Serotonin induces peripheral antinociception via the opioidergic system

Diniz, Danielle Aguiar; Petrocchi, Júlia Alvarenga; Navarro, Larissa Caldeira; Souza, Tâmara Cristina; Castor, Marina Gomes Miranda e; Duarte, Igor Dimitri Gama; Romero, Thiago Roberto Lima

doi:10.1016/j.biopha.2017.11.048

Cited by 19 publications

(5 citation statements)

References 29 publications

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“…TRP is the amino acid precursor of serotonin (5‐HT), synthesized via the TRP hydroxylase enzyme, and of the end product 5‐hydroxyindoleacetic acid (5‐HIAA). The serotoninergic system plays a pivotal role in the regulation of the pain threshold, acting on brainstem nuclei that discriminate and modulate incoming pain sensations from the spinal cord . In order to evaluate the role of the indoles in CH, 5‐HT and 5‐HIAA were measured in plasma of a group of episodic CH patients.…”

Section: Trp Metabolism In Episodic Chmentioning

confidence: 99%

“…As previously mentioned, TRP is the amino acid precursor of 5‐HT and 5‐HIAA via the decarboxylation of tryptamine (TRY). The role of TRY in the CNS was unknown until the discovery that TRY is an agonist of 5‐HT 1A and 5‐HT 2A receptors located in the descending ventrolateral orbital cortex projecting to the peri‐aqueductal gray (PAG) to and, as such, modulates, together with 5‐HT, the pain threshold . This amine, acting on 5‐HT 1A receptors, reduces the release of gamma‐aminobutryic acid from the inhibitory interneurons of the cortical and subcortical serotoninergic neurons.…”

Section: Trp Metabolism Cchmentioning

confidence: 99%

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Pathogenesis of Cluster Headache: From Episodic to Chronic Form, the Role of Neurotransmitters and Neuromodulators

D’Andrea¹,

Gucciardi

Perini

et al. 2019

Headache

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Objective.-To describe the role of biochemical anomalies of tyrosine (TYR), tryptophan (TRP), and arginine (ARG) metabolism in patients suffering from episodic and chronic cluster headache (CCH).Background.-The pathogenesis of cluster headache (CH) and the process that transforms the episodic into the chronic form are unknown. However, the accompanying symptoms suggest a dysfunction of the sympathetic system and hypothalamus along with anomalies of metabolism of catecholamines, elusive amines, and nitric oxide (NO) metabolism.Methods.-We describe the results obtained from the last papers published on this issue. The level of metabolites were analyzed by different high-performance liquid chromatography methods.Results.-In both episodic and CH patients, the levels of dopamine and elusive amines are very elevated. The only biochemical difference found in studies between episodic and chronic cluster was that norepinephrine levels were significantly lower in episodic cluster in comparison to control and chronic subjects. In addition, the levels of ARG, homoarginine, and citrulline, precursors of synthesis of NO, were significantly lower in chronic cluster.Conclusions.-All these results suggest that TYR, TRP, and ARG metabolism is abnormal and may constitute a biochemical fingerprint of CH patients. The increased levels of norepinephrine in chronic cluster constitute a possible cause of chronicity of this primary headache. The high levels of tryptamine and its activity on the central serotoninergic system may explain why the length of CH is brief in comparison to migraine and tension-type headache. The low levels of ARG, homoarginine, and citrulline may be the consequence of high circulating levels of α 1 -agonists, such as epinephrine and norepinephrine, and their biochemical interaction with endothelial trace amine-associated receptor 1 that induces activation of NO synthase, resulting in NO synthesis in the circulation, NO release, intense vasodilation, and as a result, the cluster attack.

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Section: Trp Metabolism In Episodic Chmentioning

confidence: 99%

Section: Trp Metabolism Cchmentioning

confidence: 99%

Pathogenesis of Cluster Headache: From Episodic to Chronic Form, the Role of Neurotransmitters and Neuromodulators

D’Andrea¹,

Gucciardi

Perini

et al. 2019

Headache

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“…Pain-related blood markers include proinflammatory cytokines, anti-inflammatory cytokines, cortisol, and serotonin. [ 2 , 3 , 12 , 13 , 15 , 18 , 20 , 33 ]. Cytokines influence the activity, differentiation, proliferation, and survival of immune cells, and they regulate the production and activity of other cytokines that can increase (proinflammatory) or decrease (anti-inflammatory) the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been reported that salivary and plasma cortisol levels are closely related to stress or pain [ 10 , 18 , 20 ]. Serotonin possibly induces peripheral antinociception through the release of endogenous opioid peptides [ 13 ]. Pain and the immune system influence each other, making it difficult to determine whether blocking nociception contributes to a reduction in the production of proinflammatory cytokines or vice-versa, with a reduction in the formation of proinflammatory cytokines resulting in less severe pain [ 18 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine combined with suprascapular nerve block and axillary nerve block has a synergistic effect on relieving postoperative pain after arthroscopic rotator cuff repair

