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 language | English |
|---|---|
| Pages (from-to) | 33-42 |
| Number of pages | 10 |
| Journal | Clinical Drug Investigation |
| Volume | 17 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1999 |
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ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology
Cite this
Dynorphin A(1-13) analgesia in opioid-treated patients with chronic pain. A controlled pilot study. / Portenoy, Russell K.; Caraceni, Augusto; Cherny, Nathan I.; Goldblum, Ronald; Ingham, Jane; Inturrisi, Charles E.; Johnson, Jian H.; Lapin, Jeanne; Tiseo, Paul J.; Kreek, Mary Jeanne.
In: Clinical Drug Investigation, Vol. 17, No. 1, 1999, p. 33-42.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dynorphin A(1-13) analgesia in opioid-treated patients with chronic pain. A controlled pilot study
AU - Portenoy, Russell K.
AU - Caraceni, Augusto
AU - Cherny, Nathan I.
AU - Goldblum, Ronald
AU - Ingham, Jane
AU - Inturrisi, Charles E.
AU - Johnson, Jian H.
AU - Lapin, Jeanne
AU - Tiseo, Paul J.
AU - Kreek, Mary Jeanne
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0032959282&partnerID=8YFLogxK
U2 - 10.2165/00044011-199917010-00004
DO - 10.2165/00044011-199917010-00004
M3 - Article
AN - SCOPUS:0032959282
VL - 17
SP - 33
EP - 42
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
SN - 1173-2563
IS - 1
ER -