Curcumin Exerts Antinociceptive Effects in Cancer-Induced Bone Pain via an Endogenous Opioid Mechanism

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.

Hawaiian Plants with Beneficial Effects on Sleep, Anxiety, and Mood, etc.

“…The results also indicate that the enhanced expression of DRG neuron β-endorphin and enkephalin contributes to curcumin’s pain-relieving effects in conditions characterized by heightened pain sensitivity. This is the first time that curcumin has been shown to have an antinociceptive effect in pain hypersensitivity conditions, and the effects may be mediated by increased expression of β-endorphin and enkephalin which was demonstrated by Zhao et al in 2021 [ 70 ].…”

Anti-Inflammatory and Analgesic Effects of Curcumin Nanoparticles Associated with Diclofenac Sodium in Experimental Acute Inflammation

“…Curcumin administration (cC and nC) also had an analgesic effect ( Figure 2 ). Its analgesic effect could be explained by the stimulation of protein expression of β-endorphin and encephalin, which are endogenous opioid peptides [ 18 ]. We observed that the association of cC and nC to D has better analgesic effects ( Figure 2 ), most probably because the combination acts on two mechanisms to reduce the pain threshold.…”

Analgesic Potential Comparison Between Piperine-Combined Curcumin Patch and Non-Piperine Curcumin Patch: A Pragmatic Trial on Post-Cleft Lip/Palate Surgery Pediatric Patients

“…Curcumin has been known for its multiple therapeutic potentials, including its analgesic potentials. [11][12][13][14][15][16] As an analgesic agent, including in the orofacial region, curcumin has been evaluated and delivered in several forms, capsule, gel, paste, powder, as well as in a form of a patch. 17,18 A previous study revealed that transdermal delivery of an analgesic agent, will eliminate unwanted side effects such as sedation and cognition.…”