Effect of a second-generation  2  ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome

Houghton, Lesley A.; Fell, Catherine; Whorwell, Peter J.; Jones, Ieuan; Sudworth, David; Gale, Jeremy D.

doi:10.1136/gut.2006.110858

Cited by 179 publications

(143 citation statements)

References 30 publications

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“…9,[15][16][17][18][19] The barostat was programmed to deliver a series of phasic isobaric rectal distensions 60 s in duration, separated by 60 s periods, during which bag pressure returned to the IOP. Distension stimuli were programmed to increase by 4 mmHg with each distension until the subject reported pain.…”

Section: Distension Protocolmentioning

confidence: 99%

Rectal hyposensitivity for non-noxious stimuli, postprandial hypersensitivity and its correlation with symptoms in complete spinal cord injury with neurogenic bowel dysfunction

et al. 2012

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Study design: Prospective clinical study. Objectives: To assess fasting and postprandial (PP) perception of rectal distension and its correlation with symptoms in patients with spinal cord injury (SCI) and neurogenic bowel dysfunction compared to ten healthy subjects (HS). Setting: Experimental Medicine and Motility Unit, Mexico General Hospital and National Institute of Rehabilitation. Methods: Twenty patients with complete SCI at cervical, thoracic and lumbar levels [American Spinal Injury Association (ASIA) A] were studied. Rectal sensitivity was evaluated with a barostat. Results: In SCI patients, while lower the rectal tone more time was used for defecate (R ¼ 0.50, P ¼ 0.048) and more PP episodes of fecal incontinence occur (R ¼ 0.54, P ¼ 0.030). The thresholds for non-noxious stimuli of first (23.6 mmHg, CI 19.5-27.7) vs 14.0 (CI 10.9-17.1), P ¼ 0.004; gas (27.9 mmHg, CI 19.9-35.8) vs 17.9 mmHg (CI 14.25-21.69), P ¼ 0.02 and urge-to-defecate sensation (33.2 mmHg, CI 27.5-38.8) vs 22.4 mmHg (CI 17.9-26.9), P ¼ 0.01 were reported by SCI patients at higher pressure than HS, respectively. SCI patients reported PP pain sensation at a lower pressure than controls (27.8 mmHg, CI 21.5-34.2 vs 36.5 mmHg, CI 31.8-41.2), P ¼ 0.04. Conclusion: SCI patients preserve rectal sensation, present rectal hyposensitivity for non-noxious stimuli and PP hypersensitivity. Lower rectal tone was related to the time used for defecate and with fecal incontinence. The results suggest that an intact neural transmission between the spinal cord and higher centres is indispensable for noxious stimulus, but not for non-noxious stimuli. Also, barostat sensitivity studies can complement ASIA criteria to verify a complete injury. Spinal Cord (2013) 51, 94-98;

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Section: Distension Protocolmentioning

confidence: 99%

Rectal hyposensitivity for non-noxious stimuli, postprandial hypersensitivity and its correlation with symptoms in complete spinal cord injury with neurogenic bowel dysfunction

et al. 2012

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“…19 Viscerosomatic responses can also be evoked by colorectal distension, but we chose a writhing test since colonic distension has a lower degree of inflammation and is more conducive for specific abdominal pain associated with altered colonic sensitivity such as in irritable bowel syndrome. 10,11,23,28 Availability and ease of management were the main reasons for using mice instead of rats 7,14-18 and intraperitoneal injection instead of other routes of administration. The duration of the test was set at 30 min to reduce variability and obtain a rapid result.…”

