Abstract
Oxaliplatin, a chemotherapy drug, often leads to neuropathic cold allodynia after a single administration. Bee venom acupuncture (BVA) has been used in Korea to relieve various pain symptoms and is shown to have a potent antiallodynic effect in nerve-injured rats. We examined whether BVA relieves oxaliplatin-induced cold allodynia and which endogenous analgesic system is implicated. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. BVA (1.0 mg/kg, s.c.) at Yaoyangguan (GV3), Quchi (LI11), or Zusanli (ST36) acupoints significantly reduced cold allodynia with the longest effect being shown in the GV3 group. Conversely, a high dose of BVA (2.5 mg/kg) at GV3 did not show a significant antiallodynic effect. Phentolamine (α-adrenergic antagonist, 2 mg/kg, i.p.) partially blocked the relieving effect of BVA on allodynia, whereas naloxone (opioid antagonist, 2 mg/kg, i.p.) did not. We further confirmed that an intrathecal administration of idazoxan (α 2-adrenergic antagonist, 50 μg) blocked the BVA-induced anti-allodynic effect. These results indicate that BVA alleviates oxaliplatin-induced cold allodynia in rats, at least partly, through activation of the noradrenergic system. Thus, BVA might be a potential therapeutic option in oxaliplatin-induced neuropathy.
Highlights
Colorectal cancer (CRC) was the third most common cancer in both men and women, and it caused about 608,000 deaths in 2008 worldwide, making it the fourth most common cause of death from cancer [1]
No significant difference in tail withdrawal latency (TWL) before and after a light immobilization without Bee venom acupuncture (BVA) or N/S injection at GV3 (P > 0.05, Figure 3(d)) was observed. These results suggest that BVA treatments has potent analgesic actions, of which efficacy is dependent on acupoint
This study clearly shows that BVA has a potent antiallodynic effect in oxaliplatin-injected rats (Figures 2 and 3)
Summary
Colorectal cancer (CRC) was the third most common cancer in both men and women, and it caused about 608,000 deaths in 2008 worldwide, making it the fourth most common cause of death from cancer [1]. Oxaliplatin is an important chemotherapy drug for the treatment of patients with metastatic CRC [2, 3]. Because of its platinum-based molecular structure, it causes a neurotoxic side effect, characterized by the rapid onset of spontaneous severe pain and cold allodynia in the hands, feet, perioral area, or throat, even from a single administration [4, 5]. Since the mechanism is still unclear, an effective treatment of established neuropathic allodynia has yet to be found [7]. It would be highly important to find the potential therapeutic options to manage oxaliplatin-induced neuropathic pain
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