Molecular and behavioral changes in nociception in a novel rat model of chronic pancreatitis for the study of pain.
The approach to the management of painful chronic pancreatitis has been empirical, primarily due to the lack of information about biological mechanisms producing pain. To facilitate research into pain mechanisms, our aim was to assess a rat model of chronic pancreatitis induced by pancreatic infusion of trinitrobenzene sulfonic acid as a model of painful pancreatitis. Nociception was assessed by measuring mechanical sensitivity of the abdomen and by recording the number of nocifensive behaviors in response to electrical stimulation of the pancreas. Expression of neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) in the thoracic dorsal root ganglia receiving input from the pancreas and nerve growth factor (NGF) in the pancreas were measured. Rats with pancreatitis exhibited marked increase in sensitivity to mechanical probing of the abdomen and increased sensitivity to noxious electrical stimulation of the pancreas. There were significant increases in NGF protein in the pancreas and in expression of neuropeptides CGRP and SP in the sensory neurons from dorsal root ganglia receiving input from the pancreas. We have established quantitative measures of referred nociception and pancreatic hyperalgesia in a rat model of chronic pancreatitis that bears histological similarities to the human disease. This model has considerable construct, face and predictive validity for the human condition. It is of importance for the study of the pathogenesis of pain in this condition and can facilitate the development of new therapeutic options.
Winston
John H
JH
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The University of Texas Medical Branch, 4.106 McCullough Building, 301 University Boulevard, Galveston TX 77555-0764, USA.
He
Zhi-Jun
ZJ
Shenoy
Mohan
M
Xiao
Shu-Yuan
SY
Pasricha
Pankaj Jay
PJ
D000681:Amylases / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D010147:Pain Measurement / Q000379:methods; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D010812:Physical Stimulation / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013373:Substance P / Q000378:metabolism; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
D012333:RNA, Messenger; D013373:Substance P; D014302:Trinitrobenzenesulfonic Acid; D020932:Nerve Growth Factor; D000681:Amylases; D015740:Calcitonin Gene-Related Peptide