Research paperAcetylsalicylic acid-induced changes in the chemical coding of extrinsic sensory neurons supplying the prepyloric area of the porcine stomach
Introduction
Acetylsalicylic acid (ASA), also known as aspirin, is a very popular antipyretic, anti-inflammatory and analgesic drug, which has been known since the end of the 19th century [1]. The mechanism of action of ASA is based on inactivation of the cyclooxygenase (COX) enzyme, which takes part in the synthesis of prostaglandins, prostacyclin, as well as thromboxane A. It is known that there are three isoforms of cyclooxygenase: COX-1, which is present in the large number of cells in various tissues such as the mucosal layer of the digestive tract, kidneys, endothelium of blood vessels or thrombocytes; COX-2, which is induced by inflammatory processes and COX-3 (variant of COX-1)—described in some species (dogs) within the central nervous system [1], [2]. The action of aspirin, consisting of acetylation of the active site of above-mentioned enzyme, causes complete and irreversible inactivation of COX-1 and significant changes in the functioning of COX-2 [1], [2]. Unfortunately, this action not only determines the widespread therapeutic use of ASA, but is also the cause of a wide range of undesirable actions of this drug, which are clearly visible especially within the stomach [3]. Previous studies show that even a single dose of aspirin may result in damage to the gastric mucosa. This damage is superficial and minor, but during long-term treatment with ASA, pathological changes in the gastric mucosa can increase due to a disturbance in mucus secretion, connected with inhibition of COX-1 [3], [4].
Although the various mechanisms of action of ASA have become better known, the influence of this drug on the nervous system supplying the digestive tract still remains unclear [5]. The stomach, where the negative action of aspirin on the living organism is relatively well established [3], is innervated by both the enteric nervous system and extrinsic nerves. The former is located within the wall of the stomach and consists of two kinds of enteric ganglia: myenteric ganglia located between the longitudinal and circular muscle layers and submucous ganglia near the lamina propria of gastric mucosa [6], [7]. Neurons supplying the stomach are also located within the vagal nuclei, dorsal root ganglia and celiac ganglia [5], [8], [9], [10], [11]. It is well-known that both the enteric nervous system as well as extrinsic innervation of the gastrointestinal tract are able to undergo structural, functional or chemical changes as a result of adaptive or reparative processes in response to physiological and pathological stimuli, such as development or aging, diet, drugs, nerve injury or intestinal and extra-intestinal diseases [12], [13], [14]. Contrary to intestinal enteric neurons, where the influences of various pathological stimuli on the expression of active substances are relatively well-known [15], [16], [17], knowledge of changes in extrinsic gastric and intestinal innervation is rather scanty [8], [9]. Therefore, the aim of the present study was to investigate, for the first time, the possible changes of the number of neurons expressing selected active substances in extrinsic sensory neurons supplying the porcine stomach located in nodose ganglia and thoracic dorsal root ganglia following the long-term administration of aspirin. This study seems to be especially justified due to the worldwide use of acetylsalicylic acid as a medicine.
It should be pointed out that selection of the pig as an experimental animal during this study is not accidental. This species, in view of previous investigations, seems to be the optimal animal model of various pathological mechanisms in humans due to many well-known similarities in anatomical, histological, biochemical and physiological properties between humans and pigs [18], [19].
Section snippets
Materials and methods
The study was performed on eight immature female pigs of the Large White Polish breed (approximately 8 weeks old, about 20 kg b.w). The animals were kept in standard laboratory conditions with access to species-specific feed and water ad libitum. All surgical operations were performed in compliance with the instructions of the Local Ethical Committee in Olsztyn (Poland), (decision number 05/2010). All pigs were subjected to general anesthesia using azaperone (Stresnil, Janssen Pharmaceutica
Results
The majority of the FB-positive neurons were found within nodose ganglia. Their average number in control animals amounted to 144.75 ± 19.77 and 180 ± 23.33 in right and left ganglion, respectively. The number of the FB+ neuronal cells in DRG, which were observed within neuromers Th3-Th8, was smaller and, under physiological conditions, amounted to 51 and 61 within right and left ganglia, respectively (the total number of neurons of all experimental animals). After ASA administration, the number of
Discussion
During the present study, sensory neurons supplying the prepyloric region of the porcine stomach were found in both nodose ganglia as well as within thoracic dorsal root ganglia, which is in agreement with previous studies which found that neuronal cells in NG supply various parts of the gastrointestinal tract from the esophagus to the descending colon [21], [22] and neurons in thoracic and lumbar DRG receive input from different regions of the stomach and intestine [21], [23], [24].
The
Acknowledgements
This study was supported by the Polish State Committee for Scientific Research number 1890/B/P01/2010/39 and the University of Warmia and Mazury in Olsztyn (statutory research) grant No. 15.610.003-300
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