Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats

2008 ◽  
Vol 294 (4) ◽  
pp. G1033-G1040 ◽  
Author(s):  
Muriel Larauche ◽  
Sylvie Bradesi ◽  
Mulugeta Million ◽  
Peter McLean ◽  
Yvette Taché ◽  
...  
Keyword(s):  
Psychological Stress ◽  
Functional Gastrointestinal Disorders ◽  
Visceral Hypersensitivity ◽  
Pathophysiological Mechanism ◽  
Visceral Hyperalgesia ◽  
Before And After ◽  
Visceromotor Response ◽  
Male Wistar Rats ◽  
Factor Type

Visceral hypersensitivity has been implicated as an important pathophysiological mechanism in functional gastrointestinal disorders. In this study, we investigated whether the sustained visceral hyperalgesia induced by repeated psychological stress in rats involves the activation of CRF1 signaling system using two different antagonists. Male Wistar rats were exposed to 10 consecutive days of water avoidance stress (WAS) or sham stress for 1 h/day, and the visceromotor response to phasic colorectal distension (CRD) was assessed before and after the stress period. Animals were injected subcutaneously with the brain penetrant CRF1 antagonist, CP-154,526, acutely (30 min before the final CRD) or chronically (via osmotic minipump implanted subcutaneously, during stress) or with the peripherally restricted, nonselective CRF1 and CRF2 antagonist, astressin, chronically (15 min before each stress session). Repeated WAS induced visceral hypersensitivity to CRD at 40 and 60 mmHg. CP-154,526 injected acutely significantly reduced stress-induced visceral hyperalgesia at 40 mmHg but not at 60 mmHg. Chronic subcutaneous delivery of astressin reduced the stress-induced visceral hyperalgesia to baseline at all distension pressures. Interestingly, chronically administered CP-154,526 eliminated hyperalgesia and produced responses below baseline at 40 mmHg and 60 mmHg, indicating a hypoalgesic effect of the compound. These data support a major role for CRF1 in both the development and maintenance of visceral hyperalgesia induced by repeated stress and indicate a possible role of peripheral CRF receptors in such mechanisms.

Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats

2009 ◽  
Vol 296 (2) ◽  
pp. G302-G309 ◽  
Author(s):  
Sylvie Bradesi ◽  
Vicente Martinez ◽  
Lijun Lao ◽  
Håkan Larsson ◽  
Emeran A. Mayer
Keyword(s):  
Single Dose ◽  
Psychological Stress ◽  
Functional Gastrointestinal Disorders ◽  
Repeated Administration ◽  
Visceral Hypersensitivity ◽  
Gastrointestinal Disorders ◽  
Attractive Alternative ◽  
Visceral Hyperalgesia ◽  
Before And After ◽  
Visceromotor Response

Visceral hypersensitivity and stress have been implicated in the pathophysiology of functional gastrointestinal disorders. We used a selective vasopressin 3 (V3) receptor antagonist SSR149415 to investigate the involvement of the vasopressin (AVP)/V3 signaling system in the development of stress-induced visceral hyperalgesia in rats. Rats were exposed to a daily 1-h session of water avoidance stress (WAS) or sham WAS for 10 consecutive days. The visceromotor response to phasic colorectal distension (CRD, 10–60 mmHg) was assessed before and after stress. Animals were treated daily with SSR149415 (0.3, 1, or 3 mg/kg ip 30 min before each WAS or sham WAS session), with a single dose of SSR149415 (1 mg/kg ip), or the selective corticotropin-releasing factor 1 (CRF1) antagonist DMP-696 (30 mg/kg po) before CRD at day 11. Effects of a single dose of SSR149415 (10 mg/kg iv) on acute mechanical sensitization during repetitive CRD (12 distensions at 80 mmHg) were also assessed. In vehicle-treated rats, repeated WAS increased the response to CRD, indicating visceral hypersensitivity. Repeated administration of SSR149415 at 1 or 3 mg/kg completely prevented stress-induced visceral hyperalgesia. Similarly, a single dose of DMP-696 or SSR149415 completely blocked hyperalgesic responses during CRD. In contrast, a single dose of SSR149415 did not affect the acute hyperalgesic responses induced by repeated, noxious distension. These data support a major role for V3 receptors in repeated psychological stress-induced visceral hyperalgesia and suggest that pharmacological manipulation of the AVP/V3 pathway might represent an attractive alternative to the CRF/CRF1 pathway for the treatment of chronic stress-related gastrointestinal disorders.

scholarly journals Microglia: a newly discovered role in visceral hypersensitivity?

2006 ◽  
Vol 2 (4) ◽  
pp. 271-277 ◽  
Author(s):  
Carl Y. Saab ◽  
Jing Wang ◽  
Chunping Gu ◽  
Kirsten N. Garner ◽  
Elie D. Al-Chaer
Keyword(s):  
Visceral Pain ◽  
Thermal Hyperalgesia ◽  
Radiant Heat ◽  
Pain Modulation ◽  
Visceral Hypersensitivity ◽  
Visceral Sensitivity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After

AbstractGiven the growing body of evidence for a role of glia in pain modulation, it is plausible that the exaggerated visceral pain in chronic conditions might be regulated by glial activation. In this study, we have investigated a possible role for microglia in rats with chronic visceral hypersensitivity and previously documented altered neuronal function. Experiments were performed on adult male Sprague-Dawley rats pre-treated with neonatal colon irritation (CI) and on control rats. Effects of fractalkine (FKN, a chemokine involved in neuron-to-microglia signaling) and of minocycline (an inhibitor of microglia) on visceral sensitivity were examined. Visceral sensitivity was assessed by recording the electromyographic (EMG) responses to graded colorectal distension (CRD) in mildly sedated rats. Responses to CRD were recorded before and after injection of FKN, minocycline or vehicle. Somatic thermal hyperalgesia was measured by latency of paw withdrawal to radiant heat. The pattern and intensity of microglial distribution at L6–S2 in the spinal cord was also compared in rats with CI and controls by fluorescence microscopy using OX-42. Results show that: (1) FKN significantly facilitated EMG responses to noxious CRD by >52% in control rats. FKN also induced thermal hyperalgesia in control rats, consistent with previous reports; (2) minocycline significantly inhibited EMG responses to noxious CRD by >70% in rats with CI compared to controls 60 min after injection. The anti-nociceptive effect of minocycline lasted for 180 min in rats with CI, reaching peak values 60 min after injection. Our results show that FKN enhances visceral and somatic nociception, whereas minocycline inhibits visceral hypersensitivity in chronically sensitized rats, which indicates a role for microglia in visceral hypersensitivity.

Peptides in the parabrachial nucleus modulate visceral input to the thalamus

1993 ◽  
Vol 264 (4) ◽  
pp. R668-R675 ◽  
Author(s):  
T. M. Saleh ◽  
D. F. Cechetto
Keyword(s):  
Neuronal Activity ◽  
Vagal Stimulation ◽  
Fold Increase ◽  
Parabrachial Nucleus ◽  
Artificial Cerebrospinal Fluid ◽  
Calcitonin Gene ◽  
Before And After ◽  
Male Wistar Rats ◽  
Sensory Pathway

The role of neuropeptides in ascending visceral pathways was investigated by recording the changes in the response of thalamic neuronal activity evoked by vagal stimulation before and after peptide injection in the parabrachial nucleus (PB). Male Wistar rats (n = 25) were anesthetized with chloral hydrate and ventilated, and blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity in the parvocellular visceral relay nuclei in the ventral basal thalamus. Peristimulustime histograms of thalamic activity were made before and after 200-nl injections of peptides or artificial cerebrospinal fluid (CSF) controls in the PB. Injection of calcitonin gene-related peptide (CGRP) at 5 mM or substance P (SP) at 2 mM into the PB significantly attenuated the evoked response of thalamic neuronal activity by 87-100% and 85-100%, respectively. Injections of somatostatin (SOM; 1 mM) did not significantly alter the response evoked by vagal stimulation but significantly inhibited the spontaneous firing of thalamic units, resulting in a 10-fold increase in the response-to-background ratio. This suggests that SOM in the PB inhibits cells in a parallel pathway that terminates on thalamic visceral neurons but that are not part of the ascending visceral sensory pathway. Spontaneous thalamic neuronal activity and vagally evoked responses were significantly enhanced (278-508%) by injection of 1 mM neurotensin (NT) in the PB. Cholecystokinin (CCK) at low doses (0.0002-0.2 mM) attenuated while the highest dose, 2 mM, briefly excited the spontaneous activity of thalamic units before inhibiting their activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed stress-induced colonic hypersensitivity in male Wistar rats: role of neurokinin-1 and corticotropin-releasing factor-1 receptors

