Rejected

Symptomatic uncomplicated diverticular disease (SUDD) is characterized by abdominal pain and altered bowel function and may affect quality of life. When symptoms are severe and conservative therapy is ineffective, surgical intervention becomes an option.

The current review evaluates current recommendations for pain management in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) with a specific focus on evidence for opioid analgesia, including the partial agonist, buprenorphine.

Structural modifications of the neuronal calcium channel blocker MONIRO-1, including constraining the phenoxyaniline portion of the molecule and replacing the guanidinium functionality with tertiary amines, led to compounds with significantly improved affinities for the endogenously expressed Ca2.2 channel in the SH-SY5Y neuroblastoma cell line. These analogues also showed promising activity towards the Ca3.2 channel, recombinantly expressed in HEK293T cells. Both of these ion channels have received attention as likely targets for the treatment of neuropathic pain. The dibenzoazepine and dihydrobenzodiazepine derivatives prepared in this study show an encouraging combination of neuronal calcium ion channel inhibitory potency, plasma stability and potential to cross the blood-brain-barrier.

Many health care professions have reacted swiftly to the COVID-19 pandemic. In-person care has been ramped down and telemedicine/telehealth has been thrust to the forefront of clinical care. For people living with chronic pain and often concomitantly dealing with opioid-related issues, this is a time of great stress. With population-wide movements to shelter in place, people living with pain are more isolated, more stressed, and more vulnerable to mental health concerns like depression and anxiety that can increase pain-related suffering. This article presents two case reports of patients struggling with chronic pain and opioid dependence in which a telemedicine-based buprenorphine-naloxone conversion was chosen as a treatment option by two Canadian programs: The Transitional Pain Service at the Toronto General Hospital in Toronto, Ontario, and The Opioid Deprescribing Program in Calgary, Alberta. Both cases presented highlight the use of telemedicine during the COVID-19 pandemic and suggest that there will be substantial need for these services well beyond the apex of the crisis. A buprenorphine-naloxone home induction protocol is presented and we provide insight into important lessons learned regarding the appropriate selection of patients with chronic pain struggling with opioid use disorder for buprenorphine-naloxone conversion. The provision of health care during the COVID-19 pandemic has rapidly forced practitioners to evolve novel health care practices, and these changes will have long-term implications.

The prevalence of older adults with pain and comorbid cardiovascular conditions is increasing in the United States (U.S.). This retrospective, cross-sectional database study used 2017 Medical Expenditure Panel Survey data and hierarchical logistic regression models to identify predictive characteristics of opioid use among a nationally representative sample of older U.S. adults (aged ≥50 years) with pain in the past four weeks and comorbid hypertension (pain-hypertension group) or hypercholesterolemia (pain-hypercholesterolemia group). The pain-hypertension group included 2733 subjects ( = 803 opioid users) and the pain-hypercholesterolemia group included 2796 subjects ( = 795 opioid users). In both groups, predictors of opioid use included: White race versus others, Hispanic versus non-Hispanic ethnicity, 1 versus ≥5 chronic conditions, little/moderate versus quite a bit/extreme pain, good versus fair/poor perceived mental health, functional limitation versus no functional limitation, smoker versus non-smoker, and Northeast versus West census region. In addition, Midwest versus West census region was a predictor in the pain-hypertension group, and 4 versus ≥5 chronic conditions was a predictor in the pain-hypercholesterolemia group. In conclusion, several characteristics of older U.S. adults with pain and comorbid hypertension or hypercholesterolemia were predictive of opioid use. These characteristics could be addressed to optimize individuals' pain management and help address the opioid overdose epidemic.

The aim of the study is to estimate the association between spinal cord injuries related medical factors and subjective sleep disturbance in individuals with short-duration chronic spinal cord injury. Seventy-nine individuals with traumatic spinal cord injuries were included in our study and evaluated using the Beck Depression Index for severity of depressive symptoms, Short-Form Health Survey for quality of life, Douleur Neuropathique 4 score for neuropathic pain severity, and the Pittsburgh Sleep Quality Index for subjective sleep disturbances in a tertiary rehabilitation center. Associated subjective sleep disturbance factors were predicted using multivariate binary logistic regression analysis. Subjective sleep disturbance frequency was 74.7 %, and significantly higher in individuals with paraplegia (P = 0.025, odds ratio, 9.74, 95% confidence interval, 1.21-78.14). Intermittent nighttime catheterization frequency and neuropathic pain severity levels were significantly higher in individuals with subjective sleep disturbance, and quality of life and depressive symptoms were significantly worse in individuals with subjective sleep disturbance. Poor-sleep quality was associated significantly with shorter spinal cord injury duration. The strongest associated factors for sleep disturbance were paraplegic involvement, severity of depressive symptoms (Beck Depression Index score), and quality of life (Short-Form Health Survey general health perceptions score) (odds ratio: 95% confidence interval, 29.75; 1.66-534.36, 1.47; 1.11-1.95, and 0.91; 0.85-0.97, respectively). Our study suggests that paraplegic involvement, low quality of life, and depressive mood are related to sleep disturbance in individuals with traumatic spinal cord injury.

