Differential induction of c-fos expression in brain nuclei by noxious and non-noxious colonic distension:

Mönnikes, Hubert; Rüter, Jens; König, Matthias; Grote, Christoph; Kobelt, Peter; Klapp, Burghard F.; Arnold, R.; Wiedenmann, Bertram; Tebbe, Johannes J.

doi:10.1016/s0006-8993(02)04197-5

Cited by 73 publications

(55 citation statements)

References 68 publications

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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: 99%

“…Research on brain responses to visceral stimuli in animals has relied predominantly on measuring c-fos expression [43,49,64,67]. Unlike human studies, c-fos studies typically require prolonged exposure of the animal to high-intensity visceral stimuli, which may lead to the integration of a variety of nonspecific stimuli over the duration of pain exposure, including acute sensitization of the visceral afferent system.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…CRD stimulations of 60 and 80 mmHg did not induce a significant change in the HR and cardiac sympathetic nerve activity in these animals, suggesting that the reflex center that mediates CRD-induced bradycardia is supraspinal in its location. Recent evidence showed that there was an increase in c-fos-like immunoreactive neurons in the nucleus of the tractus solitarius and the rostral ventrolateral medulla in the brainstem in response to colonic distension [14]. Thus these supraspinal regions may act as the reflex center for CRD-induced bradycardia.…”

Section: Resultsmentioning

confidence: 99%

Reflex Inhibition of Heart Rate and Efferent Cardiac Sympathetic Outflow Induced by Colorectal Distension in Anesthetized Rats

Suzuki²

2006

J. Physiol. Sci

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Colorectal distensions of 60 and 80 mmHg significantly reduced heart rate (HR) and cardiac sympathetic nerve activity in anesthetized rats. This bradycardiac response was not influenced by the intravenous administration of atropine, but was abolished by propranolol, suggesting that it was elicited by sympathetic but not vagal efferent nerves.Key words: colorectal distension, heart rate, cardiac sympathetic nerve activity.It has been reported that cardiovascular function is reflexively regulated by visceral noxious stimulation, such as distension of stomach [1], colorectum [2], biliary system [3], and uterus [4], in anesthetized animals. Our recent study demonstrated that a noxious range of colorectal distension (CRD) produced a reflexive decrease in blood pressure in anesthetized central nervous system (CNS)-intact rats via a reflexive inhibition of sympathetic vasoconstrictor nerve (renal sympathetic nerve) activity [5]. The decrease response of blood pressure induced by CRD in CNS-intact rats was reversed to increase response by spinalization at the 2nd cervical level (C2). Thus it was suggested that the reflex center of the CRD-induced inhibitory reflex modulation of blood pressure was at supraspinal levels in CNS-intact rats. There was also CRD-induced excitatory reflex modulation of blood pressure at the propriospinal levels, though the excitatory reflex was inhibited by the supraspinal structure in CNS-intact preparation [5].During these experiments on the blood pressure, we had observed that CRD produced bradycardia in association with a decrease in blood pressure in CNS-intact rats. It is well known that bradycardia is induced by visceral manipulation during surgery in human [6,7]. And these responses have been considered as a reflex response whose efferent is the cardiac vagus nerve. Using anesthetized rats, Grundy and Davison [8] suggested that the efferent path of bradycardia to a distension of the stomach was the cardiac vagus nerve. On the other hand, Robbins and Sato [4] reported that bradycardic responses to a distension of the uterus was not influenced by a bilateral vagotomy in anesthetized rats and suggested a contribution of the cardiac sympathetic nerve. It is interesting to learn the efferent paths and the reflex center of bradycardia induced by CRD.It has been reported that the cardiovascular response to CRD stimulation in anesthetized rats was unstable and fluctuated based on the depth of anesthesia [2]. Our previous study developed an anesthetized rat model of stable depressor response induced by CRD [5]. Using this rat model in the present study, we aimed to clarify the involvement of the cardiac sympathetic and parasympathetic nerves as efferent paths in the CRD-induced reflexive bradycardia. We also examined this reflex in spinalized rats to determine whether its reflex center was in the brain and/or the spinal cord. MethodsAdult male Wistar rats weighing 330-380 g (n = 16) were housed in a climate-controlled environment with food and water ad libitum. All animal experiments ...

