Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of anticancer drugs but lacks an effective treatment strategy. Bee venom or Scolopendra subspinipes (SS) has been used in traditional medicine to treat chronic neuronal diseases. Moreover, pharmacopuncture with BV (BVP) or SS (SSP) produces potent analgesia in humans and experimental animals. In this study, we examined the effect of BVP or SSP into the ST36 acupoint on oxaliplatin-induced mechanical allodynia in mice.
Mice were given a single administration of oxaliplatin (10 mg/kg) at day 0. At day 14, BVP or SSP was injected into ST36 acupoint and mechanical withdrawal thresholds for hind paws were measured for 4 hours.
Acupoint treatment with BVP or SSP significantly reduced mechanical allodynia produced by a single oxaliplatin injection, which was completely prevented by acupoint pre-injection of lidocaine. Intrathecal treatment with yohimbine, an α2-adrenoceptor antagonist, prevented the anti-allodynic effect of BVP or SSP. On the other hand, a high dose of clonidine, suppressed oxaliplatin-induced mechanical allodynia, but produced severe side effects including hypotension, bradycardia, and motor impairment. Combination of BVP or SSP with a lower dose of clonidine produced a comparable analgesic effect without side effects.
Our findings demonstrate that BVP or SSP produces an analgesic effect in oxaliplatin-induced pain via neuronal conduction at the acupoint and activation of spinal α2-adrenoceptors. Moreover, a combination of low-dose clonidine with BVP or SSP represents a novel and safe therapeutic strategy for chemotherapy-induced chronic pain.