Potenzieri Carl, Harding-Rose Catherine, Simone Donald A
Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
Brain Res. 2008 Jun 18;1215:69-75. doi: 10.1016/j.brainres.2008.03.063. Epub 2008 Apr 6.
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.
多项证据表明，大麻素可通过外周机制减轻各种类型的疼痛和痛觉过敏。啮齿动物癌症疼痛模型的发展为研究治疗这种常见疼痛形式的新方法提供了机会。在本研究中，我们检测了外周给予大麻素减轻小鼠癌症疼痛模型中肿瘤诱发的机械性痛觉过敏的能力。将溶骨性纤维肉瘤细胞单侧注射到跟骨及其周围，导致注射侧后爪形成肿瘤并出现机械性痛觉过敏。机械性痛觉过敏定义为后爪足底表面受到超阈值（3.4 mN）的von Frey细丝刺激时，爪退缩频率增加。将WIN 55,212-2（1.5至10微克）皮下注射到荷瘤后爪，可使对超阈值von Frey细丝刺激的爪退缩频率产生剂量依赖性降低。将WIN 55,212-2（10微克）注射到对侧后爪，并未降低荷瘤后爪的爪退缩频率。通过棒状试验确定，注射最高抗痛觉过敏剂量的WIN 55,212-2（10微克）未产生僵住症。WIN 55,212-2与大麻素1（AM251）或大麻素2（AM630）受体拮抗剂共同给药可减弱WIN 55,212-2的抗痛觉过敏作用。总之，外周给予WIN 55,212-2通过激活外周大麻素1和大麻素2受体减轻肿瘤诱发的机械性痛觉过敏。这些结果表明，外周给予大麻素可能有效减轻癌症疼痛。
