title: The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain.
abstract: BACKGROUND
  Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally.
  
  
  METHODS
  The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist.
  
  
  RESULTS
  When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam.
  
  
  CONCLUSIONS
  Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Do Yun
authors.initials: do Y
authors.lastname: Kim
authors.affiliation: Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Joo Wung
authors.initials: JW
authors.lastname: Chae
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Lim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Bong Ha
authors.initials: BH
authors.lastname: Heo
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Keun Suk
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hyung Gon
authors.initials: HG
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Myung Ha
authors.initials: MH
authors.lastname: Yoon
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.; Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Woong Mo
authors.initials: WM
authors.lastname: Kim
keywords: Analgesia; Dopamine; Microdialysis; Nefopam; Spinal cord; Sulpiride