Enhanced Pain Sensitivity with Systemic
Ultrastructural Changes of the Nervous Systems
after Cobra Venom Injection is Reversed by
Electroacupuncture Treatment
Authors: An Jian-xiong 
Published: October 2019

Background: Electroacupuncture (EA) has been proved to be effective in treating certain neuropathic
pain conditions. The mechanisms of pain relief by EA are not fully understood. There have been sporadic
reports of damage in the peripheral nervous system (PNS) and regions of the central nervous system
(CNS) at the ultrastructural level following peripheral nerve injury. However, information about possible
systemic changes in the PNS and CNS after nerve injury is scarce.
Objectives: The goal of this study was to examine the ultrastructural changes of the nervous system
induced by a local injection of cobra venom into the sciatic nerve and to compare the ultrastructural
changes in rats with or without treatment with EA or pregabalin.
Study Design: An experimental study.
Setting: Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation General
Hospital of China Medical University.
Methods: In this study, using an established model of sciatic neuralgia induced by local injection of
cobra venom into the sciatic nerve, we examined ultrastructural changes of the PNS and CNS and how
they respond to EA and pregabalin treatment. EA and pregabalin were given daily from postoperative
day (POD) 14 to 36. Based on previous works, the frequency of EA stimulation of the ST36 and GB34
acupoints was held to 2/100 Hz variable. Pain sensitivity in the sciatic neuralgia rats with and without
treatments was assessed using the von Frey test. Ultrastructural alterations were examined bilaterally in
the prefrontal cortex, hippocampus, medulla oblongata; and the cervical, thoracic, and lumbar spinal
cords on PODs 14, 40, and 60. Ultrastructural examinations were also carried out on the bilateral sciatic
nerves and dorsal root ganglion (DRG) at the cervical, thoracic and lumbar levels. In rats treated with EA
or pregabalin, the ultrastructure was examined on PODs 40 and 60.
Results: Behavioral signs of pain and systemic ultrastructural changes including demyelination were
observed at all levels of the PNS and CNS in rats with sciatic neuralgia. After intervention, the mechanical
withdrawal thresholds of the EA group and pregabalin group were significantly higher than that of
the cobra venom group (P < 0.05). Both EA and pregabalin treatments partially reversed increased
cutaneous sensitivity to mechanical stimulation. However, only the EA treatment was able to repair the
ultrastructural damages caused by cobra venom.
Limitations: The results confirm that peripheral nerve injury led to the ultrastructural damage at
different levels of the CNS as demonstrated with electron microscopy; however, we need to further
verify this at both the molecular level and in light microscope level. Sciatic neuralgia induced by cobra
venom is a chemical injury, and whether this exactly mimics a peripheral nerve mechanical injury is still
unclear.
Conclusions: Local cobra venom injection leads to systemic neurotoxicity. EA and pregabalin alleviate
pain via different mechanisms.
Key words: Sciatic neuralgia, cobra venom, demyelination, electroacupuncture, pregabalin, rat model