A double blind parallel group pilot study of the effects of CJ-11,974 and placebo on perceptual and emotional responses to rectosigmoid distension in IBS patients

Lee, Oh-Young; Munakata, Julie; Naliboff, Bruce D.; Chang, Lin; Mayer, Emeran A.

doi:10.1016/s0016-5085(00)85527-4

Cited by 28 publications

(15 citation statements)

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“…This finding is also consistent with functional neuroimaging studies, which show that IBS patients do not engage PFC to the same extent as HCs or IBD patients while anticipating noxious visceral stimulation [46,56]. Moreover, when IBS patients are treated with NK-1R antagonists, they report attenuated pain to acute visceral stimulation [39,76], coupled with reduced activity in amygdala, hippocampus, and ACC [76], regions associated with nociceptive processing that have high levels of NK-1R expression.…”

Section: Discussionsupporting

confidence: 85%

“…NK-1Rs have therefore been considered a promising pharmacological target for treating chronic pain and psychopathology [30,50]. Despite encouraging outcomes in patients with irritable bowel syndrome [39,76], clinical trials with NK-1R antagonists for depression and other chronic pain syndromes have been disappointing [25,37,52]. Disease-related specificity in NK-1R expression may contribute to these inconsistent findings.…”

Section: Introductionmentioning

confidence: 99%

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Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain

Jarcho

Feier

Bert

et al. 2013

Pain

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Central sensitization and dysregulation of peripheral substance P and neurokinin-1 receptor (NK-1R) signaling are associated with chronic abdominal pain in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Although positron emission tomography (PET) has demonstrated that patients with injury-related chronic pain have diminished NK-1R availability in the brain, it is unknown whether these deficits are present in IBD and IBS patients, who have etiologically distinct forms of non-injury-related chronic pain. This study's aim was to determine if patients with IBD or IBS exhibit deficits in brain expression of NK-1Rs relative to healthy controls (HCs), the extent to which expression patterns differ across patient populations, and if these patterns differentially relate to clinical parameters. PET with [18F]SPA-RQ was used to measure NK-1R availability by quantifying binding potential (BP) in the 3 groups. Exploratory correlation analyses were performed to detect associations between NK-1R BP and physical symptoms. Compared to HCs, IBD patients had NK-1R BP deficits across a widespread network of cortical and subcortical regions. IBS patients had similar, but less pronounced deficits. BP in a subset of these regions was robustly related to discrete clinical parameters in each patient population. Widespread deficits in NK-1R BP occur in IBD and, to a lesser extent, IBS; however, discrete clinical parameters relate to NK-1R BP in each patient population. This suggests that potential pharmacological interventions that target NK-1R signaling may be most effective for treating distinct symptoms in IBD and IBS.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain

Jarcho

Feier

Bert

et al. 2013

Pain

Self Cite

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“…Oral administration of a single 50 mg dose of the neurokinin 1 (NK1) receptor antagonist CJ-11974 has been compared with placebo in seven patients with IBS. 48 Although the NK1 antagonist showed a trend towards increased pressure thresholds for discomfort following repetitive sigmoid distension, the effect was not statistically significant. However, subjects' emotional responses to rectosigmoid stimulation in terms of reduced anger ratings suggested that the central effects of CJ-11974 might potentially be beneficial in patients with IBS.…”

Section: Tachykinin Antagonistsmentioning

confidence: 88%

Pharmacotherapy: non-serotonergic mechanisms

Spiller

2002

Gut

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“…2002]. Data regarding the antinociceptive role of NK 1 R in humans is limited, with only one study showing a trend in reducing emotional responses to rectal balloon distensions after a 7-day trial of ezlopitant in 14 IBS patients [Lee, 2000]. …”

Section: Central and Peripheral-acting Drugsmentioning

confidence: 99%

Review: Therapeutic advances in functional gastrointestinal disease: irritable bowel syndrome

Gaman

Bucur

Kuo

2009

Therap Adv Gastroenterol

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Reported prevalence rates of irritable bowel syndrome (IBS) are between 8% to 20% in the US general population with an average medical expenditure of US$1.35 billion direct and US$205 million indirect costs. Current pathophysiologic theories are based on abnormalities of both the brain and gut, thus setting a new stage for current and future therapeutic approaches. There are numerous treatment options in IBS acting centrally and peripherally by influencing motility and visceral sensitivity. Clinical evidence is variable; however, newer emerging treatments are being evaluated using better-designed clinical trials. Accurate assessment of IBS drug efficacy is still hampered by heterogeneity of the IBS population. Novel methods such as pharmacogenomics or brain imaging may be helpful in the future to better understand and characterize IBS patient subtypes, and this in turn will lead to more specific and efficient therapeutic options. Patient subpopulation measurement of side effects is also a clinical challenge and further understanding could improve treatment efficacy by enhancing the patient compliance.

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A double blind parallel group pilot study of the effects of CJ-11,974 and placebo on perceptual and emotional responses to rectosigmoid distension in IBS patients

Cited by 28 publications

References 0 publications

Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain

Diminished neurokinin-1 receptor availability in patients with two forms of chronic visceral pain

Pharmacotherapy: non-serotonergic mechanisms

Review: Therapeutic advances in functional gastrointestinal disease: irritable bowel syndrome

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