MicroPET detection of regional brain activation induced by colonic distention in a rat model of visceral hypersensitivity
2008
Ohashi, K.(Pfizer Gｌobal Research and Development, Nagoya (Japan). Nagoya Labs.) | Ichikawa, K. | Chen, L. | Callahan, M. | Zasadny, K. | Kurebayashi, Y.
Using microPET and sup(18)F-fluorodeoxyglucose (sup(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 sup(18)F-FDG uptake in the thalamus and sensory cortex I of TNBS-treated rats. Since the increases in sup(18)F-FDG uptake in the brain regions were completely abolished by an analgesic dose of morphine (375 micro g/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.
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