The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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Antinociceptive Effect of Intrathecal Nefopam and Interaction with Morphine in Formalin-Induced Pain of Rats

  • Cho, Soo Young (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital) ;
  • Park, A Reum (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) ;
  • Lee, Hyung Gon (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) ;
  • Choi, Jeong Il (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital)
  • Received : 2012.11.07
  • Accepted : 2012.12.05
  • Published : 2013.01.01
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Abstract

Background: Nefopam, a non-opiate analgesic, has been regarded as a substance that reduces the requirement for morphine, but conflicting results have also been reported. The inhibition of monoamine reuptake is a mechanism of action for the analgesia of nefopam. The spinal cord is an important site for the action of monoamines however, the antinociceptive effect of intrathecal nefopam was not clear. This study was performed to examine the antinociceptive effect of intrathecal (i.t.) nefopam and the pattern of pharmacologic interaction with i.t. morphine in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an i.t. catheter, and were randomly treated with a vehicle, nefopam, or morphine. Formalin was injected into the hind-paw 10 min. after an i.t. injection of the above experiment drugs. After obtaining antinociceptive $ED_{50}$ of nefopam and morphine, the mixture of nefopam and morphine was tested for the antinociceptive effect in the formalin test at a dose of 1/8, 1/4, 1/2 of $ED_{50}$, or $ED_{50}$ of each drug followed by an isobolographic analysis. Results: Intrathecal nefopam significantly reduced the flinching responses in both phases of the formalin test in a dose-dependent manner. Its effect, however, peaked at a dose of $30{\mu}g$ in phase 1 (39.8% of control) and $10{\mu}g$ during phase 2 (37.6% of control). The isobolograhic analysis indicated an additive interaction of nefopam and morphine during phase 2, and a synergy effect in antinociception during phase 1. Conclusions: This study demonstrated that i.t. nefopam produces an antinociceptive effect in formalin induced pain behavior during both phases of the formalin test, while interacting differently with i.t. morphine, synergistically during phase 1, and additively during phase 2.

Keywords

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