Evidence for the hypersensitivity of lumbar splanchnic afferents in irritable bowel syndrome

Lembo, Tony; Munakata, Julie; Mertz, Howard; Niazi, Negar; Kodner, Anatoly; Nikas, Vasilas; Mayer, Emeran A.

doi:10.1016/0016-5085(94)90809-5

Cited by 274 publications

(221 citation statements)

References 26 publications

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“…Interestingly, sensation evoked by slow ramp distension in the human rec-tum was reduced by luminal application of the local anaesthetic, lidocaine, which suggests a possible role for muscular-mucosal afferents with endings close to the mucosal surface. 147 Although pain from the gut is ubiquitous in response to high amplitude distension, other modalities of sensation are commonly experienced, particularly at the proximal and distal ends of the gastrointestinal tract. For example, humans can discriminate between solid, liquid and gaseous content in the distal rectum and anal canal, 148 although the sensory receptors responsible are not clear.…”

Section: Extrinsic Afferent Pathways and Sensationmentioning

confidence: 99%

“…149 Consistent with this idea, studies in patients with spinal cord lesions suggest that painful rapid rectal distension might be preferentially detected by splanchnic pathways, whereas slow ramp distension activates pelvic pathways, with urge preceding discomfort. 147 The proximal gastrointestinal tract is also dually innervated via vagal and splanchnic pathways. Gastric distension gives rise to sensations of fullness and has a potent effect on food intake, via gastric mechanoreceptors rather than chemoreceptors.…”

Section: Extrinsic Afferent Pathways and Sensationmentioning

confidence: 99%

See 1 more Smart Citation

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

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Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors, and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that there are just five structurally distinct types of sensory endings in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators.Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.2

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Section: Extrinsic Afferent Pathways and Sensationmentioning

confidence: 99%

Section: Extrinsic Afferent Pathways and Sensationmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

View full text Add to dashboard Cite

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“…The EMG activity was rectified, and the increase in the area under the curve (AUC) of EMG amplitude (over baseline) was recorded as the response. Baseline responses to graded intensities of phasic CRD (10,20,40,60, and 80 mmHg; 20 s duration; 4 min interstimulus interval) were obtained in MS180 as well as NH rats. The animals were then exposed to water avoidance stress (WA) for 1 h, and responses to phasic CRD were obtained again.…”

Section: Assessment Of Viscerosomatic Sensitivitymentioning

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

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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...

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“…Peripheral terminals of sensory neurons innervating the colon are equipped to detect a variety of mechanical stimuli, including organ distension (Su and Gebhart, 1998) and circumferential stretch of the muscle layers (Lynn and Blackshaw, 1999), and the sensitization of colon afferent fiber function contributes to the mechanical hypersensitivity and abdominal pain of patients with irritable bowel syndrome (Lembo et al, 1994). However, the molecules responsible for mechanosensation and sensitization in the viscera are unknown but present promising targets for novel treatments of visceral pain.…”

Section: Introductionmentioning

confidence: 99%

The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

Jones¹,

Xu²,

Gebhart³

2005

J. Neurosci.

383

308

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Mechanical hypersensitivity of the colon underlies in part the chronic abdominal pain experienced by patients with irritable bowel syndrome, yet the molecules that confer mechanosensitivity to colon sensory neurons and their contribution to visceral pain are unknown. We tested the hypothesis that transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel 3 (ASIC3) are peripheral mechanosensors in colon afferent neuronal fibers that mediate visceral nociceptive behavior in mice. Visceral nociception, modeled by the visceromotor response to colorectal distension, and colon afferent fiber mechanosensitivity were assessed in control (C57BL/6) mice and two congenic knock-out mouse strains with deletions of either TRPV1 or ASIC3. Phasic colon distension (15-60 mmHg) produced graded behavioral responses in all three mouse strains. However, both TRPV1 and ASIC3 knock-out mice were significantly less sensitive to distension, with an average response magnitude only 58 and 50% of controls, respectively. The behavioral deficits observed in both strains of knock-out mice were associated with a significant and selective reduction in afferent fiber sensitivity to circumferential stretch of the colon, an effect that was mimicked in control preparations by pretreatment with capsazepine, a TRPV1 antagonist, but not amiloride, a nonselective ASIC antagonist (both 500 M). In addition, whereas stretch-evoked afferent fiber responses were enhanced by chemical inflammatory mediators in control mice, this effect was differentially impaired in both knock-out mouse strains. These results demonstrate a peripheral mechanosensory role for TRPV1 and ASIC3 in the mouse colon that contributes to nociceptive behavior and possibly peripheral sensitization during tissue insult.

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Evidence for the hypersensitivity of lumbar splanchnic afferents in irritable bowel syndrome

Cited by 274 publications

References 26 publications

Extrinsic primary afferent signalling in the gut

Extrinsic primary afferent signalling in the gut

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

The Mechanosensitivity of Mouse Colon Afferent Fibers and Their Sensitization by Inflammatory Mediators Require Transient Receptor Potential Vanilloid 1 and Acid-Sensing Ion Channel 3

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