title: 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.
authors.affiliation: Department of Dental Medicine, Section of Orofacial Pain and Jaw Function, Karolinska Institutet, and the Scandinavian Center for Orofacial Neurosciences (SCON), Huddinge, Huddinge, Sweden.
authors.forename: Sofia
authors.identifier: http://orcid.org/0000-0001-8391-5991
authors.initials: S
authors.lastname: Louca Jounger
authors.affiliation: Department of Dental Medicine, Section of Orofacial Pain and Jaw Function, Karolinska Institutet, and the Scandinavian Center for Orofacial Neurosciences (SCON), Huddinge, Huddinge, Sweden.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Christidis
authors.affiliation: Department of Dental Medicine, Section of Orofacial Pain and Jaw Function, Karolinska Institutet, and the Scandinavian Center for Orofacial Neurosciences (SCON), Huddinge, Huddinge, Sweden.|Department of Clinical Oral Physiology at the Eastman Institute, Stockholm, Public Dental Health, Stockholm, Sweden.
authors.forename: Britt
authors.initials: B
authors.lastname: Hedenberg-Magnusson
authors.affiliation: Department of Orofacial Pain and Jaw Function, Faculty of Odontology, Malmö University, and the Scandinavian Center for Orofacial Neurosciences (SCON), Malmö, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: List
authors.affiliation: Department of Dental Medicine, Section of Orofacial Pain and Jaw Function, Karolinska Institutet, and the Scandinavian Center for Orofacial Neurosciences (SCON), Huddinge, Huddinge, Sweden.|Section of Orofacial Pain and Jaw Function, School of Dentistry, University of Aarhus, and the Scandinavian Center for Orofacial Neurosciences (SCON), Aarhus C, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Svensson
authors.affiliation: Center for Molecular Medicine, Karolinska Institutet, Solna, Stockholm, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Schalling
authors.affiliation: Department of Dental Medicine, Section of Orofacial Pain and Jaw Function, Karolinska Institutet, and the Scandinavian Center for Orofacial Neurosciences (SCON), Huddinge, Huddinge, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Ernberg
mesh_terms: D000328:Adult; D000483:Alleles; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D017829:Granisetron / Q000627:therapeutic use*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D063806:Myalgia / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000517:prevention & control; D017288:Pain Threshold / Q000502:physiology; D015990:Placebo Effect; D020641:Polymorphism, Single Nucleotide; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000627:therapeutic use*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D017829:Granisetron; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; C509409:HTR3A protein, human; C509410:HTR3B protein, human