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Serotonin이 痛覺에 미치는 影響에 關한 實驗的 硏究

Experimental studies concerning the effects of serotonin on the sense of pain

중앙의학 1963년 5권 3호 p.209 ~ 217
김혜성,
소속 상세정보
김혜성 (  ) - 이화여자대학교 의과대학 약리학교실

Abstract


The sense of pain is difficult to determine quantitatively in experimental animals since it is a subjective symptom, The analgesic action of drugs, therefore, is generally determined indirectly by measuring the response of animals to external stimuli applied experimentally. Numerous methods employing various kinds of stimulation -electrical, mechanical and thermal- have been devised to evaluate experimentally the pain threshold in animals.
The pinch method, using one of the mechanical stimuli, was developed by Haffner and Collier who applied it to measure the analgesic effects of drugs on mice. Keasiing devised a method of applying electrical stimulation through an embedded metal filling to the rabbits teeth tor measuring pain threshold. The radient heat apparatus (D´ Amour and Smith) and hot plate method (McDonald and Eddy) have been used for determining analgesic effeets of drugs.
The above mentioned methods, however, have been often proved quite unsatisfactory to get accurate experimental data due to the difficulty of maintaining a constant intensity of stimulation. In addition, injuries may often occur after frequent repetition of the stimulation. To eliminate such disadvantages, the author has devised an Automatic Thermostimulator, which is comparatively simple in determining pain reflex in rats and more assurable of accuracy in the results.
Apparatus
This apparatus constitutes two parts : a heat regulator and a stimulator. Heat regul ator consists of bridge, 1). C. amplifier, power amplifier, saturatable reactor and transformer and is made in the principle of the serbo-mechanism. There is a theimose cope in the stimulator and the temperature in the stimulator is maintained constantly by a heat regulator and the variation in each set temperature is not exceed ±0. 3°C.
Materials and Method :
Male albino rats weighing 150----200 grams were employed in this experiment. The animal was comfortably "immobilized" in an individual cage which has an opening front gate and a back wire gate with a slit in the middle of it, which allows the animal to protrude its tail. The tail was put into the hole of the stimulator and exposured to the heat stimulus.
Analgesic potency was measured by determining the withdrawal time of the tail (pseudopain sense reflex) after the stimulus was applied. When the withdrawal time of tail in the animals treated with drugs was prolonged twice the time in normal animals, it was considered that the drug had an analgesic effect and when the time was more than three times normal the experiment was stopped in order to avoid the possibility of injury.
Results
1) Preliminary experiments showed that the mean withdrawal time of tails in normal rats was 120 ± 14.9 sec. 95.9 ± 11.3 sec. , 73.6 ± 8.0 sec. , and 56.7 8. 4sec. at the set temperature of 60°C., 65°C. ,700C. and 75°C. of the Automatic Thermostimulator respectively. A remarkable decrease in the withdrawal time of a tail by elevating the temperature of this apparatus was observed. The react-ion time of animals at the same set temperature was fairly constant, even if the stimulus was repeated every 30 min. for several hours.
2) It was found that the optimal set temperature for testing analgesic effect of drugs with this method was 65°C and 70°C. When the temperature in the stimulator is set below 60°C the withdrawal time is so prolonged that the tail may get burned and at above 75°C. the intensity of heat stumulus is too strong to evaluate accuratly the analgesic activity.
3) Intraperitoneal injection of morphine 6 mg/kg into the rats slightly prolonged the withdrawal time at the temperature of 65°G (of the Automatic Thermostimulator) immediatly after the injection, and returned to the normal value within 60 min. However, 8 mg/kg of morphine prolonged considerably and 12 mg/kg of morphine markedly the reaction time of rats following the injection.
4) The administration of codeine also prolonged the withdrawal time of tail at the temperature of 65°C of the Automatic Thermostimulator but the onset of the action of codeine was slower than that of morphine. According to Kissel et al. and Sollman, the analgesic potency of codeine is less than one fourth of that of morphine. Grollman reported that 60 mg/kg of codeine relieved pain in about the same degree as 10 mg of morphine. in this experiment to produce the comparable levels of analgesic effect, only three time as much codeine was require ed of morphine.
From these results, it may be concluded that the Automatic Thermostinlulator devised in this experiment is simple, convenient and easy to handle and may be applied to evaluate analgesic effects of. morphine, codeine and other unknown analgesics. The adventages of this method are that it supplys a constant intensity of stimulus and repetition does not produce a noticeable injury,

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