Restoration of spontaneous exploratory behaviors with an intrathecal NMDA receptor antagonist or a PKC inhibitor in rats with acute pancreatitis.
The aim of this study was to determine the influence of a glutamate receptor antagonist or a protein kinase C (PKC) inhibitor on the central visceral nociceptive amplification process present in an experimental pancreatitis model. The acute pancreatitis model was produced by combining intraductal infusion of an irritative bile salt, glycodeoxycholic acid (GDOC), with intraperitoneal injection of a CCK analogue, caerulein, in male Sprague-Dawley rats. Exploratory activities were measured with an automated photobeam activity system and compared among different treatment groups. To confirm the inflammation, the pancreas was weighed and compared histologically with those taken from naive rats. Exploratory activity changed significantly in rats with experimental pancreatitis (i.e., rearing events, rearing time, active time, distance traveled, and total activity all were decreased; whereas resting time was increased). The inflamed pancreatic tissues were edematous, with moderate to marked acinar atrophy and inflammatory infiltrate. Intrathecal administration (at the T7-T9 spinal levels) of an NMDA receptor antagonist (D-AP5, 1 microg) or a selective PKC inhibitor (GF109203X, 0.15 microg) significantly reversed the changes in exploratory activity when compared with the vehicle-treated group of rats with experimental pancreatitis. Our results demonstrate that pancreatitis pain is the result of central pain processes that play a role in the amplification of responses to peripheral visceral input through NMDA receptor activation and PKC phosphorylation signaling pathways.
Zhang
Liping
L
Department Anatomy and Neurosciences, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1043, USA.
Zhang
Xuan
X
Westlund
Karin N
KN
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D007278:Injections, Spinal; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy* / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C056639:2-amino-5-phosphopentanoic acid; D011493:Protein Kinase C; D014633:Valine