Browse by Audience
To investigate suicidality related to cluster headache and factors associated with increased suicidality in cluster headache patients.
Learn More >Although there have been many studies on the link between chronic pain and suicidality, surprisingly little research has focused on resilience and recovery among those in chronic and disabling pain who have had suicidal thoughts. The objectives of this study were to identify the prevalence and correlates of recovery from suicidal thoughts among those in chronic pain. A secondary analysis of a nationally representative sample of Canadians in chronic and disabling pain who had ever had serious suicidal thoughts (N = 635) was conducted to identify the prevalence and characteristics of those who are no longer considering suicide. Data were drawn from the Canadian Community Health Survey-Mental Health. Three in five Canadians in chronic pain (63%) who had seriously considered suicide at some point in their life had been free of these thoughts in the past year. Those free of suicidal ideation were significantly more likely to be older, women, white, better educated, with a confidant, and to use spirituality to cope, but less likely to have low household incomes, difficulties meeting basic expenses, and a history of depression and anxiety disorders. PERSPECTIVE: Almost two-thirds of formerly suicidal Canadians with chronic pain were free from suicidal thoughts in the past year. These findings provide a hopeful message of resilience and recovery in the context of disabling pain and help to improve targeted outreach to those most at risk for unremitting suicidality.
Learn More >In palliative care, opioids and other controlled drugs are among the most commonly used and important medications. Opioids are associated with significant risk of dependence and misuse. In many developed countries, there is an epidemic of prescription opioid misuse and overdose deaths. Palliative care has a critical role educating patients about the safe use of opioids, providing universal screening and close monitoring, and prescribing opioids appropriately balancing the risks and benefits. This is particularly important in the era of early palliative care, when patients have much longer survival and potentially greater risk of misuse while on chronic opioid therapy. Here, we provided a critical appraisal of opioid use in the context of opioid crisis and early palliative care. We also present a pragmatic 10-step approach for the judicious use of opioids.
Learn More >The adverse effects of opioids are largely mediated by central μ-opioid receptorsCentral μ- and δ-opioid receptors synergistically provide analgesia WHAT THIS ARTICLE TELLS US THAT IS NEW: The administration of a selective δ-opioid agonist, oxymorphindole, and a peripherally-restricted μ-agonist, loperamide, provided synergistic analgesia in a mouse inflammatory pain modelThe use of combinations of peripherally-restricted opioid ligands may provide analgesia with reduced side effects when compared with centrally acting opioids BACKGROUND:: The long-term use of opioids for analgesia carries significant risk for tolerance, addiction, and diversion. These adverse effects are largely mediated by μ-opioid receptors in the central nervous system. Based on the authors' previous observation that morphine and δ-opioid receptor agonists synergize in spinal cord in a protein kinase Cε-dependent manner, they predicted that this μ-opioid receptor-δ-opioid receptor synergy would take place in the central terminals of nociceptive afferent fibers and generalize to their peripheral terminals. Therefore, the authors hypothesized that loperamide, a highly efficacious μ-opioid receptor agonist that is excluded from the central nervous system, and oxymorphindole, a δ-opioid receptor agonist that was shown to synergize with morphine spinally, would synergistically reverse complete Freund's adjuvant-induced hyperalgesia.
Learn More >High-frequency burst-like electrical conditioning stimulation (HFS) applied to human skin induces an increase in mechanical pinprick sensitivity of the surrounding unconditioned skin (a phenomenon known as secondary hyperalgesia). The present study assessed the effect of frequency of conditioning stimulation on the development of this increased pinprick sensitivity in humans. In a first experiment we compared the increase in pinprick sensitivity induced by HFS using monophasic non-charge-compensated pulses and biphasic charge-compensated pulses. High-frequency stimulation, traditionally delivered using non-charge-compensated square-wave pulses, may induce a cumulative depolarization of primary afferents and/or changes in pH at the electrode-tissue interface due to the accumulation of a net residue charge after each pulse. Both could contribute to the development of the increased pinprick sensitivity in a frequency-dependent fashion. We found no significant difference in the increase in pinprick sensitivity between HFS delivered using charge-compensated and non-charge-compensated pulses, indicating that the possible contribution of charge accumulation when non-charge-compensated pulses are used is negligible. In a second experiment, we assessed the effect of different frequencies of conditioning stimulation (5, 20, 42 and 100 Hz) using charge-compensated pulses on the development of increased pinprick sensitivity. The maximal increase in pinprick sensitivity was observed at intermediate frequencies of stimulation (20 and 42 Hz). It is hypothesized that the stronger increase in pinprick sensitivity at intermediate frequencies may be related to the stronger release of substance P and/or neurokinin-1 receptor activation expressed at lamina I neurons following C-fiber stimulation.
