screening
In vivo methods for testing central analgesic activity
H.1.2.1
General considerations
Although the in vivo methods have been used more extensively in the past, they are still necessary in present research analgesic tests in animals before a compound can be given to man. Mostly, rodents, such as mice or rats, are used for analgesic tests, but in some instances experiments in higher animals such as monkeys are necessary.
Several methods are available for testing central analgesic activity, such as
• HAFFNER’s tail clip method in mice,
• tail flick or other radiant heat methods,
• tail immersion tests,
• hot plate methods in mice or rats,
• electrical stimulation (grid shock, stimulation of tooth pulp or tail),
• monkey shock titration,
• formalin test in rats.
H.1.2.2
HAFFNER’s tail clip method
PURPOSE AND RATIONALE
The method was described as early as 1929 by Haffner who observed the raised tail (Straub phenomenon) in mice treated with morphine or similar opioid drugs and found the tail after drug treatment to be less sensitive to noxious stimuli. He already described the high sensitivity of this method to morphine. Since then, the method has been used and modified by many authors.
PROCEDURE
An artery clip is applied to the root of the tail of mice and the reaction time is noted. Male mice (Charles River strain or other strains) with a weight between 18 and 25 g are used. The control group consists of 10 mice.
The test compounds are administered subcutaneously to fed mice or orally to fasted animals. The test groups and the control group consist of 7–10 mice. The drug is administered 15, 30 or 60 min prior testing. An artery clip is applied to the root of the tail (approximately
1 cm from the body) to induce pain. The animal quickly responds to this noxious stimuli by biting the clip or the tail near the location of the clip. The time between stimulation onset and response is measured by a stopwatch in 1/10 seconds increments.
EVALUATION
A
H.1.2.1
General considerations
Although the in vivo methods have been used more extensively in the past, they are still necessary in present research analgesic tests in animals before a compound can be given to man. Mostly, rodents, such as mice or rats, are used for analgesic tests, but in some instances experiments in higher animals such as monkeys are necessary.
Several methods are available for testing central analgesic activity, such as
• HAFFNER’s tail clip method in mice,
• tail flick or other radiant heat methods,
• tail immersion tests,
• hot plate methods in mice or rats,
• electrical stimulation (grid shock, stimulation of tooth pulp or tail),
• monkey shock titration,
• formalin test in rats.
H.1.2.2
HAFFNER’s tail clip method
PURPOSE AND RATIONALE
The method was described as early as 1929 by Haffner who observed the raised tail (Straub phenomenon) in mice treated with morphine or similar opioid drugs and found the tail after drug treatment to be less sensitive to noxious stimuli. He already described the high sensitivity of this method to morphine. Since then, the method has been used and modified by many authors.
PROCEDURE
An artery clip is applied to the root of the tail of mice and the reaction time is noted. Male mice (Charles River strain or other strains) with a weight between 18 and 25 g are used. The control group consists of 10 mice.
The test compounds are administered subcutaneously to fed mice or orally to fasted animals. The test groups and the control group consist of 7–10 mice. The drug is administered 15, 30 or 60 min prior testing. An artery clip is applied to the root of the tail (approximately
1 cm from the body) to induce pain. The animal quickly responds to this noxious stimuli by biting the clip or the tail near the location of the clip. The time between stimulation onset and response is measured by a stopwatch in 1/10 seconds increments.
EVALUATION
A