Browse by Audience
Opioid-induced constipation (OIC) is a common side effect of chronic opioid therapy. Previously, naldemedine, a peripherally acting ì-opioid receptor antagonist demonstrated efficacy in the treatment of OIC. In this exploratory analysis, the onset of action of naldemedine was evaluated in 2 identically designed phase 3, randomized, placebo-controlled trials. Proportion of patients experiencing a spontaneous bowel movement (SBM) within 24 hours of treatment initiation, time from initial dose to first SBM and weekly SBM frequency were assessed. Naldemedine was associated with significant increases in the proportion of patients experiencing an SBM at 4, 8, 12, and 24 hours after the initial dose compared with placebo (all P<0.0001). Within 24 hours in both studies, statistically significantly (P<0.0001) more patients treated with naldemedine compared with placebo experienced an SBM (61.2% vs. 28.3% and 56.5% vs. 33.6%, respectively). Median times to first SBM were significantly shorter in the naldemedine group versus placebo (COMPOSE-1, 16.1 vs. 46.7 hours; COMPOSE- 2, 18.3 vs 45.9 hours; P<0.0001). Naldemedine was also associated with significant increases in weekly SBM frequency versus placebo within 1 week (P<0.001). Most common treatment-emergent adverse event (TEAE) were gastrointestinal-related (abdominal pain, diarrhea, and nausea). TEAEs were reported most frequently on day 1, followed by a decrease from days 2-7. Naldemedine had a timely onset of effect, and gastrointestinal AEs largely resolved within the first week. These findings should assist clinicians counseling patients with chronic noncancer pain on expectations when initiating naldemedine for OIC. ClinicalTrials.gov Registration: NCT01965158 and NCT01993940This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Learn More >Sleep problems are common for individuals living with physical disabilities and chronic pain. However, the factors that influence the relationship between pain and sleep problems in these populations remain unknown.
Learn More >Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.
Learn More >Despite the heightened urgency of the current prescription opioid crisis, few psychotherapies have been evaluated for chronic pain patients receiving long-term opioid analgesics. Current psychological pain treatments focus primarily on ameliorating negative affective processes, yet basic science suggests that risk for opioid misuse is linked with a dearth of positive affect. Interventions that modulate positive psychological processes may produce therapeutic benefits among patients with opioid-treated chronic pain. The aim of this study was to conduct a theory-driven mechanistic analysis of proximal outcome data from a Stage 2 randomized controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE), an integrative intervention designed to promote positive psychological health.
Learn More >The opioid epidemic is a significant public health crisis and prescription opioids are often used to manage chronic pain, despite questionable long-term efficacy. Furthermore, co-substance (mis)use is also common among individuals with chronic pain who use opioids. Alcohol has been consistently used to manage chronic pain, partly due to its acute analgesic properties. Cannabis has also recently garnered attention in the context of pain management, though research examining its efficacy for pain has produced mixed results. Nevertheless, there is accumulating evidence that concurrent substance co-use is positively associated with use and misuse of additional substances, particularly among individuals with chronic pain. Thus, the goal of this study was to examine the main and interactive effects of alcohol use problems and cannabis use problems in relation to opioid misuse among adults with chronic pain who use opioids.
Learn More >Neuropathic pain represents one of the most common complications associated with diabetes mellitus (DM) that impacts quality of life. Accumulating studies have highlighted the involvement of microRNAs (miRNAs) in DM. Thus, the current study aimed to investigate the roles of microRNA-155 (miR-155) in diabetic peripheral neuropathy (DPN). In vitro DPN models were established using rat Schwann cells (SCs) by treatment with 5.5 mM glucose. Gain- or loss-of-function studies were conducted to determine the effect of miR-155 on Nrf2, cellular function, reactive oxygen species, and inflammation. Rat DNP models were established by streptozotocin injection and damage of sciatic nerve. Next, miR-155 antagomir or agomir was employed to investigate the effects associated with miR-155 on motor and sciatic nerve conduction velocity (MNCV, SNCV), angiogenesis and inflammatory response in vivo. Nrf2 was identified to be a target of miR-155 by dual-luciferase reporter gene assay. Silencing of miR-155 or restoration of Nrf2 promoted cell proliferation, inhibited apoptosis and alleviated inflammation in vitro. miR-155 antagomir-induced inhibition increased MNCV and SNCV, strengthened angiogenesis and alleviated inflammation in DPN rats. Additionally, the effects exerted by miR-155 were reversed when Nrf2 was restored both in vitro and in vivo. Taken together, the key findings of our study provide evidence indicating that miR-155 targeted and suppressed Nrf2 in DPN. miR-155 silencing was found to alleviate sciatic nerve injury in DPN, highlighting its potential as a therapeutic target for DPN.
Learn More >Persistent postoperative pain (PPP) is a significant source of morbidity in our population. An excellent opportunity to understand the transition from acute to chronic pain states. Understanding the mechanisms that drive this and modulators that influence this transition is essential to both prevent and manage this condition.
Learn More >Effective peri-operative pain management is a prerequisite for optimal recovery after surgery. Despite published evidence-based guidelines from several professional groups, postoperative pain management remains inadequate. The procedure-specific pain management (PROSPECT) collaboration consists of anaesthetists and surgeons with broad international representation that provide healthcare professionals with practical and evidence-based recommendations formulated in a way that facilitates clinical decision-making across all stages of the peri-operative period on a procedure-specific basis. The aim of this manuscript is to provide a detailed description of the current PROSPECT methodology with the intention of providing the rigour and transparency in which procedure-specific pain management recommendations are developed. The high methodological standards of the recommendations should improve the quality of clinical practice.
Learn More >The gastrointestinal symptoms of migraine attacks have invited numerous dietary hypotheses for migraine etiology through the centuries. Substantial efforts have been dedicated to identifying dietary interventions for migraine attack prevention, with limited success. Meanwhile, mounting evidence suggests that the reverse relationship may also exist – that the biological mechanisms of migraine may influence dietary intake. More likely, the truth involves some combination of both, where the disease influences food intake, and the foods eaten impact the manifestations of the disease. In addition, the gut's microbiota is increasingly suspected to influence the migraine brain via the gut-brain axis, though these hypotheses remain largely unsubstantiated.
Learn More >Chronic itch is notoriously difficult to treat. Counter-stimuli are able to inhibit itch, but this principle is difficult to apply in clinical practice, and the mechanisms behind counter-stimulation-induced itch suppression in humans are unclear.
Learn More >