Spinal cord Toll like receptor 4 and its co-stimulatory molecule heat shock protein 90 may participate in electroacupuncture analgesia in rats with chronic neuropathic pain
|更新时间:2023-08-11
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Spinal cord Toll like receptor 4 and its co-stimulatory molecule heat shock protein 90 may participate in electroacupuncture analgesia in rats with chronic neuropathic pain
GAO Yong-hui, WANG Jun-ying, HAN Yan-jing, et al. Spinal cord Toll like receptor 4 and its co-stimulatory molecule heat shock protein 90 may participate in electroacupuncture analgesia in rats with chronic neuropathic pain[J]. Acupuncture research, 2021, 46(9): 735-741.
DOI:
GAO Yong-hui, WANG Jun-ying, HAN Yan-jing, et al. Spinal cord Toll like receptor 4 and its co-stimulatory molecule heat shock protein 90 may participate in electroacupuncture analgesia in rats with chronic neuropathic pain[J]. Acupuncture research, 2021, 46(9): 735-741. DOI: 10.13702/j.1000-0607.201103.
Spinal cord Toll like receptor 4 and its co-stimulatory molecule heat shock protein 90 may participate in electroacupuncture analgesia in rats with chronic neuropathic pain
Objective To observe the effect of electroacupuncture(EA) on the expression of Toll like receptor 4(TLR4)and heat shock protein 90(HSP90) in the spinal cord of rats with chronic constriction injury(CCI) of sciatic nerve
so as to explore the mechanism of spinal cord TLR4 and HSP90 in alleviating chronic neuropathic pain by EA. Methods Male Wistar rats were randomized into control
model
EA
HSP90 inhibitor(inhibitor) and EA+ inhibitor groups(n=10 in each group). The neuropathic pain model was established by ligature of the right sciatic nerve to induce CCI. EA(1 mA
2 Hz/15 Hz)was applied at bilateral “Zusanli”(ST36) and “Yanglingquan”(GB34) for 30 min
once daily for 5 days. Rats of the inhibitor and EA+inhibitor groups were given a subcutaneous injection of HSP90 inhibitor geldanamycin(50 μg/kg) at the neck before daily EA. The paw withdrawal latency(PWL) of the bilateral hind-limbs was detected by using an algesia-detector. The contents of interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the lumbar spinal cord(L2—L4) tissue were detected by enzyme-linked immunosorbent assay. The relative expression levels of HSP90 and TLR4 proteins in the lumbar spinal cord(L2—L4) were detected using Western blot and immunofluorescence double labeling
respectively. Results Following CCI
a strong thermal hyperalgesia
an apparent up-regulation of expression of HSP90 and TLR4 proteins and TLR4 in microglia
and increasing levels of IL-1β and TNF-α in the spinal cord were induced in the model group relevant to the control group(P<0.01
P<0.05). Five sessions of EA intervention or inhibitor injection significantly attenuated hyperalgesia
reversed the increase of IL-1β and TNF-α
and down-regulated the expression of TLR4 in microglia(P<0.05). Compared with the model group
the expression of HSP90 was further increased(P<0.05)
and those of TLR4 in microglia and neurons were significantly decreased and increased
respectively in the EA group(P<0.05). Compared with the EA group
the levels of PWLD
TLR4 and HSP90 expression
and the proportions of neuronal nuclei antigen(NeuN) and TLR4
and ionized calcium binding adapter molecule(Iba1) and TLR4 co-expressed cells were significantly decreased in the inhibitor group and EA+inhibitor group(P<0.05). The proportion of NeuN and TLR4 co-expression cells in the EA+inhibitor group was significantly higher than that of the inhibitor group(P<0.05). Conclusion EA stimulation of ST36 and GB34 can alleviate thermal hyperalgesia in CCI rats
which is closely associated with its effect in regulating the expression of TLR4 in the spinal cord neurons and microglia. HSP90 in the spinal cord may be a co-stimulatory molecule for EA induced relief of neuropathic pain by regulating TLR4.
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Related Author
SONG Zong-sheng
LI Zhen
WANG Yu
LI Meng-xing
LIU Qing
SHI Ke-jian
YAO Xiao-wen
DING Hui
Related Institution
College of Acupuncture-moxibustion, Anhui University of Chinese Medicine
School of Physical Education, Anqing Normal University
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College of Acupuncture-moxibustion and Orthopaedics, Hubei University of Chinese Medicine
Hubei Provincial Collaborative Innovation Center of Preventive Treatment of Diseases by Acupuncture-Hmoxibustion