Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain

Iryna Khasabova, Anisha Chandiramani, Catherine A Harding-Rose, Donald A Simone, Virginia S. Seybold

Research output: Contribution to journalArticle

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Abstract

Metastatic and primary bone cancers are usually accompanied by severe pain that is difficult to manage. In light of the adverse side effects of opioids, manipulation of the endocannabinoid system may provide an effective alternative for the treatment of cancer pain. The present study determined that a local, peripheral increase in the endocannabinoid 2-arachidonoyl glycerol (2-AG) reduced mechanical hyperalgesia evoked by the growth of a fibrosarcoma tumor in and around the calcaneous bone. Intraplantar (ipl) injection of 2-AG attenuated hyperalgesia (ED50 of 8.2 μg) by activation of peripheral CB2 but not CB1 receptors and had an efficacy comparable to that of morphine. JZL184 (10 μg, ipl), an inhibitor of 2-AG degradation, increased the local level of 2-AG and mimicked the anti-hyperalgesic effect of 2-AG, also through a CB2 receptor-dependent mechanism. These effects were accompanied by an increase in CB2 receptor protein in plantar skin of the tumor-bearing paw as well as an increase in the level of 2-AG. In naïve mice, intraplantar administration of the CB2 receptor antagonist AM630 did not alter responses to mechanical stimuli demonstrating that peripheral CB2 receptor tone does not modulate mechanical sensitivity. These data extend our previous findings with anandamide in the same model and suggest that the peripheral endocannabinoid system is a promising target for the management of cancer pain.

Original languageEnglish (US)
Pages (from-to)60-67
Number of pages8
JournalPharmacological Research
Volume64
Issue number1
DOIs
StatePublished - Jul 1 2011

Fingerprint

Bone Neoplasms
Hyperalgesia
Cannabinoid Receptor CB2
Endocannabinoids
Cannabinoid Receptor CB1
Fibrosarcoma
Morphine
Opioid Analgesics
2-arachidonylglycerol
Cancer Pain
Neoplasms
Bone and Bones
Pain
Skin
Injections
Growth
Proteins

Keywords

  • 2-arachidonoyl glycerol
  • Cancer
  • Cannabinoid receptor
  • Endocannabinoid
  • Monoglycerol lipase
  • Pain

Cite this

Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain. / Khasabova, Iryna; Chandiramani, Anisha; Harding-Rose, Catherine A; Simone, Donald A; Seybold, Virginia S.

In: Pharmacological Research, Vol. 64, No. 1, 01.07.2011, p. 60-67.

Research output: Contribution to journalArticle

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