Descending facilitation from the rostral ventromedial medulla maintains visceral pain in rats with experimental pancreatitis.
OBJECTIVE
Pain is a main complaint of patients with pancreatitis. We hypothesized that such pain is mediated through ascending pathways via the nucleus gracilis (NG) and is dependent on descending facilitatory influences from the rostral ventromedial medulla (RVM).


METHODS
A rat model of persistent experimental pancreatitis was used. After establishment of pancreatitis, rats received microinjection of lidocaine in the NG or in the RVM to determine the importance of neural activity at these supraspinal sites in the expression of abdominal hypersensitivity evoked by von Frey filaments (ie, pancreatic pain). Rats also were pretreated for 28 days before induction of pancreatitis with a single RVM microinjection of dermorphin-saporin to eliminate cells that drive descending facilitation. Dynorphin content was measured in the spinal cord of pancreatitic rats and the effects of spinal antidynorphin antiserum in pancreatic pain were assessed.


RESULTS
Microinjection of lidocaine into either the NG or the RVM produced a time-related reversal of pancreatitis-induced pain. Pancreatitis significantly increased thoracic spinal dynorphin content and spinal antidynorphin antiserum elicited a time-related reversal of abdominal hypersensitivity. RVM dermorphin-saporin injection prevented the maintenance, but not the expression, of pancreatitis abdominal hypersensitivity and also prevented the increase of spinal dynorphin content in animals with pancreatitis.


CONCLUSIONS
Our findings suggest that descending facilitation from the RVM plays a critical role in the maintenance, but not the expression, of pancreatic pain. These results provide a novel insight into the role of descending pathways and spinal plasticity in the maintenance of visceral pain from pancreatitis.
Vera-Portocarrero
Louis P
LP
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona 85724, USA.
Xie
Jennifer Y
JY
Yie
Jennifer X
JX
Kowal
Justin
J
Ossipov
Michael H
MH
King
Tamara
T
Porreca
Frank
F
D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D004347:Drug Interactions; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism / Q000494:pharmacology*; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology*; D010147:Pain Measurement; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010195:Pancreatitis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012720:Severity of Illness Index; D013127:Spinal Nerves / Q000187:drug effects
D018847:Opioid Peptides; D054789:Ribosome Inactivating Proteins, Type 1; C431163:dermorphin-saporin; D008012:Lidocaine; D009699:N-Glycosyl Hydrolases; D000076985:Saporins