Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis

Gut ◽  
2016 ◽  
Vol 66 (12) ◽  
pp. 2121-2131 ◽  
Author(s):  
Raquel Guerrero-Alba ◽  
Eduardo E Valdez-Morales ◽  
Nestor N Jimenez-Vargas ◽  
Cintya Lopez-Lopez ◽  
Josue Jaramillo-Polanco ◽  
...  
Keyword(s):  
G Protein ◽  
Imaging Techniques ◽  
Stress Hormones ◽  
Endogenous Opioids ◽  
Opioid Use ◽  
Chronic Colitis ◽  
Drg Neurons ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Stress Changes

Aims and backgroundPsychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways.MethodsMouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca2+imaging techniques.ResultsSupernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca2+responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits.ConclusionsStress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD.

scholarly journals Impaired empathy and increased anger following social exclusion in non-intoxicated opioid users

2019 ◽  
Vol 237 (2) ◽  
pp. 419-430
Author(s):  
Molly Carlyle ◽  
Megan Rowley ◽  
Tobias Stevens ◽  
Anke Karl ◽  
Celia J. A. Morgan
Keyword(s):  
Social Functioning ◽  
Social Exclusion ◽  
Positive Emotions ◽  
Physiological Responses ◽  
Cognitive Empathy ◽  
Self Report ◽  
Opioid Use ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Opioid Users

Abstract Rationale Social functioning is modulated by the endogenous opioid system. In opioid use disorder, social functioning appears disrupted, but little research has delineated the nature of these deficits and their relationship to acute opioid use. Objectives The current study aimed to assess both emotional and cognitive empathy, along with subjective and physiological responses to social exclusion in opioid users who were either acutely intoxicated or non-intoxicated from using opioids. Methods Individuals on an opioid substitution medication (OSM) were divided into ‘intoxicated users’ (had taken their OSM the same day as testing, n = 20) and ‘non-intoxicated users’ (had taken their OSM > 12 h ago, n = 20) and compared with opioid-naïve controls (n = 24). Empathy was assessed using the multifaceted empathy test and self-report questionnaire. Participants also underwent a period of social exclusion (Cyberball Game) and completed measures of mood and physiological responses (salivary cortisol and heart rate). Results Non-intoxicated users had significantly lower emotional empathy (the ability to experience others’ emotions), as well as greater anger after social exclusion when compared with the intoxicated users and controls. Anger did not change with social exclusion in the intoxicated user group and cortisol levels were lower overall. Conclusions Reduced ability to spontaneously share the emotions of others was reported in non-intoxicated users, particularly regarding positive emotions. There was some support for the idea of hyperalgesia to social pain, but this was restricted to an enhanced anger response in non-intoxicated users. Equivalent rates of empathy between the intoxicated users and controls could indicate some remediating effects of acute opioids.

scholarly journals  The role of beta-endorphin in horses: a review

2011 ◽  
Vol 56 (No. 9) ◽  
pp. 423-429 ◽  
Author(s):  
M. Golynski ◽  
W. Krumrych ◽  
K. Lutnicki
Keyword(s):  
Pain Threshold ◽  
Social Activity ◽  
Prognostic Indicator ◽  
Endogenous Opioids ◽  
Oxygen Species ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Beta Endorphin ◽  
Opium Alkaloids

  Opium alkaloids counterparts are secreted by human and animal organisms but the role of endogenous opioid peptides in horses has not yet been fully elucidated. Endogenous opioids are involved in regulating food intake, sexual and social activity, pain relief and pain threshold regulation in horses as well as in regulating the functions of the immune system. The aim of this review is to describe the endogenous opioid system in the horse and its function during stress, illness, reproduction, and its influence on immunity and on the formation of reactive oxygen species (ROS) in horses. What is currently known concerning beta-endorphin suggests that they can be a promising diagnostic or prognostic indicator of many pathologic states in horses.

Opioids in Remote Ischemic Preconditioning-Induced Cardioprotection

2016 ◽  
Vol 22 (2) ◽  
pp. 112-121 ◽  
Author(s):  
Puneet Kaur Randhawa ◽  
Amteshwar Singh Jaggi
Keyword(s):  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Endogenous Opioids ◽  
Remote Ischemic Preconditioning ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Cardioprotective Effects

