Influence of centrally administered diltiazem on behavioural responses, clinical symptoms, reticulo-ruminal contractions and plasma catecholamine level after experimentally induced duodenal distension in sheep.
A different role of L-type antagonists for voltage-gated calcium channels (VGCC) has been previously identified in different types of experimental and clinical pain in man and animals. Present study examined the role of VGCC blocker - diltiazem administered icv (0.25, 0.5, 1.0 and/or 2.0mg in toto) on the development of pain related symptoms, clinical signs, plasma catecholamine level and the inhibition of reticulo-rumen motility caused by 5min lasting mechanical duodenum distension (DD) in the sheep. Experimental DD was conducted by insertion (during surgery) of rubber balloon into the duodenum and the distension by 40ml of warm water. Duodenal distension resulted in a significant increase of behavioural pain responses, tachycardia, hyperventilation, inhibition of reticulo-rumen contractions rate (from 85% to 45% during 15-20min), an increase of plasma catecholamine concentration (over sevenfold increase of epinephrine during 2h following DD, two-times norepinephrine and 84% increase of dopamine). Diltiazem infusion given 10min before DD decreased intensity of visceral nocifensive responses such as: behavioural changes, tachycardia, hyperventilation, reticulo-rumen motility and efficiently prevented appearance of catecholamine release. These data demonstrated that the development and persistence of acute duodenal pain depends on the activation of Ca(2+) ion flux leading to neurotransmitters release and modulation of membrane excitability. It seems that diltiazem given icv 10min prior to DD (as a source of acute visceral pain), inhibited specific receptors α(1) subunits of VGCCs in target tissues, prevent depolarization of cell membranes and release of neurotransmitters responsible for pain sensitivity in sheep. The observed antinociceptive action of VGCCs type-L blockers suggests that these channels play a crucial role in the modulation of acute visceral pain in sheep.
Kania
B F
BF
Experimental and Clinical Physio-Pharmacological Laboratory, Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland. bogdan_kania@sggw.pl
Sutiak
V
V
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002395:Catecholamines / Q000097:blood*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000502:physiology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D057967:Infusions, Intraventricular; D010146:Pain / Q000188:drug therapy / Q000662:veterinary; D012756:Sheep / Q000097:blood / Q000378:metabolism*
D002121:Calcium Channel Blockers; D002395:Catecholamines; D004110:Diltiazem