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“…Visceral pain-related neurochemical changes were found in the central nucleus of the amygdala (CeA). These included increased c-fos mRNA ) and c-fos protein expression (Lazovic et al 2005;Monnikes et al 2003;Stam et al 2002;Traub et al 1996) following CRD and increased corticotropin-releasing factor (CRF) mRNA in a colitis pain model (Greenwood-Van Meerveld et al 2006). Behavioral data also implicate the CeA in visceral pain.…”

mentioning

confidence: 99%

Reactive Oxygen Species Are Involved in Group I mGluR-Mediated Facilitation of Nociceptive Processing in Amygdala Neurons

Neugebauer

2010

Journal of Neurophysiology

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Ji G, Neugebauer V. Reactive oxygen species are involved in group I mGluR-mediated facilitation of nociceptive processing in amygdala neurons. J Neurophysiol 104: 218 -229, 2010. First published May 12, 2010 doi:10.1152/jn.00223.2010. Recent biochemical and behavioral data implicate reactive oxygen species (ROS) in peripheral and spinal pain mechanisms. However, pain-related functions of ROS in the brain and mechanisms of pain-related ROS activation remain to be determined. Our previous studies showed that the amygdala plays a key role in emotional-affective pain responses and pain modulation. Hyperactivity of amygdala neurons in an animal pain model depends on group I metabotropic glutamate receptors (subtypes mGluR1 and mGluR5), but their signaling pathway remains to be determined. Here we tested the hypothesis that activation of group I mGluRs increases nociceptive processing in amygdala neurons through a mechanism that involves ROS. Extracellular single-unit recordings were made from neurons in the laterocapsular division of the central nucleus of the amygdala (CeLC) in anesthetized adult male rats. Administration of a group I mGluR agonist (DHPG) into the CeLC by microdialysis increased the responses to innocuous and noxious somatosensory (knee joint compression) and visceral (colorectal distention [CRD]) stimuli. A ROS scavenger (PBN) and a superoxide dismutase mimetic (TEMPOL) reversed the facilitatory effects of DHPG. An mGluR5 antagonist (MPEP) also inhibited the effects of DHPG on the responses to innocuous and noxious somatosensory and visceral stimuli, whereas an mGluR1 antagonist (LY367385) decreased only the responses to visceral stimulation. The results show for the first time that ROS mediate group I mGluR-induced facilitation of nociceptive processing in amygdala neurons. The antagonist data may suggest differential contributions of subtypes mGluR1 and mGluR5 to the processing of somatosensory and visceral nociceptive information in the amygdala. I N T R O D U C T I O NCytotoxicity and oxidative stress through reactive oxygen species (ROS) formation play a critical role in apoptosis, stroke pathology, spinal cord injury, neurodegenerative disorders, and aging (Chinopoulos and Adam-Vizi 2006;Maher and Schubert 2000). However, ROS, such as superoxide and hydrogen peroxide, also serve as important signaling molecules in physiological plasticity and may be required for normal cognitive functions (Hu et al. 2006; Kishida and Klann 2007; Klann 1998). A novel concept views ROS as a major factor in persistent pain (Chung 2004).Peripheral and spinal ROS, such as superoxide and hydrogen peroxide, have been implicated in inflammatory and neuropathic pain (Gao et al. 2007; Keeble et al. 2009; Kim et al. 2004Kim et al. , 2009Schwartz et al. 2008Schwartz et al. , 2009Wang et al. 2004).Peripheral or spinal administration of exogenous ROS has pronociceptive effects (Keeble et al. 2009;Schwartz et al. 2008). Production of endogenous ROS is increased in injured peripheral nerve and inflamed tissue (Keeble et a...

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Differential induction of c-fos expression in brain nuclei by noxious and non-noxious colonic distension:

Cited by 73 publications

References 68 publications

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

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

Reflex Inhibition of Heart Rate and Efferent Cardiac Sympathetic Outflow Induced by Colorectal Distension in Anesthetized Rats

Reactive Oxygen Species Are Involved in Group I mGluR-Mediated Facilitation of Nociceptive Processing in Amygdala Neurons

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