Assessment of the hot-plate antinociceptive test in mice A new method for the statistical treatment of graded data

doi:10.1016/0160-5402(85)90063-4

Journal of Pharmacological Methods

Volume 13, Issue 1, February 1985, Pages 1-7

https://doi.org/10.1016/0160-5402(85)90063-4 Get rights and content

Abstract

The use of graded data from hot-plate antinociceptive tests is complicated by the problem of how to treat responses that are greater than the cut-off time. This paper describes a statistical procedure for analysis of antinociceptive data that circumvents this problem. The method is based upon the likelihood function and the data is assumed to follow a Weibull distribution. The technique can be implemented with the use of a computer and provides a more comprehensive assessment of antinociceptive data.

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Cited by (18)

Ejaculation induced changes in escape latency in the hot plate test: Pharmacological analysis of anxiolytic versus analgesic effect
1994, Behavioural Brain Research
The possible changes in nociception at various stages of male sexual behaviour were explored in the hot plate test. Although other authors have reported an antinociceptive effect of mating, we failed to find this effect on the hot plate test after several sexual behaviour events. To further explore the possible antinociceptive action of copulation we administered a suboptimal analgesic dose of morphine (0.3 mg/kg i.p.). No change in nociception were observed in animals treated with a subthreshold dose of morphine and tested in the nociception test after ejaculation were observed. Since previous reports have refered that ejaculation produces hypoalgesia when measured in the hot plate test, we attempted to replicate these findings. We found that one ejaculation produces an increase in the latency to escape in male rats previously habituated to the hot plate test. These results suggest a hypoalgesic effect. However, such changes could also be interpreted as alterations in the animals emotionality. Thus, a group of habituated animals was tested on the switched off plate. An important increase in the escape latency behaviour after ejaculation was observed, while no differences between control animals, without sexual behaviour display, tested on switched on and switched off plate were observed. The participation of the benzodiazepine and opiod systems in the ejaculation effect on the switched off plate was explored. A similar increase in escape latency to that induced by ejaculation was caused by diazepam (1.0 and 2.0 mg/kg). The increase in escape latency induced by ejaculation was prevented by the benzodiazepine antagonist, flumazenil (20.0 mg/kg). Conversely, the opiate antagonist, naloxone (1.0 mg/kg), was unable to reverse the increase in escape latency provoked by ejaculation. Morphine (0.5 mg/kg) did not elicit an increase in the escape latency behaviour. All data support the idea that the hot plate test might reveal false data respect a putative algesic change after ejaculation in male rats.
High-intensity nociceptive stimuli minimize behavioral effects induced by restraining stress during the tail-flick test
1992, Journal of Pharmacological and Toxicological Methods
Analgesia following exposure to various stressors is a well-documented phenomenon. Restraint of an animal during the tail-flick test (TFT) represents a potent stressor that can induce both altered baseline latencies and enhanced response to opioids. The present study shows that the use of higher stimulus intensities during TFT minimizes the stress influences produced by restraint on the animal's response rendering the test more sensitive to the pharmacological action of analgesic drugs.
A nonparametric method for evaluating results from laboratory antinociceptive tests
1988, Journal of Pharmacological Methods
A method is presented in which Cox's proportional hazards model, a survival analysis technique, is used to assess the results of hot-plate antinociceptive testing. The method appropriately handles censored data values and variable pretest latency times without making arbitrary assumptions about the distribution of the data. It may be used to characterize and compare dose-response curves or to examine the effect of agent or other treatment variables on the response. The technique is easily implemented using the SAS statistical software package.
Due to the similar way in which data is obtained, we believe the method to be applicable to several other laboratory models of pain, including the tail-flick, tailimmersion, and paw-pressure (Randall-Selitto) assays.
Interactions between anticholinesterase poisoning and opioid analgesia and locomotion in mice
1988, Neurotoxicology and Teratology
