Protagonist Role of Opioidergic System on Post-Traumatic Stress Disorder and Associated Pain

Nikbakhtzadeh, Marjan; Borzadaran, Fatemeh Mohtashami; Zamani, Elham; Shabani, Mohammad

doi:10.30773/pi.2020.0002

Cited by 6 publications

(4 citation statements)

References 117 publications

(141 reference statements)

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“…22 It is also important to underline that during a traumatic event, endogenous opioid release helps the individual to endure pain and to not experience emotional sensation, but after several minutes or hours from the event, flashbacks are exaggerated along with intrusive thoughts as a PTSD symptom. 20 Aligned with these premises, this study shows that all survivors after the disaster in Amatrice had psychological distress, perceiving the burial as a devastating experience. It is possible to hypothesize that this experience was probably capable of modifying the neuronal circuits responsible for memory, despite early interventions with SAs aimed not only at facilitating the extrication maneuvers, but also at containing emotional distress and pain.…”

Section: Discussionsupporting

confidence: 55%

“…8 In addition, early administration of opioids for pain relief in trapped individuals has been demonstrated to have a negative role in fear memory consolidation, preventing the memory formation of stress via increasing the brain-derived neurotropic factor (BDNF) mRNA in regions like locus coeruleus (LC), medial prefrontal cortex (mPFC), ventral tegmental area (VTA), and amygdala. 20 On the other hand, ketamine is an antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor that is involved in mediating stress responses and formation of traumatic memories.…”

Section: Discussionmentioning

confidence: 99%

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Health Status Perception and Psychological Sequelae in Buried Victims: An Observational Study on Survivors of the Earthquake in Amatrice (Italy), Three Years Later

Petrucci

Cofini

Pizzi³

et al. 2023

Prehosp. Disaster med.

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Introduction: The extrication from rubble is particularly critical for the survival of the victims of an earthquake. Early repeated infusion of sedative agents (SAs) in the acute trauma phase may interfere with neural processes leading to posttraumatic stress disorder (PTSD). Study Objective: This study aimed to analyze the psychological status reported by the buried victims of the earthquake in Amatrice (August 24, 2016; Italy) by considering type of the SAs administered during the extrication maneuvers. Methods: This was an observational study on data from 51 patients directly rescued under the rubble during the earthquake in Amatrice. During extrication maneuvers, a moderate sedation was administered by titrating ketamine (0.3-0.5mg/kg) or morphine (0.1-0.15mg/kg) with respect to the Richmond Agitation and Sedation Scale (RASS; between -2 and -3) in buried victims. Three years following the rescue, the survivors were interviewed on their perceived health status and stress using a questionnaire which consisted of 17 items: the standard four-item set of healthy days core questions (CDC HRQOL-4); the 12-item General Health Questionnaire (GHQ-12); and in addition, survivors were asked if they had a diagnosis for anxiety, depression, or for PTSD. Results: The study analyzed data from the complete clinical documentation of 51 survivors; 30 were males and 21 females, with an average age of 52 years. Twenty-six (26) subjects were treated with ketamine, while 25 were treated with morphine, during the extrication procedures. Concerning the quality-of-life analysis, only 10 survivors out of 51 perceived their health status as good; the others reported psychological disorders. The GHQ-12 scores showed that all survivors had psychological distress with a mean total score of 22.2 (SD = 3.5). Eighteen (18) victims declared to have had a diagnosis of generalized anxiety (35%), while 29 were treated for depression (57%) and PTSD (57%) by a specialist. With regards to the perceived distress level and the anxiety disorder, this analysis showed significant associations with SAs used during extrication, with a better performance for ketamine than for morphine. Conclusion: These findings suggest investigating whether early sedation with ketamine directly in the disaster setting may promote the prophylaxis and reduce the risk of developing trauma-related disorders (TRDs) on the buried victims of major natural disasters in future studies.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Health Status Perception and Psychological Sequelae in Buried Victims: An Observational Study on Survivors of the Earthquake in Amatrice (Italy), Three Years Later

Petrucci

Cofini

Pizzi³

et al. 2023

Prehosp. Disaster med.

