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The mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort.
Learn More >In this clinical and psychophysical study, we aimed to verify whether patients with fibromyalgia with and without small-fibre pathology and patients with pure small-fibre neuropathy share common sensory phenotypes.
Learn More >The risk of opioid addiction among people with chronic pain is elevated in those using opioids to self-medicate physical or emotional pain or distress. The purpose of this study is to test the main effect of distress tolerance (DT) on opioid use disorder (OUD) status in people with chronic pain, and the potential moderating effect of DT in the relationship between known addiction risk factors and the development of OUD.
Learn More >The opioid crisis remains a major public health concern. In ambulatory surgery, persistent postoperative opioid use is poorly described and temporal trends are unknown. A population-based retrospective cohort study was undertaken in Ontario, Canada using routinely collected administrative data for adults undergoing ambulatory surgery between 1 January 2013 and 31 December 2017. The primary outcome was persistent postoperative opioid use, defined using best-practice methods. Multivariable generalised linear models were used to estimate the association of persistent postoperative opioid use with prognostic factors. Temporal trends in opioid use were examined using monthly time series, adjusting for patient-, surgical- and hospital-level variables. Of 340,013 patients, 44,224 (13.0%, 95%CI 12.9-13.1%) developed persistent postoperative opioid use after surgery. Following multivariable adjustment, the strongest predictors of persistent postoperative opioid use were pre-operative: utilisation of opioids (OR 9.51, 95%CI 8.69-10.39); opioid tolerance (OR 88.22, 95%CI 77.21-100.79); and utilisation of benzodiazepines (OR 13.75, 95%CI 12.89-14.86). The time series model demonstrated a small but significant trend towards decreasing persistent postoperative opioid use over time (adjusted percentage change per year -0.51%, 95%CI -0.83 to -0.19%, p = 0.003). More than 10% of patients who underwent ambulatory surgery experienced persistent postoperative opioid use; however, there was a temporal trend towards a reduction in persistent opioid use after surgery. Future studies are needed that focus on interventions which reduce persistent postoperative opioid use.
Learn More >We have made great strides in understanding how the human brain constructs the multidimensional experience of pain – both acute and chronic – over the past few decades. Pain wears many guises, but at its core, it hurts. How is this core component of pain represented in the brain, and how can we target it for relief?
Learn More >: To identify epigenetic alterations of differentially expressed genes and screen out targeted therapeutic drugs in endometriosis. : Based on the Gene Expression Omnibus database and a series of biological information analysis tools, supplemented by validation of clinical samples, aberrant DNA methylation-driven genes and their functions were explored, as well as possible targeted drugs. : This study screened out a range of DNA methylation-driven genes that were associated with powerful properties and corresponding pathways. Among them, and were key genes in the development of endometriosis. Four chemical agents have been flagged as potential treatments for endometriosis. : These candidate genes and small-molecule agents may be further explored as potential targets and drugs for endometriosis diagnosis and therapy, respectively.
Learn More >P2X receptors are ATP-gated ion channels which play a role in many pathophysiological conditions. They are considered as novel drug targets, particularly in the fields of pain, (neuro) inflammation, and cancer. Due to difficulties in developing drug-like orthosteric ligands that bind to the highly polar ATP binding site, the design of positive and negative allosteric modulators (PAMs and NAMs) is a promising strategy. The P2X4 receptor was proposed as a novel target for neuropathic and inflammatory pain (antagonists), and for the treatment of alcoholism (PAMs). So far, little is known about the allosteric binding site(s) of P2X4 receptors. The aim of this study is to identify the binding site (s) of the macrocyclic natural product ivermectin, the urea derivative BX430, and the antidepressant drug paroxetine that act as allosteric modulators of P2X4 receptors.
Learn More >The objective of this cross-sectional study was to investigate the impact of the COVID-19 pandemic on physical activity (PA) levels of patients with rheumatic and musculoskeletal diseases (RMDs) and to examine factors associated with decreased PA.
