Psychosensory modulation of colonic sensation in the human transverse and sigmoid colon

Ford, Michael J.; Camilleri, Michael; Zinsmeister, Alan R.; Hanson, Russell B.

doi:10.1016/0016-5085(95)90743-2

Cited by 156 publications

(101 citation statements)

References 41 publications

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“…During distensions, participants rated the intensity of gas and pain perception using a 100-mm VAS with the words "unnoticeable" and "unbearable" anchored at the left and right ends of the lines. This has been shown to be an adequate model of visceral sensation in humans (25,40).…”

Section: Assessment Of Colonic Motor and Sensory Functionmentioning

confidence: 99%

Effects of a κ-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans

Delgado-Aros

Chial

Camilleri

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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105

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ton, and Alan R. Zinsmeister. Effects of a -opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans. Am J Physiol Gastrointest Liver Physiol 284: G558-G566, 2003; 10.1152 10. /ajpgi.00360.2002pare the effects of the -opioid agonist asimadoline and placebo on visceral sensation and gastrointestinal (GI) motor functions in humans, 91 healthy participants were randomized in a double-blind fashion to 0.15, 0.5, or 1.5 mg of asimadoline or placebo orally twice a day for 9 days. We assessed satiation (nutrient drink test), colonic compliance, tone, perception of colonic distension (barostat), and whole gut transit (scintigraphy). Treatment effect was assessed by analysis of covariance. Asimadoline increased nutrient drink intake (P ϭ 0.03). Asimadoline decreased colonic tone during fasting (P ϭ 0.03) without affecting postprandial colonic contraction, compliance, or transit. Gas scores in response to colonic distension were decreased with 0.5 mg of asimadoline at low levels (8 mmHg above operating pressure) of distension (P ϭ 0.04) but not at higher levels of distension. Asimadoline at 1.5 mg increased gas scores at 16 mmHg of distension (P ϭ 0.03) and pain scores at distensions of 8 and 16 mmHg (P ϭ 0.003 and 0.03, respectively) but not at higher levels of distension. Further studies of this compound in diseases with altered satiation or visceral sensation are warranted. sensation; visceral; stomach; colon; barostat VISCERAL PAIN AND DISCOMFORT are relevant clinical features of many medical processes, including functional gastrointestinal (GI) disorders (57). These are frequent and chronic-relapsing conditions with a great impact on quality of life (23), yet no satisfactory treatment is available for treatment of pain in these highly prevalent conditions.The three major opioid receptors, , ␦, and , are distributed in the peripheral and central nervous systems (45, 53) and are known to modulate visceral nociception (16,22,29).

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Section: Assessment Of Colonic Motor and Sensory Functionmentioning

confidence: 99%

Effects of a κ-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans

Delgado-Aros

Chial

Camilleri

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

105

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“…Ford et al (15) published very interesting results of a study where they compared the effects of stress (dichotomous listening) with the effects of active relaxation in 22 volunteers. These authors evaluated the effects of these stressful and relaxing periods on imposed distensions.…”

Section: Studies In Humansmentioning

confidence: 99%

Stress and Visceral Perception

Delvaux

1999

Canadian Journal of Gastroenterology and Hepatology

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MM Delvaux. Stress and visceral perception. Can J Gastroenterol 1999;13(Suppl A):32A-36A. Functional bowel disorders are characterized by the presence of a visceral hyperalgesia in most patients. This visceral hyperalgesia is related to an enhanced perception of sensations originating from the gut. Stressful events can dramatically influence the course of functional bowel disorders, and patients suffering from these syndromes appear to be more susceptible to the stressful events of daily life. However, until now, few studies have evaluated the relationship between stress and visceral perception. Some studies of healthy volunteers indicated contradictory results, but the studies used different methodologies. During stress conditions, either physical or mental, thresholds of perception of rectal distension were increased, suggesting a 'distraction effect', or were decreased, supporting a sensitizing effect of stress. In most studies, rectal compliance was not affected, but stress has been shown to alter the rectal tone, as measured by a barostat. One study comparing irritable bowel syndrome patients with controls demonstrated the importance of cognitive processes in the modulation of visceral perception by stress. Animal studies have also demonstrated the sensitizing effect of stress on the perception of rectal distension. Mediators involved may be numerous, but corticotropin-releasing factor has been demonstrated to play a major role at the central level. Mast cells and histamine release may play a role at the peripheral level. Stress can thus be included in an integrative model explaining the pathophysiology of functional bowel disorders. Advances in the understanding of the relationship between stress and visceral perception may constitute a basis for a therapeutic approach of functional bowel disorders targeted on the central nervous system. Key Words: Functional bowel disorders, Irritable bowel syndrome, Stress, Visceral perception Stress et perception viscérale RÉSUMÉ:Les troubles intestinaux fonctionnels se caractérisent par la présence d'une hyperalgésie viscérale chez la plupart des patients. Cette hyperalgésie viscérale est liée à une perception plus aiguë des sensations émanant de l'intestin. Les événements stressants peuvent influer de façon dramatique sur l'évolution des troubles intestinaux et les patients qui en souffrent semblent plus sujets aux événements stressants dans la vie de tous les jours. Par contre, jusqu'à présent, peu d'études ont porté sur le lien entre le stress et la perception viscérale. Certaines, menées auprès de volontaires en bonne santé, ont fait état de résultats contradictoires, mais elles ont utilisé des méthodologies différentes. En présence de stress physique ou mental, les seuils de perception de la distension rectale s'élèvent, ce qui suggère un ‹‹ effet de distraction ››, ou s'abaissent et appuient alors l'hypothèse d'un effet sensibilisant du stress. Dans la plupart des études, la compliance rectale n'a pas été affectée mais le stress s'est révélé apte à modifier le to...

