and, when treated, the therapy is commonly ineffective. Treating pain in children with serious illness is not profoundly different than advanced pain management for children with complex acute conditions or diseases such as major trauma, burns, cancer, or those with sickle cell disease in vaso-occlusive crisis. It is important to appreciate that children with serious illness are more likely to simultaneously suffer from acute pain, neuropathic pain, visceral pain, total pain, and chronic pain. As such, multimodal analgesic (i.e., multiple agents, interventions, rehabilitation, psychological modalities, and integrative (“nonpharmacologic,” e.g., behavioral, physiological, and psychological) therapies that act synergistically for more effective pediatric pain and symptom control with fewer side effects than a single analgesic or modality must be employed. Opioids, such as morphine, fentanyl, hydromorphone, oxycodone, and methadone, remain the mainstay medications to effectively treat pain in children with serious illness. However, medications alone are often insufficient for optimal pain control. In fact, the paradigm shift away from “medications only” toward offering “multimodal analgesia” to children with serious illness experiencing pain, including addressing chronic pain/primary pain disorders and total pain has become a “game changer” in advancing PPC to ensure that patients can live as long as possible, as well as possible.

scholarly journals Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase

2019 ◽  
Vol 316 (6) ◽  
pp. G692-G700 ◽  
Author(s):  
Emmeline Salameh ◽  
Mathieu Meleine ◽  
Guillaume Gourcerol ◽  
Jean-Claude do Rego ◽  
Jean-Luc do Rego ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Visceral Pain ◽  
Myeloperoxidase Activity ◽  
Therapeutic Approaches ◽  
Chronic Colitis ◽  
Functional Symptoms ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation. Chronic colitis was induced by a weekly intrarectal injection of increasing concentrations of trinitrobenzene sulfonic acid (TNBS) for 3 wk (15–45 mg of TNBS) in 30 rats, whereas the control rats ( n = 24) received the vehicle. At 50 days post-TNBS, visceral sensitivity was assessed by visceromotor response to colorectal distension, and transient receptor potential vanilloid type 1 (TRPV1) expression was also quantified in the colon and dorsal root ganglia. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein, myeloperoxidase activity, histological score, and cytokine production (IL-6, IL-10, and TNF-α). Anxiety behavioral tests were performed from 50 to 64 days after the last TNBS injection. Chronic TNBS induced 1) a visceral hypersensitivity ( P = 0.03), 2) an increased colon weight-to-length ratio ( P = 0.01), 3) higher inflammatory and fibrosis scores ( P = 0.0390 and P = 0.0016, respectively), and 4) a higher colonic IL-6 and IL-10 production ( P = 0.008 and P = 0.005, respectively) compared with control rats. Intestinal permeability, colonic production of TNF-α, myeloperoxidase activity, and TRPV1 expression did not differ among groups. Chronic TNBS increased anxiety-related behavior in the open-field test and in the acoustic stress test. In conclusion, chronic colitis induced functional sequelae such as visceral hypersensitivity and increased anxiety with a low-grade intestinal inflammation. Development of a representative animal model will allow defining novel therapeutic approaches to achieve a better management of IBD-related sequelae.NEW & NOTEWORTHY Patients with inflammatory bowel diseases have impaired quality of life. Therapeutic progress to control mucosal inflammation provides us an opportunity to develop novel approaches to understand mechanisms behind postinflammatory sequelae. We used a chronic colitis model to study long-term sequelae on visceral pain, gut barrier function, and psychological impact. Chronic colitis induced functional symptoms and increased anxiety in the remission period. It might define novel therapeutic approaches to achieve a better inflammatory bowel disease-related sequelae management.

scholarly journals Walnut Oil Alleviates Intestinal Inflammation and Restores Intestinal Barrier Function in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1302
Author(s):  
Adrian Bartoszek ◽  
Adam Makaro ◽  
Agnieszka Bartoszek ◽  
Radzisław Kordek ◽  
Jakub Fichna ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Dietary Habits ◽  
Intestinal Inflammation ◽  
Visceral Pain ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Walnut Oil ◽  
Wide Range ◽  
Bowel Diseases ◽  
Anti Inflammatory

