The pathophysiological role of serotonin receptor systems in opioid analgesia and tolerance

Özdemir, Ercan

doi:10.18203/2319-2003.ijbcp20170312

Cited by 10 publications

(3 citation statements)

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“…Endothelial cells express enzymes for synthesis and degradation of serotonin ( 18 , 102 – 106 ). There are two TPH genes for the metabolism of tryptophan to 5HTP which is then metabolized to serotonin and there are 14 receptors (HTRs) for serotonin ( 61 , 62 ). To focus our studies on HTRs that may be involved in eosinophil recruitment during allergic diseases and regulation of airway function, we determined if there are HTR s or TPH s in human chromosomal locations that are also chromosomal locations associated with asthma/allergic disease in genome-wide association studies (GWAS).…”

Section: Resultsmentioning

confidence: 99%

5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function

Walker,

Bloodworth,

Kountz

et al. 2024

Front. Allergy

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BackgroundPrevious research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers.ObjectiveIt is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans.MethodsSerotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts.ResultsPharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil transendothelial migration. In contrast, eosinophil transendothelial migration was not inhibited by siRNA knockdown of HTR1A or HTR1B in eosinophils. Surprisingly, these HTRs were intracellular in endothelial cells and an extracellular supplementation with serotonin did not inhibit eosinophil transendothelial migration. This is consistent with the inability of serotonin to cross membranes, the lack of selective serotonin reuptake receptors on endothelial cells, and the studies showing minimal impact of selective serotonin reuptake inhibitors on asthma. To extend our HTR studies to humans with asthma, we examined the CHIRAH and GALA cohorts for HTR SNPs that affect HTR function or are associated with behavior disorders. A polygenic index of SNPs in HTRs was associated with lower lung function in asthmatics.ConclusionsSerotonin receptors mediate 5HTP inhibition of transendothelial migration and HTR SNPs associate with lower lung function. These results may serve to aid in design of novel interventions for allergic inflammation.

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Section: Resultsmentioning

confidence: 99%

5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function

Walker,

Bloodworth,

Kountz

et al. 2024

Front. Allergy

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“…Клінічні спостереження вказують на необхідність застосування альтернативних медикаментозних схем антистресорного захисту емоційно лабільних стоматологічних хворих при їх підготовці до планових хірургічних втручань, оскільки стандартна схема передопераційної седації хворих виявилась неефективною. Опіатна та серотонінергічна системи відіграють значну роль у гальмуванні розвитку больового синдрому, його емоційних та поведінкових проявів [28,29]. Біологічним прекурсором серотоніну є амінокислота Lтриптофан [30].…”

Section: психологічний та пупілоалгометричний моніторинги стоматологі...unclassified

Psychological and Pupillo-Algometrical Monitoring of Dental Patients during Their Antistress Therapy

Mokryk¹,

Sorokivska²,

Sorokivskyi³

et al. 2022

Ukr. ž. med. bìol. sportu

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The purpose of the study was to investigate the psychological status and pain sensitivity by the pupillometric method in dental patients during preoperative antistress drug therapy. Materials and methods. In 100 patients, during their initial examination, signs of psychological stress were detected in them in social conditions during the last month before surgical interventions, using the PSM-25 scale of Lemoureux-Tessier-Fillion. The level of anxiety and depressive symptoms were determined using the Hospital Anxiety and Depression Scale. Pain sensitivity in patients was studied by measuring the reaction of the pupil of the eye to the action of an algogenic mechanical factor using the developed proprietary technique of digital pupillometry. Depending on the applied schemes of antistress drug therapy, patients were divided into two clinical groups. The control group included 50 people with different levels of psychological stress. During premedication, they were given Gidazepam for sedation. The main group included 50 patients who were under psychological stress. At the stage of preoperative preparation (for 7 days), they were prescribed a course of antistress therapy: enterally the drug “Antistress” (which contains L-tryptophan) and endonasally – dalargin solution. Results and discussion. Psychological stress acquired by patients in social conditions is a favorable background for the appearance of clinical manifestations of anxiety and depression before the start of operations. The use of Gidazepam by stress-labile dental patients of the control group during premedication made it possible to provide antistressor protection only in 8 cases. These patients had a moderate level of psychological stress. The results of psychological testing and pupillo-algometry confirm the need to use alternative medication schemes of antistressor protection for emotionally labile dental patients during their preparation for planned surgical interventions. In patients of the main group with an average level of psychological stress before surgical interventions, antistressor protection was achieved in 100% of cases. The effectiveness of the applied medicinal scheme was statistically significant in comparison with the standard scheme of treatment of psychoemotional tension used by patients of the control group – χ2 - 15.771 (р<0.001). Preoperative antistress therapy was not sufficiently effective for only 16.7% of patients in the main group with a high level of psychological stress. When comparing the results of stress-protective therapy with those of patients in the control group, statistically significant differences were also found – χ2 - 16.875 (р<0.001). Conclusion. In dental patients who are in a state of chronic psychological stress, psychoemotional tension (reactive anxiety) increases and pain sensitivity increases before the start of planned surgical interventions, which is confirmed by psychological tests and digital pupillo-algometry. One-time use of Gidazepam by stress-sensitive patients during premedication is not effective enough to normalize their psycho-emotional state. Prescribing a course of drug antistress therapy (L-tryptophan and dalargin) to dental patients diagnosed with chronic psychological stress allows to statistically reliably normalize their psychoemotional state and reduce pain sensitivity before the start of surgical interventions