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“…Each distention lasted 1 min and was followed by an equilibration period at the operating pressure for 2 min. A 100-mm visual analog scale (VAS) was used to assess the rating of arousal and stress experienced by each subject before performing the phasic distentions (2,3,15,18,22). Levels of stress were also assessed using two similar scales anchored with the terms "peaceful" and "tense" and "worried" and "relaxed", respectively.…”

Section: Experimental Protocol To Assess Colonic Motor and Sensory Fumentioning

confidence: 99%

Effect of the α2δ ligand, pregabalin, on colonic sensory and motor functions in healthy adults

Iturrino¹,

Camilleri²,

Busciglio³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Pregabalin, an ␣2␦ ligand, is used clinically to treat somatic pain. A prior study suggested that pregabalin reduces distension-induced pain while increasing rectal compliance. We aimed to quantify effects of pregabalin on colonic sensory and motor functions and assess relationships between sensory effects and colonic compliance. We conducted a randomized, double-blind, placebo-controlled, parallel-group study of a single oral administration of 75 or 200 mg of pregabalin in 62 healthy adults (aged 18 -75 yr). Subjects underwent left colon intubation. We assessed "stressarousal symptoms", compliance, sensation thresholds, sensation ratings averaged over four levels of distension, fasting and postprandial colonic tone, and phasic motility index (MI). Analysis of covariance (adjusted for age, sex, body mass index, and corresponding predrug response) and proportional hazard models were used. There were no clinically important differences among treatment groups for demographics, predrug compliance, tone, MI, and sensation. Treatment was associated with reduced energy and increased drowsiness but no change in tension or relaxation. Sensation ratings averaged over the four distension levels were lower for gas sensation [overall effect P ϭ 0.14, P ϭ 0.05 (pregabalin 200 mg vs. placebo)] and for pain sensation [overall effect P ϭ 0.12, P ϭ 0.04 (pregabalin 200 mg vs. placebo)]. The magnitude of the effect of 200 mg of pregabalin relative to placebo is on average a 25% reduction of both gas and pain sensation ratings. Pregabalin did not significantly affect colonic compliance, sensation thresholds, colonic fasting tone, and MI. Thus 200 mg of pregabalin reduces gas and pain sensation and should be tested in patients with colonic pain. colonic compliance; gas sensation; pain sensation THE HETEROMULTIMERIC voltage-sensitive calcium (Ca 2ϩ ) channel is involved in the function of excitable tissues including sensory nerves. It comprises a primary ␣1 subunit and auxiliary ␣2␦, ␤, and ␥ subunits, and the associated ␣2␦ ligandbinding site (26). Pregabalin binds potently to the ␣2␦ auxiliary protein associated with voltage-gated calcium channels (12), reducing depolarization-induced calcium influx at the nerve terminals. Consequently, pregabalin may reduce the release of several excitatory neurotransmitters, including glutamate, noradrenaline, substance P, and calcitonin gene-related peptide, which have been involved in pain mechanisms (1, 4). Recently, Needham et al. (21) showed that intrinsic primary afferent neurons in the small bowel of guinea pigs express functional N (␣1B) channel-forming subunits that are associated with ␣2␦1 modulatory subunits and are inhibited by pregabalin.Pregabalin, a second generation ␣ 2 ␦ ligand, has been shown to be effective in several animal models of visceral pain including trinitrobenzene sulfonic acid colitis (10), septic shock-induced rectal hypersensitivity (11), and a repeated colonic distension model in normal rat colon (20). These studies led to pregabalin being proposed as a trea...

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Psychosensory modulation of colonic sensation in the human transverse and sigmoid colon

Cited by 156 publications

References 41 publications

Effects of a κ-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans

Effects of a κ-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans

Stress and Visceral Perception

Effect of the α2δ ligand, pregabalin, on colonic sensory and motor functions in healthy adults

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