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.

This study investigated whether and how electroacupuncture (EA) attenuates cold hypersensitivity (allodynia) in a rat model of oxaliplatin-induced neuropathic pain. Cold allodynia [evaluated by immersing the tail into cold water (4 °C) and measuring the withdrawal latency] was induced 3 days after an oxaliplatin administration (6 mg/kg, i.p.). EA stimulation (2/100 Hz, 0.3-ms pulse duration, 0.2-0.3 mA) was delivered to ST36 acupoint or non-acupoint for 20 min. Low-frequency (2 Hz) EA at ST36 relieved cold allodynia more effectively than high-frequency EA at ST36 or low-frequency EA at non-acupoint. Naloxone (opioid antagonist, 2 mg/kg, i.p.) completely blocked such EA-induced anti-allodynia, whereas phentolamine (α-adrenergic antagonist, 2 mg/kg, i.p.) did not. Moreover, plasma β-endorphin levels significantly increased right after the end of EA and subsequently decreased. These results indicate that low-frequency EA at ST36 in rats has a marked relieving effect on oxaliplatin-induced cold allodynia that is mediated by the endogenous opioid, but not noradrenergic, system.

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Abstract:The technique of rotating acupuncture needles has long been used to enhance the effects of acupuncture in Oriental medicine. However, it is difficult to standardize and quantify this stimulation condition. Thus we developed an automatically controlled rotating acupuncture (ACRA) system. The present study was conducted to evaluate the analgesic effects of ACRA using 4 different stimulation conditions (i.e., angle and frequency of rotation: 90° + 1 Hz, 90° + 1/4 Hz, 360° + 1 Hz, and 360° + 1/4 Hz) in Sprague-Dawley rats. Tail-flick latency to a noxious radiant heat stimulus in lightly anesthetized rats was measured before and after 15 min of ACRA stimulation at the Zusanli (ST36) acupoint. ACRA stimulations under all of the conditions above produced more potent analgesic effects than plain acupuncture (PA, acupuncture needle insertion only), but only the 90° + 1/4 Hz ACRA condition showed a statistically significant effect versus PA (P < 0.01). Further, the analgesic effect of 90° + 1/4 Hz ACRA was reversed by pretreatment with naloxone (2 mg/kg, i.p.). These results indicate that the 90° + 1/4 Hz ACRA stimulation has the most potent analgesic effect in rats and that this is mediated by the endogenous opioid system.