前列腺酸性磷酸酶可能通过突触前机制参与骨癌痛大鼠脊髓镇痛

AN ELECTROPHYSIOLOGICAL MECHANISM ON SPINAL ANALGESIA OF PROSTATIC ACID PHOSPHATASE IN CANCER-INDUCED BONE PAIN RAT MODEL

目的:运用神经电生理学方法,观察前列腺酸性磷酸酶(prostatic acid phosphatase,PAP)对骨癌痛(cancer-induced bone pain,CIBP)大鼠脊髓背角神经元兴奋性的影响。方法:SD雌性大鼠12只,随机分为两组(n=6):CIBP模型组和假手术组,CIBP组于右侧胫骨骨髓腔内接种5μl大鼠乳腺癌细胞(2×105个),14天后造模完成。运用腰髓薄片全细胞膜片钳记录两组大鼠脊髓背角神经元兴奋性的变化,在灌流液中加入PAP,观察PAP对两组大鼠脊髓背角神经元兴奋性的影响。结果:脊髓薄片全细胞电压钳研究表明,与假手术组大鼠对比,骨癌痛大鼠脊髓背角Ⅱ层神经元自发的兴奋性突触后电流(spontaneous excitatory post-synaptic currents,sEPSCs)和刺激电极诱发的兴奋性突触后电流(evoked excitatory post-synaptic currents,eEPSCs)的幅度显著增大,而sEPSCs的频率未见变化。给予PAP灌流,PAP显著降低骨癌痛大鼠脊髓背角Ⅱ层神经元的sEPSCs发放频率,而对其幅度未见明显影响;且该效应可被腺苷A1R的拮抗剂CPX翻转。PAP对于假手术组大鼠脊髓背角神经元兴奋性没有明显影响。结论:PAP可能通过突触前机制参与骨癌痛模型大鼠的脊髓镇痛过程。

Objective：To observe the effects of prostatic acid phosphatase （PAP） on the excitability of spinal dorsal horn neurons in a rat model of cancer-induced bone pain （CIBP） using electrophysiological method.Methods：Twelve adult female Sprague-Dawley rats were randomly divided into 2 groups （n =6）：cancerinduced bone pain group and sham operation group.A model of bone cancer pain was established 14 days later after inoculating 5 μl Walker 256 mammary gland carcinoma cells （2 × 105） into the right side of the tibial medullary cavity.The influence of drugs on neuronal excitability in spinal dorsal horn of the two groups was observed with whole cell recording.Results：Whole-cell voltage-clamp studies in spinal cord slice have shown that the amplitude of spontaneous excitatory postsynaptic currents （sEPSCs） and evoked excitatory postsynaptic currents （eEPSCs） in dorsal horn laminae Ⅱ neurons were significantly increased in the CIBP group compared with that of the sham group,but no obvious change of the frequency of sEPSCs was found in the CIBP group.However,the frequency of sEPSCs was significantly decreased after the slice was perfused with PAP in the CIBP group.Such effects were blocked by CPX,an antagonist of A1R.PAP had no effect on neuronal excitability of SDH in sham group rats.Conclusion：PAP may play a role in the process of analgesia in the rat CIBP model via presynaptic mechanisms.