Lee

Kim

Hwang

et al. 2020

Knee Surg Sports Traumatol Arthrosc

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Purpose Suprascapular nerve block (SSNB) is the most commonly used block for the relief of postoperative pain from arthroscopic rotator cuff repair and can be used in combination with axillary nerve block (ANB). Dexmedetomidine (DEX) is a type of alpha agonist that can elongate the duration of regional block. The aim of this study was to compare the effects of the use of dexmedetomidine combined with SSNB and ANB with those of the use of SSNB and ANB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair. Methods Forty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single-center, double-blinded randomized controlled trial study. Twenty patients were randomly allocated to group 1 and received ultrasound-guided SSNB and ANB using a mixture of 0.5 ml (50 μg) of DEX and 9.5 ml of 0.75% ropivacaine preemptively. The other 20 patients were allocated to group 2 and underwent ultrasound-guided SSNB and ANB alone using a mixture of 0.5 ml of normal saline and 9.5 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were postoperatively checked within 48 h. The plasma interleukin (IL)-6, IL-8, IL-1β, cortisol, and serotonin levels were also postoperatively measured within 48 h. Results Group 1 showed a significantly lower mean VAS (visual analog scale of pain) score 1, 3, 6, 12, 18 and 24 h after operation, and a significantly higher mean SAT (patient satisfaction) score 1, 3, 6, 12, 18, 24 and 36 h after the operation than group 2. Group 1 showed a significantly lower mean plasma IL-8 level 1 and 48 h after the operation, and a significantly lower mean IL-1β level 48 h after the operation than group 2. Group 1 showed a significantly lower mean plasma serotonin level 12 h after the operation than group 2. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (36 h > 23 h, p = 0.007). Six patients each in groups 1 and 2 showed rebound pain. The others did not show rebound pain. Conclusions Ultrasound-guided SSNA and ANB with DEX during arthroscopic rotator cuff repair resulted in a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h after the operation than SSNB and ANB alone. Additionally, SSNB and ANB with DEX tended to result in a later mean timing of rebound pain accompanied by significant changes in IL-8, IL-1β, and serotonin levels within 48 h after the operation. The present study could provide the basis for selecting objective parameters of postoperative pain in deciding the optimal use of medication for relieving pain. Level of Evidence Level I. Trial Registration 2015–20, ClinicalTrials.gov Identifier: NCT04398589. IRB number 2015–20, Hallym University Chunc...

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“…Der Zusammenhang zwischen Serotonin und Schmerz ist sehr komplex (202). Zum einen zeigen unterschiedliche Arbeiten, dass die Ausschüttung von Serotonin auf spinaler und peripherer Ebene einen positiven Einfluss auf die induzierte Analgesie hat (203)(204)(205). Zum anderen kann Serotonin auch pro-nozizeptiv wirken (206,207…”

Section: Einfluss Endogener Neurotransmitterunclassified

Liver lobe and strain differences in the activity of murine cytochrome P450 enzymes

et al. 2018

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The cytochrome P450 (CYP) enzyme superfamily is the most important enzyme system for phase I biotransformation. For toxico- and pharmacokinetic studies, use of liver-based microsomes, including those of mice, is state-of-the-art to study CYP-dependent metabolism. However, reproducibility and interpretation of these data is still very variable, partly because current testing guidelines do not cover details on organ sampling and potential liver lobe differences. Hence, we analyzed CYP activity, CYP protein content, mRNA expression of CYP1A, CYP2C, CYP2D and CYP3A isozymes, and cytochrome P450 reductase (CPR) activity of the four different liver lobes and processus papillaris of male C57BL/6J mice in comparison to whole liver. Additionally, we used whole liver of Balb/cJ and 129S1/SvImJ for strain comparison. Our data show significant differences in CYP activity, being most prominent in lobus sinister lateralis and lobus medialis, and lowest in processus papillaris. These differences were not caused by varying Cyp gene expression or CYP protein level, but partly correspond with lobe specific CPR activities. We also observed significant strain differences in CYP mRNA expression and activities with overall high activities in 129S1/SvImJ mice and low activities in Balb/cJ mice compared to C57BL/6J mice. In addition, strain specific differences in CYP2C and CYP2D activity seem to be reflected in strain dependent differences in CPR activity. In summary, our results indicate that in mice CYP activity and gene expression are strain dependent and may vary highly between liver lobes. To ensure reproducibility and comparability of different probes and studies, this should be taken into account when liver samples are collected for the analysis of CYP-dependent metabolism.

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Serotonin induces peripheral antinociception via the opioidergic system

Cited by 19 publications

References 29 publications

Pathogenesis of Cluster Headache: From Episodic to Chronic Form, the Role of Neurotransmitters and Neuromodulators

Pathogenesis of Cluster Headache: From Episodic to Chronic Form, the Role of Neurotransmitters and Neuromodulators

Dexmedetomidine combined with suprascapular nerve block and axillary nerve block has a synergistic effect on relieving postoperative pain after arthroscopic rotator cuff repair

Liver lobe and strain differences in the activity of murine cytochrome P450 enzymes

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