CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain

Iryna Khasabova, James Gielissen, Anisha Chandiramani, Catherine A Harding-Rose, Desiree Abu Odeh, Donald A Simone, Virginia S. Seybold

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In light of the adverse side-effects of opioids, cannabinoid receptor agonists may provide an effective alternative for the treatment of cancer pain. This study examined the potency and efficacy of synthetic CB1 and CB2 receptor agonists in a murine model of tumor pain. Intraplantar injection of the CB1 receptor agonist arachidonylcyclopropylamide (ED50 of 18.4 μg) reduced tumor-related mechanical hyperalgesia by activation of peripheral CB1 but not CB2 receptors. Similar injection of the CB2 receptor agonist AM1241 (ED50 of 19.5 μg) reduced mechanical hyperalgesia by activation of peripheral CB2 but not CB1 receptors. Both agonists had an efficacy comparable with that of morphine (intraplantar), but their analgesic effects were independent of opioid receptors. Isobolographic analysis of the coinjection of arachidonylcyclopropylamide and AM1241 determined that the CB1 and CB2 receptor agonists interacted synergistically to reduce mechanical hyperalgesia in the tumor-bearing paw. These data extend our previous findings that the peripheral cannabinoid receptors are a promising target for the management of cancer pain and mixed cannabinoid receptor agonists may have a therapeutic advantage over selective agonists.

Original languageEnglish (US)
Pages (from-to)607-616
Number of pages10
JournalBehavioural Pharmacology
Volume22
Issue number5-6
DOIs
StatePublished - Sep 1 2011

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Cannabinoid Receptor CB2
Cannabinoid Receptor CB1
Analgesia
Hyperalgesia
Cannabinoid Receptor Agonists
Pain
Opioid Receptors
Neoplasms
Artificial Receptors
Cannabinoid Receptors
Injections
Morphine
Analgesics
Therapeutics
AM 1241
arachidonylcyclopropylamide
Cancer Pain

Keywords

  • cancer
  • cannabinoid
  • hyperalgesia
  • mouse

Cite this

CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain. / Khasabova, Iryna; Gielissen, James; Chandiramani, Anisha; Harding-Rose, Catherine A; Odeh, Desiree Abu; Simone, Donald A; Seybold, Virginia S.

In: Behavioural Pharmacology, Vol. 22, No. 5-6, 01.09.2011, p. 607-616.

Research output: Contribution to journalArticle

Khasabova, Iryna ; Gielissen, James ; Chandiramani, Anisha ; Harding-Rose, Catherine A ; Odeh, Desiree Abu ; Simone, Donald A ; Seybold, Virginia S. / CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain. In: Behavioural Pharmacology. 2011 ; Vol. 22, No. 5-6. pp. 607-616.
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