Sex and oestrous cycle differences in visceromotor responses and vasopressin release in response to colonic distension in male and female rats anaesthetized with halothane †

Holdcroft, Anita; Sapsed-Byrne, S.; Ma, Daqing; Hammal, D; Forsling, Mary L.

doi:10.1093/bja/85.6.907

Cited by 50 publications

(43 citation statements)

References 8 publications

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“…We have previously reported that the magnitude of the visceromotor response (a suprathreshold response) does not fluctuate with the estrous cycle (Ji et al 2006), although the threshold to evoke the visceromotor response does fluctuate across the estrous cycle (Sapsed-Byrne et al, 1996;Holdcroft et al 2000). These data and our previous reports that E2 replacement reverses the antinociceptive effect of ovariectomy (Ji et al, 2003b;Ji et al, 2005), suggests female gonadal hormones modulate visceral nociceptive processing.…”

Section: Discussionsupporting

confidence: 58%

Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat

Tang¹,

Ji²,

Traub

2008

Pain

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Pain symptoms in several chronic pain disorders in women, including irritable bowel syndrome, fluctuate with the menstrual cycle suggesting a gonadal hormone component. In female rats, estrogens modulate visceral sensitivity although the underlying mechanism(s) are unknown. In the present study the effects of 17-β estradiol on N-methyl-D-aspartate (NMDA) receptor signaling of colorectal nociceptive processing in the spinal cord were examined. Estrogen receptor alpha and the NR1 subunit of the NMDA receptor are co-expressed in dorsal horn neurons, supporting a direct action of estradiol on NMDA receptors. Intrathecal administration of the NMDA receptor antagonist D(−)-2-amino-5-phosphonopetanoic acid (APV) dose-dependently attenuated the visceromotor response with greater potency in ovariectomized (OVx) rats compared to OVx with estradiol replacement (E2) rats. Estradiol significantly increased protein expression of NR1 in the lumbosacral spinal cord compared to OVx rats. Colorectal distention significantly increased phosphorylation of NR1ser-897, a PKA phosphorylation site on the NR1 subunit in E2, but not OVx rats. Intrathecal administration of a PKA inhibitor significantly attenuated the visceromotor response, decreased NR1 phosphorylation and increased the potency of APV to attenuate the visceromotor response compared to vehicle-treated E2 rats. These data suggest that estradiol increases spinal processing of visceral nociception by increasing NMDA receptor NR1 subunit expression and increasing site specific receptor phosphorylation on the NR1 subunit contributing to an increase in NMDA receptor activity.

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Section: Discussionsupporting

confidence: 58%

Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat

Tang¹,

Ji²,

Traub

2008

Pain

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“…It is possible that alterations in the pattern of oscillations in PER2 are associated with changes in neuronal response to different types of inputs, with the processing of information within these structures, and͞or with the modulation of their output pathways. For example, cyclic variation in GABAergic tone or in neuropeptide content associated with changes in PER2 expression within the BNST-OV and CEA could contribute to the variation in stress responsivity observed across the estrous cycle (44,45).…”

Section: Discussionmentioning

confidence: 99%

The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle

Perrin

Segall

Harbour

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Daily behavioral and physiological rhythms are linked to circadian oscillations of clock genes in the brain and periphery that are synchronized by the master clock in the suprachiasmatic nucleus. In addition, there are a number of inputs that can influence circadian oscillations in clock gene expression in a tissue-specific manner. Here we identify an influence on the circadian oscillation of the clock protein PER2, endogenous changes in ovarian steroids, within two nuclei of the limbic forebrain: the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala. We show that the daily rhythm of PER2 expression within these nuclei but not in the suprachiasmatic nucleus, dentate gyrus, or basolateral amygdala is blunted in the metestrus and diestrus phases of the estrus cycle. The blunting of the PER2 rhythm at these phases of the cycle is abolished by ovariectomy and restored by phasic estrogen replacement suggesting that fluctuations in estrogen levels or their sequelae are necessary to produce these effects. The finding that fluctuations in ovarian hormones have area-specific effects on clock gene expression in the brain introduces a new level of organizational complexity in the control of circadian rhythms of behavior and physiology.circadian clock ͉ circadian rhythm ͉ estrogen T he core molecular mechanism generating circadian rhythms within the suprachiasmatic nucleus (SCN), the master circadian clock, is based on feedback loops among several rhythmically expressed clock genes and their protein products (1, 2). Circadian rhythms in clock gene expression are observed not only in the SCN but also in other brain areas as well as peripheral tissues. These include but are not limited to the olfactory bulb, several hypothalamic nuclei, the eyes, pituitary gland, heart, and lung (3-13). Because synchronized expression of clock genes in these tissues requires an intact SCN, it has been proposed that these oscillations in clock gene expression serve to gate circadian signals from the SCN into tissue-specific rhythmic outputs (10,12,13).In addition, there is growing evidence to suggest that circulating hormones as well as metabolic signals can modulate circadian oscillations of clock gene expression in some brain regions and peripheral structures (14). For example, the pineal hormone melatonin modulates the rhythm of the clock gene Per1 in the pituitary gland, striatum, and adrenal cortex (15-17). Furthermore, adrenal glucocorticoids induce Per1 expression in peripheral tissues such as the liver (18,19) and modulate the rhythm of expression of the clock protein, PER2, in the oval nucleus of the bed nucleus of the stria terminal (BNST-OV) and central nucleus of the amygdala (CEA) (12, 13). By contrast, adrenalectomy has no effect on PER2 expression in the SCN, basolateral amygdala (BLA), or dentate gyrus (DG) (12, 13), and melatonin does not affect rhythms of clock gene expression in the SCN, limbic forebrain, eye, or heart (20). The ability of circulating hormones to modulate clock gene ...

