Abstract
Simple SummaryThe purpose of this review is to provide current data on the definition and types of pain, describe its neuropharmacological and pathological mechanisms, and present a comparative analysis of the results obtained after intracerebroventricular (ICV) infusion of voltage-gated calcium channel inhibitors (VGCCIs) such as diltiazem, nifedipine, and verapamil, cholecystokinin receptor antagonists (PD, proglumide), and glutamatergic receptor antagonists (L-AP3, DL-AP3) during experimental distension of the duodenal and/or descending colonic wall. This method was used as a model for suppressing pain in sheep based on viscero-visceral inhibitory reflex, measured by the inhibition of behavioral symptoms of stress, degree of reticulo-ruminal motility, and changes in plasma cortisol and catecholamine concentration. After ICV infusion, all tested substances suppressed, to varying degrees, the viscero-visceral inhibitory reflex, tachycardia, hyperventilation, bleating, and gnashing of the teeth, whereas they increased the levels of cortisol and plasma catecholamines in sheep. These substances could be potential non-narcotic agents for the treatment of visceral intestinal pain (intestinal colic) in sheep, but clinical confirmation of the substances’ efficacy for treating intestinal colic is needed.Relief from suffering is the guiding principle of medical and veterinary ethics. Medical care for animals should be carried out to meet all welfare conditions. The need for pain management is demonstrated by recent monographs devoting attention to this urgent ethical need. Little data, however, are available on the prevention and attenuation of pain in sheep. After administration of narcotic analgesics used for severe visceral pain, sheep react with a state of excitement. Therefore, it was decided to experimentally investigate the usefulness of potential non-narcotic drugs to relieve pain in sheep with intestinal colic caused by 10 min of mechanical distension of their duodenal and/or descending colonic wall. The results indicate the potential usefulness of VGCCIs (diltiazem, nifedipine, verapamil), cholecystokinin receptor antagonists (PD, proglumide), and metabotropic glutaminergic receptor antagonists (mGluRAs), such as L-AP3, DL-AP3. As a premedication, these substances prevented the occurrence of symptoms of acute intestinal pain including atony of reticulo-rumen, tachycardia, hyperventilation, moaning, gnashing of teeth, hypercortisolemia, and catecholaminemia; hence, these substances are considered potential agents in the treatment of sheep visceral pain.
Highlights
Since the earliest times, living organisms receive stimuli from their environment.Many of these stimuli are beneficial; some stimuli cause discomfort to individuals.These adverse stimuli usually cause discomfort of a painful, even damaging, and sometimes toxic nature
The aim of the study was a comparative analysis of the results obtained in our laboratory on the experimental search for alternative analgesics in sheep visceral/intestinal pain on a model of intestinal colic caused by mechanical distension of the duodenal wall (Figure 5)
The aim of this study was to determine the influence of 5 min mechanically induced duodenal distension (DD), proglumide, and PD 140.548 N-methyl-D-glucamine premedication on mechano-graphical, reticuloruminal activity, animal general behavior, CA, and the blood plasma cortisol levels, as well as the clinical symptoms of visceral pain induced by DD in sheep (30 males, 3–4 years of age) (Tables 4 and 5, Figures 6–15)
Summary
Since the earliest times, living organisms receive stimuli from their environment.Many of these stimuli are beneficial; some stimuli cause discomfort to individuals.These adverse stimuli usually cause discomfort of a painful (nociceptive), even damaging (noxa), and sometimes toxic nature. Since the earliest times, living organisms receive stimuli from their environment. Many of these stimuli are beneficial; some stimuli cause discomfort to individuals. These adverse stimuli usually cause discomfort of a painful (nociceptive), even damaging (noxa), and sometimes toxic nature. Organisms have to avoid or counter situations when the body’s homeostasis is disturbed by these adverse factors or painful stimuli [1], regardless of the nature of the stimulus (physical, chemical, or psychological) [2]. Homeostasis is restored in humans by neuroendocrine reactions or, when these are not sufficient, e.g., when the nociceptive factor exceeds the adaptability of organisms, by using substances that restore a sense of comfort. The same procedure applies to all vertebrate animals that react to humans
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