Section: Resultsmentioning

confidence: 99%

Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain

Meymandi

Keyhanfar

2012

Can J Anesth/J Can Anesth

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Purpose Pregabalin is probably more effective than prototype gabapentin in different kinds of pain treatments. This study was performed to compare the potency of gabapentin, pregabalin, and morphine in a well-established model of visceral pain. Methods The number of abdominal contractions was counted for 30 min in adult male mice that received different doses of pregabalin, gabapentin, morphine, or placebo intraperitoneally 30 min before receiving 0.6% acetic acid 10 mLÁkg -1 .The antinociceptive effect of each drug dose was determined as a percentage of the reduction in the number of acetic acid-induced writhes. The effective doses, for 20%, 50%, and 80% response (ED 20 , ED 50 , and ED 80 , respectively), of each drug were calculated using least squares linear regression analysis, and then dose-response curves were compared. Results Pregabalin, gabapentin, and morphine produced a linear dose-dependent antinociceptive effect (coefficient of determination [r 2 ] [ 0.9). No difference was observed between slopes of dose-response curves. The ED 50 estimates (95% confidence interval) for pregabalin, gabapentin, and morphine were 17.1 (12.9 to 22.1) mgÁkg -1 , 87.1 (45.8 to 129.8) mgÁkg -1 , and 0.2 (0.1 to 0.3) mgÁkg -1 , respectively. Conclusion In this animal model of visceral pain, all three drugs exhibited parallel dose-response curves. Pregabalin had five times the potency of gabapentin and 1/85 th the potency of morphine. Similar potency ratios may apply in clinical practice. Despite some limitations of animal studies, this model could be useful for comparing new analgesics in visceral pain treatment.Résumé ObjectifLa pre´gabaline est probablement plus efficace que son prototype, la gabapentine, dans divers traitements contre la douleur. Cette e´tude a e´te´re´alise´e pour comparer la puissance de la gabapentine, de la pre´gabaline et de la morphine dans un mode`le bien e´tabli de douleur visce´rale. Méthode Le nombre de contractions abdominales a e´teć ompte´pendant 30 min chez des souris maˆles adultes recevant diffe´rentes doses de pre´gabaline, de gabapentine, de morphine ou de placebo par voie intrape´ritone´ale 30 min avant 0,6 % d'acide ace´tique (10 mLÁkg -1 ). L'effet antinociceptif de chaque dose de me´dicament a e´ted e´termine´en tant que pourcentage de re´duction du nombre de contorsions induites par l'acide ace´tique. Les doses efficaces (DE) 20 %, 50 % et 80 % (DE 20 , DE 50 et DE 80 ) de chaque me´dicament ont e´te´calcule´es a`l'aide de l'analyse de re´gression line´aire des moindres carre´s et les courbes de dose-re´ponse ont ensuite e´te´compare´es. Résultats La pre´gabaline, la gabapentine et la morphine ont produit un effet antinociceptif de´pendant line´airement de la dose (coefficient de de´termination [r 2 ] [ 0,9).

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“…A clinical trial with irritable bowel syndrome patients suffering from rectal hypersensitivity showed that pregabalin increased the distension sensory thresholds to normal levels Houghton et al [30] . This is supported by the recent work of Meymandi and Keyhanfar [2] who stated that pregabalin had five times the potency of gabapentin and 1/85 th the potency of morphine in animal models of visceral pain.…”

Section: Discussionmentioning

confidence: 99%

The Analgesic Effect of Pregabalin, a Comparative Study With Morphine

A.Shabayek

A.Mustafa

Khorshid

et al. 2014

Zagazig University Medical Journal

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Objectives: this study was designed to assess and compare the effects of pregabalin and morphine on acute thermal pain and on nerve injury associated pain (chronic neuropathic pain). Methods: 72 male albino rats were divided into two major groups: group I (acute pain group) 30 rats divided into 5 equal subgroups (1)control, (2) pregabalin 30 mg/kg, (3)morphine 0.5 mg/kg, (4) pregabalin 60 mg/kg, (5)morphine 1mg/kg, and group II(chronic pain group) 42 rats were divided into 7 equal subgroups (1)sham operated, (2)control normal, (3) control postoperative, (4) pregabalin 30mg/kg, (5) morphine 0.5 mg/kg, (6) pregabalin 60 mg/kg, (7) morphine 1mg/kg. For acute pain the reaction times, which indicate the tolerability of the animals to acute thermal pain, was measured using analgesia meter. However chronic neuropathic pain was induced in experimental animals by unilateral ligation of the sciatic nerve in the thigh. Results: The result of the present study revealed that neither 30 nor 60 mg/kg pregabalin produced any significant effects on the tolerability of rats to acute thermal pain. On the other hand, pregabalin (30 and 60 mg/kg) markedly reversed allodynia and hyperalgesia in rats subjected to sciatic nerve ligation. The effect of pregabalin 30 mg/kg was noticed after 60 minutes and persist for 90 minutes but the higher dose (60 mg/kg) produced analgesic effect all over the experiment. On the other hand morphine 0.5 and 1 mg/kg significantly increased the tolerability of normal and sciatic nerve ligated rats to thermal nociception. The analgesic effect of morphine was more significant than that of pregabalin all over the experiments. Conclusion: in contradiction to morphine, pregabalin was not effective for treatment of acute pain. Both pregabalin and morphine produced significant analgesic effect in neuropathic pain. The effect of morphine was more significant than that of pregabalin.

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Effect of a second-generation 2 ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome

Cited by 179 publications

References 30 publications

Rectal hyposensitivity for non-noxious stimuli, postprandial hypersensitivity and its correlation with symptoms in complete spinal cord injury with neurogenic bowel dysfunction

Rectal hyposensitivity for non-noxious stimuli, postprandial hypersensitivity and its correlation with symptoms in complete spinal cord injury with neurogenic bowel dysfunction

Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain

The Analgesic Effect of Pregabalin, a Comparative Study With Morphine

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