Selective dysfunction of mechanosensitive intestinal afferents in irritable bowel syndrome

Accarino, Anna; Azpiroz, Fernando; Malagelada, Juan R.

doi:10.1016/0016-5085(95)90434-4

Cited by 253 publications

(197 citation statements)

References 14 publications

Supporting

Mentioning

186

Contrasting

Unclassified

Order By: Relevance

“…For example, since maternal licking of the anogenital area is a key component of motherpup interaction, manipulations of this area by colonic catheterization or instillation of chemicals may result in altered licking behavior. In contrast to the findings in the current report, and in contrast to observations in IBS patients (1,13,16), Al-Chaer et al (2) observed indirect evidence for both visceral and somatic hyperalgesia in the same dermatome, consistent with a role for long-lasting sensitization of dorsal horn neurons, which receive converging viscerosomatic input. For example, the authors observed neuronal sensitization in the responses to somatic stimuli applied within the receptive field of the neuron (2).…”

Section: Comparison To Other Animal Models Of Prolonged Stress Sensitcontrasting

confidence: 99%

Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat

Coutinho¹,

Plotsky

Sablad³

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

404

372

View full text Add to dashboard Cite

Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am J Physiol Gastrointest Liver Physiol 282: G307-G316, 2002. First published October 3, 2001 10.1152/ajpgi.00240.2001.-This study investigated the combined effect of neonatal maternal separation and acute psychological stress on pain responses in adult rats. Long-Evans dams and their male pups were reared under two conditions: 1) 180 min daily maternal separation (MS180) on postnatal days 2-14 or 2) no handling or separation (NH). At 2 mo of age, visceromotor responses to graded intensities of phasic colorectal distension (10-80 mmHg) at baseline as well as following acute 60 min water avoidance stress (WA) were significantly higher in MS180 rats. Both groups showed similar stress-induced visceral hyperalgesia in the presence of naloxone (20 mg/kg ip). MS180 rats had smaller stress-induced cutaneous analgesia in the tail-flick test compared with NH rats, with a residual naloxone-resistant component. MS180 rats showed an enhanced fecal pellet output following WA or exposure to a novel environment. These data suggest that early life events predispose adult Long-Evans rats to develop visceral hyperalgesia, reduced somatic analgesia, and increased colonic motility in response to an acute psychological stressor, mimicking the cardinal features of irritable bowel syndrome. irritable bowel syndrome; stress; analgesia; naloxone IRRITABLE BOWEL SYNDROME (IBS) is a disorder characterized by chronic abdominal pain and discomfort associated with alterations in bowel habits in the absence of a demonstrable pathology (67). Although IBS is likely a heterogeneous disorder in terms of etiology and pathophysiology, alterations in bowel habits are likely related to alterations in autonomic regulation of the gut, whereas symptoms of abdominal pain and discomfort are thought to involve additional changes in the perception of visceral events, in the form of visceral hyperalgesia or allodynia (46, 48). Additionally, in IBS patients without a concurrent diagnosis of fibromyalgia, visceral hypersensitivity is associated with a normal or diminished somatic pain sensitivity to noxious stimuli (13).Progress in the development of more effective therapies has been hampered due to the lack of animal models that mimic the key features of IBS, in particular the enhanced perception of visceral events. Many investigations have utilized acute inflammatory insults to the gut using agents such as glycerol, mustard oil, acetic acid, or zymosan to produce acute visceral hypersensitivity, thereby mimicking inflammatory bowel disorders. However, IBS is a chronic disorder characterized by the absence of inflammatory changes in the gut mucosa. More recently, several potential IBS models have been reported, all of which mimic certain aspects of the human syndrome (2, 15, 62, 72). They include an early life colon irritation model (2), an adult stress sensitization model (62), and an adult postinfection model in the rat (15) and in the mouse (72). Alt...

