The mucosal potential elicited by noxious chemical stimuli with CO2 in rats: Is it a peripheral nociceptive event?

Thürauf, Norbert; Friedel, I; Hummel, Cornélia; Kobal, Gerd

doi:10.1016/0304-3940(91)90283-y

Cited by 102 publications

(69 citation statements)

References 9 publications

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“…CSSERP reflect changes in the perception of painful stimuli in a more specific manner [15,20]. That is, CSSERP reflect certain, limited aspects of the processing of nociceptive information in man and experimental animals [12,49]. On the other hand, it appears that CSSERP do not reflect pain-relief mediated by unspecific pathby imipramine.…”

Section: Discussionmentioning

confidence: 99%

“…To investigate its potential analgesic action in man we have used a technique involving measurement of chemo-somatosensory event-related potentials (CSSERP) after painful stimulation of the nasal mucosa with carbon dioxide [9]. These chemical stimuli are considered to be natural, specific stimuli for the excitation of the trigeminal nociceptive system [10][11][12][13]. The late nearfield event-related potentials [14] elicited in the EEG are highly correlated with subjective pain ratings [15].…”

Section: Introductionmentioning

confidence: 99%

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A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline [see comments]

Hummel

Friedel

et al. 1994

Brit J Clinical Pharma

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1 The pain relieving properties of imipramine (100 mg orally), tramadol (150 mg orally), and anpirtoline (60 mg orally) were compared in 16 healthy subjects in a cross-over, double-blind, randomized, and placebo-controlled study. Anpirtoline exhibits analgesia which is possibly mediated via serotoninergic pathways, whereas tramadol exerts its effects at opioid receptors. The pain-relieving effect of the tricyclic antidepressant imipramine may involve both serotoninergic and opioid mechanisms. 2 Chemo-somatosensory event-related potentials (CSSERP) were recorded after painful stimulation of the nasal mucosa with carbon dioxide. Subjects rated the perceived intensity of the stimuli by means of a visual analogue scale. In addition, acoustically evoked responses were recorded, the spontaneous EEG was analyzed in the frequency domain, the subjects' vigilance was assessed in a tracking task, and side effects of the drugs were monitored. 3 Anpirtoline and tramadol produced a decrease of both CSSERP amplitudes and subjective estimates of pain, the effects of the former compound being greater. In contrast, after administration of imipramine no change of CSSERP amplitudes could be detected, whereas the subjective estimate of pain intensity decreased significantly. This was accompanied by a significant decrease of arousal indicating that pain relief produced by acute administration of imipramine was primarily related to its sedation action.4 The analgesic properties of anpirtoline were demonstrated in man. Tramadol was characterized as a weak opioid analgesic. In contrast, imipramine appeared to produce its pain-relieving effects predominantly by non-specific actions. It is hypothesized that different analgesics may change ERP sources in a drug-specific manner.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline [see comments]

Hummel

Friedel

et al. 1994

Brit J Clinical Pharma

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“…The accumulation of CO 2 also causes acidification of nasal mucosa (Anton et al 1992, AVMA 2001. There is evidence that nonmyelinated nerve endings that sense chemicals (Thurauf et al 1991) and CO 2 -sensitive olfactory receptors are present in the nasal mucosa of mammals, including rats (Coates 2001) and humans (Alvaro et al 1993). The existence of these nerve endings and olfactory receptors indicate the ability to sense any pain that may be associated with CO 2 .…”

Section: Physiological Effects/actions Of Comentioning

confidence: 99%

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

et al. 2005

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SummaryCarbon dioxide (CO 2 ) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO 2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO 2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO 2 flow rate and final concentration, presence of oxygen, and prefilled chambers (the animal is added to the chamber once a predetermined concentration and flow rate have been reached) versus gradual induction (the animal is put into an empty chamber and the gas agent(s) is gradually introduced at a fixed rate). Internationally, animal research standards specify that any procedure that would cause pain or distress in humans should be assumed to do so in non-human animals as well (Public Health Service 1986, US Department of Agriculture 1997, Organization for Economic Cooperation and Development 2000). European Union guidelines, however, specify a certain threshold of pain or distress, such as 'skilled insertion of a hypodermic needle', as the starting point at which regulation of the use of animals in experimental or other scientific procedures begins (Biotechnology Regulatory Atlas n.d.). There is clear evidence in the human literature that CO 2 exposure is painful and distressful, while the non-human literature is equivocal. However, the fact that a number of studies do conclude that CO 2 causes pain and distress in animals indicates a need for careful reconsideration of its use. Finally, this review offers recommendations for alternatives to the use of CO 2 as a euthanasia agent.Keywords Carbon dioxide; euthanasia; pain; distress; anaesthesia; welfare; rodents Carbon dioxide (CO 2 ) is commonly used for euthanasia and anaesthesia of laboratory rodents, largely because of its ease of use, relative safety, and low cost, as well as its capacity to euthanize large numbers of animals in a short time span (Ambrose et al. 2000). In large institutions and those with significant rodent-breeding programmes, large numbers of rodents are often euthanized in a short time (Kline et al. 1963) and an appropriate gas agent is often the best way to approach such a challenge. However, CO 2 is not physiologically inert and the published evidence on whether or not CO 2 administration causes pain or distress in animals raises questions about its routine use. This paper reviews this published evidence and includes information on the effects of CO 2 in both humans and nonhumans. Methodological details are included when possible in order to provide a clear

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“…Theoretically, it could also represent axon reflexes of trigeminal stimulation. Subsequent work ruled out various epiphenomenal sources, such as blood flow, olfaction, and activity from sympathetic fibers [27][28][29]. The finding that the NMP correlates closely with feelings of irritation, expressed in ratings of magnitude, argues for a trigeminal source [27,30,31].…”

Section: Negative Mucosal Potential (Nmp)mentioning

confidence: 99%

Chemesthesis from volatile organic compounds: Psychophysical and neural responses

Cain

Lee

Wise

et al. 2006

Physiology & Behavior

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In Experiment 1, subjects sought to localize the nostril stimulated, left or right, in tests with nine esters (acetates, propionates, and butyrates) at concentrations meant to trigger chemesthesis (pungency, irritation). The task produced psychometric functions for chemesthetic detection unconfounded by olfactory sensations. The functions indicated a sharp transition from no detection to perfect detection, rather uniform across the esters, which themselves varied in potency by two log units. The correlation between the thresholds for the eight materials that yielded thresholds and predictions from a published linear free energy relationship (LFER) equaled 0.99. In Experiment 2, amplitude of the negative mucosal potential (NMP) was recorded from the septum. The resulting functions also increased with concentration sharply. Against a criterion amplitude of the NMP, thresholds measured in the first experiment (and predictions from the LFER) correlated 0.99. The NMP seems to offer an adequate objective measure of sensory irritation. The LFER, although effective predictively, could stand to have a parameter to anticipate that molecules beyond a certain size fail to trigger irritation. In the present case, a cut-off of chemesthetic potency occurred between butyl butyrate and hexyl butyrate for the group of subjects, with some variation of the boundary among individuals.

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The mucosal potential elicited by noxious chemical stimuli with CO2 in rats: Is it a peripheral nociceptive event?

Cited by 102 publications

References 9 publications

A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline [see comments]

A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline [see comments]

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

Chemesthesis from volatile organic compounds: Psychophysical and neural responses

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