Abstract:

Objective The purpose of this research was to test whether the CB2 receptor is involved in morphine tolerance by up-regulating β-endorphin in spinal cord in cancer pain. Methods Walker 256 cells were implanted into the plantar region of the rat right hind paw. Tumor-bearing animals received intrathecal injections of a CB2 receptor agonist or antagonist with or without subcutaneous injections of morphine twice daily for 8 days. Mechanical paw withdrawal threshold and thermal paw withdrawal latency were assessed daily using the von Frey test and hot plate test. Expression of β-endorphin in the spinal cord was detected by ELISA after the last day of drug administration. Results Repeated morphine treatments reduced the mechanical withdrawal threshold and thermal latency， as well as down-regulated β-endorphin in the spinal cord[（5.24±1.41） ng vs （12.46±3.50） ng，P<0.001]. Repeated co-administration of AM1241 with morphine for 8 days significantly inhibited the development of mechanical withdrawal threshold [（19.33±3.36） g vs （9.5±1.07） g，P< 0.001] and thermal latency [（21.83±2.89） s vs （9.5±2.01） s，P<0.001）]， and reversed the down-regulation of β-endorphin expression in tumor-bearing rats[（10.11±2.08） ng vs（5.24±1.41） ng，P<0.05]. Conclusions Intrathecal injection of the CB2 receptor agonist alleviated morphine tolerance in tumor-bearing rats by up-regulating β-endorphin expression in spinal cord.

Key words: Cancer pain, Morphine tolerance, Cannabinoid type 2 receptor, β-endorphin