Effect of a second-generation α 2 δ ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome
Open accessAbstract
Background: Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the α 2 δ ligand pregabalin reduces both visceral allodynia and hyperalgesia, but is inactive on basal sensitivity. Aim: To assess the effect of pregabalin on the perception of rectal distension in hypersensitive IBS patients. Methods: Twenty-six patients with Rome-II-defined IBS (aged 18–46 years, 7 male) were included in a randomized, double-blind, placebo-controlled, parallel-group study in which they received either 3 weeks oral pregabalin (titrated: 50 mg tid days 1–3, 100 mg tid days 4–7, 150 mg tid days 8–11; fixed 200 mg tid days 12–21 ±4) or placebo control. Rectal sensitivity was assessed using a barostat technique, in which sensory thresholds were determined using the ascending method of limits, followed by tracking both before and after treatment. Only patients with a pain threshold of ⩽28 mmHg were included in the study. Results: Pregabalin significantly increased the sensory thresholds from baseline for first sensation (p = 0.045), desire to defecate (p = 0.008) and pain (p = 0.048) compared with placebo control. In addition, pregabalin significantly increased rectal compliance (p<0.0001), although this appeared to be unrelated to the changes in sensitivity. Despite the occurrence of mild dizziness and somnolence, pregabalin was generally well tolerated. Conclusions: Pregabalin increased distension sensory thresholds to normal levels in IBS patients with rectal hypersensitivity. A concomitant increase in rectal compliance appeared to be unrelated to the reduction in sensitivity. These data suggest that α 2 δ ligands are worthy of further investigation in the treatment of visceral pain disorders, including IBS.
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Pregabalin improved visceral hypersensitivity in one small trial, and in a recent RCT recruiting 85 patients with IBS, 12 weeks of pregabalin 225 mg twice daily led to significant improvements in global symptoms, abdominal pain, diarrhoea and bloating versus placebo.
“Pregabalin improved visceral hypersensitivity in one small trial, 227 and in a recent RCT recruiting 85 patients with IBS, 12 weeks of pregabalin 225 mg twice daily led to significant improvements in global symptoms, abdominal pain, diarrhoea and bloating versus placebo.228”
From British Society of Gastroenterology guidelines on the management of irritable bowel syndrome (2021) · cites this paper as [227]
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Cites
Nonparametric Statistical Methods
(1999) · Technometrics · doi:10.1080/00401706.1999.10485954 · Cited by 6,117 · see citing works
Longstreth, G. F., Thompson, W. G., Chey, W. D., Houghton, L. A., Mearin, F., & Spiller, R. C. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.061 · Cited by 4,856 · see citing works
Self-citationFunctional bowel disorders and functional abdominal pain
Thompson, W. G., Longstreth, G. F., Drossman, D. A., Heaton, K. W., Irvine, E. J., & Müller-Lissner, S. A. (1999) · Gut · doi:10.1136/gut.45.2008.ii43 · Cited by 2,440 · see citing works
Clinical pharmacokinetics; concepts and applications
(1989) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(89)90348-0 · Cited by 2,232 · see citing works
Role of impaired gastric accommodation to a meal in functional dyspepsia
Tack, J. F., Piessevaux, H. H., Coulie, B. J., Caenepeel, P., & Janssens, J. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70012-5 · Cited by 1,061 · see citing works
Altered rectal perception is a biological marker of patients with irritable bowel syndrome
Mertz, H., Naliboff, B. D., Munakata, J., Niazi, N., & Mayer, E. A. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90267-8 · Cited by 976 · see citing works
Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome
Ritchie, J. (1973) · Gut · doi:10.1136/gut.14.2.125 · Cited by 832 · see citing works
(2011) · Springer eBooks · doi:10.1007/springerreference_44317 · Cited by 549 · see citing works
Pregabalin Pharmacology and Its Relevance to Clinical Practice
Ben‐Menachem, E. (2004) · Epilepsia · doi:10.1111/j.0013-9580.2004.455003.x · Cited by 543 · see citing works
Non-parametric Statistical Methods
Gastwirth, J. L. (1990) · Palgrave Macmillan UK eBooks · doi:10.1007/978-1-349-20865-4_24 · Cited by 516 · see citing works
Bouin, M., Plourde, V., Boivin, M., Riberdy, M., Lupien, F., Laganière, M., Verrier, P., & Poitras, P. (2002) · Gastroenterology · doi:10.1053/gast.2002.33601 · Cited by 470 · see citing works