2004 ◽  
Vol 286 (4) ◽  
pp. G683-G691 ◽  
Author(s):  
Ines Schwetz ◽  
Sylvie Bradesi ◽  
James A. McRoberts ◽  
Marciano Sablad ◽  
Jerry C. Miller ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Wistar Rats ◽  
Corticotropin Releasing Factor ◽  
Chemical Sympathectomy ◽  
Visceromotor Response ◽  
Male Wistar Rats ◽  
Sympathetic Nervous ◽  
Neurokinin 1

The mechanism(s) underlying stress-induced colonic hypersensitivity (SICH) are incompletely understood. Our aims were to assess the acute and delayed (24 h) effect of water avoidance (WA) stress on visceral nociception in awake male Wistar rats and to evaluate the role of two stress-related modulation systems: the substance P/neurokinin-1 receptor (SP/NK1R) and the corticotropin-releasing factor (CRF)/CRF1 receptor (CRF/CRF1R) systems, as well as the possible involvement of the sympathetic nervous system. Visceral pain responses were measured as the visceromotor response to colorectal distension (CRD) at baseline, immediately after WA and again 24 h later. The NK1R antagonists RP-67580 and SR-140333 and the CRF1R antagonist CP-154526 were injected 15 min before WA or 1 h before the CRD on day 2. Chemical sympathectomy was performed by repeated injection of 6-hydroxydopamine. WA stress resulted in a significant increase in the visceromotor response on day 2, but no change immediately after WA. Injection of CP-154526 abolished delayed SICH when applied either before WA stress or before the CRD on day 2. Both NK1R antagonists only decreased SICH when injected before the CRD on day 2. Chemical sympathectomy did not affect delayed SICH. Our results indicate that in male Wistar rats, both NK1R and CRF1R activation, but not sympathetic nervous system activation, play a role in the development of SICH.

scholarly journals Acute physical and psychological stress effects on visceral hypersensitivity in male rat: role of central nucleus of the amygdala

2017 ◽  
Vol 37 (2) ◽  
pp. 88-94
Author(s):  
Hamideh Afzali ◽  
Fatemeh Nabavizadeh ◽  
Seyed Morteza Karimian ◽  
Hamid Sohanaki ◽  
Jalal Vahedian ◽  
...  
Keyword(s):  
Psychological Stress ◽  
Visceral Hypersensitivity ◽  
Central Nucleus ◽  
Male Rat ◽  
Stress Effects

scholarly journals Optogenetic silencing of primary afferents reduces evoked and ongoing bladder pain

2017 ◽  
Author(s):  
Vijay K. Samineni ◽  
Aaron D. Mickle ◽  
Jangyeol Yoon ◽  
Jose G. Grajales-Reyes ◽  
Melanie Pullen ◽  
...  
Keyword(s):  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Bladder Function ◽  
Optoelectronic System ◽  
Sensory Afferents ◽  
Bladder Pain ◽  
Before And After ◽  
Visceromotor Response ◽  
Cutaneous Hypersensitivity

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of bladder sensory afferents could be used to modulate bladder pain. Specifically, we chose to study the role of Nav1.8+ sensory afferents before and after induction of a mouse model of bladder pain. The light-activated inhibitory proton pump Archaerhodopsin (Arch) was expressed under control of the Nav1.8+ promoter to selectively silence these neurons. Optically silencing Nav1.8+ afferents significantly blunted the evoked visceromotor response to bladder distension and led to small but significant changes in bladder function. To study of the role of these fibers in freely behaving mice, we developed a fully implantable, flexible, wirelessly powered optoelectronic system for the long-term manipulation of bladder afferent expressed opsins. We found that optogenetic inhibition of Nav1.8+ fibers reduced both ongoing pain and evoked cutaneous hypersensitivity in the context of cystitis, but had no effect in uninjured, naïve mice. These results suggest that selective optogenetic silencing of bladder afferents may represent a potential future therapeutic strategy for the treatment of bladder pain.

