title: The preventive effect of resiniferatoxin on the development of cold hypersensitivity induced by spinal nerve ligation: involvement of TRPM8.
abstract: Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL.
  
  
  
  RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG.
  
  
  
  Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea.
authors.forename: Won Uk
authors.initials: WU
authors.lastname: Koh
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea.
authors.forename: Seong-Soo
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea.
authors.forename: Hye Joo
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea.
authors.forename: Ho-Soo
authors.initials: HS
authors.lastname: Ahn
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea.
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea.
authors.forename: Jeong Gil
authors.initials: JG
authors.lastname: Leem
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea.
authors.forename: Jun Gol
authors.initials: JG
authors.lastname: Song
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43 gil, Songpa-Gu, Seoul, 05505, Korea. sjinwoo@hotmail.com.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Shin
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003080:Cold Temperature; D056587:Cryopyrin-Associated Periodic Syndromes / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D004224:Diterpenes / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006358:Hot Temperature; D008026:Ligation; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism; D050053:TRPM Cation Channels / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D000700:Analgesics; D004224:Diterpenes; D018696:Neuroprotective Agents; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C498947:Trpm8 protein, rat; C493922:Trpv1 protein, rat; C024353:resiniferatoxin
keywords: Hypersensitivity; Resiniferatoxin; Spinal nerve ligation; Transient receptor potential