Zhao Yu-Xue, Yao Ming-Jiang, Liu Qun, Xin Juan-Juan, Gao Jun-Hong, Yu Xiao-Chun
Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, People's Republic of China.
Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, People's Republic of China.
J Pain Res. 2020 Jan 29;13:239-250. doi: 10.2147/JPR.S241101. eCollection 2020.
Neuropathic pain is a major side-effect of paclitaxel (PTX) chemotherapy. Although the precise mechanisms responsible for this pain are unclear, the activation of neuroglia and upregulation of the TLR4/NF-κB pathway are known to be involved. In this study, we determined whether electroacupuncture (EA) could limit mechanical hypersensitivity resulting from the chemotherapeutic drug PTX in rats, and investigated the potential mechanisms involved.
Rats intraperitoneally received a cumulative dose of 8 mg/kg PTX (2 mg/kg per day) or vehicle control on alternate days (day 0, 2, 4 and 6). EA treatment (10 Hz, 1 mA) was applied at bilateral ST36 acupoints in rats once every other day on days 0-14. For sham EA, needles were inserted at ST36 acupoints without electrical stimulation. Mechanical allodynia was measured by mechanical withdrawal latency (MWL) of paws to a mechanical stimulus every 2 days. Protein expression of TLR4 and NF-κB p65, as well as TMEM119 and GFAP (indicators of microglia and astrocytes, respectively) in spinal cord was quantified by Western blot analysis. Levels of inflammatory cytokines IL-1β and TNF-α in spinal cord and serum were detected by ELISA.
Mechanical allodynia induced by PTX in both paws (right and left) of rats was significantly attenuated by EA but not sham EA treatment. In addition, EA, but not sham EA, inhibited the activation of both microglia (TMEM119) and astrocytes (GFAP) in lumbar spinal cord. Moreover, Western blot analysis revealed that protein expression of TLR4 and NF-κB in spinal cord was suppressed by EA but not sham EA treatment. PTX significantly increased inflammatory cytokines in spinal cord and serum, which were ameliorated by EA treatment but not by sham EA.
These results indicate that EA treatment attenuates PTX-induced mechanical allodynia. The putative mechanism corroborating this finding could be related to the suppression of activated microglia and astrocytes in spinal cord, as well as the inhibition of the activated TLR4/NF-κB signaling pathway by EA treatment.
神经性疼痛是紫杉醇（PTX）化疗的主要副作用。尽管导致这种疼痛的确切机制尚不清楚，但已知神经胶质细胞的激活和TLR4/NF-κB通路的上调与之有关。在本研究中，我们确定了电针（EA）是否可以减轻大鼠因化疗药物PTX引起的机械性超敏反应，并研究了其中的潜在机制。
大鼠每隔一天（第0、2、4和6天）腹腔注射累积剂量为8mg/kg的PTX（每天2mg/kg）或赋形剂对照。在第0至14天，每隔一天对大鼠双侧足三里穴位进行一次EA治疗（10Hz，1mA）。假EA组则在足三里穴位插入针但不进行电刺激。每2天通过测量爪对机械刺激的机械退缩潜伏期（MWL）来检测机械性异常性疼痛。通过蛋白质印迹分析定量脊髓中TLR4和NF-κB p65以及TMEM119和GFAP（分别为小胶质细胞和星形胶质细胞的指标）的蛋白表达。通过酶联免疫吸附测定法检测脊髓和血清中炎性细胞因子IL-1β和TNF-α的水平。
EA治疗可显著减轻PTX诱导的大鼠双爪（右爪和左爪）机械性异常性疼痛，而假EA治疗则无此效果。此外，EA而非假EA可抑制腰段脊髓中小胶质细胞（TMEM119）和星形胶质细胞（GFAP）的激活。此外，蛋白质印迹分析显示，EA治疗可抑制脊髓中TLR4和NF-κB的蛋白表达，而假EA治疗则无此作用。PTX可显著增加脊髓和血清中的炎性细胞因子，EA治疗可改善这种情况，而假EA治疗则不能。
这些结果表明，EA治疗可减轻PTX诱导的机械性异常性疼痛。支持这一发现的推测机制可能与EA治疗抑制脊髓中活化的小胶质细胞和星形胶质细胞以及抑制活化的TLR4/NF-κB信号通路有关。
