Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway

Abstract

Yu-Xue Zhao, 1 Ming-Jiang Yao, 2, 3 Qun Liu, 1 Juan-Juan Xin, 1 Jun-Hong Gao, 1 Xiao-Chun Yu 1 1Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 2Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, People’s Republic of China; 3Key Laboratory of Pharmacology of Chinese Materia Medica, Beijing 100091, People’s Republic of ChinaCorrespondence: Yu-Xue Zhao; Xiao-Chun YuInstitute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, People’s Republic of ChinaEmail [email protected]; [email protected] and Purpose: 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.Methods: 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.Results: 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.Conclusion: 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.Keywords: electroacupuncture, neuropathic pain, paclitaxel, TLR4/NF-κB pathway, neuroglia

Keywords

• electroacupuncture
• neuropathic pain
• paclitaxel
• tlr4/nf-κb pathway
• neuroglia