Inguinal hernioplasty is the standard treatment for inguinal hernia in adults. Mesh fixation was used to keep mesh in place for which various mesh fixation techniques have been used in laparoscopic inguinal hernia repair in adults, but their effectiveness has remained inconclusive.

Spontaneous rupture of mesenteric vasculature associated with fibromuscular dysplasia is an unreported phenomenon. We describe a case in a 28-year-old male with a history of chronic abdominal pain who presented to our facility in hemorrhagic shock secondary to a ruptured transverse mesocolon middle colic aneurysm status post emergent transverse colectomy. He was found to have chronic vertebral, renovisceral, and iliac aneurysms as well as acute superior and inferior mesenteric artery dissection and chronic bilateral vertebral artery dissections. He subsequently developed disseminated intravascular coagulopathy resulting in saddle pulmonary embolus as well as right renal artery and splenic artery thrombosis. Ultimately, the patient expired.

An impaired gut barrier, possibly leading to visceral hypersensitivity has been recently recognized to be one of the pivotal pathophysiology of irritable bowel syndrome (IBS). We previously showed that lipopolysaccharide (LPS), corticotropin-releasing factor (CRF), and repeated water avoidance stress (WAS) induce visceral hypersensitivity and colonic hyperpermeability via pro-inflammatory cytokine signaling (rat IBS models). Although the precise mechanisms of action are unclear, imipramine, a tricyclic antidepressant, improves IBS symptoms, and also has anticytokine properties. In this study, we hypothesized that imipramine improves the gut barrier to ameliorate IBS symptoms. To test this hypothesis, we determined its effects on visceral hypersensitivity and colonic hyperpermeability in rat IBS models. The visceral pain threshold in response to colonic balloon distention was electrophysiologically estimated by abdominal muscle contractions, and colonic permeability was measured by quantifying the absorbed Evans blue in colonic tissue in vivo. Subcutaneous imipramine injection (7, 20, 50 mg/kg) dose-dependently inhibited LPS-induced (1 mg/kg, subcutaneously) visceral hypersensitivity and colonic hyperpermeability. Imipramine also blocked these gastrointestinal (GI) changes induced by CRF (50 μg/kg, intraperitoneally) or repeated WAS (1 h daily for 3 days). Yohimbine (an α-adrenoceptors antagonist), sulpiride (a dopamine D receptor antagonist), and naloxone hydrochloride (an opioid receptor antagonist) reversed these effects of imipramine in the LPS model. Therefore, imipramine may block GI changes in IBS via α-adrenoceptors, dopamine D, and opioid signaling. The improvement in the gut barrier resulting in inhibition of visceral pain is considered a valid mechanism of imipramine to ameliorate IBS symptoms.

Pyridazine derivatives, such as arylpiperazinylalkyl pyridazinones, display antinociceptive effects to thermal and chemical stimuli. Here, we extended our previous knowledge on the pharmacological profile of 4-amino-6-methyl-2-(3-(4-(4-methylcyclohexa-1,3-dien-1-yl)piperazin-1-yl)propyl)-5-vinylpyridazin-3(2H)-one, here referred as ET1, paving the way for the comprehension of its complete mechanism of action. To this aim, we have evaluated the mouse behavioural responses in several animal models of pain, the effect of ET1 in the murine model of zymosan-induced paw oedema and air-pouch, assessing the cytokines and the cellular phenotype and finally, an in vitro radioligand binding study was performed on a panel of 30 different receptors. In the formalin test, ET1 reduced both neurogenic and inflammatory phase of nociception induced by the aldehyde. Similarly, ET1 strongly reduced paw licking response in the capsaicin test, the abdominal stretching in the writhing test and the carrageenan-induced thermal hyperalgesia. ET1 also evoked a long-lasting reduction of thermal hyperalgesia. Furthermore, ET1 produced a long-lasting anti-inflammatory effect in the zymosan-induced mouse paw oedema and air-pouch through the selective inhibition of inflammatory monocytes recruitment and the modulation of IL-1β, IL-6, TNF-α and MCP-1. Binding experiments confirmed an inhibitory effect on adrenergic α, α and α receptors subtypes and, for the first time, a moderate affinity was observed for the following receptors: histamine H, imidazoline I, sigma non-opioid intracellular receptor 1 and σ2. These results prompt ET1 as a potent analgesic and anti-inflammatory agent, and support the possibility that it may be suitable for clinical applications in a wide-range of inflammatory-based diseases.