Browse by Audience
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 >Animals have evolved specialized neural circuits to defend themselves from pain- and injury-causing stimuli. Using a combination of optical, behavioral and genetic approaches in the larval zebrafish, we describe a novel role for hypothalamic oxytocin (OXT) neurons in the processing of noxious stimuli. In vivo imaging revealed that a large and distributed fraction of zebrafish OXT neurons respond strongly to noxious inputs, including the activation of damage-sensing TRPA1 receptors. OXT population activity reflects the sensorimotor transformation of the noxious stimulus, with some neurons encoding sensory information and others correlating more strongly with large-angle swims. Notably, OXT neuron activation is sufficient to generate this defensive behavior via the recruitment of brainstem premotor targets, whereas ablation of OXT neurons or loss of the peptide attenuates behavioral responses to TRPA1 activation. These data highlight a crucial role for OXT neurons in the generation of appropriate defensive responses to noxious input.
Learn More >Migraine is one of the most disabling and prevalent of all disorders. To improve understanding of migraine mechanisms and to suggest a new therapeutic target, we investigated whether opening of ATP-sensitive potassium channels (KATP) would cause migraine attacks. In this randomized, double-blind, placebo-controlled, crossover study, 16 patients aged 18-49 years with one to five migraine attacks a month were randomly allocated to receive an infusion of 0.05 mg/min KATP channel opener levcromakalim and placebo on two different days (ClinicalTrials.gov number, NCT03228355). The primary endpoints were the difference in incidence of migraine attacks, headaches and the difference in area under the curve (AUC) for headache intensity scores (0-12 h) and for middle cerebral artery blood flow velocity (0-2 h) between levcromakalim and placebo. Between 24 May 2017 and 23 November 2017, 16 patients randomly received levcromakalim and placebo on two different days. Sixteen patients (100%) developed migraine attacks after levcromakalim compared with one patient (6%) after placebo (P = 0.0001); the difference of incidence is 94% [95% confidence interval (CI) 78-100%]. The incidence of headache over the 12 h observation period was higher but not significant after levcromakalim (n = 16) than after placebo (n = 7) (P = 0.016) (95% CI 16-71%). The AUC for headache intensity was significantly larger after levcromakalim compared to placebo (AUC0-12h, P < 0.0001). There was no change in mean middle cerebral artery blood flow velocity after levcromakalim compared to placebo (AUC0-2hP = 0.46). Opening of KATP channels caused migraine attacks in all patients. This suggests a crucial role of these channels in migraine pathophysiology and that KATP channel blockers could be potential targets for novel drugs for migraine.
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 >