MicroPET Detection of Regional Brain Activation Induced by Colonic Distention in a Rat Model of Visceral Hypersensitivity

Abstract

ABSTRACT. 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 TNBStreated 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 µg/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. KEY WORDS: brain activation, microPET, morphine, sensory cortex I, visceral hypersensitivity.The irritable bowel syndrome (IBS) is one of the most common disorders in gastroenterological practice [8,26]. IBS is clinically characterized by stressful abdominal pain or discomfort, and altered bowel habits [7,30]. Although the type and nature of altered bowel habits varies across the patients, abdominal pain has been demonstrated in the majority of patients suffering from IBS. Accumulated clinical data have shown that colonic sensory threshold to mechanical distention stimuli is markedly decreased in IBS patients [23,31,34], indicating a visceral hypersensitivity. Since alterations of the processing of sensory stimuli in the brain-gut axis are believed to play etiological or modulatory roles in the visceral hypersensitivity, the CNS sensation in IBS has been a focus of much attention [4][5][6]. Recent studies in humans employ non-invasive imaging technologies, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), to investigate the mechanisms and pathways involved in the CNS processing of sensory stimuli in normal and visceral pain states [2,18,29,34]. These studies have generally revealed that multiple brain structures, such as the insular and cingulate cortices, prefrontal cortex and thalamus, are activated to a greater extent during the colonic distention stimuli in IBS patients compared to the normal subjects [16,34]. The use of bioimaging technologies has been further applied to determine the CNS mechanisms and sites of action of new...

A selective, high affinity 5-HT2Breceptor antagonist inhibits visceral hypersensitivity in rats

“…Visceral hypersensitivity was induced by an injection of TNBS into the proximal colon, as previously described 25,26 . Rats were fasted overnight and then anaesthetized by intramuscular administration of ketamine (40 mg kg −1 ) and xylazine (6 mg kg −1 ).…”

18F-FDG PET/MRI Can Be Used to Identify Injured Peripheral Nerves in a Model of Neuropathic Pain

“…18 F-FDG is a well-established metabolic activity marker using PET and, by extension, can be considered a marker for increased neuronal activity in the setting of nerve injury and neuropathic pain. 18 F-FDG has already been used to study neuronal metabolic activity changes in the cerebrum (13)(14)(15) and specifically in relation to chronic pain (16). To our knowledge, this study was the first to address nociception-related 18 F-FDG uptake in peripheral nerves.…”

Application of microPET imaging approaches in the study of pediatric anesthetic‐induced neuronal toxicity

“…[ 18 F]‐FDG is the most widely used radiotracer for the assessment of glucose metabolism in the brain and other tissue and the uptake of [ 18 F]‐FDG by neurons can be used to evaluate neuronal metabolic activation (Chen et al ., ; Paul et al ., ; Ohashi et al ., ). Thus, microPET imaging of [ 18 F]‐FDG was employed to evaluate the effects of PND 7 ketamine exposure on the metabolic activity of the rat brain when assessed 4 weeks later on PND 35.…”