Whitehead, W. E., & Delvaux, M. (1997) · Digestive Diseases and Sciences · doi:10.1023/a:1018885028501 · Cited by 387 · see citing works
Field, M. J., Oles, R. J., Lewis, S., et al. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701320 · Cited by 331 · see citing works
WHITEHEAD, W., & PALSSON, O. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70099-x · Cited by 314 · see citing works
The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain
Hunter, J. C., Gogas, K. R., Hedley, L. R., Jacobson, L. O., Kassotakis, L., Thompson, J., & Fontana, D. J. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)00070-8 · Cited by 310 · see citing works
Field, M. J., McCleary, S., Hughes, J. M., & Singh, L. (1999) · Pain · doi:10.1016/s0304-3959(98)00239-5 · Cited by 294 · see citing works
Pregabalin for Treatment of Generalized Anxiety Disorder
Rickels, K., Pollack, M. H., Feltner, D. E., Lydiard, R. B., Zimbroff, D. L., Bielski, R. J., Tobias, K., Brock, J., Zornberg, G. L., & Pande, A. C. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.9.1022 · Cited by 280 · see citing works
Evaluation of Gabapentin and S-(+)-3-Isobutylgaba in a Rat Model of Postoperative Pain
Field, M. J., Holloman, E. F., McCleary, S., Hughes, J. M., & Singh, L. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36908-3 · Cited by 248 · see citing works
Heightened visceral sensation in functional gastrointestinal disease is not site-specific
Trimble, K. C., Farouk, R., Pryde, A., Douglas, S., & Heading, R. C. (1995) · Digestive Diseases and Sciences · doi:10.1007/bf02212678 · Cited by 243 · see citing works
Dysmotility of the small intestine in irritable bowel syndrome.
Kellow, J. E., Phillips, S. F., Miller, L. J., & Zinsmeister, A. R. (1988) · Gut · doi:10.1136/gut.29.9.1236 · Cited by 237 · see citing works
Houghton, L. A., Lea, R., Jackson, N., & Whorwell, P. J. (2002) · Gut · doi:10.1136/gut.50.4.471 · Cited by 235 · see citing works
Self-citationMATTE, H. O., Rodriguez, O., & CASTRO, E. A. (1955) · PubMed · Cited by 231 · see citing works
Pande, A. C., Feltner, D. E., Jefferson, J. W., Davidson, J. R. T., Pollack, M., Stein, M. B., Lydiard, R. B., Futterer, R., Robinson, P., Slomkowski, M., et al. (2004) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000117423.05703.e7 · Cited by 227 · see citing works
Mertz, H., Fass, R., Kodner, A., Yan‐Go, F. L., Fullerton, S. C., & Mayer, E. A. (1998) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1998.00160.x · Cited by 219 · see citing works
Functional bowel disorders and functional abdominal pain
Thompson, W., Irvine, E., Drossman, D., et al. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/x3mq-ct28 · Cited by 204 · see citing works
Modulation of gastric sensory and motor functions by nitrergic and α2-adrenergic agents in humans
Thumshirn, M., Camilleri, M., Choi, M., & Zinsmeister, A. R. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70179-4 · Cited by 186 · see citing works
Lea, R., Houghton, L. A., Calvert, E. L., Larder, S., Gonsalkorale, W. M., Whelan, V., Randles, J., Cooper, P., Cruickshanks, P., Miller, V., et al. (2003) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.2003.01486.x · Cited by 172 · see citing works
Self-citationHWANG, J., & Yaksh, T. L. (1997) · Regional Anesthesia & Pain Medicine · doi:10.1016/s1098-7339(06)80010-6 · Cited by 172 · see citing works
Efficacy of Pregabalin in the Treatment of Generalized Anxiety Disorder
Pohl, R. B., Feltner, D. E., Fieve, R. R., & Pande, A. C. (2005) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000155820.74832.b0 · Cited by 167 · see citing works
Rectal tone, distensibility, and perception: reproducibility and response to different distensions
Hammer, H. F., Phillips, S. F., Camilleri, M., & Hanson, R. B. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.274.3.g584 · Cited by 159 · see citing works
The proximal stomach and postprandial symptoms in functional dyspeptics
Boeckxstaens, G. E., Hirsch, D. P., Kuiken, S. D., Heisterkamp, S. H., & Tytgat, G. N. J. (2002) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2002.05421.x · Cited by 150 · see citing works
Altered esophageal pain threshold in irritable bowel syndrome
Costantini, M., Sturniolo, G. C., Zaninotto, G., D'Inc�, R., Polo, R., Naccarato, R., & Ancona, E. (1993) · Digestive Diseases and Sciences · doi:10.1007/bf01307536 · Cited by 99 · see citing works
Systemic gabapentin and S(+)-3-isobutyl-γ-aminobutyric acid block secondary hyperalgesia
Jones, D. L., & Sorkin, L. S. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00890-7 · Cited by 99 · see citing works
Origin of chronic right upper quadrant pain.
