Effect of a κ-opioid agonist, i.v. JNJ-38488502, on sensation of colonic distensions in healthy male volunteers

B. N. Floyd, M. Camilleri, I. Busciglio, S. Sweetser, D. Burton, G. Y. Wong, S. Kell, S. Khanna, S. Hwang, A. R. Zinsmeister

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Kappa-opioid receptors are located on visceral pain fibres. JNJ-38488502 is a highly selective tetrapeptide κ-opioid agonist with little access to the central nervous system and low risk of central nervous system side effects. The aim of the study was to evaluate the effects of i.v. JNJ-38488502 on sensations, including pain, during colonic distension. In a single-centre study, 23 healthy adult males underwent a single-dose, randomized, double-blind crossover study of JNJ-38488502 (0.42 mg kg-1 i.v. infusion) vs placebo on left colon compliance, sensory thresholds and ratings during standard distensions. One participant could not undergo sensation studies. In the other 22, JNJ-38488502 increased colonic compliance (pressure at half-maximum volume 17.9 ± 0.8 mmHg) compared to placebo (21.6 ± 0.9 mmHg, P = 0.007). There was no significant effect on sensory thresholds which, however, were not reached by 44 mmHg in >50% of participants in both treatment phases. There were no significant treatment effects on sensory ratings to distensions at 8, 16, 24, 32 and 36 mmHg above baseline operating pressure. JNJ-38488502 was associated with increased urine output and plasma prolactin, consistent with κ-opioid receptor activation. This study concluded that i.v. JNJ-38488502 induced κ-opioid effects, but did not attenuate colonic sensations following random order colonic distension. Further studies of effects on pain sensations in health and disease are required.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalNeurogastroenterology and Motility
Issue number3
StatePublished - Mar 2009


  • Functional gastrointestinal disorders
  • Visceral pain
  • κ-opioid

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology


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