HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Cancer-related bone pain is attenuated by a systemically available delta-opioid receptor agonist.

Abstract
Patients with bone cancer report severe pain and receive mu-opioids. We developed a family of peptidomimetic delta-agonists, one of which H2N-Tyr-dVal-Gly-Phe-Ala-OH ([dVal(L)2,Ala(L)5]E) binds with a 1700x affinity at the delta versus mu receptor. To examine the systemic analgesic efficacy of this delta-agonist versus morphine in osteosarcoma pain, osteosarcoma cells are injected into one femur of the anesthetized mouse. After 10-18 days, a decalcification of the injected femur occurs along with a pronounced tactile allodynia. IP morphine and [dVal(L)2,Ala(L)5]E produced a dose-dependent reversal of allodynia with the respective ED50 values being 5.3+/-1.9 mg/kg for morphine and 1.3+/-0.3 mg/kg for [dVal(L)2,Ala(L)5]E. Plotting peak effect versus area under the analgesic curve for doses of morphine and [dVal(L)2,Ala(L)5]E revealed overlapping curves suggesting that for a given effect, [dVal(L)2,Ala(L)5]E produced a similar duration of action as morphine. These effects were reversed by IP naloxone (3 mg/kg). IP naltrindole (1 mg/kg) preferentially reversed [dVal(L)2,Ala(L)5]E. The upper dose effects of morphine but not [dVal(L)2,Ala(L)5]E were limited by pronounced hyperactivity. No other effects were noted. These results show that IP [dVal(L)2,Ala(L)5]E through a delta receptor produces analgesia equal in efficacy to that of morphine but with a 4.5-fold greater potency. Over the doses examined, morphine actions were side effect limited. The delta side effects were not so limited, suggesting a favorable therapeutic ratio for delta-agonists in this pain model. These studies suggest that a systemically delivered delta-opioid agonist has pronounced analgesic properties on a preclinical cancer pain model.
AuthorsJosue Brainin-Mattos, Nicole D Smith, Shelle Malkmus, Yosup Rew, Murray Goodman, Joseph Taulane, Tony L Yaksh
JournalPain (Pain) Vol. 122 Issue 1-2 Pg. 174-81 (May 2006) ISSN: 1872-6623 [Electronic] United States
PMID16545911 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Analgesics
  • Receptors, Opioid, delta
  • Morphine
Topics
  • Analgesics (administration & dosage)
  • Animals
  • Arthralgia (etiology, physiopathology, prevention & control)
  • Bone Neoplasms (complications, drug therapy, physiopathology)
  • Dose-Response Relationship, Drug
  • Hyperalgesia (etiology, physiopathology, prevention & control)
  • Male
  • Mice
  • Mice, Inbred C3H
  • Morphine (administration & dosage)
  • Osteosarcoma (complications, drug therapy, physiopathology)
  • Pain Threshold (drug effects)
  • Receptors, Opioid, delta (agonists)
  • Touch
  • Treatment Outcome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: