Abstract
Cancer pain is one of the main complications in advanced cancer patients, and its management is still challenging. Therefore, there is an urgent need to develop novel pharmacotherapy for cancer pain. Several natural products have attracted the interest of researchers. In previous studies, curcumin has proved to exhibit antitumor, antiviral, antioxidant, anti-inflammatory, and analgesic effects. However, the analgesic mechanism of curcumin has not been elucidated. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of curcumin in cancer-induced bone pain. Our results showed that consecutive curcumin treatment (30, 60, 120 mg/kg, i.p., twice daily for 11 days) produced significant analgesic activity, but had no effect on the progress of the bone cancer pain. Notably, pretreatment with naloxone, a non-selective opioid receptor antagonist, markedly reversed the antinociceptive effect induced by curcumin. Moreover, in primary cultured rat dorsal root ganglion (DRG) neurons, curcumin significantly up-regulated the expression of proopiomelanocortin (Pomc) and promoted the release of β-endorphin and enkephalin. Furthermore, pretreatment with the antiserum of β-endorphin or enkephalin markedly attenuated curcumin-induced analgesia in cancer-induced bone pain. Our present study, for the first time, showed that curcumin attenuates cancer-induced bone pain. The results also suggested that stimulation of expression of DRG neurons β-endorphin and enkephalin mediates the antinociceptive effect of curcumin in pain hypersensitivity conditions.
Highlights
Cancer pain, considered to be a major complication of many advanced malignancies, including lung, breast, and prostate cancers, severely affects patients’ quality of life (Mercadante, 1997; Portenoy and Lesage, 1999; Delaney et al, 2008; Breivik et al, 2009)
The results showed that curcumin at a dose of 60 and 120 mg/kg exerted significant analgesic effect at 4 h after administration on Day 5, 7, 9, and 11 after surgery
We found that dorsal root ganglion (DRG) neurons-expressed β-endorphin and enkephalin were involved in curcumin-induced analgesic effect
Summary
Cancer pain, considered to be a major complication of many advanced malignancies, including lung, breast, and prostate cancers, severely affects patients’ quality of life (Mercadante, 1997; Portenoy and Lesage, 1999; Delaney et al, 2008; Breivik et al, 2009). According to the statistics issued by a recent study, there are approximately two-thirds of patients with advanced and Curcumin in Cancer-Induced Bone Pain metastatic cancer suffering from pain (van den Beuken-van Everdingen et al, 2016). Opioid analgesics are still the most common used drugs in the treatment of cancer pain. Several opioid-related side effects, such as tolerance, constipation, and respiratory depression, adversely limited its clinical utility (Bruera and Kim, 2003). The development of new pharmacotherapy for alleviating cancer pain is one of the greatest social and clinical needs
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