title: TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity.
abstract: Differential thermal nociception across inbred mouse strains has genetic determinants. Thermal nociception is largely attributed to the heat/capsaicin receptor transient receptor potential vanilloid 1 (TRPV1); however, the contribution of this channel to the genetics of thermal nociception has not been revealed. In this study we compared TRPV1 expression levels and electrophysiological properties in primary sensory neurons and thermal nociceptive behaviors between two (C57BL/6 and BALB/c) inbred mouse strains. Using immunofluorescence and patch-clamp physiology methods, we demonstrated that TRPV1 expression was significantly higher in isolectin B4 (IB4)-positive trigeminal sensory neurons of C57BL/6 relative to BALB/c; the expression in IB4-negative neurons was similar between the strains. Furthermore, using electrophysiological cell classification (current signature method), we showed differences between the two strains in capsaicin sensitivity in IB4-positive neuronal cell types 2 and 13, which were previously reported as skin nociceptors. Otherwise electrophysiological membrane properties of the classified cell types were similar in the two mouse strains. In publicly available nocifensive behavior data and our own behavior data from the using the two mouse strains, C57BL/6 exhibited higher sensitivity to heat stimulation than BALB/c, independent of sex and anatomical location of thermal testing (the tail, hind paw, and whisker pad). The TRPV1-selective antagonist JNJ-17203212 inhibited thermal nociception in both strains; however, removing IB4-positive trigeminal sensory neurons with IB4-conjugated saporin inhibited thermal nociception on the whisker pad in C57BL/6 but not in BALB/c. These results suggest that TRPV1 expression levels in IB4-positive type 2 and 13 neurons contributed to differential thermal nociception in skin of C57BL/6 compared with BALB/c.
authors: Bluestone Center for Clinical Research, New York University College of Dentistry, New York, New York; and.
authors: Kentaro
authors: K
authors: Ono
authors: Bluestone Center for Clinical Research, New York University College of Dentistry, New York, New York; and.
authors: Yi
authors: Y
authors: Ye
authors: Bluestone Center for Clinical Research, New York University College of Dentistry, New York, New York; and Department of Oral Maxillofacial Surgery, New York University College of Dentistry, New York, New York.
authors: Chi T
authors: CT
authors: Viet
authors: Bluestone Center for Clinical Research, New York University College of Dentistry, New York, New York; and.
authors: Dongmin
authors: D
authors: Dang
authors: Bluestone Center for Clinical Research, New York University College of Dentistry, New York, New York; and Department of Oral Maxillofacial Surgery, New York University College of Dentistry, New York, New York bls322@nyu.edu.
authors: Brian L
authors: BL
authors: Schmidt
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects; D002211:Capsaicin / Q000009:adverse effects; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000502:physiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000294:innervation*; D013045:Species Specificity; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology
chemical_list: C500065:4-(3-trifluoromethylpyridin-2-yl)piperazine-1-carboxylic acid (5-trifluoromethylpyridin-2-yl)amide; D000631:Aminopyridines; D006023:Glycoproteins; D010879:Piperazines; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C473590:isolectin B4-binding glycoprotein, mouse; D002211:Capsaicin
keywords: TRPV1; capsaicin; electrophysiological property; heat pain sensitivity; trigeminal ganglion