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“…Future studies will need to address the relative importance of V 3 receptor antagonism of hypothalamic and extrahypothalamic AVP signaling in the development and expression of chronic visceral hyperalgesia. Although V 3 receptors are also expressed in the gastrointestinal tract (38), AVP is released by CRD (21), and peripherally administered AVP or AVP analogs exert significant effects on colonic secretomotor functions in animals and humans (44,45,54), a peripheral effect of SSR149415 on visceral afferent pathways explaining the observed pattern of antihyperalgesia is unlikely. Similarly, even if the antagonist had exerted a modulatory effect on colonic tone (which was not evaluated in the present study), the employed barostat technique would have compensated for such a peripheral effect.…”

Section: Effect Of Repeated Dosing With Ssr149415 On the Development mentioning

confidence: 99%

“…For example, preclinical and clinical data suggest that AVP signaling may be involved in stress-and CRF-induced modulation of intestinal motility (10,21,54). However, a role of AVP/V 3 signaling in stress-induced visceral hyperalgesia has not been demonstrated.…”

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confidence: 99%

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

Bradesi¹,

Martínez²,

Lao³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Bradesi S, Martinez V, Lao L, Larsson H, Mayer EA. Involvement of vasopressin 3 receptors in chronic psychological stressinduced visceral hyperalgesia in rats. Am J Physiol Gastrointest Liver Physiol 296: G302-G309, 2009. First published November 25, 2008 doi:10.1152/ajpgi.90557.2008.-Visceral hypersensitivity and stress have been implicated in the pathophysiology of functional gastrointestinal disorders. We used a selective vasopressin 3 (V 3) receptor antagonist SSR149415 to investigate the involvement of the vasopressin (AVP)/V 3 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 (CRF 1) 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 V 3 receptors in repeated psychological stress-induced visceral hyperalgesia and suggest that pharmacological manipulation of the AVP/V 3 pathway might represent an attractive alternative to the CRF/CRF 1 pathway for the treatment of chronic stress-related gastrointestinal disorders. corticotropin-releasing factor; DMP-696; functional gastrointestinal disorders; irritable bowel syndrome; SSR149415RECURRENT ABDOMINAL PAIN ASSOCIATED with altered bowel habits and increased perception of physiological and experimental colonic stimuli (visceral hypersensitivity) are characteristic findings in patients with irritable bowel syndrome (IBS) (4). Although the pathophysiological basis of IBS is incompletely understood, epidemiological and experimental data indicate an important role of altered brain-gut interactions in this disorder. For example, many studies have highlighted the importance of certain types of psychological stress in the onset, maintenance, and exacerbation of IBS symptoms (5, 6, 32, 33). Furthermore, higher levels of anxiety, symptom-related anxiety, and comorbidity with anxiety disorders or depression are common in patients with IBS (32,33,49). Recent brain imaging studies have shown greater activation of limbic and paralimbic brain regions (including the amygdala) in patient...

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Sex and oestrous cycle differences in visceromotor responses and vasopressin release in response to colonic distension in male and female rats anaesthetized with halothane †

Cited by 50 publications

References 8 publications

Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat

Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat

The expression of the clock protein PER2 in the limbic forebrain is modulated by the estrous cycle

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

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