Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, Republic of Korea.
Evid Based Complement Alternat Med. 2012;2012:784713. doi: 10.1155/2012/784713. Epub 2012 Aug 27.
Cold allodynia is an important distinctive feature of neuropathic pain. The present study examined whether single or repetitive treatment of diluted bee venom (DBV) reduced cold allodynia in sciatic nerve chronic constriction injury (CCI) rats and whether these effects were mediated by spinal adrenergic receptors. Single injection of DBV (0.25 or 2.5 mg/kg) was performed into Zusanli acupoint 2 weeks post CCI, and repetitive DBV (0.25 mg/kg) was injected for 2 weeks beginning on day 15 after CCI surgery. Single treatment of DBV at a low dose (0.25 mg/kg) did not produce any anticold allodynic effect, while a high dose of DBV (2.5 mg/kg) significantly reduced cold allodynia. Moreover, this effect of high-dose DBV was completely blocked by intrathecal pretreatment of idazoxan (α2-adrenoceptor antagonist), but not prazosin (α1-adrenoceptor antagonist) or propranolol (nonselective β-adrenoceptor antagonist). In addition, coadministration of low-dose DBV (0.25 mg/kg) and intrathecal clonidine (α2-adrenoceptor agonist) synergically reduced cold allodynia. On the other hand, repetitive treatments of low-dose DBV showing no motor deficit remarkably suppressed cold allodynia from 7 days after DBV treatment. This effect was also reversed by intrathecal idazoxan injection. These findings demonstrated that single or repetitive stimulation of DBV could alleviate CCI-induced cold allodynia via activation of spinal α2-adrenoceptor.
冷感觉异常是神经病理性疼痛的一个重要特征。本研究探讨了单次或重复使用稀释蜂毒液（DBV）是否能减轻坐骨神经慢性缩窄性损伤（CCI）大鼠的冷感觉异常，以及这些作用是否通过脊髓肾上腺素能受体介导。CCI 后 2 周，在足三里穴位单次注射 DBV（0.25 或 2.5mg/kg），CCI 手术后第 15 天开始连续 2 周内重复注射 DBV（0.25mg/kg）。单次低剂量 DBV（0.25mg/kg）治疗没有产生任何抗冷感觉异常作用，而高剂量 DBV（2.5mg/kg）则显著减轻冷感觉异常。此外，这种高剂量 DBV 的作用完全被鞘内预先给予伊达唑（α2-肾上腺素能受体拮抗剂）阻断，但不被普萘洛尔（α1-肾上腺素能受体拮抗剂）或心得安（非选择性β-肾上腺素能受体拮抗剂）阻断。此外，低剂量 DBV（0.25mg/kg）与鞘内可乐定（α2-肾上腺素能受体激动剂）联合给药协同减轻冷感觉异常。另一方面，重复给予低剂量 DBV（显示无运动缺陷）可显著抑制从 DBV 治疗后 7 天开始的冷感觉异常。这种作用也被鞘内伊达唑注射所逆转。这些发现表明，单次或重复刺激 DBV 可通过激活脊髓α2-肾上腺素能受体减轻 CCI 引起的冷感觉异常。