Remote ischemic preconditioning (RIPC) is an intriguing process whereby transient regional ischemia and reperfusion episodes to remote tissues including skeletal, renal, mesenteric provide protection to the heart against sustained ischemia–reperfusion-induced injury. Clinically, this technique has been used in patients undergoing various surgical interventions including coronary artery bypass graft surgery, abdominal aortic aneurysm repair, percutaneous coronary intervention, and heart valve surgery. The endogenous opioid system is extensively expressed in the brain to modulate pain sensation. Besides the role of opioids in relieving pain, numerous researchers have found their critical involvement in evoking cardioprotective effects. Endogenous opioids including endorphins, enkephalins, and dynorphins are released during RIPC and are critically involved in mediating RIPC-induced cardioprotective effects. It has been suggested that during RIPC, the endogenous opioids may be released into the systemic circulation and may travel via bloodstream that act on the myocardial opioid receptors to induce cardioprotection. The present review describes the potential role of opioids in mediating RIPC-induced cardioprotection.

scholarly journals The aetiology of social deficits within mental health disorders: The role of the immune system and endogenous opioids

2019 ◽  
Author(s):  
Sarah Jane Charles ◽  
Miguel Farias ◽  
R. I. M. Dunbar
Keyword(s):  
Mental Health ◽  
Immune System ◽  
Mental Health Disorders ◽  
Social Bonding ◽  
Endogenous Opioids ◽  
Future Research ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Health Disorders

The American National Institute for Mental Health (NIMH) has put out a set of research goals that include a long-term plan to identify more reliable endogenous explanations for a wide variety of mental health disorders (Insel, 2013). In response to this, we have identified a major symptom that underlies multiple mental health disorders – social bonding dysfunction. We suggest that endogenous opioid abnormalities can lead to altered social bonding, which is a symptom of various mental health disorders, including depression, schizophrenia and ASD. This article first outlines how endogenous opioids play a role in social bonding. Then we show their association with the body’s inflammation immune function, and review recent literature linking inflammation to mental health ‘immunophenotypes’. We finish by explaining how these immunophenotypes may be caused by alterations in the endogenous opioid system. This is the first overview of the role of inflammation across multiple disorders where we provide a biochemical explanation for why immunophenotypes might exist across diagnoses. We propose a novel mechanism of how the immune system may be causing ‘sickness-type’ behaviours (fatigue, appetite change, social withdrawal and inhibited motivation) in those who have these immunophenotypes. We hope that this novel aetiology can be used as a basis for future research in mental health.

Effects of naloxone on the sensation of dyspnea during acute respiratory stress in normal adults

1993 ◽  
Vol 74 (2) ◽  
pp. 590-595 ◽  
Author(s):  
Y. Akiyama ◽  
M. Nishimura ◽  
S. Kobayashi ◽  
A. Yoshioka ◽  
M. Yamamoto ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Endogenous Opioids ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Specific Effects ◽  
Mouth Pressure ◽  
End Tidal ◽  
Visual Analogue Scaling ◽  
The Brain ◽  
Normal Adults

To clarify whether endogenous opioids modulate the dyspnea intensity and, if so, by what mechanism they act on it, we examined 12 healthy male volunteers aged 19–27 yr for ventilatory and peak mouth pressure (Pm) responses to hypoxic progressive hypercapnia with inspiratory flow-resistive loading after the intravenous infusion of 3 mg of naloxone or saline. The intensity of dyspnea was simultaneously assessed by visual analogue scaling every 15 s. Naloxone administration increased both ventilatory and Pm responses to hypoxic progressive hypercapnia (P < 0.05 for both). The increase in dyspnea intensity for a given increase in end-tidal PCO2 was significantly greater after naloxone infusion than after saline (P < 0.05). However, there were no differences in the increase in dyspnea intensity for a given increase in minute ventilation or Pm. These results suggest that the endogenous opioid system suppresses the respiratory output under a strong, acute respiratory stress in normal adults and that this system may relieve the dyspnea sensation secondary to the suppression of the brain stem respiratory center without specific effects on the processing of respiratory sensations in the higher brain.

scholarly journals Biased signaling by endogenous opioid peptides

2020 ◽  
Vol 117 (21) ◽  
pp. 11820-11828 ◽  
Author(s):  
Ivone Gomes ◽  
Salvador Sierra ◽  
Lindsay Lueptow ◽  
Achla Gupta ◽  
Shawn Gouty ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Cultured Cells ◽  
Opioid Use Disorder ◽  
Receptor Activity ◽  
Prolonged Treatment ◽  
Opioid Use ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Biased Signaling ◽  
Brain Slice Preparation