show abstract

Section: Comparison To Other Animal Models Of Prolonged Stress Sensitcontrasting

confidence: 99%

Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat

Coutinho¹,

Plotsky

Sablad³

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

404

372

View full text Add to dashboard Cite

show abstract

“…In fact recent investigations suggest that in both animal models and patients with chronic visceral pain there is evidence of referred somatic hypersensitivity [19,[45][46][47][48]. These findings are different from earlier studies which have revealed somatic hyposensitivity in patients with chronic visceral pain disorders such as inflammatory bowel disease and IBS [3,4,[49][50][51][52]. One very plausible explanation for these different findings in humans may be due to the specific type of nociceptive stimuli used.…”

Section: Discussionmentioning

confidence: 76%

Visceral and Somatic Hypersensitivity in TNBS-Induced Colitis in Rats

et al. 2007

View full text Add to dashboard Cite

Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200g-250g) were treated with 20 mg of TNBS in 50% ethanol (n=40) or an equivalent volume of ethanol (n=40) or saline (n=25) via the colon. Colonic distension, Von-Frey, Hargreaves, and tail reflex test were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2-28 days following TNBS (p<0.0001). The ethanol treated rats also demonstrated visceral hypersensitivity that resolved after day 14. TNBS treated rats demonstrated somatic hypersensitivity at days 14-28 (p<0.0001) in response to somatic stimuli of the hind-paw. TNBS colitis is associated with visceral and somatic hypersensitivity in areas of somatotopic overlap. This model of colitis should allow further investigation into the mechanisms of visceral and somatic hypersensitivity.

show abstract

“…Laser Doppler flowmetry is a reproducible and validated 14,15 measure of hindgut extrinsic autonomic innervation. Transmucosal electrostimulation induces intensityrelated perception in the lower and upper 16,17 gut allowing quantitative assessment for hindgut extrinsic neurological impairment. A primary aim was to identify whether laser Doppler measurement of rectal mucosal blood flow corresponded with the level of injury, particularly in relation to level of sympathetic outflow.…”

Section: Introductionmentioning

confidence: 99%

Relationship between gut-specific autonomic testing and bowel dysfunction in spinal cord injury patients

et al. 2009

View full text Add to dashboard Cite

Study design: Investigation of bowel function in 55 patients and 26 healthy volunteers using radiological, anorectal physiological and laser Doppler blood flow monitoring. Objectives: Bowel dysfunction is common after spinal cord injury (SCI). We aimed to determine whether hindgut testing of autonomic innervation provides insight into presence of symptoms, altered motor function (transit) and level of injury. Setting: St Mark's Hospital, UK and The Spinal Injuries Unit, Royal National Orthopaedic Hospital, UK. Methods: A total of 55 patients with chronic complete SCI and 26 healthy volunteers were studied. Twenty-four patients had lesions above T5 and 31 had lesions below T5. Thirty-five patients complained of constipation: 75% (18/24) of patients with lesions above T5 and 55% (17/31) of those with lesions below T5. Gut transit, rectal electrosensitivity and rectal blood flow were measured. Results: Slow gut transit occurred in 65% of patients and in all the 35 patients complaining of constipation. Delay was pancolonic. All patients had an elevated sensory threshold. The threshold was significantly higher in those with subjective constipation (Po0.01), slow transit (Po0.04) and high SCI (P ¼ 0.046). Mucosal blood flow was lower in SCI patients with constipation (Po0.04) and slow transit (Po0.03). It was higher than normal in high-SCI volunteers (P ¼ 0.056), reflecting loss of sympathetic inhibition. Conclusions: In SCI, subjective constipation correlates closely with slow gut transit. Delay is pancolonic, regardless of the site of lesion. Sensory testing provides evidence for completeness of lesion, offering further evidence for pain transmission through sympathetic pathways. Studies in SCI patients provide further evidence of mucosal blood flow as a marker of altered autonomic innervation.

show abstract

Selective dysfunction of mechanosensitive intestinal afferents in irritable bowel syndrome

Cited by 253 publications

References 14 publications

Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat

Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat

Visceral and Somatic Hypersensitivity in TNBS-Induced Colitis in Rats

Relationship between gut-specific autonomic testing and bowel dysfunction in spinal cord injury patients

Contact Info

Product

Resources

About