Effects of Naloxone on Morphine Analgesia and Spinal c-fos Expression in Rat Formalin Test.
10.3344/kjp.2005.18.2.124
- Author:
Sun Ok SONG
1
;
Je Hong SEOK
;
Deok Hee LEE
;
Dae Pal PARK
;
Seong Yong KIM
;
Jeong Sook LIM
;
Sun Kyo SONG
;
Nam Hyuk LEE
Author Information
1. Department of Anesthesiology and Pain Medicine, College of Medicine, Yeungnam University, Daegu, Korea. sosong@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
analgesia;
c-fos expression;
formalin test;
morphine;
naloxone;
pain behavior
- MeSH:
Analgesia*;
Animals;
Formaldehyde*;
Morphine*;
Naloxone*;
Pain Measurement*;
Rats*;
Real-Time Polymerase Chain Reaction
- From:The Korean Journal of Pain
2005;18(2):124-132
- CountryRepublic of Korea
- Language:Korean
-
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 (5microgram), 10: 1 (10microgram), and 1: 1 (100microgram) 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.