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The inhibition of experimentally induced visceral hyperalgesia by nifedipine - a voltage-gated Ca(2+) channels blocker (VGCCs) in sheep |
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| Authors: | Kania B F Kowalczyk M Brytan M Tomaszewska D Przekop F |
| Institution: | a Department of Physiological Sciences, Veterinary Medicine Faculty, Experimental and Clinical Physio-Pharmacological Laboratory, Agricultural University of Warsaw, Nowoursynowska 159, 02-776 Warsaw, Poland b Department of Pharmacology and Toxicology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland c Department of Neurophysiology, Institute of Physiology and Animal Feeding, Polish Academy of Sciences in Jablonna, n/Warsaw, Poland |
| Abstract: | Present study examined the effect of VGCC L-type blocker - nifedipine given i.c.v. (0.25, 0.5, 1 and/or 2 mg in toto) on the development of nociceptive behavior, clinical symptoms, plasma catecholamin concentration and reticulo-rumen motility following 5 min lasting mechanical duodenal distension (DD) in sheep. After 24 h of fasting, all animals received i.m. ketamine analgesia (20 mg kg−1 B.W) and anesthetized with pentobarbital (20 mg kg−1 B.W., i.v. infusion) The permanent stainless steel cannula 29 mm in length and 2 mm in diameter was inserted into the lateral cerebral ventricle (controlled by cerebro-spinal efflux) 10 mm above the bregma and 5 mm laterally from the midline sutures using stereotaxic method.Under the same general anesthesia/analgesia a T-shaped silicon cannula (inside diameter of 21 mm), was inserted into the duodenum (12 cm from pylorus). Second identical cannule was inserted into the dorsal sac of the rumen, a previously described. After surgery each animal was kept in individual boxes for 10 days prior to experiment and was treated i.m. with benzyl procaine penicillin 30,000 I.U kg−1 B.W.) + dihydrostreptomycine sulfate (10 g kg−1 B.W.) + prednisolone acetate (1.2 mg kg−1 B.W.) combination and i.m. ketamine (20 mg kg−1 B.W.) every day by seven consecutive days.Experimental DD was conducted by insertion and then distension of rubber balloon (containing 40 ml of warm water) inserted into sheep duodenum. Duodenal distension produced a significant increase in behavioral pain manifestations, tachycardia, hyperventilation, inhibition of reticulo-ruminal contractions rate (from 87.2 to 38.0% during 15-20 min), an increase of plasma catecholamine concentration (over 6.4-fold increase of epinephrine during 2 h following DD, 2-times norepinephrine and 84% increase of dopamine). Nifedipine infusion administered 10 min prior to DD decreased intensity of visceral pain manifestations such as: behavioral changes, hyperventilation, reticulo-rumen motility and efficiently prevent appearance of catecholamine release. These data demonstrated that the development and persistence of duodenal hyperalgesia depends on the activation of Ca2+ ion flux leading to neurotransmitters release and modulation of membrane excitability. It seems that nifedipine given i.c.v. 10 min prior to DD (as a source of visceral pain), inhibited specific receptors 1 subunits of VGCCs in target tissues, prevented depolarization of cell membranes and release of neurotransmitters responsible for pain sensitivity in sheep. The observed antinociceptive action of VGCCs type L blockers suggest that these channels play a crucial role in the modulation of acute visceral hyperalgesia in sheep. |
| Keywords: | Duodenal distension Central effects of nifedipine Behavioral changes Cortisol and catecholamine changes in the blood plasma |
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