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Spinal Noradrenergic Modulation and the Role of the Alpha-2 Receptor in the Antinociceptive Effect of Intrathecal Nefopam in the Formalin Test

  • Jeong, Shin Ho (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital) ;
  • Heo, Bong Ha (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital) ;
  • Park, Sun Hong (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital) ;
  • Kim, Woong Mo (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital) ;
  • Lee, Hyung Gon (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital) ;
  • Yoon, Myung Ha (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital) ;
  • Choi, Jeong Il (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital)
  • 투고 : 2013.12.12
  • 심사 : 2013.12.17
  • 발행 : 2014.01.01

초록

Background: Nefopam has shown an analgesic effect on acute pain including postoperative pain. The reuptake of monoamines including serotonin and noradrenaline has been proposed as the mechanism of the analgesic action of nefopam, but it remains unclear. Although alpha-adrenergic agents are being widely used in the perioperative period, the role of noradrenergic modulation in the analgesic effect of nefopam has not been fully addressed. Methods: Changes in the antinociceptive effect of intrathecal (i.t.) nefopam against formalin-elicited flinching responses were explored in Sprague-Dawley rats pretreated with i.t. 6-hydroxydopamine (6-OHDA), which depletes spinal noradrenaline. In addition, antagonism to the effect of nefopam by prazosin and yohimbine was evaluated to further elucidate the antinociceptive mechanism of i.t. nefopam. Results: Pretreatment with i.t. 6-OHDA alone did not alter the flinching responses in either phase of the formalin test, while it attenuated the antinociceptive effect of i.t. nefopam significantly during phase 1, but not phase 2. The antagonist of the alpha-2 receptor, but not the alpha-1 receptor, reduced partially, but significantly, the antinociceptive effect of i.t. nefopam during phase 1, but not during phase 2. Conclusions: This study demonstrates that spinal noradrenergic modulation plays an important role in the antinociceptive effect of i.t. nefopam against formalin-elicited acute initial pain, but not facilitated pain, and this action involves the spinal alpha-2 but not the alpha-1 receptor.

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참고문헌

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