Psychoneuroimmunological approach to gastrointestinal related pain

BACKGROUND AND PURPOSE (AIMS): Psychoneuroimmunology is both a theoretical and practical field of medicine in which human biology and psychology are considered an interconnected unity. Through such a framework it is possible to elucidate complex syndromes in gastrointestinal related pain, particularly chronic non-malignant. The aim is to provide insight into pathophysiological mechanisms and suggest treatment modalities according to a comprehensive paradigm. The article also presents novel findings that may guide clinicians to recognize new targets or scientists to find new research topics. ----- METHODS: A literature search of 'PubMed' and 'Google Scholar' databases was performed. Search terms included: 'Visceral pain', 'Psychoneuroimmunology', 'Psychoneuroimmunology and pain', 'Pain in GI system', 'GI related pain', 'Pain and microbiota', 'Enteric nervous system', 'Enteric nervous system and inflammation', 'CNS and pain', 'Inflammation and pain in GI tract', 'Neurogastroenterology', 'Neuroendocrinology', 'Immune system in GI pain'. After searching and reading sources deemed recent and relevant, a narrative review was written with a tendency to discriminate the peripheral, intermediate, and central pathophysiological mechanisms or treatment targets. ----- RESULTS: Recent evidence point out the importance of considering the brain-gut axis as the main connector of the central and peripheral phenomena encountered in patients suffering from chronic non-malignant gastrointestinal related pain. This axis is also a prime clinical target with multiple components to be addressed in order for therapy to be more effective. Patients suffering from inflammatory bowel disease or functional gastrointestinal disorders represent groups that could benefit most from the proposed approach. ----- CONCLUSIONS (BASED ON OUR FINDINGS): Rather than proceeding with established allopathic single-target central or peripheral treatments, by non-invasively modulating the brain-gut axis components such as the psychological and neuroendocrinological status, microbiota, enteric nervous system, or immune cells (e.g. glial or mast cells), a favourable clinical outcome in various chronic gastrointestinal related pain syndromes may be achieved. Clinical tools are readily available in forms of psychotherapy, prebiotics, probiotics, nutritional advice, and off-label drugs. An example of the latter is low-dose naltrexone, a compound which opens the perspective of targeting glial cells to reduce neuroinflammation and ultimately pain. ----- IMPLICATIONS (OUR OPINION ON WHAT OUR FINDINGS MEAN): Current findings from basic science provide sound mechanistic evidence and once entering clinical practice should yield more effective outcomes for patients. In addition to well-established pharmacotherapy comprised notably of anti-inflammatories, antibiotics, and proton-pump inhibitors, valid treatment strategies may contain other options. These disease modulating add-ons include probiotics, prebiotics, food supplements with anti-inflammatory properties, various forms of psychotherapy, and low-dose naltrexone as a glial modulator that attenuates neuroinflammation. Clearly, a broader and still under exploited set of evidence-based tools is available for clinical use

Vasovagal Reactions during Interventional Pain Management Procedures—A Review of Pathophysiology, Incidence, Risk Factors, Prevention, and Management

Vasovagal reactions are a benign but common outcome of interventional pain management procedures that can negatively impact patient care, including aborted procedures and fear of future procedures that would otherwise help the patient. Research has been done on the incidence, risk factors, and management of vasovagal reactions resulting from such procedures, but less is known about how to prevent these reactions from occurring. In this paper, we present a literature review of the pathophysiology, incidence, risk factors, prevention, and management of vasovagal reactions during interventional pain management procedures, with an emphasis on the relative lack of research and conflicting advice on preventive measures. We found that moderate sedation and anxiolytics have been used prophylactically to prevent vasovagal reactions, but their side-effect profiles prevent them from being used commonly. Less studied is the prophylactic administration of antimuscarinics and IV fluids, despite the potential benefit of these measures and relatively low side-effect profile. We explore these topics here and offer advice for future research to fill the gaps in our knowledge

Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization

Naltrexone and naloxone are classical opioid antagonists. In substantially lower than standard doses, they exert different pharmacodynamics. Low-dose naltrexone (LDN), considered in a daily dose of 1 to 5 mg, has been shown to reduce glial inflammatory response by modulating Toll-like receptor 4 signaling in addition to systemically upregulating endogenous opioid signaling by transient opioid-receptor blockade. Clinical reports of LDN have demonstrated possible benefits in diseases such as fibromyalgia, Crohn’s disease, multiple sclerosis, complex-regional pain syndrome, Hailey-Hailey disease, and cancer. In a dosing range at less than 1 μg per day, oral naltrexone or intravenous naloxone potentiate opioid analgesia by acting on filamin A, a scaffolding protein involved in μ-opioid receptor signaling. This dose is termed ultra low-dose naltrexone/naloxone (ULDN). It has been of use in postoperative control of analgesia by reducing the need for the total amount of opioids following surgery, as well as ameliorating certain side-effects of opioid-related treatment. A dosing range between 1 μg and 1 mg comprises very low-dose naltrexone (VLDN), which has primarily been used as an experimental adjunct treatment for boosting tolerability of opioid-weaning methadone taper. In general, all of the low-dose features regarding naltrexone and naloxone have been only recently and still scarcely scientifically evaluated. This review aims to present an overview of the current knowledge on these topics and summarize the key findings published in peer-review sources. The existing potential of LDN, VLDN, and ULDN for various areas of biomedicine has still not been thoroughly and comprehensively addressed

