Abstract
Despite the availability of the current drug arsenal for pain management, there is still a clinical need to identify new, more effective, and safer analgesics. Based on our earlier study, newly synthesized 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone, especially 10b and 13b, seem to be promising as potential analgesics. The current study was designed to investigate whether novel derivatives attenuate nociceptive response in animals subjected to thermal or chemical noxious stimulus, and to compare this effect to reference drugs. The antinociceptive effect of novel compounds was studied using the tail-flick and formalin test. Pretreatment with novel compounds at all studied doses increased the latency time in the tail-flick test and decreased the licking time during the early phase of the formalin test. New derivatives given at the medium and high doses also reduced the late phase of the formalin test. The achieved results indicate that new derivatives dose-dependently attenuate nociceptive response in both models of pain and exert a lack of gastrotoxicity. Both studied compounds act more efficiently than indomethacin, but not morphine. Compound 13b at the high dose exerts the greatest antinociceptive effect. It may be due to the reduction of nociceptor sensitization via prostaglandin E2 and myeloperoxidase levels decrease.
Highlights
The primary function of pain is its warning and protective role
Stomach specimens demonstrating macroscopic injury of the greater extent collected from each mouse pretreated with studied compound or reference drug, or equivalent stomach specimens from control mice, were selected for the histological assessment
Selected specimens were fixed in 4% buffered formalin, embedded in paraffin, and cut into 4 μm-thick slices, which were mounted on the glass slides and stained by the routine hematoxylin-eosin (H&E) method
Summary
The primary function of pain is its warning and protective role. It forewarns about threatening tissue damage due to injury or disease and triggers the organism’s reflex and behavioral response to minimize the effects of this damage [1]. The importance of such behaviors is well illustrated in the pathological cases of congenital insensitivity to painful stimuli, in which natural experiences can have disastrous consequences [2]. Appropriate analgesic management, as well as natural.
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