期刊论文详细信息
Molecular Pain
GCH1-polymorphism and pain sensitivity among women with provoked vestibulodynia
Ulrika Johannesson3  Kent W Nilsson1  Fred Nyberg2  Alfhild Grönbladh2  Nina Bohm-Starke3  Ulrika Heddini3 
[1] Center for clinical research, Uppsala University, County Council of Västmanland Central Hospital, Västerås, Sweden;Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, Sweden;Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Division of Obstetrics and Gynecology, Stockholm, Sweden
关键词: Hormonal contraceptives;    SNP;    Polymorphism;    Gene;    GCH1;    Pain;    Provoked vestibulodynia;   
Others  :  863379
DOI  :  10.1186/1744-8069-8-68
 received in 2012-04-17, accepted in 2012-08-24,  发布年份 2012
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【 摘 要 】

Background

Provoked vestibulodynia (PVD) is a pain disorder localized in the vestibular mucosa. It is the most common cause of dyspareunia among young women and it is associated with general pain hypersensitivity and other chronic pain conditions. Polymorphism in the guanosine triphosphate cyclohydrolase (GCH1) gene has been found to influence general pain sensitivity and the risk of developing a longstanding pain condition. The aim of this study was to investigate GCH1-polymorphism in women with PVD and healthy controls, in correlation to pain sensitivity.

Results

We found no correlation between the previously defined pain-protective GCH1-SNP combination and the diagnosis of PVD. Nor any correlation with pain sensitivity measured as pressure pain thresholds on the arm, leg and in the vestibule, coital pain scored on a visual analog scale and prevalence of other bodily pain conditions among women with PVD (n = 98) and healthy controls (n = 102). However, among patients with current treatment (n = 36), there was a significant interaction effect of GCH1-gene polymorphism and hormonal contraceptive (HC) therapy on coital pain (p = 0.04) as well as on pressure pain thresholds on the arm (p = 0.04). PVD patients carrying the specified SNP combination and using HCs had higher pain sensitivity compared to non-carriers. In non-HC-users, carriers had lower pain sensitivity.

Conclusions

The results of this study gave no support to the hypothesis that polymorphism in the GCH1-gene contributes to the etiology of PVD. However, among patients currently receiving treatment an interaction effect of the defined SNP combination and use of hormonal contraceptives on pain sensitivity was found. This finding offers a possible explanation to the clinically known fact that some PVD patients improve after cessation of hormonal contraceptives, indicating that PVD patients carrying the defined SNP combination of GCH1 would benefit from this intervention.

