Dataset Information

Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

ABSTRACT: The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP) contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613) and HTR3B (rs1176744). First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL) into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL) and on the other side with 0.5 mL placebo (isotonic saline) followed by another HS injection (0.2 mL). Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs) were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023), but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A) (P = 0.015) and pain intensity higher in women with the A/C alleles (HTR3B) (P = 0.019). Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P < 0.05), but the SNPs did not in general influence the efficacy of granisetron. Women carrying the C/T & T/T (HTR3A) genotype had less reduction of pain intensity (P = 0.041) and area (P = 0.005), and women with the C/C genotype (HTR3B) had less reduction of pain intensity (P = 0.030), duration (P = 0.030) and area compared to men (P = 0.017). In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn.

SUBMITTER: Louca Jounger S

PROVIDER: S-EPMC5176308 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

Louca Jounger Sofia S Christidis Nikolaos N Hedenberg-Magnusson Britt B List Thomas T Svensson Peter P Schalling Martin M Ernberg Malin M

PloS one 20161221 12

The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP) contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613) and HTR3B (rs1176744). First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL) into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 m ...[more]

PMID: 28002447

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Project description:Background: The aim of this study was to investigate if single nucleotide polymorphisms (SNPs) related to monoaminergic neurotransmission, in particular the serotonergic pathway, contribute to pain perception in patients with temporomandibular disorder (TMD) myalgia and if there is a correlation to jaw function as well as psychosocial factors such as stress, anxiety and depression. Materials and Methods: One hundred and seventeen individuals with TMD myalgia were included. A venous blood or saliva sample was taken for genetic analyses and genotyped regarding HTR2A (rs9316233) HTR3A (rs1062613), HTR3B (rs1176744), SERT (5-HTTLPR) and COMT (rs4680). A clinical examination according to Diagnostic Criteria for TMD (DC/TMD) was performed and axis II data (psychosocial factors) were compared between participants with different genotypes for each gene using Kruskall-Wallis test. The characteristic pain intensity (CPI) was tested for correlations to scores for the Perceived Stress Scale, Generalized Anxiety Disorder, and Patient Health Questionnaires using Spearman's rank correlation test with Bonferroni correction for multiple testing. To further explore data factor analysis was performed to identify latent factors associated to the outcome variables. Results: Participants carrying at least one copy of the rare allele of the HTR2A (rs9316233) and HTR3A (rs1062613) had higher CPI compared with the participants with the homozygous common genotype (P = 0.042 and P = 0.024, respectively). Correlation analyses showed several significant positive correlations between CPI on one hand, and self-reported psychosocial distress and jaw function on the other hand for several genotypes that mostly were weak to moderate. The factor analysis identified two latent variables. One was positively correlated to the HTR3B gene, jaw function and self-reported parafunctions, and the other was positively correlated to psychological distress and negatively correlated to SERT. Conclusion: Taken together, the polymorphism rs1062613 in the HTR3A gene contributes to pain intensity in TMD myalgia. This together with positive interactions between pain variables and psychological factors in genotypes strengthens that pain and psychological distress are related. Further research is needed to explore this as well as the influence of gene-to-gene interactions on pain and psychological distress.

Project description:Background: The specific serotonin type 3 (5-HT3)-receptor antagonist granisetron effectively reduces clinical as well as experimental muscle pain and hyperalgesia and with a duration that exceeds that of lidocaine. Hence, it may be an alternative to lidocaine as a local anesthetic. There are also some indications that granisetron in addition to 5-HT3 receptors blocks sodium channels. Thus, the local anesthetic effect by granisetron may resemble that of lidocaine, but this has not been tested. The aim of this study was therefore to compare the effect granisetron has on facial skin sensitivity to the effect of lidocaine and isotonic saline. Methods: This was a randomized, controlled, and double-blind study, in which 1 ml of either granisetron (test-substance), lidocaine (positive control), or isotonic saline (negative control) was injected into the skin over the masseter muscle at three different occasions in 18 healthy males (27.2 ± 5.8 years old). Skin detection thresholds and pain thresholds for thermal stimuli as well as mechanical detection thresholds and sensitivity to a painful mechanical (pinprick) stimulus were assessed before (baseline) and 5, 20, 40, and 60 min after injection. The quality and area of subjective sensory change over the cheek were assessed 20 min after injection. Results: All substances increased the mechanical detection threshold (granisetron: p = 0.011; lidocaine: p = 0.016; saline: p = 0.031). Both granisetron and lidocaine, but not isotonic saline, increased the heat detection thresholds (p < 0.001 and p < 0.02, respectively), but not the cold detection thresholds. Granisetron and lidocaine also reduced pinprick pain (p = 0.001 for each comparison). There were no significant differences between granisetron and lidocaine for any of these variables. There was no effect on thermal pain thresholds for any substance. Conclusion: The similar analgesic patterns on mechanical sensory and pain thresholds as well as thermal sensory thresholds over the facial skin by subcutaneous injection of granisetron and lidocaine shown in this study and the absence of paresthesia, in combination with the reduced pain intensity and pressure pain sensitivity shown in previous studies, indicate that granisetron might be a novel candidate as a local anesthetic.

Project description:BackgroundA reasonable and effective control of chemotherapy-induced nausea and vomiting (CINV) plays an important role in the comprehensive treatment of cancer. Megestrol belongs to the 17α-hydroxyprogesterone derivative and is a highly effective synthetic progesterone. Recorded in the instructions may improve appetite and cachexia in patients with advanced tumors. In recent years, clinical practice and small sample studies have shown that megestrol combined with chemotherapy can improve CINV. This randomized controlled trial aimed to evaluate the clinical efficacy and safety of megestrol acetate combined with a 5-Hydroxytryptamine (5-HT3) receptor antagonist and dexamethasone in patients with CINV.MethodsPatients with malignant tumors who were treated with cisplatin-containing chemotherapy in our hospital from September 2018 to December 2019 were enrolled. A total of 120 patients were selected and randomly assigned to receive either megestrol acetate dispersible tablets with a 5-HT3 receptor antagonist and dexamethasone (megestrol group) or a 5-HT3 receptor antagonist plus dexamethasone (control group). Megestrol acetate dispersible tablets: 160 mg orally every morning from the day of chemotherapy until it lasts for ten days. Abstract IV of the quality-of-life scale for cancer patients in China was used to assess the quality of life (QOL) of the participants. All adverse reactions during chemotherapy were assessed according to the CTCAE 4.03 evaluation standard issued by the National Cancer Institute and divided into five grades according to severity.ResultsFor the control of nausea, the rates of complete prevention were significantly higher in the megestrol group than in the control patients during the delayed [53.3% (31/60) vs. 30.0% (18/60), P=0.012] and overall [40.0% (24/60) vs. 15.0% (9/60), P=0.002] observation periods. Moreover, the megestrol combination treatment group also achieved markedly higher rates of complete remission of vomiting than the control group during the delayed observation period [76.7% (46/60) vs. 51.7% (31/60), P=0.001], achieving an overall higher proportion of remission during the study period [68.3% (41/60) vs. 46.6% (28/60), P=0.0016].ConclusionsThe triple antiemetic protocol using megestrol acetate with a 5-HT3 receptor antagonist plus dexamethasone can improve CINV symptoms caused by highly emetogenic chemotherapy (HEC) with cisplatin, with an excellent control effect and few adverse reactions, especially for delayed CINV.Trial registrationChinese Clinical Trial Registry ChiCTR1800017953.

Dataset Information

Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

Publications

Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

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