ACIS ET GALATHEE - Masque (sélection) / Georg-Friedrich HAENDEL - Texte de J. GAY - A. POPE - J. DRYDEN J. HUGUES

Titre uniforme : [Acis and Galatea. HWV 49a]Comprend : O the pleasure of the plains - For us the zephyr blows (choeur des Nymphes et des Bergers avec solos d'Acis et Galathée) - Ye verdant plains - Hush, ye pretty warbling choir - (Récitatif et air de Galathée) - Where shall I seek the charming fair ? (Air d'Acis) - Lo ! here my love - Love in her eyes sits playing (Récitatif et air d'Acis) - O didst thou know - As when the dove laments her love (Récitatif et Air de Galathée) - Happy we (duo Acis et Galathée) / Maria HARVEY, soprano - (Galathée) - Richard van VROOMAN, ténor (Acis) - Choeur Oberlin du Mozarteum de Salzbourg dir. G. ANDER ? SSEN et Camerata Academica du Mozarteum de Salzbourg dir. Bernhard PAUMGARTNER - Wretched lovers (Choeur) - I rage, I melt, I burn (Récitatif de Polyphème) - Cease to beauty to be suing (Air de Polyphème) - His hideous love - Love sounds the alarm (Récitatif et Air d'Acis) - Cease, o cease, thou gentle youth (Récitatif de Galathée) - The flocks shall leave the mountains (Trio Acis-Galathée et Polyphème) - Help, Galatea (Récitatif d'Acis) - Mourn, all ye Muses (Choeur) - 'Tis done - Heart, the seat of soft delight (Récitatif d'Acis) - Galatea, dry thy tears (Choeur) / Maria HARVEY, soprano (Galathée) - Richard van VROOMAN, ténor (Acis) - David BRUCE, basse (Polyphème) - Choeur OBERLIN du Mozarteum de Salzbourg et la Camerata du Mozarteum de Salzbourg dir. Bernhard PAUGARTNERBnF-Partenariats, Collection sonore - BelieveContient une table des matière

ACIS ET GALATHEE / HAENDEL

Titre uniforme : [Acis and Galatea. HWV 49a]BnF-Partenariats, Collection sonore - BelieveContient une table des matière

Prospective, randomized, multicenter study of intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 12-month results

IntroductionVertebral endplates, innervated by the basivertebral nerve (BVN), are a source of chronic low back pain correlated with Modic changes. A randomized trial comparing BVN ablation to standard care (SC) recently reported results of an interim analysis. Here, we report the results of the full randomized trial, including the 3-month and 6-month between-arm comparisons, 12-month treatment arm results, and 6-month outcomes of BVN ablation in the former SC arm.MethodsProspective, open label, 1:1 randomized controlled trial of BVN ablation versus SC in 23 US sites with follow-up at 6 weeks, 3, 6, 9, and 12 months. SC patients were re-baselined and followed up for 6 months post BVN ablation. The primary endpoint was the between-arm comparison of mean Oswestry Disability Index (ODI) change from baseline. Secondary endpoints were Visual Analog Scale (VAS), Short Form (SF-36), EuroQual Group 5 Dimension 5-Level Quality of Life (EQ-5D-5L), responder rates, and rates of continued opioid use.Results140 were randomized. Results from BVN ablation (n=66) were superior to SC (n=74) at 3 months for the primary endpoint (mean ODI reduction, difference between arms of -20.3 (CI -25.9 to -14.7 points; p<0.001)), VAS pain improvement (difference of -2.5 cm between arms (CI -3.37 to -1.64, p<0.001)) and quality of life outcomes. At 12 months, basivertebral ablation demonstrated a 25.7±18.5 point reduction in mean ODI (p<0.001), and a 3.8±2.7 cm VAS reduction (p<0.001) from baseline, with 64% demonstrating ≥50% reduction and 29% pain free. Similarly, the former SC patients who elected BVN ablation (92%) demonstrated a 25.9±15.5 point mean ODI reduction (p<0.001) from baseline. The proportion of opioid use did not change in either group (p=0.56).Discussion/conclusionBVN ablation demonstrates significant improvements in pain and function over SC, with treatment results sustained through 12 months in patients with chronic low back pain of vertebrogenic origin