Kingham, J. G. C., & Dawson, A. M. (1985) · Gut · doi:10.1136/gut.26.8.783 · Cited by 95 · see citing works
Diop, L., Raymond, F., Fargeau, H., Pétoux, F., Chovet, M., & Doherty, A. M. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.302.3.1013 · Cited by 93 · see citing works
Effects of venlafaxine, buspirone, and placebo on colonic sensorimotor functions in healthy humans
Chial, H. J., Camilleri, M., Ferber, I. J., Delgado-Aros, S., Burton, D. D., McKinzie, S., & Zinsmeister, A. R. (2003) · Clinical Gastroenterology and Hepatology · doi:10.1016/s1542-3565(03)70038-x · Cited by 84 · see citing works
Antinociceptive Effect of Pregabalin in Septic Shock-Induced Rectal Hypersensitivity in Rats
Eutamène, H., Coelho, A.-M., Théodorou, V., Toulouse, M., Chovet, M., Doherty, A. M., Fioramonti, J., & Bueno, L. P. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38882-2 · Cited by 59 · see citing works
Symptomatic responses to stimulation of sensory pathways in the jejunum
Accarino, A. M., Azpiroz, F., & Malagelada, J. R. (1992) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1992.263.5.g673 · Cited by 59 · see citing works
Spollett, G. R. (1989) · The Nurse Practitioner · doi:10.1097/00006205-198908000-00007 · Cited by 52 · see citing works
Fate of Newborn Dentate Granule Cells after Early Life Status Epilepticus
Porter, B. E., Maronski, M., & Brooks‐Kayal, A. R. (2003) · Epilepsia · doi:10.1111/j.0013-9580.2004.23903.x · Cited by 49 · see citing works
Houghton, A. K., Lu, Y., & Westlund, K. N. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37417-8 · Cited by 47 · see citing works
Palsson, O. S., & Whitehead, W. E. (2021) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/erff-y391 · Cited by 31 · see citing works
Effects of venlafaxine, buspirone, and placebo on colonic sensorimotor functions in healthy humans
Chial, H. J., Camilleri, M., Ferber, I., et al. (2003) · Clinical Gastroenterology and Hepatology · doi:10.1053/jcgh.2003.50031 · Cited by 22 · see citing works
Huckle, R. (2004) · PubMed · Cited by 10 · see citing works
Hammonds, R. M., Houghton, L. A., & Whorwell, P. J. (2000) · Gastroenterology · doi:10.1016/s0016-5085(00)82634-7 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [15]15. Xiao W, Bennett GI. Gabapentin relieves abdominal pains in a rat model of painful peripheral neuropathy [abstract]. Soc Neurosci 1995;21:356.
