Dynorphin A(1-13) analgesia in opioid-treated patients with chronic pain. A controlled pilot study

Russell K. Portenoy, Augusto Caraceni, Nathan I. Cherny, Ronald Goldblum, Jane Ingham, Charles E. Inturrisi, Jian H. Johnson, Jeanne Lapin, Paul J. Tiseo, Mary Jeanne Kreek

Research output: Contribution to journalArticle

Abstract

Objective: This pilot study was developed to acquire preliminary data concerning the analgesic efficacy and tolerability of dynorphin A(1-13), a 13 amino acid fragment of the endogenous opioid peptide dynorphin A(1-17), in opioid-treated patients. Design and Setting: Randomised, double-blind, placebo-controlled, graded dose, 3-way crossover pilot study conducted in a comprehensive cancer centre. Patients: Nine chronic pain patients receiving morphine > 150 mg/day for at least 2 weeks, or the equivalent dose of hydromorphone. Interventions: Each patient was given a study treatment on each of 3 successive days after the opioid regimen was stabilised. On each day, a patient received 50% of the usual oral opioid dose when pain was at least moderate, followed 15 minutes later by a brief intravenous infusion of either dynorphin A(1-13) 150 μg/kg, dynorphin A(1-13) 500 μg/kg, or saline placebo. The sequence of administration was randomly ordered. Main Outcome Measures: Pain intensity, pain relief, mood and adverse effects were recorded for 8 hours after each treatment. Blood was sampled for dynorphin levels beginning 15 minutes after the infusion. Results: The data demonstrated linear dose-response trends for most of the parameters evaluated. Using analysis of variance (ANOVA), the differences among lower dose dynorphin A(1-13), higher dose dynorphin A(1-13), and the control were strongest for the sum of pain intensity differences (categorical scale) [p = 0.08], peak relief (p = 0.10), and total mood effect (p = 0.08). Post hoc pairwise comparisons consistently demonstrated the largest differences between the higher dose dynorphin A(1-13) and control. The major adverse effect was flushing. Dynorphin was detected only in the first sample, which was drawn 15 minutes after drug administration. Conclusions: This controlled pilot study identified trends suggesting that a brief intravenous infusion of dynorphin A(1-13) could potentially augment analgesia in opioid-treated patients. Based on this experience, a larger controlled trial is warranted. A 500 μg/kg dose would be an appropriate minimum dose for such studies.

Original languageEnglish
Pages (from-to)33-42
Number of pages10
JournalClinical Drug Investigation
Volume17
Issue number1
DOIs
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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    Portenoy, R. K., Caraceni, A., Cherny, N. I., Goldblum, R., Ingham, J., Inturrisi, C. E., Johnson, J. H., Lapin, J., Tiseo, P. J., & Kreek, M. J. (1999). Dynorphin A(1-13) analgesia in opioid-treated patients with chronic pain. A controlled pilot study. Clinical Drug Investigation, 17(1), 33-42. https://doi.org/10.2165/00044011-199917010-00004