Learn More >P2Y receptors are G-protein-coupled receptors (GPCRs) for extracellular nucleotides. There are eight mammalian P2Y receptor subtypes divided into two subgroups (P2Y, P2Y, P2Y, P2Y, and P2Y) and (P2Y, P2Y, and P2Y). The P2Y receptors are expressed in various cell types and play important roles in physiology and pathophysiology including inflammatory responses and neuropathic pain. The antagonism of P2Y receptors is used in pharmacotherapy for the prevention and therapy of cardiovascular events. The nucleoside analogue ticagrelor and active metabolites of the thienopyridine compounds ticlopidine, clopidogrel and prasugrel inhibit platelet P2Y receptors and reduce thereby platelet aggregation. The P2Y receptor agonist diquafosol is used for the treatment of the dry eye syndrome. The P2Y receptor subtypes differ in their amino acid sequences, their pharmacological profiles and their signaling transduction pathways. Recently, selective receptor ligands have been developed for all subtypes. The published crystal structures of the human P2Y and P2Y receptors as well as receptor models will facilitate the development of novel drugs for pharmacotherapy.
Learn More >"Congenital insensitivity to pain (CIP)" is an umbrella term used to describe a group of rare genetic diseases also classified as "Hereditary Sensory Autonomic Neuropathies (HSAN)". These are intriguing conditions with potential to shed light on the poorly understood relationship concerning nociception and the experience of pain. However, the term CIP is epistemologically incorrect and is the product of historical circumstances. The term conflates pain and nociception and thus prevents researchers and caregivers from grasping the full dimensions of these conditions. The aims of this article are to review the epistemological problems surrounding the term, to demonstrate why the term is inaccurate and to suggest a new term: "Congenital Nociceptor Deficiency". The suggested term better reflects the nature of the conditions, and incorporates current understandings of nociception. Perspective: The umbrella term "Congenital Insensitivity to Pain" conflates pain and nociception, which is epistemologically unacceptable. We suggest a new term – Congenital Nociceptor Deficiency – that overcomes this problem and is concordant with current neurobiological knowledge.
Learn More >Opioids are highly effective analgesics, however their therapeutic use is limited by adverse effects that include respiratory depression, dependence, and tolerance. Inflammation has been implicated as a significant driver for the development of tolerance to opioids. Recent studies show that chronic morphine in mice results in gut microbial dysbiosis and inflammation in the colon. In the present study we examined whether colonic inflammation results in tolerance to the antinociceptive effects of morphine. Colonic inflammation was induced in mice by intrarectal administration of 2,4,6-trinitro-benzene sulfonic acid (TNBS). The development of antinociceptive tolerance was determined by warm-water tail-immersion assay in mice implanted with 25 mg, 50 mg or 75 mg morphine pellet. Colonic inflammation significantly enhanced the rate at which tolerance developed in each cohort of chronic morphine treated mice. At the lowest dose of morphine pellet (25 mg), antinociceptive tolerance only developed in the presence of colonic inflammation; whereas, in 50 mg and 75 mg pelleted mice, tolerance developed faster in the inflamed animals than the non-inflamed mice. The enhanced antinociceptive tolerance was attenuated with daily administration of peripheral opioid receptor antagonist, 6β-N-heterocyclic substituted naltrexamine derivative (NAP), irrespective of colonic inflammation. Collectively, these findings show that the rate of tolerance to morphine antinociception is exaggerated in the presence of colonic inflammation and tolerance is prevented by a peripheral mu-opioid receptor antagonist. These studies suggest a peripheral component to the development of antinociceptive tolerance to opioids. Furthermore, peripherally selective opioid antagonists may be useful adjuncts in opioid based pain management. SIGNIFICANCE STATEMENT: Our study supports the notion that inflammation influences the development of antinociceptive tolerance to chronic morphine exposure. We found that as the dose of morphine increased in the presence of colonic inflammation, the more tolerant the mice became to the antinociceptive effects of morphine. We also found that treatment with a peripheral opioid receptor antagonist prevented morphine antinociceptive tolerance. By increasing opioid intake during an inflammatory state would result in decreased analgesia and enhanced analgesic tolerance, which puts patients with inflammatory bowel diseases, inflammatory joint diseases, and sickle cell anemia at risk for a heavy opioid use.
Learn More >This review aims to quantify the effect of minority status on analgesia use for acute pain management in US Emergency Department (ED) settings.
Learn More >