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“…Furthermore, analyses of anecdotal and self-reported data support the consideration of psychedelics for treatment of OUD ( Savage and McCabe, 1973 ; Garcia-Romeu et al, 2019 ; Argento et al, 2022 ; Jones et al, 2022 ), and several clinical trials with psilocybin are ongoing for OUD (e.g., NCT0416066, NCT0542029, NCT06005662) and pain conditions (e.g., NCT06001749, NCT05224336, NCT05068791). MOR function is fundamentally integrated with 5-HT neurotransmission ( Tao et al, 1998 ; Tao and Auerbach, 2002b ; Tao et al, 2003 ; Ozdemir, 2017 ) with a prominent role for the 5-HT 2A R ( Aira et al, 2012 ; Heijmans et al, 2021 ; Li et al, 2021 ; Sierra et al, 2022 ), from the 5-HT 2 R family (5-HT 2A R, 5-HT 2B R, 5-HT 2C R) ( Barnes et al, 2021 ). As opposed to the MOR, the coupling of the 5-HT 2A R to Gα q/11 heterotrimeric G proteins triggers phosphatidylinositol-4,5-bisphosphate hydrolysis and subsequent release of inositol triphosphate, diacylglycerol, and other effectors ( Barnes et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges

Salinsky,

Merritt,

Zamora

et al. 2023

Front. Pharmacol.

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Opioid misuse and opioid-involved overdose deaths are a massive public health problem involving the intertwined misuse of prescription opioids for pain management with the emergence of extremely potent fentanyl derivatives, sold as standalone products or adulterants in counterfeit prescription opioids or heroin. The incidence of repeated opioid overdose events indicates a problematic use pattern consistent with the development of the medical condition of opioid use disorder (OUD). Prescription and illicit opioids reduce pain perception by activating µ-opioid receptors (MOR) localized to the central nervous system (CNS). Dysregulation of meso-corticolimbic circuitry that subserves reward and adaptive behaviors is fundamentally involved in the progressive behavioral changes that promote and are consequent to OUD. Although opioid-induced analgesia and the rewarding effects of abused opioids are primarily mediated through MOR activation, serotonin (5-HT) is an important contributor to the pharmacology of opioid abused drugs (including heroin and prescription opioids) and OUD. There is a recent resurgence of interest into psychedelic compounds that act primarily through the 5-HT2A receptor (5-HT2AR) as a new frontier in combatting such diseases (e.g., depression, anxiety, and substance use disorders). Emerging data suggest that the MOR and 5-HT2AR crosstalk at the cellular level and within key nodes of OUD circuitry, highlighting a major opportunity for novel pharmacological intervention for OUD. There is an important gap in the preclinical profiling of psychedelic 5-HT2AR agonists in OUD models. Further, as these molecules carry risks, additional analyses of the profiles of non-hallucinogenic 5-HT2AR agonists and/or 5-HT2AR positive allosteric modulators may provide a new pathway for 5-HT2AR therapeutics. In this review, we discuss the opportunities and challenges associated with utilizing 5-HT2AR agonists as therapeutics for OUD.

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The pathophysiological role of serotonin receptor systems in opioid analgesia and tolerance

Cited by 10 publications

References 100 publications

5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function

5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function

Psychological and Pupillo-Algometrical Monitoring of Dental Patients during Their Antistress Therapy

μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges

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