Spinal Noradrenergic Modulation and the Role of the Alpha-2 Receptor in the Antinociceptive Effect of Intrathecal Nefopam in the Formalin Test
The Korean Journal of Pain 2014³â 27±Ç 1È£ p.23 ~ p.29
(Jeong Shin-Ho) - Chonnam National University Medical School Department of Anesthesiology and Pain Medicine
ÇãºÀÇÏ(Heo Bong-Ha) - Chonnam National University Medical School Department of Anesthesiology and Pain Medicine
¹Ú¼±È«(Park Sun-Hong) - Chonnam National University Medical School Department of Anesthesiology and Pain Medicine
±è¿õ¸ð(Kim Woong-Mo) - Chonnam National University Medical School Department of Anesthesiology and Pain Medicine
ÀÌÇü°ï(Lee Hyung-Gon) - Chonnam National University Medical School Department of Anesthesiology and Pain Medicine
À±¸íÇÏ(Yoon Myung-Ha) - Chonnam National University Medical School Department of Anesthesiology and Pain Medicine
ÃÖÁ¤ÀÏ(Choi Jeong-Il) - Chonnam National University Medical School Department of Anesthesiology and Pain Medicine
Abstract
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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alpha-2 receptor, formalin, nefopam, noradrenergic system, spinal cord
KMID :
0363120140270010023
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