title: Effects of nefopam on streptozotocin-induced diabetic neuropathic pain in rats.
abstract: BACKGROUND
  Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats.
  
  
  METHODS
  Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated.
  
  
  RESULTS
  Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG.
  
  
  CONCLUSIONS
  These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae Sik
authors.initials: JS
authors.lastname: Nam
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yu Seon
authors.initials: YS
authors.lastname: Cheong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Myong Hwan
authors.initials: MH
authors.lastname: Karm
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 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, Seoul, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Sim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.
authors.forename: Jin Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 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, Seoul, Korea.
authors.forename: Jeong Gil
authors.initials: JG
authors.lastname: Leem
keywords: TRPA1; TRPM8; allodynia; nefopam; painful diabetic neuropathy; streptozotocin