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Published on: July 29, 2014
The cannabinoid receptor agonist, WIN 55, 212-2, attenuates tumor-evoked hyperalgesia through peripheral mechanisms
Carl Potenzieri1, Catherine Harding-Rose, Donald A Simone
1Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
Abstract:
Several lines of evidence suggest that cannabinoids can attenuate various types of pain and hyperalgesia through peripheral mechanisms. The development of rodent cancer pain models has provided the opportunity to investigate novel approaches to treat this common form of pain. In the present study, we examined the ability of peripherally administered cannabinoids to attenuate tumor-evoked mechanical hyperalgesia in a murine model of cancer pain. Unilateral injection of osteolytic fibrosarcoma cells into and around the calcaneus bone resulted in tumor formation and mechanical hyperalgesia in the injected hindpaw. Mechanical hyperalgesia was defined as an increase in the frequency of paw withdrawals to a suprathreshold von Frey filament (3.4 mN) applied to the plantar surface of the hindpaw. WIN 55, 212-2 (1.5 to 10 microg) injected subcutaneously into the tumor-bearing hindpaw produced a dose-dependent decrease in paw withdrawal frequencies to suprathreshold von Frey filament stimulation. Injection of WIN 55,212-2 (10 microg) into the contralateral hindpaw did not decrease paw withdrawal frequencies in the tumor-bearing hindpaw. Injection of the highest antihyperalgesic dose of WIN 55,212-2 (10 microg) did not produce catalepsy as determined by the bar test. Co-administration of WIN 55,212-2 with either cannabinoid 1 (AM251) or cannabinoid 2 (AM630) receptor antagonists attenuated the antihyperalgesic effects of WIN 55, 212-2. In conclusion, peripherally administered WIN 55,212-2 attenuated tumor-evoked mechanical hyperalgesia by activation of both peripheral cannabinoid 1 and cannabinoid 2 receptors. These results suggest that peripherally-administered cannabinoids may be effective in attenuating cancer pain.
Insights
Peripherally administered cannabinoids, like WIN 55,212-2, effectively reduced cancer pain and mechanical hyperalgesia in mice. This pain relief involved activating both cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors.
Area of Science:
- Pharmacology
- Pain Research
- Oncology
Background:
- Cannabinoids show potential for pain relief through peripheral mechanisms.
- Cancer pain is a significant clinical challenge, necessitating novel therapeutic strategies.
- Rodent models are crucial for investigating cancer pain mechanisms and treatments.
Purpose of the Study:
- To evaluate the efficacy of peripherally administered cannabinoids in a murine model of cancer pain.
- To investigate the role of cannabinoid receptors in mediating pain relief.
- To assess the safety profile of cannabinoid administration in this model.
Main Methods:
- A murine model of cancer pain was established by injecting fibrosarcoma cells into the calcaneus bone.
- Mechanical hyperalgesia was quantified by measuring paw withdrawal responses to von Frey filament stimulation.
- WIN 55,212-2 was administered peripherally, and its effects were assessed alone and with cannabinoid receptor antagonists (AM251, AM630).
Main Results:
- Peripherally administered WIN 55,212-2 dose-dependently reduced tumor-evoked mechanical hyperalgesia.
- The antihyperalgesic effect was specific to the tumor-bearing paw and did not cause catalepsy at effective doses.
- Co-administration of WIN 55,212-2 with CB1 and CB2 receptor antagonists diminished its pain-relieving effects.
Conclusions:
- Peripherally administered WIN 55,212-2 effectively attenuates cancer pain and mechanical hyperalgesia in a murine model.
- The therapeutic effects are mediated through the activation of both peripheral cannabinoid 1 and cannabinoid 2 receptors.
- These findings support the potential of peripherally acting cannabinoids as a treatment for cancer pain.
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