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Effects of Naloxone on Morphine Analgesia and Spinal c-fos Expression in Rat Formalin Test  

Song, Sun Ok (Department of Anesthesiology and Pain Medicine, College of Medicine, Yeungnam University)
Seok, Je Hong (Department of Anesthesiology and Pain Medicine, College of Medicine, Yeungnam University)
Lee, Deok Hee (Department of Anesthesiology and Pain Medicine, College of Medicine, Yeungnam University)
Park, Dae Pal (Department of Anesthesiology and Pain Medicine, College of Medicine, Yeungnam University)
Kim, Seong Yong (Department of Biochemistry & Molecular Biology, College of Medicine, Yeungnam University)
Lim, Jeong Sook (Department of Biochemistry & Molecular Biology, College of Medicine, Yeungnam University)
Song, Sun Kyo (Department of Surgery, College of Medicine, Yeungnam University)
Lee, Nam Hyuk (Department of Surgery, College of Medicine, Yeungnam University)
Publication Information
The Korean Journal of Pain / v.18, no.2, 2005 , pp. 124-132 More about this Journal
Abstract
Background: This study was performed to evaluate the dose-related effects of naloxone on morphine analgesia in the rat formalin test, and observe the correlation of pain behavior and spinal c-fos expression induced by a formalin injection. Methods: Fifty rats were divided into five groups; control, morphine (morphine pre-treated, intra-peritoneal injection of 0.1 mg of morphine 5 min prior to formalin injection), and three naloxone groups, which were divided according to the administered dose-ratio of naloxone to morphine 20 : 1 ($5{\mu}g$), 10 : 1 ($10{\mu}g$), and 1 : 1 ($100{\mu}g$) representing the low-, medium-, and high-dose naloxone groups, respectively, were injected intra-peritoneally 16 min after a formalin. A fifty ul of 5% formalin was injected into the right hind paw. All rats were observed for their pain behavior according to the number of flinches during phases 1 (2-3, 5-6 min) and 2 (1 min per every 5 min from 10 to 61 min). The spinal c-fos expression was quantitatively analyzed at 1 and 2 hours after the formalin injection using a real-time PCR. Results: The morphine pre-treated (morphine and three naloxone) groups during phase 1, and the morphine, low- and medium-dose naloxone groups during phase 2, showed significantly less flinches compared to those of the control (P < 0.05). In the three naloxone groups, the numbers of flinches were transiently reduced following the naloxone injection in the low- and medium-dose groups compared to those of the morphine group (P < 0.05). The duration of the reduced flinches was longer in the medium-dose group (P < 0.05). The high-dose group revealed immediate increases in flinches immediately after the naloxone injection compared to those of the morphine, low- and medium-dose groups (P < 0.05 for each). The spinal c-fos expression showed no significant patterns between the experimental groups. Conclusions: Our data suggest that relatively low-dose naloxone (1/20 to 1/10 dose-ratio of morphine) transiently potentiates morphine analgesia; whereas, high-dose (equal dose-ratio of morphine) reverses the analgesia, and the spinal c-fos expression does not always correlate with pain behavior in the rat formalin test.
Keywords
analgesia; c-fos expression; formalin test; morphine; naloxone; pain behavior;
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