Ulcerative colitis belongs to inflammatory bowel diseases, which is a group of chronic disorders of the gastrointestinal tract. It is a debilitating condition with a wide range of symptoms including rectal bleeding, diarrhea, and visceral pain. Current dietary habits often lead to imbalance in n-6/n-3 polyunsaturated fatty acids (PUFA) in favor of n-6 PUFA. Recent data showed the potential anti-inflammatory advantage of n-3 PUFA. Walnut oil (WO) is rich in those fatty acids and mainly consists of linoleic and linolenic acids that may act via free fatty acids receptors (FFARs). We assessed the anti-inflammatory effect of WO in the mouse model of dextran sulfate sodium (DSS)-induced colitis. Moreover, we examined changes in the expression of tight junction proteins (TJ), pro-inflammatory cytokines, and FFAR proteins in the inflamed mouse colon. WO improves the damage score in inflamed tissue, significantly restoring ion transport and colonic wall permeability. Inflammation caused changes in TJ, FFAR, and pro-inflammatory gene proteins expression, which WO was able to partially reverse. WO has anti-inflammatory properties; however, its exact mechanism of action remains unclear. This stems from the pleiotropic effects of n-3 PUFA ligands associated with receptor distribution and targeted signaling pathways.

Pharmacotherapy of pain in cancer patients – recommendations of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons

2018 ◽  
Vol 90 (4) ◽  
pp. 51-80 ◽  
Author(s):  
Jerzy Wordliczek ◽  
Aleksandra Kotlińska-Lemieszek ◽  
Wojciech Leppert ◽  
Jarosław Woroń ◽  
Jan Dobrogowski ◽  
...  
Keyword(s):  
Family Medicine ◽  
Cancer Patients ◽  
Palliative Medicine ◽  
Visceral Pain ◽  
Pain Treatment ◽  
Breakthrough Pain ◽  
Intensive Therapy ◽  
Opioid Analgesics ◽  
Cochrane Central Register ◽  
Polish Society

Guidelines for the pharmacotherapy of pain in cancer patients were developed by a group of 21 experts of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons. During a series of meetings, the experts carried out an overview of the available literature on the treatment of pain in cancer patients, paying particular attention to systematic reviews and more recent randomized studies not included in the reviews. The search was performed in the EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials databases using such keywords as “pain”, “cancer”, “pharmacotherapy”, “analgesics”, and similar. The overviewed articles included studies of pathomechanisms of pain in cancer patients, methods for the assessment of pain in cancer patients, and drugs used in the pharmacotherapy of pain in cancer patients, including non-opioid analgesics (paracetamol, metamizole, non-steroidal anti-inflammatory drugs), opioids (strong and weak), coanalgesics (glucocorticosteroids, α2-adrenergic receptor agonists, NMDA receptor antagonists, antidepressants, anticonvulsants, topical medications) as well as drugs used to reduce the adverse effects of the analgesic treatment and symptoms other than pain in patients subjected to opioid treatment. The principles of opioid rotation and the management of patients with opioidophobia were discussed and recommendations for the management of opioid-induced hyperalgesia were presented. Drugs used in different types of pain experienced by cancer patients, including neuropathic pain, visceral pain, bone pain, and breakthrough pain, were included in the overview. Most common interactions of drugs used in the pharmacotherapy of pain in cancer patients as well as the principles for the management of crisis situations. In the final part of the recommendations, the issues of pain and care in dying patients are discussed. Recommendations are addressed to physicians of different specialties involved in the diagnostics and treatment of cancer in their daily practice. It is the hope of the experts who took part in the development of these recommendations that the recommendations would become helpful in everyday medical practice and thus contribute to the improvement in the quality of care and the efficacy of pain treatment in this group of patients.

scholarly journals Development of an index to define overall disease severity in IBD

Gut ◽  
2016 ◽  
Vol 67 (2) ◽  
pp. 244-254 ◽  
Author(s):  
Corey A Siegel ◽  
Cynthia B Whitman ◽  
Brennan M R Spiegel ◽  
Brian Feagan ◽  
Bruce Sands ◽  
...  
Keyword(s):  
Disease Severity ◽  
Intestinal Resection ◽  
Delphi Panel ◽  
Intestinal Damage ◽  
Reactive Protein ◽  
Modified Delphi ◽  
Bowel Diseases ◽  
History Of ◽  
Mucosal Lesions ◽  
Consistent Assessment

Background and aimDisease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.MethodsUsing a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.ResultsFor CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.ConclusionsBased on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.

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