Acute and chronic administration of the cannabinoid receptor agonist CP 55,940 attenuates tumor-evoked hyperalgesia

Darryl T. Hamamoto, Subhalakshmi Giridharagopalan, Donald A Simone

Research output: Contribution to journalArticle

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Abstract

Patients with cancer frequently report pain that can be difficult to manage. This study examined the antihyperalgesic effects of a cannabinoid receptor agonist, CP 55,940, in a murine model of cancer pain. Implantation of fibrosarcoma cells into and around the calcaneous bone in mice produced mechanical hyperalgesia (decreased paw withdrawal thresholds and increased frequency of paw withdrawals). On day 13 after implantation, mechanical hyperalgesia, nociception, and catalepsy were assessed. Mice were randomly assigned to receive CP 55,940 (0.01-3 mg/kg, i.p.) or vehicle and behavioral measures were redetermined. CP 55,940 dose-dependently attenuated tumor-evoked mechanical hyperalgesia. To examine the effect of catalepsy on the antihyperalgesic effect of CP 55,940, mice with tumor-evoked hyperalgesia were pretreated with the dopamine agonist apomorphine prior to administration of CP 55,940. Apomorphine attenuated the cataleptic effect of CP 55,940 but did not attenuate its antihyperalgesic effect. In a separate group of mice with tumor-evoked hyperalgesia, administration of the dopamine antagonist spiperone produced catalepsy that was ∼ 2.5 fold greater than that produced by CP 55,490. Whereas this dose of CP 55,940 completely reversed tumor-evoked mechanical hyperalgesia, spiperone only attenuated mechanical hyperalgesia by ∼ 35%. Thus, the cataleptic effects of CP 55,940 did not fully account for its antihyperalgesic effect. The antihyperalgesic effect of CP 55,940 was mediated via the cannabinoid CB1 but not CB2 receptor. Finally, repeated administration of CP 55,940 produced a short-term and a longer-term attenuation of tumor-evoked hyperalgesia. These results suggest that cannabinoids may be a useful alternative or adjunct therapy for treating cancer pain.

Original languageEnglish (US)
Pages (from-to)73-87
Number of pages15
JournalEuropean Journal of Pharmacology
Volume558
Issue number1-3
DOIs
StatePublished - Mar 8 2007

Fingerprint

Cannabinoid Receptor Agonists
Hyperalgesia
Neoplasms
Catalepsy
Spiperone
Cannabinoids
Apomorphine
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
Cannabinoid Receptor CB2
Nociception
Dopamine Antagonists
Fibrosarcoma
Dopamine Agonists

Keywords

  • Cancer pain
  • Cannabinoid
  • Catalepsy
  • Dopamine
  • Fibrosarcoma
  • Mechanical hyperalgesia
  • Nociception

Cite this

Acute and chronic administration of the cannabinoid receptor agonist CP 55,940 attenuates tumor-evoked hyperalgesia. / Hamamoto, Darryl T.; Giridharagopalan, Subhalakshmi; Simone, Donald A.

In: European Journal of Pharmacology, Vol. 558, No. 1-3, 08.03.2007, p. 73-87.

Research output: Contribution to journalArticle

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abstract = "Patients with cancer frequently report pain that can be difficult to manage. This study examined the antihyperalgesic effects of a cannabinoid receptor agonist, CP 55,940, in a murine model of cancer pain. Implantation of fibrosarcoma cells into and around the calcaneous bone in mice produced mechanical hyperalgesia (decreased paw withdrawal thresholds and increased frequency of paw withdrawals). On day 13 after implantation, mechanical hyperalgesia, nociception, and catalepsy were assessed. Mice were randomly assigned to receive CP 55,940 (0.01-3 mg/kg, i.p.) or vehicle and behavioral measures were redetermined. CP 55,940 dose-dependently attenuated tumor-evoked mechanical hyperalgesia. To examine the effect of catalepsy on the antihyperalgesic effect of CP 55,940, mice with tumor-evoked hyperalgesia were pretreated with the dopamine agonist apomorphine prior to administration of CP 55,940. Apomorphine attenuated the cataleptic effect of CP 55,940 but did not attenuate its antihyperalgesic effect. In a separate group of mice with tumor-evoked hyperalgesia, administration of the dopamine antagonist spiperone produced catalepsy that was ∼ 2.5 fold greater than that produced by CP 55,490. Whereas this dose of CP 55,940 completely reversed tumor-evoked mechanical hyperalgesia, spiperone only attenuated mechanical hyperalgesia by ∼ 35{\%}. Thus, the cataleptic effects of CP 55,940 did not fully account for its antihyperalgesic effect. The antihyperalgesic effect of CP 55,940 was mediated via the cannabinoid CB1 but not CB2 receptor. Finally, repeated administration of CP 55,940 produced a short-term and a longer-term attenuation of tumor-evoked hyperalgesia. These results suggest that cannabinoids may be a useful alternative or adjunct therapy for treating cancer pain.",
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