Antinociceptive effect of intrathecal nefopam and interaction with morphine in formalin-induced pain of rats.
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 µg in phase 1 (39.8% of control) and 10 µg 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.
Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School and Hospital, Gwangju, Korea.
Soo Young
SY
Cho
A Reum
AR
Park
Myung Ha
MH
Yoon
Hyung Gon
HG
Lee
Woong Mo
WM
Kim
Jeong Il
JI
Choi
antinociception; formalin; interaction; morphine; nefopam