Cited by
Sorted by citations
British Society of Gastroenterology guidelines on the management of irritable bowel syndrome
Vasant, D. H., Paine, P. A., Black, C. J., Houghton, L. A., Everitt, H. A., Corsetti, M., Agrawal, A., Aziz, I., Farmer, A. D., Eugenicos, M. P., et al. (2021) · Gut · doi:10.1136/gutjnl-2021-324598 · Cited by 547 · see citing works
Self-citationDrossman, D. A., Tack, J., Ford, A. C., Szigethy, E., Törnblom, H., & Van Oudenhove, L. (2018) · Gastroenterology · doi:10.1053/j.gastro.2017.11.279 · Cited by 470 · see citing works
Crouzet, L., Gaultier, E., Del'Homme, C., Cartier, C., Delmas, E., Dapoigny, M., Fioramonti, J., & Bernalier‐Donadille, A. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12103 · Cited by 280 · see citing works
Paediatric functional abdominal pain disorders
Thapar, N., Benninga, M. A., Crowell, M. D., Di Lorenzo, C., Mack, I., Nurko, S., Saps, M., Shulman, R. J., Szajewska, H., van Tilburg, M. A. L., et al. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00222-5 · Cited by 221 · see citing works
Bloating and Distention in Irritable Bowel Syndrome: The Role of Visceral Sensation
Agrawal, A., Houghton, L. A., Lea, R., Morris, J., Reilly, B., & Whorwell, P. J. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.02.096 · Cited by 114 · see citing works
Self-citationPain management in patients with inflammatory bowel disease: insights for the clinician
Srinath, A. I., Walter, C., Newara, M. C., & Szigethy, E. M. (2012) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x12446158 · Cited by 111 · see citing works
Visceral hypersensitivity in endometriosis: a new target for treatment?
Issa, B., Onon, T. S., Agrawal, A., Shekhar, C., Morris, J., Hamdy, S., & Whorwell, P. J. (2012) · Gut · doi:10.1136/gutjnl-2011-300306 · Cited by 90 · see citing works
Self-citationRandomised clinical trial: pregabalin vs placebo for irritable bowel syndrome
Saito, Y. A., Almazar, A. E., Tilkes, K. E., Choung, R. S., Van Norstrand, M. D., Schleck, C. D., Zinsmeister, A. R., & Talley, N. J. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15077 · Cited by 79 · see citing works
Different faces of gastroparesis
Bielefeldt, K., Raza, N., & Zickmund, S. L. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.6052 · Cited by 71 · see citing works
Awad, R. A., & Camacho, S. (2010) · Colorectal Disease · doi:10.1111/j.1463-1318.2009.01990.x · Cited by 62 · see citing works
Recent developments in the therapy of irritable bowel syndrome
Saad, R. J., & Chey, W. D. (2008) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.17.2.117 · Cited by 21 · see citing works
Challenges and prospects for pharmacotherapy in functional gastrointestinal disorders
Sanger, G. J., Chang, L., Bountra, C., & Houghton, L. A. (2010) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x10369922 · Cited by 17 · see citing works
Self-citationPearson, J. S., Pollard, C., & Whorwell, P. J. (2014) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x14540028 · Cited by 12 · see citing works
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- Authors
- Houghton, L. A., Fell, C., Whorwell, P. J., Jones, I., Sudworth, D. P., & Gale, J. D.
- Affiliations
- University of Manchester (GB)
- Pfizer (United States) (US)
- Corresponding author
- Houghton, L A
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2007-04-19
- Volume
- 56
- Issue
- 9
- Pages
- 1218-1225
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC1954959
- OpenAlex
- W2117456715
- Cited by
- 204
- References
- 45
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 15 · 2020: 9 · 2019: 7 · 2018: 11 · 2017: 8 · 2016: 8 · 2015: 12 · 2014: 9 · 2013: 9 · 2012: 14
- FWCI
- 13.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
- Keywords
- pregabalin, irritable bowel syndrome, visceral hypersensitivity, visceral pain, rectal distension, rectal sensory threshold, rectal compliance
- MeSH terms
- Pregabalin, Administration, Oral, Adolescent, Adult, Analgesics, Double-Blind Method, Female, gamma-Aminobutyric Acid, Humans, Male, Middle Aged, Pain, Pain Measurement, Pressure, Rectum, Sensation, Sensory Thresholds, Pain Threshold, Irritable Bowel Syndrome
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