The interplay of chronic stress and genetic traits discriminates between patients suffering from multisomatoform disorder with pain as the leading symptom and matched controls

Buhck, M; Achenbach, Johannes; Wiese, Birgit; Tran, Anh-Thu; Stuhrmann, Manfred; Jaeger, B; Bernateck, Michael; Schneider, Nico; Karst, Matthias

doi:10.1016/j.jad.2022.04.094

Cited by 3 publications

(3 citation statements)

References 58 publications

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“…Chronic pain is highly individual and dependent on genetic, epigenetic, and biographical factors in terms of gene-environment interactions 101 . In this context, large interindividual differences in the expression of the ECS are also found 102 .…”

Section: Challenges and Cautionsmentioning

confidence: 99%

Overview: Chronic Pain and Cannabis-Based Medicines

Karst

2024

Pharmacopsychiatry

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Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems. The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain effect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain. The analgesic effect appears to be largely independent of the cause of pain. In this context, CBM preferentially regulates stress-associated pain processing.

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Section: Challenges and Cautionsmentioning

confidence: 99%

Overview: Chronic Pain and Cannabis-Based Medicines

Karst

2024

Pharmacopsychiatry

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“…Part of the variability in pain and stress among individuals can be explained by genetics. Genetic polymorphisms affecting the activity of COMT or monoamine oxidase A and B (MAO-A/B), which are both catecholamine-degrading enzymes and thus influence catecholamine levels and ANS functioning, have been associated with increased stress responsiveness and pain sensitivity in both animals and humans [ 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 ]. Typically, polymorphisms that lower enzymatic activity and thus elevate catecholamine levels are associated with higher pain sensitivity [ 112 ].…”

Section: A Key Regulatory Role For Genetics and Epigenetics In Stress...mentioning

confidence: 99%

The Biology of Stress Intolerance in Patients with Chronic Pain—State of the Art and Future Directions

Wyns

Hendrix

Lahousse

et al. 2023

JCM

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Stress has been consistently linked to negative impacts on physical and mental health. More specifically, patients with chronic pain experience stress intolerance, which is an exacerbation or occurrence of symptoms in response to any type of stress. The pathophysiological mechanisms underlying this phenomenon remain unsolved. In this state-of-the-art paper, we summarised the role of the autonomic nervous system (ANS) and hypothalamus-pituitary-adrenal (HPA) axis, the two major stress response systems in stress intolerance. We provided insights into such mechanisms based on evidence from clinical studies in both patients with chronic pain, showing dysregulated stress systems, and healthy controls supported by preclinical studies, highlighting the link between these systems and symptoms of stress intolerance. Furthermore, we explored the possible regulating role for (epi)genetic mechanisms influencing the ANS and HPA axis. The link between stress and chronic pain has become an important area of research as it has the potential to inform the development of interventions to improve the quality of life for individuals living with chronic pain. As stress has become a prevalent concern in modern society, understanding the connection between stress, HPA axis, ANS, and chronic health conditions such as chronic pain is crucial to improve public health and well-being.

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“…Most outpatient cases suffer from chronic pain which is of more than one type of pain (Buhck et al, 2022) and the cost of pain management exceeds greatly the costs from cancer, diabetes and cancer management. 67% of patients with chronic pain suffer from comorbid maniac disorder (Annagür et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic profiling of compounds similar to paracetamol from zinc database: an in silico analysis

2023

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Introduction: Paracetamol is the most used drug for the management of pain and as an antipyretic through its mechanism of action on Cox 1,2 and 3 receptors. Paracetamol is a lipid-soluble molecule that can pass through the Blood Brain Barrier. Paracetamol has been formulated differently to ensure the optimal onset and duration of action as both analgesic and as antipyretic. Paracetamol overdose is associated with major side effects such as liver damage through its metabolite N-acetyl-p-benzoquinone Imine. Methods: This study generated zinc compounds that are similar in structure to Paracetamol through Ligand-based virtual screening. Molecular docking of these compounds to Cox 1, 2, and 3 receptors followed through Structure-based virtual screening. Compounds with better docking scores to these receptors were analyzed for pharmacokinetics and toxicity profiles. Results: ZINC01714506; 0.986; ZINC01714507; 0.986; and ZINC00394165; 0.987 showed the highest docking scores to cox 3 receptor with probability scores of -6.7kcal/mol, -6.4 and -6.2 kcal/ mol as compared to Paracetamol with -5.3kcal/mol. ZINC01714507; 0.986; ZINC01714506; 0.986; and ZINC00394165; 0.987; showed higher docking scores to Cox 2 with docking scores of -8.3kcal.mol, -8.1kcal/mole and -8.0 kcal/mol compared to paracetamol with -6.6kcal/mol. ZINC00394165; 0.987; ZINC00406627; 0.980; and ZINC01714506; 0.986; showed highest docking scores to Cox-1 than paracetamol with scores of -7.7kcal/mol, -7.6 and-7.6kcal/mol. ZINC01714506; 0.986 was predicted the safest with oral LD50 of 2000mg/kg as compared to paracetamol’s 338mg/kg. ZINC00294715; 0.980, ZINC01747085; 0.985, ZINC00394165; 0.987, ZINC00406627; 0.980, ZINC01557001; 0.987 and ZINC19281575; 0.992 were predicted hepatoactive. ZINC00294715; 0.980; ZINC01557001; 0.987; and ZINC19281575; 0.992; lack Blood Brain Barrier permeation. All compounds showed high GIT absorption and all conform to Lipinski’s rule of five. Conclusion: ZINC01557001; 0.987; ZINC01714506; 0.986; ZINC34120167; 0.994; ZINC00394165; 0.987, ZINC01714507; 0.986; and ZINC01747085; 0.985; are promising in drug discovery for new analgesic and antipyretic drugs, based on better docking scores and better oral LD50

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The interplay of chronic stress and genetic traits discriminates between patients suffering from multisomatoform disorder with pain as the leading symptom and matched controls

Cited by 3 publications

References 58 publications

Overview: Chronic Pain and Cannabis-Based Medicines

Overview: Chronic Pain and Cannabis-Based Medicines

The Biology of Stress Intolerance in Patients with Chronic Pain—State of the Art and Future Directions

Pharmacokinetic and pharmacodynamic profiling of compounds similar to paracetamol from zinc database: an in silico analysis

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