MicroPET detection of regional brain activation induced by colonic distention in a rat model of visceral hypersensitivity.
Using microPET and (18)F-fluorodeoxyglucose ((18)F-FDG) as a tracer, we investigated regional brain activation in a rat model of visceral hypersensitivity induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS injection into the proximal colon through laparotomy resulted in a significant, sustained decrease in the pain threshold to mechanical distention of the distal colon, indicating a phenomenon referred to as visceral hypersensitivity. When TNBS-induced colonic hypersensitivity was fully developed, all the TNBS-treated rats presented characteristic pain behaviors in response to colonic distention at previously innocuous pressure (0-35 mmHg) that produced no abdominal pain in sham-operated control animals. In microPET study, colonic distention at the normally non-painful pressure produced significant increases in (18)F-FDG uptake in the thalamus and sensory cortex I of TNBS-treated rats. Since the increases in (18)F-FDG uptake in the brain regions were completely abolished by an analgesic dose of morphine (375 microg/kg, s.c.), it is most likely that the regional brain activation detected by microPET is a pain-related central event. The pharmacological and microPET data indicate that colonic distention at the normally non-painful pressure activates specific brain regions in rats with TNBS-induced visceral hypersensitivity, and the microPET protocol described here could provide an objective measure to test visceral analgesic compounds.
Ohashi
Katsuyo
K
Discovery Research, Pfizer Global Research and Development, Nagoya Laboratories, Aichi, Japan.
Ichikawa
Katsuomi
K
Chen
Laigao
L
Callahan
Michael
M
Zasadny
Kenneth
K
Kurebayashi
Yoichi
Y
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000502:physiology*; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D009020:Morphine; D014302:Trinitrobenzenesulfonic Acid