Over the past few years, significant progress has been made in
cancer therapy. Indeed, the lifespan of
cancer patients has significantly increased. Although patients live longer,
cancer-related pain remains a daily problem affecting their quality of life, especially when
metastases reach the bone. In patients coping with
cancer-induced bone
pain,
morphine and
NSAIDs, often used in combination with other medications, are the most commonly used drugs to alleviate
pain. However, these drugs have dose-limiting side effects.
Morphine and other routinely used
opioids are
mu opioid receptor (MOPR) agonists. The MOPR is responsible for most
opioid-related adverse effects. In the present study, we revealed potent
analgesic effects of an intrathecally-administered selective
delta opioid receptor (DOPR) agonist,
deltorphin II, in a recently developed rat
bone cancer model. Indeed, we found that
deltorphin II dose-dependently reversed
mechanical allodynia 14 days post-surgery in this
cancer pain model, which is based on the implantation of mammary MRMT-1 cells in the femur. This effect was DOPR-mediated as it was completely blocked by
naltrindole, a selective DOPR antagonist. Using the complete
Freund's adjuvant model of inflammatory
pain, we further demonstrated that
deltorphin II was equipotent at alleviating inflammatory and
cancer pain (i.e. similar ED50 values). Altogether, the present results show, for the first time, that activation of spinal DOPRs causes significant
analgesia at doses sufficient to reduce inflammatory
pain in a rat
bone cancer pain model. Our results further suggest that DOPR represents a potential target for the development of novel
analgesic therapies to be used in the treatment of
cancer-related pain.