【 授权许可】

   
2012 Heddini et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Danielsson I, Sjoberg I, Stenlund H, Wikman M: Prevalence and incidence of prolonged and severe dyspareunia in women: results from a population study. Scand J Publ Health 2003, 31:113-118.
  • [2]Moyal-Barraco M, Lynch PJ: 2003 ISSVD terminology and classification of vulvodynia: a historical perspective. J Reprod Med 2004, 49:772-777.
  • [3]Witkin SS, Gerber S, Ledger WJ: Differential characterization of women with vulvar vestibulitis syndrome. Am J Obstet Gynecol 2002, 187:589-594.
  • [4]Danielsson I, Eisemann M, Sjoberg I, Wikman M: Vulvar vestibulitis: a multi-factorial condition. BJOG 2001, 108:456-461.
  • [5]Granot M, Lavee Y: Psychological factors associated with perception of experimental pain in vulvar vestibulitis symdrome. J Sex Marital Ther 2005, 31:285-302.
  • [6]van Lankveld JJ, Granot M, Weijmar Schultz WC, Blinik YM, Wesselmann U, Pukall CF, Bohm-Starke N, Achtrari C: Women's sexual pain disorders. J Sex Med 2010, 7:615-631.
  • [7]Bouchard C, Brisson J, Fortier M, Morin C, Blanchette C: Use of oral contraceptive pills and vulvar vestibulitis: a case–control study. Am J Epidemiol 2002, 156:254-261.
  • [8]Johannesson U, Blomgren B, Hilliges M, Rylander E, Bohm-Starke N: The vulval vestibular mucosa-morphological effects of oral contraceptives and menstrual cycle. Br J Dermatol 2007, 157:487-493.
  • [9]Haefner HK, Collins ME, Davis GD, Edwards L, Foster DC, Hartmann ED, Kaufman RH, Lynch PJ, Margesson LJ, Moyal-Barraco M, Piper CK, Reed BD, Stewart EG, Wilkinson EJ: The vulvodynia guideline. J Low Genit Tract Dis 2005, 9:40-51.
  • [10]Bohm-Starke N, Hilliges M, Falconer C, Rylander E: Increased intraepithelial innervation in women with vulvar vestibulitis syndrome. Gynecol Obstet Invest 1998, 46:256-260.
  • [11]Bohm-Starke N, Hilliges M, Blomgren B, Falconer C, Rylander E: Increased blood flow and erythema in the posterior vestibular mucosa in vulvar vestibulitis. Obstet Gynecol 2001, 98:1067-1074.
  • [12]Bornstein J, Goldschmid N, Sabo E: Hyperinnervation and mast cell activation may be used as histopathologic diagnostic criteria for vulvar vestibulitis. Gynecol Obstet Invest 2004, 58:171-178.
  • [13]Bohm-Starke N, Hilliges M, Brodda-Jansen G, Rylander E, Torebjork E: Psychophysical evidence of nociceptor sensitization in vulvar vestibulitis syndrome. Pain 2001, 94:177-183.
  • [14]Pukall CF, Binik YM, Khalife S, Amsel R, Abbott FV: Vestibular tactile and pain thresholds in women with vulvar vestibulitis syndrome. Pain 2002, 96:163-175.
  • [15]Granot M, Friedman M, Yarnitsky D, Zimmer EZ: Enhancement of the perception of systemic pain in women with vulvar vestibulitis. BJOG 2002, 109:863-866.
  • [16]Bohm-Starke N, Brodda-Jensen G, Linder J, Danielsson I: The result of treatment on vestibular and general pain thresholds in women with provoked vestibulodynia. Clin J Pain 2007, 23:598-604.
  • [17]Johannesson U, de Boussard CN, Brodda Jansen G, Bohm-Starke N: Evidence of diffuse noxious inhibitory controls (DNIC) elicited by cold noxious stimulation in patients with provoked vestibulodynia. Pain 2007, 130:31-39.
  • [18]Arnold LD, Bachmann GA, Rosen R, Kelly S, Rhoads GG: Vulvodynia: characteristics and associations with comorbidities and quality of life. Obstet Gynecol 2006, 107:617-624.
  • [19]Buskila D, Sarzi-Puttini P, Ablin JN: The genetics of fibromyalgia syndrome. Pharmacogenomics 2007, 8:67-74.
  • [20]Saito YA, Petersen GM, Larson JJ, Atkinson EJ, Fridley BL, de Andrade M, Locke GR, Zimmerman JM, Almazar-Elder AE, Talley NJ: Familial aggregation of irritable bowel syndrome: a family case–control study. Am J Gastroenterol 2010, 105:833-841.
  • [21]Jeremias J, Ledger WJ, Witkin SS: Interleukin 1 receptor antagonist gene polymorphism in women with vulvar vestibulitis. Am J Obstet Gynecol 2000, 182:283-285.
  • [22]Foster DC, Sazenski TM, Stodgell CJ: Impact of genetic variation in interleukin-1 receptor antagonist and melanocortin-1 receptor genes on vulvar vestibulitis syndrome. J Reprod Med 2004, 49:503-509.
  • [23]Gerber S, Bongiovanni AM, Ledger WJ, Witkin SS: Interleukin-1beta gene polymorphism in women with vulvar vestibulitis syndrome. Eur J Obstet Gynecol Reprod Biol 2003, 107:74-77.
  • [24]Babula O, Danielsson I, Sjoberg I, Ledger WJ, Witkin SS: Altered distribution of mannose-binding lectin alleles at exon I codon 54 in women with vulvar vestibulitis syndrome. Am J Obstet Gynecol 2004, 191:762-766.
