Abstract
Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2-adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.
Highlights
Oxaliplatin is a third-generation platinum-based chemotherapy drug commonly used for colorectal cancer [1], which is the third most common cancer in men and the second most common cancer in women worldwide [2]
Some articles have reported that morphine effectively attenuates neuropathic pain [28], and that morphine can significantly suppress the neuropathic pain induced by a single injection of oxaliplatin in rats [29], suggesting that morphine might be effective in chemotherapy induced peripheral neuropathy (CIPN)
These results let us speculate that the combination treatment of Bee venom acupuncture (BVA) and morphine might have an additive effect, as the analgesic effect of BVA is mediated by spinal noradrenergic and/or serotonergic receptors, and the effect of morphine is mediated by opioidergic receptors
Summary
Oxaliplatin is a third-generation platinum-based chemotherapy drug commonly used for colorectal cancer [1], which is the third most common cancer in men and the second most common cancer in women worldwide [2]. Morphine is a well-known analgesic drug and its effect is most likely mediated via opioid receptors [23] Whether it can efficaciously attenuate neuropathic pain is still a controversial issue. Some articles have reported that morphine effectively attenuates neuropathic pain [28], and that morphine can significantly suppress the neuropathic pain induced by a single injection of oxaliplatin in rats [29], suggesting that morphine might be effective in CIPN These results let us speculate that the combination treatment of BVA and morphine might have an additive effect, as the analgesic effect of BVA is mediated by spinal noradrenergic and/or serotonergic receptors, and the effect of morphine is mediated by opioidergic receptors.
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