Interactions between anticholinesterases and opioid drugs on antinociception and locomotor behaviour have been studied in the mouse. The anticholinesterases di-isopropylfluorophosphate (DFP) (1 mg/kg), pyridostigmine (1 mg/kg) and neostigmine (200 μg/kg) or drugs used to treat anticholinesterase poisoning (atropine, pralidoxime and diazepam) were not antinociceptive. DFP, at doses which produced marked neurotoxicity (2 mg/kg), produced antinociception which was not mediated by opioid receptors. The antinociceptive effects of alfentanil, but not fentanyl or morphine, were potentiated by DFP, whereas pyridostigmine and neostigmine were without effect. The potentiating activity of DFP was unaffected by atropine, pralidoxime and diazepam. DFP (1 mg/kg) produced a small degree of hypolocomotion whilst atropine and pralidoxime produced marked hyperlocomotion. Diazepam alone and with DFP, atropine, pralidoxime or opioid drugs produced marked motor incapacitation. Hyperlocomotion induced by morphine and alfentanil was reduced by DFP but fentanyl hyperlocomotion was unaffected. Treatment of DFP toxicity with atropine and pralidoxime reversed the effects on alfentanil locomotion but failed to alter DFP's action upon morphine or fentanyl locomotion. Atropine and pralidoxime treatment alone did not affect fentanyl hyperlocomotion, attenuated alfentanil hyperlocomotion and produced marked hypolocomotion in morphine-treated mice. Opioids and anticholinesterases do not exhibit common interactions and their effects are dependent on both opioid, anticholinesterase and the behaviour studied.
Attenuation of morphine-induced analgesia in mice by exposure to magnetic resonance imaging: Separate effects of the static, radiofrequency and time-varying magnetic fields
1987, Magnetic Resonance Imaging
Exposure of adult male mice to a magnetic resonance imaging (MRI) procedure has been shown to abolish the nocturnal analgesic responses observed following treatment with morphine. The field component(s) responsible for this inhibitory effect were examined by exposing mice to either the static, time-varying or rf magnetic field components associated with an MRI procedure. In the middle of the night portion of their day-night cycle, mice were exposed for 23.2 min to one of the above field components, intraperitoneally injected with morphine sulphate (10 mg/kg) and then exposed to the field conditions for another 23.2 min, after which analgesic responses were determined. Analgesia was quantitated by determining the length of time mice were content to be on a hot surface (50°C) before they showed discomfort by licking their paws. It was observed that the time-varying magnetic field completely abolished, the rf field significantly reduced, while the static field component (0.15 T) had no evident effect on morphine-induced analgesia. These results indicate that the time-varying, and to a lesser extent the rf, fields associated with the MRI procedure inhibit morphine-induced analgesia in mice. These data also raise the possibility that exposure in humans to some of the magnetic field components associated with MRI may have clinically relevant effects on the actions of narcotic drugs such as morphine.
A modified hot-plate test sensitivie to mild analgesics
1986, Behavioural Brain Research
The present study compares a modified hot-plate test in which the temperature is slowly increased from non-noxious levels with a standard constant temperature hot-plate test. In both tests, hindpaw lick was found to be a more reliable criterion response than forepaw lick, and was employed throughout the experiments. In the constant temperature hot-plate test, 1-min exposure to the test apparatus the day before testing significantly reduced the response latencies of both rats and mice. No effect of pre-exposure was found in the increasing temperature test. In both tests and in both species, sessions of repeated testing were conducted with only insignificant alterations in responsiveness between trials. In both rats and mice, dose-related increases in response temperature were obtained in the increasing temperature hot-plate test after administration of morphine, paracetamol and acetylsalicylic acid, whereas only morphine had consistent effects in the constant temperature test. Thus, the increasing temperature hot-plate is a useful analgesimetric test in both rats and mice, superior to the conventional hot-plate test with regard to consistency of results and sensitivity to non-narcotic analgesics.

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View full text

Assessment of the hot-plate antinociceptive test in mice A new method for the statistical treatment of graded data

Abstract

Pharmacol Biochem Behav

Eur J Pharmacol

Theoretical Statistics

A rapidly convergent descent method for minimization

Computer Journal

Comparison of the antinociceptive effect of γ aminobutyric acid (GABA) agonists: evidence for a cholinergic involvement

J Pharmacol exp Therap

Differential effects of diisopropylfluorophosphate poisoning and its treatment on opioid antinociception in the mouse

Life Sci