title: Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients.
abstract: Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p = 0.03), and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V) with cold hypoalgesia (p = 0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p = 0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients.
authors.affiliation: Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. a.binder@neurologie.uni-kiel.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Binder
authors.forename: Denisa
authors.initials: D
authors.lastname: May
authors.forename: Ralf
authors.initials: R
authors.lastname: Baron
authors.forename: Christoph
authors.initials: C
authors.lastname: Maier
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Tölle
authors.forename: Rolf-Detlef
authors.initials: RD
authors.lastname: Treede
authors.forename: Achim
authors.initials: A
authors.lastname: Berthele
authors.forename: Frank
authors.initials: F
authors.lastname: Faltraco
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.forename: Janne
authors.initials: J
authors.lastname: Gierthmühlen
authors.forename: Sierk
authors.initials: S
authors.lastname: Haenisch
authors.forename: Volker
authors.initials: V
authors.lastname: Huge
authors.forename: Walter
authors.initials: W
authors.lastname: Magerl
authors.forename: Christian
authors.initials: C
authors.lastname: Maihöfner
authors.forename: Helmut
authors.initials: H
authors.lastname: Richter
authors.forename: Roman
authors.initials: R
authors.lastname: Rolke
authors.forename: Andrea
authors.initials: A
authors.lastname: Scherens
authors.forename: Nurcan
authors.initials: N
authors.lastname: Uçeyler
authors.forename: Mike
authors.initials: M
authors.lastname: Ufer
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wasner
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhu
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
mesh_terms: D000328:Adult; D000368:Aged; D017487:Ankyrins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050916:TRPV Cation Channels / Q000235:genetics; D050051:Transient Receptor Potential Channels / Q000235:genetics*
chemical_list: C110202:ANK1 protein, human; D017487:Ankyrins; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels