Abstract
A chemotherapy drug, oxaliplatin, induces cold and mechanical hypersensitivity, but effective treatments for this neuropathic pain without side effects are still lacking. We previously showed that Cinnamomi Cortex suppresses oxaliplatin-induced pain behaviors in rats. However, it remains unknown which phytochemical of Cinnamomi Cortex plays a key role in that analgesic action. Thus, here we investigated whether and how cinnamic acid or cinnamaldehyde, major components of Cinnamomi Cortex, alleviates cold and mechanical allodynia induced by a single oxaliplatin injection (6 mg/kg, i.p.) in rats. Using an acetone test and the von Frey test for measuring cold and mechanical allodynia, respectively, we found that administration of cinnamic acid, but not cinnamaldehyde, at doses of 10, 20 and 40 mg/kg (i.p.) significantly attenuates the allodynic behaviors in oxaliplatin-injected rats with the strongest effect being observed at 20 mg/kg. Our in vivo extracellular recordings also showed that cinnamic acid (20 mg/kg, i.p.) inhibits the increased activities of spinal wide dynamic range neurons in response to cutaneous mechanical and cold stimuli following the oxaliplatin injection. These results indicate that cinnamic acid has an effective analgesic action against oxaliplatin-induced neuropathic pain through inhibiting spinal pain transmission, suggesting its crucial role in mediating the effect of Cinnamomi Cortex.
Highlights
Oxaliplatin is a widely used third-generation platinum chemotherapeutic agent usually prescribed with fluorouracil and leucovorin against metastatic colorectal [1,2], breast, ovarian and lung cancer [3].oxaliplatin has no cross-resistance and has a higher efficacy and a lower nephrotoxicity than cisplatin, which is a first generation platinum chemotherapeutic agent [4]
Significant cold and mechanical allodynia were observed from day three to seven after oxaliplatin injection [22,23]
These behavioral and electrophysiological results clearly validate the establishment of neuropathic pain four days after the injection of oxaliplatin
Summary
Oxaliplatin is a widely used third-generation platinum chemotherapeutic agent usually prescribed with fluorouracil and leucovorin against metastatic colorectal [1,2], breast, ovarian and lung cancer [3].oxaliplatin has no cross-resistance and has a higher efficacy and a lower nephrotoxicity than cisplatin, which is a first generation platinum chemotherapeutic agent [4]. The acute neuropathic pain induced by even a single treatment of oxaliplatin affect more than 90% of treated patients [5]. Cold and mechanical hypersensitivities are emphasized [7,8] This neuropathic pain can interrupt the treatment schedule, and put an end to treatments by deteriorating the patient’s quality of life [5,9,10]. Drugs used as first-line therapy for this pain are selective serotonin, norepinephrine reuptake inhibitors (duloxetine, venlafaxine) and anticonvulsants (gabapentin, pregabalin) [11]. These drugs have untoward side effects such as headache, Nutrients 2019, 11, 432; doi:10.3390/nu11020432 www.mdpi.com/journal/nutrients
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