Repeated electroacupuncture treatment attenuated hyperalgesia through suppression of spinal glial activation in chronic neuropathic pain rats

Jun-Ying Wang,Jian-Liang Zhang,Cheng-Lin Duan-Mu,Yong-Hui Gao,Ya-Xia Yan,Li-Na Qiao,Jun-Ling Liu,Shu-Ping Chen

doi:10.1186/s12906-018-2134-8

Abstract

BackgroundCumulated evidence reveals that glial cells in the spinal cord play an important role in the development of chronic neuropathic pain and are also complicated in the analgesic effect of EA intervention. But the roles of microgliacytes and astrocytes of spinal cord in the process of EA analgesia remain unknown.MethodsA total of 120 male Wistar rats were used in the present study. The neuropathic pain model was established by chronic constrictive injury (CCI) of the sciatic nerve. The rats were randomly divided into sham group, CCI group, and sham CCI + EA group, and CCI + EA group. EA was applied to bilateral Zusanli (ST36)-Yanlingquan (GB34). The mechanical (both time and force responses) and thermal pain thresholds (PTs) of the bilateral hind-paws were measured. The number of microgliacytes and activity of astrocytes in the dorsal horns (DHs) of lumbar spinal cord (L4–5) were examined by immunofluorescence staining, and the expression of glial fibrillary acidic protein (GFAP) protein was detected by western blot.ResultsFollowing CCI, both mechanical and thermal PTs of the ipsilateral hind-paw were significantly decreased beginning from the 3rd day after surgery (P < 0.05), and the mechanical PT of the contralateral hind-paw was considerably decreased from the 6th day on after surgery (P < 0.05). CCI also significantly upregulated the number of Iba-1 labeled microgliacytes and the fluorescence intensity of glial fibrillary acidic protein (GFAP) -labeled astrocyte in the superficial laminae of DHs on bilateral sides (P < 0.05). After repeated EA, the mechanical and thermal PTs at bilateral hind-paws were significantly relieved (P < 0.05). The increased of number of microgliacytes was markedly suppressed by 2 days’ EA intervention, and the average fluorescence intensity was suppressed by 2 weeks’ EA. The expression of GFAP protein were down-regulated by 1 and 2 weeks’ EA treatment, respectively (P < 0.05).ConclusionsRepeated EA can relieve neuropathic pain and mirror-image pain in chronic neuropathic pain rats, which is probably associated with its effect in downregulating glial cell activation of the lumbar spinal cord, the microgliacyte first and astrocyte later.

Highlights

Cumulated evidence reveals that glial cells in the spinal cord play an important role in the development of chronic neuropathic pain and are complicated in the analgesic effect of EA intervention
After constrictive injury (CCI), the mechanical Paw withdrawal latency (PWL) of the ipsilateral hind-paw were significantly reduced in the CCI group from day 3 on after operation, while those of the contralateral hind-paw significantly reduced from day 6 on after surgery relevant to the sham control group (P < 0.05, Fig. 1a–d), suggesting an occurrence of mirror-image pain
Following EA intervention, the PWLs of the ipsilateral paw were remarkably increased in the CCI + EA group from day 9 and day 12 on after surgery relevant to the CCI group (P < 0.05, Fig. 1a, c), while those of the contralateral paw significantly increased from day 6 on after surgery (P < 0.05, Fig. 1b, d)

Summary

Introduction

Cumulated evidence reveals that glial cells in the spinal cord play an important role in the development of chronic neuropathic pain and are complicated in the analgesic effect of EA intervention. In recent years, it was found that glial cell activation shown by hypertrophy of astrocytes and ameboid shaping of microgliacytes in the spinal cord following peripheral nerve injury, inflammation, tumor development, etc. Peripheral nerve injury activates microgliacytes and astrocytes, leading to a close contact of their synapses and processes and an aberrant release of many neurotrophic factors and pro-inflammatory cytokines as brain-derived neurotrophic factor (BDNF), glia cell line-derived neurotrophic factor (GDNF), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6(IL-6), etc. It is increasingly recognized that the glial activation within the spinal cord DHs is definitely sufficient to induce and maintain pain conditions [9, 10]

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Results

Conclusion