Repeated exposure to water avoidance stress in rats: a new model for sustained visceral hyperalgesia

2005 ◽  
Vol 289 (1) ◽  
pp. G42-G53 ◽  
Author(s):  
Sylvie Bradesi ◽  
Ines Schwetz ◽  
Helena S. Ennes ◽  
Christophe M. R. Lamy ◽  
Gordon Ohning ◽  
...  
Keyword(s):  
Mast Cell ◽  
Psychological Stress ◽  
Chronic Stress ◽  
Immune Activation ◽  
Structural Changes ◽  
Colonic Motility ◽  
Functional Gastrointestinal Disorders ◽  
Cell Number ◽  
Primary Role ◽  
Visceral Hyperalgesia

Chronic stress plays an important role in the development and exacerbation of symptoms in functional gastrointestinal disorders. To better understand the mechanisms underlying this relationship, we aimed to characterize changes in visceral and somatic nociception, colonic motility, anxiety-related behavior, and mucosal immune activation in rats exposed to 10 days of chronic psychological stress. Male Wistar rats were submitted daily to either 1-h water avoidance (WA) stress or sham WA for 10 consecutive days. The visceromotor response to colorectal distension, thermal somatic nociception, and behavioral responses to an open field test were measured at baseline and after chronic WA. Fecal pellets were counted after each WA stress or sham WA session as a measure of stress-induced colonic motility. Colonic samples were collected from both groups and evaluated for structural changes and neutrophil infiltration, mast cell number by immunohistochemistry, and cytokine expression by quantitative RT-PCR. Rats exposed to chronic WA (but not sham stress) developed persistent visceral hyperalgesia, whereas only transient changes in somatic nociception were observed. Chronically stressed rats also exhibited anxiety-like behaviors, enhanced fecal pellet excretion, and small but significant increases in the mast cell numbers and the expression of IL-1β and IFN-γ. Visceral hyperalgesia following chronic stress persisted for at least a month. Chronic psychological stress in rats results in a robust and long-lasting alteration of visceral, but not somatic nociception. Visceral hyperalgesia is associated with other behavioral manifestations of stress sensitization but was only associated with minor colonic immune activation arguing against a primary role of mucosal immune activation in the maintenance of this phenomenon.

scholarly journals Absence of diurnal variation in visceromotor response to colorectal distention in normal Long Evans rats

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 98 ◽  
Author(s):  
Sara Botschuijver ◽  
Zhumei Yu ◽  
Olaf Welting ◽  
Cathy Cailotto ◽  
Andries Kalsbeek ◽  
...  
Keyword(s):  
Rat Model ◽  
Circadian Variation ◽  
Visceral Hypersensitivity ◽  
Normal Male ◽  
Pathophysiological Mechanism ◽  
Dark Cycle ◽  
Colorectal Distension ◽  
Healthy Men ◽  
Visceromotor Response ◽  
Long Evans

Background: Enhanced colorectal sensitivity (i.e. visceral hypersensitivity) is thought to be a pathophysiological mechanism in irritable bowel syndrome (IBS). In healthy men a circadian variation in rectal perception to colonic distention was described. Disturbed day and night rhythms, which occur in shift work and trans meridian flights, are associated with the prevalence of IBS. This raises the question whether disruptions of circadian control are responsible for the observed pathology in IBS. Prior to investigating altered rhythmicity in relation to visceral hypersensitivity in a rat model for IBS, it is relevant to establish whether normal rats display circadian variation similar to healthy men. Methodology and findings: In rodents colorectal distension leads to reproducible contractions of abdominal musculature. We used quantification of this so called visceromotor response (VMR) by electromyography (EMG) to assess visceral sensitivity in rats. We assessed the VMR in normal male Long Evans rats at different time points of the light/dark cycle. Although a control experiment with male maternal separated rats confirmed that intentionally inflicted (i.e. stress induced) changes in VMR can be detected, normal male Long Evans rats showed no variation in VMR along the light/dark cycle in response to colorectal distension.Conclusions: In the absence of a daily rhythm of colorectal sensitivity in normal control rats it is not possible to investigate possible aberrancies in our rat model for IBS.