Opioids, such as morphine and fentanyl, are widely used for the treatment of severe pain; however, prolonged treatment with these drugs leads to the development of tolerance and can lead to opioid use disorder. The “Opioid Epidemic” has generated a drive for a deeper understanding of the fundamental signaling mechanisms of opioid receptors. It is generally thought that the three types of opioid receptors (μ, δ, κ) are activated by endogenous peptides derived from three different precursors: Proopiomelanocortin, proenkephalin, and prodynorphin. Posttranslational processing of these precursors generates >20 peptides with opioid receptor activity, leading to a long-standing question of the significance of this repertoire of peptides. Here, we address some aspects of this question using a technical tour de force approach to systematically evaluate ligand binding and signaling properties ([35S]GTPγS binding and β-arrestin recruitment) of 22 peptides at each of the three opioid receptors. We show that nearly all tested peptides are able to activate the three opioid receptors, and many of them exhibit agonist-directed receptor signaling (functional selectivity). Our data also challenge the dogma that shorter forms of β-endorphin do not exhibit receptor activity; we show that they exhibit robust signaling in cultured cells and in an acute brain slice preparation. Collectively, this information lays the groundwork for improved understanding of the endogenous opioid system that will help in developing more effective treatments for pain and addiction.

scholarly journals ENDOGENOUS OPIOID SYSTEM AS A MEDIATOR OF ACUTE AND LONG-TERM ADAPTATION TO STRESS. PROSPECTS FOR CLINICAL USE OF OPIOID PEPTIDES

2012 ◽  
Vol 67 (6) ◽  
pp. 73-82 ◽  
Author(s):  
Yu. B. Lishmanov ◽  
L. N. Maslov ◽  
N. Yu. Naryzhnaya ◽  
J.-M. Pei ◽  
F. Kolar ◽  
...  
Keyword(s):  
Opioid Peptides ◽  
Ischemia Reperfusion ◽  
Antiarrhythmic Effect ◽  
Endogenous Opioids ◽  
Protective Effects ◽  
Adaptive Responses ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Future Clinical Practice ◽  
Thromboxane Production

It has been well established that opioid peptides (OPs) affect various hormonal systems. Opioids exhibit stress-limiting and gastro-protective effects in stressed animals, acting via μ- and δ-opioid receptors (OR). Peripheral μ-OR stimulation by endogenous and exogenous opioids increases cardiac tolerance to pathological consequences of stress. Enhancement of prostacyclin synthesis, decrease of thromboxane production as well as suppression of lipid peroxidation can be directly responsible for cardioprotective effects of OPs in stressed animals. Adaptive responses are accompanied by increased OP levels in blood and tissues. Reduction of ventricular arrhythmias induced by repeated short-term immobilization stress is mediated via μ-OR stimulation by endogenous opioids, while δ-OR account for an antiarrhythmic effect of adaptation to chronic intermittent hypobaric hypoxia. The mechanism of infarct size-limiting effect of continuous normobaric hypoxia involves both μ- and δ-OR stimulation. Peptide OR agonists can be considered in future clinical practice for treatment of withdrawal syndrome, stress-related cardiac disease or myocardial injury caused by ischemia-reperfusion insult. 

scholarly journals The role of mu-opioids for reward and threat processing in humans: Bridging the gap from preclinical to clinical opioid drug studies

2021 ◽  
Author(s):  
Isabell M. Meier ◽  
Marie Eikemo ◽  
Siri Leknes
Keyword(s):  
Human Brain ◽  
Emotional Learning ◽  
Endogenous Opioids ◽  
Opioid System ◽  
Opioid Misuse ◽  
Opioid Use ◽  
Endogenous Opioid ◽  
Mu Opioid ◽  
Threat Processing

Purpose of review. Opioid receptors are widely expressed in the human brain. A number of features commonly associated with drug use disorder, such as difficulties in emotional learning, emotion regulation &amp; anhedonia, have been linked to endogenous opioid signaling. Whereas chronic substance use and misuse are thought to alter the function of the mu-opioid system, the specific mechanisms are not well understood. We argue that understanding exogenous and endogenous opioid effects in the healthy human brain is an essential foundation for bridging preclinical and clinical findings related to opioid misuse. Here, we will examine psychopharmacological evidence to outline the role of the mu-opioid receptor (MOR) system in the processing of threat and reward, and discuss how disruption of these processes by chronic opioid use might alter emotional learning and reward responsiveness.Recent findings. In healthy people, studies using opioid antagonist drugs indicate that the brain’s endogenous opioids downregulate fear reactivity and upregulate learning from safety. At the same time, endogenous opioids increase the liking of and motivation to engage with high reward value cues. Studies of acute opioid agonist effects indicate that with non-sedative doses, drugs such as morphine and buprenorphine can mimic endogenous opioid effects on liking and wanting. Disruption of endogenous opioid signalling due to prolonged opioid exposure is associated with some degree of anhedonia to non-drug rewards; however new results leave open the possibility that this is not directly opioid-mediated.Summary. The available human psychopharmacological evidence indicates that the healthy mu-opioid system contributes to the regulation of reward and threat processing. Overall, endogenous opioids can subtly increase liking and wanting responses to a wide variety of re-wards, from sweet tastes to feelings of being connected to close others. For threat related processing, human evidence suggests that endogenous opioids inhibit fear conditioning and reduce the sensitivity to aversive stimuli, although inconsistencies remain. The size of effects reported in healthy humans are however modest, clearly indicating that MORs play out their role in close concert with other neurotransmitter systems. Relevant candidate systems for future re-search include dopamine, serotonin and endocannabinoid signalling. Nevertheless, it is possible that endogenous opioid fine-tuning of reward and threat processing, when unbalanced by e.g. opioid misuse, could over time develop into symptoms associated with opioid use disorder, such as anhedonia and depression/anxiety.