  • [25]Lev-Sagie A, Prus D, Linhares IM, Lavy Y, Ledger WJ, Witkin SS: Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome. Am J Obstet Gynecol 2009, 200(303):e1-e6.
  • [26]Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lötsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ: GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 2006, 12:1269-1277.
  • [27]Lötsch J, Belfer I, Kirchhof A, Mishra BK, Max MB, Doehring A, Costigan M, Woolf CJ, Geisslinger G, Tegeder I: Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms. Clin Chem 2007, 53:1010-1015.
  • [28]Lötsch J, Geisslinger G: Current evidence for a modulation of nociception by human genetic polymorphisms. Pain 2007, 132:18-22.
  • [29]Fillingim RB, Wallace MR, Herbstman M, Ribeiro D, Staud R: Genetic contributions to pain: a review of findings in humans. Oral Dis 2008, 14:673-682.
  • [30]Kim DH, Dai F, Belfer I, Banco RJ, Martha JF, Tighiouart H, Tromanhauser SG, Jenis LG, Hunter DJ, Schwartz CE: Polymorphic variation of the Guanosine triphosphate cyklohydrolase 1 gene predicts outcome in patients undergoing surgical treatment for lumbar degenerative disc desease. Spine 2010, 35:1909-1914.
  • [31]Kim H, Dionne RA: Lack of influence of GTP cyclohydrolase gene (GCH1) variations on pain sensitivity in humans. Mol Pain 2007, 3:6. BioMed Central Full Text
  • [32]Campbell CM, Edwards RR, Carmona C, Uhart M, Wand G, Carteret A, Kim YK, Frost J, Campbell JN: Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain. Pain 2009, 141:114-118.
  • [33]Lötsch J, Klepstad P, Doehring A, Dale O: A GTP cyclohydrolase 1 genetic variant delays cancer pain. Pain 2010, 148:103-106.
  • [34]Holliday KL, Nicholl BI, Macfarlane GJ, Thomson W, Davies KA, McBeth J: Do genetic predictors of pain sensitivity associate with persistent widespread pain? Mol Pain 2009, 5:56. BioMed Central Full Text
  • [35]Tegeder I, Adolph J, Schmidt H, Woolf CJ, Geisslinger G, Lötsch J: Reduced hyperalgesia in homozygous carriers of a GTP cyklohydrolase 1 haplotype. Eur J Pain 2008, 12:1069-1077.
  • [36]Dabo F, Grönbladh A, Nyberg F, Sundström-Poromaa I, Åkerud H: Different SNP combinations in the GCH1 gene and use of labour analgesia. Mol Pain 2010, 6:41. BioMed Central Full Text
  • [37]Dao TT, LeResche L: Gender differences in pain. J Orofac Pain 2000, 14:169-184.
  • [38]Sherman JJ, LeResche L: Does experimental pain response vary across the menstrual cycle? A methodologic review. Am J Physiol Regul Integr Comp Physiol 2006, 291:245-256.
  • [39]Craft RM: Modulation of pain by estrogens. Pain 2007, 132(Suppl 1):3-12.
  • [40]Kowalczyk WJ, Evans SM, Bisaga AM, Sullivan MA, Comer SD: Sex differences and hormonal influences on response to cold pressor pain in humans. J Pain 2006, 7:151-160.
  • [41]Kowalczyk WJ, Sullivan MA, Evans SM, Bisaga AM, Vosburg SK, Comer SD: Sex differences and hormonal influences on response to mechanical pressure pain in humans. J Pain 2010, 11:330-342.
  • [42]Rezaii T, Ernberg M: Influence of oral contraceptives on endogenous pain control in healthy women. Exp Brain Res 2010, 203:329-338.
  • [43]Bohm-Starke N, Johannesson U, Hilliges M, Rylander E, Torebjörk E: Decreased mecanichal pain threshold in the vestibular mucosa of women using oral contraceptives: a contributing factor in vulvar vestibulitis? J Reprod Med 2004, 49:888-892.
  • [44]Mogil JS, Sorge RE, Lacriox-Fralish ML, Smith SB, Fortin A, Sotocinal SG, Ritchie J, Austin JS, Schorscher-Petcu A, Melmed K, Czerminski J, Bittong RA, Mokris JB, Neubert JK, Campbell CM, Edwards RR, Campbell JN, Crawley JN, Lariviere WR, Sternberg WF, Balaban CD, Belfer I, Fillingim RB: Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environement interaction. Nat Neurosci 2011, 14:1569-1573.
  • [45]Mogil JS: The genetic mediation of individual differences in sensitivity to pain and itás inhibition. Proc Natl Acad Sci USA 1999, 96:7744-7751.
  • [46]Belfer I, Wu T, Kingman A, Krishnaraju RK, Goldman D, Max MB: Candidate gene studies of human pain mechanisms: methods for optimizing choice of polymorphisms and sample size. Anesthesiology 2004, 100:1562-1572.
  • [47]Pukall CF, Binik YM, Khalifé S: A new instrument for pain assessment in vulvar vestibulitis syndrome. J Sex Marital Ther 2004, 30:69-78.
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