Regional activation in the rat brain during visceral stimulation detected by c‐<i>fos</i> expression and fMRI

Lazović, Jelena; Wrzos, Helena; Yang, Qing; Collins, Christopher M.; Smith, Michael B.; Norgren, Ralph; Mátyás, K; Ouyang, Ann

doi:10.1111/j.1365-2982.2005.00655.x

Cited by 38 publications

(43 citation statements)

References 41 publications

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“…This finding is in general agreement with that of a recent fMRI study [17], in which the colonic pain threshold and regional cerebral activation were determined using non-sensitized, normal rats under anesthesia. In the fMRI study, distention at 40 mmHg produced no cerebral activation, while significant activation in many brain structures was observed following distention stimuli of 60 mmHg and greater.…”

Section: Sensory Cortex Isupporting

confidence: 82%

“…Recent imaging studies of visceral pain have generally demonstrated that these pain loci are also important in the CNS processing of visceral sensation in IBS patients [2,18,29,34] which is consistent with the present observations. A previous fMRI study [17] using non-sensitized, normal rats has shown that the amygdala, hypothalamus, thalamus, cerebellum and hippocampus were significantly activated by relatively higher colonic balloon distention, i.e., 60 mmHg and above, under anesthesia. Differences between the previous fMRI study and our microPET study could be attributed to the fact that non-painful low pressure distention was used in this study, to differences in detection sensitivities between fMRI and microPET technologies, or to differences in the timing of the measurements.…”

Section: Sensory Cortex Imentioning

confidence: 99%

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

Ohashi

Ichikawa

Chen

et al. 2008

The Journal of Veterinary Medical Science

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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...

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Section: Sensory Cortex Isupporting

confidence: 82%

Section: Sensory Cortex Imentioning

confidence: 99%

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

Ohashi

Ichikawa

Chen

et al. 2008

The Journal of Veterinary Medical Science

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“…Prior studies in rats have shown activation of the amygdala by CRD, as measured by increases in c-fos expression [38,49,67] or fMRI activation [38], while others have reported no difference between CRD and sham distention [43]. In healthy human subjects, amygdala activation has been reported in response to gastric dis-tension [42], whereas decrease in activation has been reported in response to CRD (at least in female subjects) [5,11,52,63], though these studies have not provided information on subnuclei.…”

Section: Discussionmentioning

confidence: 98%

“…Other region-specific analysis of neuronal responses to CRD has been carried out using in vivo electrophysiological recording technique [1,22]. Lazovic et al conducted the only reported fMRI study in the rat CRD model [38]. However, the use of sedated animals complicated data interpretation.…”

Section: Introductionmentioning

confidence: 99%

Regional brain activation in conscious, nonrestrained rats in response to noxious visceral stimulation

Wang

Bradesi

Maarek³

et al. 2008

Pain

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Preclinical drug development for visceral pain has largely relied on quantifying pseudoaffective responses to colorectal distension (CRD) in restrained rodents. However, the predictive value of changes in simple reflex responses in rodents for the complex human pain experience is not known. Male rats were implanted with venous cannulas and with telemetry transmitters for abdominal electromyographic (EMG) recordings. [ 14 C]-iodoantipyrine was injected during noxious CRD (60 mmHg) in the awake, nonrestrained animal. Regional cerebral blood flow (rCBF)-related tissue radioactivity was quantified by autoradiography and analyzed in the threedimensionally reconstructed brain by statistical parametric mapping. 60-mmHg CRD, compared with controls (0 mmHg) evoked significant increases in EMG activity (267 ± 24% vs. 103 ± 8%), as well as in behavioral pain score (77 ± 6% vs. 3 ± 3%). CRD elicited significant increases in rCBF as expected in sensory (insula, somatosensory cortex), and limbic and paralimbic regions (including anterior cingulate cortex and amygdala). Significant decreases in rCBF were seen in the thalamus, parabrachial nucleus, periaqueductal gray, hypothalamus and pons. Correlations of rCBF with EMG and with behavioral pain score were noted in the cingulate, insula, lateral amygdala, dorsal striatum, somatosensory and motor regions. Our findings support the validity of measurements of cerebral perfusion during CRD in the freely moving rat as a model of functional brain changes in human visceral pain. However, not all regions demonstrating significant group differences correlated with EMG or behavioral measures. This suggests that functional brain imaging captures more extensive responses of the central nervous system to noxious visceral distension than those identified by traditional measures.

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“…The retrosplenial and perirhinal cortices activated and deactivated in this study, respectively. Both structures are known to participate in emotional processing of nociceptive stimuli (Lazovic et al, 2005).…”

Section: Cortical Regionsmentioning

confidence: 99%

CNS activation maps in awake rats exposed to thermal stimuli to the dorsum of the hindpaw

et al. 2011

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Regional activation in the rat brain during visceral stimulation detected by c‐fos expression and fMRI

Abstract: The two methods are not interchangeable but appeared to be complementary: fMRI was more sensitive, whereas c-fos had much greater resolution.

Cited by 38 publications

References 41 publications

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

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

Regional brain activation in conscious, nonrestrained rats in response to noxious visceral stimulation

CNS activation maps in awake rats exposed to thermal stimuli to the dorsum of the hindpaw

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