Influence of endogenous opioids on the response of selected hormones to exercise in humans

1986 ◽  
Vol 61 (3) ◽  
pp. 1051-1057 ◽  
Author(s):  
P. A. Farrell ◽  
A. B. Gustafson ◽  
T. L. Garthwaite ◽  
R. K. Kalkhoff ◽  
A. W. Cowley ◽  
...  
Keyword(s):  
Venous Blood ◽  
Endogenous Opioids ◽  
Psychological State ◽  
Opioid Antagonist ◽  
Plasma Norepinephrine ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Naltrexone Treatment ◽  
The Difference ◽  
Exercise Induced

To examine the influence of endogenous opioids on the hormonal response to isotonic exercise, eight males were studied 2 h after oral administration of placebo or 50 mg naltrexone, a long-lasting opioid antagonist. Venous blood samples were obtained before, during, and after 30 min of bicycle exercise at 70% VO2max. Naltrexone had no effect on resting cardiovascular, endocrine, or serum variables. During exercise epinephrine was higher [mean 433 +/- 100 (SE) pg/ml] at 30 min with naltrexone than during placebo (207 +/- 26 pg/ml, P less than 0.05). Plasma norepinephrine showed the same trend but the difference (2,012 +/- 340 pg/ml with naltrexone and 1,562 +/- 241 pg/ml with placebo) was not significant. Plasma glucose was higher at all times with naltrexone. However, the difference was significant only 10 min into recovery from exercise (104.7 +/- 4.7 vs. 94.5 +/- 2.8 mg/dl). Plasma growth hormone and cortisol increased during recovery and these elevations were significantly (P less than 0.05) augmented by naltrexone. Plasma vasopressin and prolactin increased with exercise as did heart rate, blood pressure, lactic acid, and several serum components; these increases were not affected by naltrexone. Psychological tension or anxiety was lower after exercise compared with before and this improved psychological state was not influenced by the naltrexone treatment. These data suggest that exercise-induced activation of the endogenous opioid system may serve to regulate the secretion of several important hormones (i.e., epinephrine) during and after exercise.

Naloxone: lack of effect of a very low dose on fluid intake and activity in rats

1991 ◽  
Vol 8 (2) ◽  
pp. 100-108
Author(s):  
Robert Bell ◽  
Sheree Davis
Keyword(s):  
Locomotor Activity ◽  
Open Field ◽  
Water Intake ◽  
Low Dose ◽  
Fluid Intake ◽  
Endogenous Opioids ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Opiate Antagonists ◽  
Reduced Water

AbstractOpiate antagonists, such as naloxone, have been employed to indicate the possible involvement of endogenous opioids in a variety of behaviours including the pathogenesis of schizophrenia. This paper describes two experiments which were performed to determine the effects of naloxone on fluid intake and activity in rats. In experiment 1, the administration of 1mg/kg naloxone significantly (p<0.001) reduced water intake. 10mg/kg naloxone considerably reduced water intake, although this result was not significant. This influence was transient, since water intake was restored to control levels at the end of the 4 hours test period, and not dose related. A low dose of naloxone 0.01mg/kg produced no effect. In experiment 2, doses of 1 and 10mg/kg did not influence locomotor activity, rearing or grooming in the open field. These results suggest that naloxone may exert a primary antidipsogenic action that does not depend upon any suppression of concomitant activity. Furthermore, mechanisms controlling water intake and activity appear to be dissociated. A speculative role for the endogenous opioid system is discussed.

Sign in / Sign up

Export Citation Format

Share Document