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“…Twin studies have shown that both exposure to trauma (combat) and the symptoms of PTSD are heritable (23). In addition, PTSD can increase pain perception (45).…”

Section: Discussionmentioning

confidence: 99%

Pain Experience in Pancreatitis: Strong Association of Genetic Risk Loci for Anxiety and PTSD in Patients With Severe, Constant, and Constant-Severe Pain

et al. 2021

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INTRODUCTION: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are progressive inflammatory syndromes with variable features. Pain is the primary feature that contributes to low physical and mental quality of life with a third of patients reporting severe pain. Pain experience is worsened by depression. Here, we tested the hypothesis that genetic risk of the psychiatric conditions of anxiety and post-traumatic stress disorder (PTSD) is associated with pain in CP and RAP + CP subjects. METHODS: The study cohort included phenotyped and genotyped RAP and CP patients from the North American Pancreatitis Study II of European Ancestry. Candidate genetic association studies were based on the absence of pain vs pain that is constant, constant-severe, or severe. Twenty-eight candidate genetic loci for anxiety and PTSD risk were identified in the literature and were the focus of this study. RESULTS: We identified 24 significant pain-associated single nucleotide polymorphisms within 13 loci across the 3 pain patterns in CP and RAP + CP (P < 0.002). Thirteen anxiety or PTSD genes were within these pain loci indicating nonrandom associations (P < 4.885 × 10−23). CTNND2 was associated with all pain categories and all pancreatitis etiologies. Implicated systems include neuronal signaling (HTR2A, DRD3, NPY, and BDNF), hypothalamic-pituitary-adrenal axis (NR3C1 and FKBP5), and cell-cell interaction (CTNND2 and THBS2). DISCUSSION: A component of constant and severe pain in patients with RAP and CP is associated with genetic predisposition to anxiety and PTSD. Identification of patients at risk eligible for trials of targeted treatment as a component of a multidisciplinary pain management strategy should be formally evaluated.

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“…Needless to say, there is an urgent need for tailored and targeted drugs to manage PTSD. If more recent data strengthen the involvement of the HPA axis and stress processes, preliminary evidence suggests that the opioid peptides, glutamate, cannabinoids, oxytocin, neuropeptide Y, and microRNA would be involved in PTSD pathophysiology [ 14 , 15 , 16 , 17 , 18 ]. Therefore, the aim of this narrative review was to present and comment on the state of the art of pharmacological treatment of PTSD and on some potential targets that might perhaps constitute novel avenues for innovative pharmacological strategies.…”

Section: Introductionmentioning

confidence: 99%

Novel Pharmacological Targets of Post-Traumatic Stress Disorders

Marazziti

Carmassi

Cappellato

et al. 2023

Life

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Post-traumatic stress disorder (PTSD) is a psychopathological condition with a heterogeneous clinical picture that is complex and challenging to treat. Its multifaceted pathophysiology still remains an unresolved question and certainly contributes to this issue. The pharmacological treatment of PTSD is mainly empirical and centered on the serotonergic system. Since the therapeutic response to prescribed drugs targeting single symptoms is generally inconsistent, there is an urgent need for novel pathogenetic hypotheses, including different mediators and pathways. This paper was conceived as a narrative review with the aim of debating the current pharmacological treatment of PTSD and further highlighting prospective targets for future drugs. The authors accessed some of the main databases of scientific literature available and selected all the papers that fulfilled the purpose of the present work. The results showed that most of the current pharmacological treatments for PTSD are symptom-based and show only partial benefits; this largely reflects the limited knowledge of its neurobiology. Growing, albeit limited, data suggests that the hypothalamic-pituitary-adrenal axis, opioids, glutamate, cannabinoids, oxytocin, neuropeptide Y, and microRNA may play a role in the development of PTSD and could be targeted for novel treatments. Indeed, recent research indicates that examining different pathways might result in the development of novel and more efficient drugs.

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Protagonist Role of Opioidergic System on Post-Traumatic Stress Disorder and Associated Pain

Cited by 6 publications

References 117 publications

Health Status Perception and Psychological Sequelae in Buried Victims: An Observational Study on Survivors of the Earthquake in Amatrice (Italy), Three Years Later

Health Status Perception and Psychological Sequelae in Buried Victims: An Observational Study on Survivors of the Earthquake in Amatrice (Italy), Three Years Later

Pain Experience in Pancreatitis: Strong Association of Genetic Risk Loci for Anxiety and PTSD in Patients With Severe, Constant, and Constant-Severe Pain

Novel Pharmacological Targets of Post-Traumatic Stress Disorders

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