scholarly journals Changes in the Interstitial Cells of Cajal and Immunity in Chronic Psychological Stress Rats and Therapeutic Effects of Acupuncture at the Zusanli Point (ST36)

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mucang Liu ◽  
Shenglin Zhang ◽  
Yue Gai ◽  
Mingzheng Xie ◽  
Qinghui Qi
Keyword(s):  
Small Intestine ◽  
Food Intake ◽  
Psychological Stress ◽  
Immune Suppression ◽  
Functional Gastrointestinal Disorders ◽  
Visceral Hypersensitivity ◽  
Therapeutic Effects ◽  
Daily Food ◽  
Immune Imbalance ◽  
Cells Of Cajal

Now, chronic psychological stress (CPS) related diseases are increasing. Many CPS patients have gastrointestinal complaints, immune suppression, and immune imbalance. Increasing evidence is indicating that acupuncture (AP) at the Zusanli point (ST36) can alleviate functional gastrointestinal disorders (FGID), immune suppression, and immune imbalance. However, few studies have investigated the potential mechanisms. In this study, CPS rat models were established, and electroacupuncture (EA) at ST36 was done for CPS rats. Daily food intake, weight, intestinal sensitivity, the morphology of interstitial cell of Cajal (ICC) in the small intestine, and serum indexes were measured. The study found that, in CPS rats, EA at ST36 could improve food intake, weight, visceral hypersensitivity, and immunity; in CPS rats, in small intestine, the morphology of ICCs was abnormal and the number was decreased, which may be part causes of gastrointestinal motility dysfunction. EA at ST36 showed useful therapeutic effects. The mechanisms may be partially related to its repairing effects on ICCs damages; in CPS rats, there were immune suppression and immune imbalance, which may be part causes of visceral hypersensitivity. EA at ST36 showed useful therapeutic effects. The mechanisms may be partially related to its regulation on immunity.

scholarly journals Role of astrocytes and altered regulation of spinal glutamatergic neurotransmission in stress-induced visceral hyperalgesia in rats

2011 ◽  
Vol 301 (3) ◽  
pp. G580-G589 ◽  
Author(s):  
Sylvie Bradesi ◽  
Viktoriya Golovatscka ◽  
Helena S. Ennes ◽  
James A. McRoberts ◽  
Iordanes Karagiannidis ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Critical Role ◽  
Nociceptive Response ◽  
Control Mechanisms ◽  
Glutamatergic Neurotransmission ◽  
Visceral Hyperalgesia ◽  
Excitatory Neurotransmitter ◽  
Pharmacological Inhibition ◽  
Male Wistar Rats

Glutamate (Glu) is the primary excitatory neurotransmitter in the central nervous system and plays a critical role in the neuroplasticity of nociceptive networks. We aimed to examine the role of spinal astroglia in the modulation of glutamatergic neurotransmission in a model of chronic psychological stress-induced visceral hyperalgesia in male Wistar rats. We assessed the effect of chronic stress on different glial Glu control mechanisms in the spinal cord including N-methyl-d-aspartate receptors (NMDARs), glial Glu transporters (GLT1 and GLAST), the Glu conversion enzyme glutamine synthetase (GS), and glial fibrillary acidic protein (GFAP). We also tested the effect of pharmacological inhibition of NMDAR activation, of extracellular Glu reuptake, and of astrocyte function on visceral nociceptive response in naive and stressed rats. We observed stress-induced decreased expression of spinal GLT1, GFAP, and GS, whereas GLAST expression was upregulated. Although visceral hyperalgesia was blocked by pharmacological inhibition of spinal NMDARs, we observed no stress effects on NMDAR subunit expression or phosphorylation. The glial modulating agent propentofylline blocked stress-induced visceral hyperalgesia, and blockade of GLT1 function in control rats resulted in enhanced visceral nociceptive response. These findings provide evidence for stress-induced modulation of glia-controlled spinal Glu-ergic neurotransmission and its involvement in chronic stress-induced visceral hyperalgesia. The findings reported in this study demonstrate a unique pattern of stress-induced changes in spinal Glu signaling and metabolism associated with enhanced responses to visceral distension.

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