Learn More >Chemotherapy-induced neuropathy (CIN) is one of the most common complications of cancer treatment with sensory dysfunctions which frequently include pain. The mechanisms underlying pain during CIN are starting to be uncovered. Neuroimaging allows the identification of brain circuitry involved in pain processing and modulation and has recently been used to unravel the disruptions of that circuitry by neuropathic pain. The present study evaluates the effects of paclitaxel, a cytostatic drug frequently used in cancer treatment, at the neuronal function in the anterior cingulate cortex (ACC), hypothalamus and periaqueductal grey (PAG) using manganese-enhanced magnetic resonance imaging (MEMRI). We also studied the metabolic profile at the prefrontal cortex (PFC) and hypothalamus using ex vivo spectroscopy. Wistar male rats were intraperitoneal injected with paclitaxel or vehicle solution (DMSO). The evaluation of mechanical sensitivity using von Frey test at baseline (BL), 21 (T21), 28 (T28), 49 (T49) and 56 days (T56) after CIN induction showed that paclitaxel-injected rats presented mechanical hypersensitivity from T21 until T56 after CIN induction. The evaluation of the locomotor activity and exploratory behaviors using open-field test at T28 and T56 after the first injection of paclitaxel revealed that paclitaxel-injected rats walked higher distance with higher velocity at late point of CIN accompanied with a sustained exhibition of anxiety-like behaviors. Imaging studies performed using MEMRI at T28 and T56 showed that paclitaxel treatment increased the neuronal activation in the hypothalamus and PAG at T56 in comparison with the control group. The analysis of data from ex vivo spectroscopy demonstrated that at T28 paclitaxel-injected rats presented an increase of N-acetyl aspartate (NAA) levels in the PFC and an increase of NAA and decrease of lactate (Lac) concentration in the hypothalamus compared to the control group. Furthermore, at T56 the paclitaxel-injected rats presented lower NAA and higher taurine (Tau) levels in the PFC. Together, MEMRI and metabolomic data indicate that CIN is associated with neuroplastic changes in brain areas involved in pain modulation and suggests that other events involving glial cells may be happening.
Learn More >Lesions to both somatic and affective pain pathways lead to decreased salience network connectivity.
Human pain is a salient stimulus composed of two main components: a sensorysomatic component, carrying peripheral nociceptive sensation via the spino-thalamic tract and brainstem nuclei to the thalamus and then to sensory cortical regions, and an affective (suffering) component, where information from central thalamic nuclei is carried to the anterior insula, dorsal anterior cingulate cortex and other regions. While the sensory component processes information about stimulus location and intensity, the affective component processes information regarding pain-related expectations, motivation to reduce pain, and pain unpleasantness. Unlike investigations of acute pain that are based on the introduction of real-time stimulus during brain recordings, chronic pain investigations are usually based on longitudinal and case-control studies, which are limited in their ability to infer the functional network topology of chronic pain. In the current study, we utilized the unique opportunity to target the central nervous system's pain pathways in two different hierarchical locations to establish causality between pain relief and specific connectivity changes seen within the salience and sensorimotor networks. We examined how lesions to the affective and somatic pain pathways affect resting-state network topology in cancer patients suffering from severe intractable pain. Two procedures have been employed: percutaneous cervical cordotomy (n = 15), hypothesized to disrupt the transmission of the sensory component of pain along the spino-thalamic tract, or stereotactic cingulotomy (n = 7), which refers to bilateral intra-cranial ablation of an area in the dorsal anterior cingulate cortex and is known to ameliorate the affective component of pain. Both procedures led to immediate significant alleviation of experienced pain and decreased functional connectivity within the salience network. However, only the sensory procedure (cordotomy) led to decreased connectivity within the sensorimotor network. Thus, our results support the existence of two converging systems relaying experienced pain, showing that pain-related suffering can be either directly influenced by interfering with the affective pathway, or indirectly influenced by interfering with the ascending spino-thalamic tract.
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