Involvement of adenosine A1 receptor in electroacupuncture-mediated inhibition of astrocyte activation during neuropathic pain

ABSTRACT Neuropathic pain is a chronic pain condition caused by damage or dysfunction of the central or peripheral nervous system. Electroacupuncture (EA) has an antinociceptive effect on neuropathic pain, which is partially due to inhibiting astrocyte activation in the spinal cord. We found that an intrathecal injection of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist, reversed the antinociceptive effects of EA in a chronic constriction injury-induced neuropathic pain model. The expression of GFAP in L4-L6 spinal cord was significantly upgraded, while DPCPX suppressed the effect of the EA-mediating inhibition of astrocyte activation, as well as wiping out the EA-induced suppression of cytokine content (TNF-α). These results indicated that the adenosine A1 receptor is involved in EA actions during neuropathic pain through suppressing astrocyte activation as well as TNF-α upregulation of EA, giving enlightenment to the mechanisms of acupuncture analgesia and development of therapeutic targets for neuropathic pain.

摘要 神经病理性疼痛（Neuropathic pain）是一类由中枢或外周神经系统损伤或功能障碍引发的慢性疼痛病症。电针（Electroacupuncture，EA）对神经病理性疼痛具有抗伤害感受效应，其部分作用机制与抑制脊髓星形胶质细胞活化相关。本研究发现，在慢性压迫性损伤诱导的神经病理性疼痛模型中，鞘内注射选择性腺苷A1受体拮抗剂（selective adenosine A1 receptor antagonist）8-环戊基-1,3-二丙基黄嘌呤（8-cyclopentyl-1,3-dipropylxanthine，DPCPX），可逆转电针的抗伤害感受效应。L4-L6节段脊髓内的胶质纤维酸性蛋白（Glial Fibrillary Acidic Protein，GFAP）表达显著升高；而DPCPX不仅可抑制电针介导的星形胶质细胞活化抑制作用，还可消除电针诱导的肿瘤坏死因子-α（TNF-α）含量抑制效应。上述结果表明，腺苷A1受体可通过抑制星形胶质细胞活化以及电针介导的肿瘤坏死因子-α上调，参与神经病理性疼痛状态下电针的镇痛作用，该发现可为阐明针刺镇痛机制及开发神经病理性疼痛治疗靶点提供新思路。