IMR Press / JIN / Volume 21 / Issue 6 / DOI: 10.31083/j.jin2106150
Open Access Original Research
Triptolide Alleviates Neuropathic Pain by Inhibiting the Activation of Microglial Toll-Like Receptor 3
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1 Department of Anesthesiology, Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, 710061 Xi’an, Shaanxi, China
*Correspondence: (Xiao-Peng Mei)
These authors contributed equally.
Academic Editor: Chul-Kyu Park
J. Integr. Neurosci. 2022, 21(6), 150;
Submitted: 26 April 2022 | Revised: 18 June 2022 | Accepted: 21 June 2022 | Published: 19 September 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Current data indicates the incidence of neuropathic pain after surgical nerve injury is as high as 50%, thus representing a major problem for patients and for the medical system. Triptolide, a traditional Chinese herb, has anti-inflammatory effects on various neurodegenerative and neuroinflammatory diseases. This agent also reduces peripheral nerve injury-induced neuropathic pain, although the mechanism underlying this effect is still unknown. Materials and Methods: The effects of triptolide on spinal nerve ligation (SNL) injury-induced neuropathic pain was studied in an animal model using behavioral, morphological and molecular biological methods. Results: Repeated administration of intrathecal triptolide was found to alleviate SNL- or Poly(I:C) (toll-like receptor 3 agonist) injection-induced mechanical allodynia without any motor impairment. The mechanism by which triptolide reduces SNL- and Poly(I:C) injection-induced microglial activation appears to be via the inhibition of OX42 expression, which is a microglial-specific marker. Intrathecal triptolide also suppressed SNL- and Poly(I:C) injection-induced expression of spinal TRIF. TRIF transmits signals from activated TLR3 and is the downstream adaptor of TLR3 in microglia. In addition, intrathecal triptolide inhibited the expression of spinal pro-inflammatory IL-1 β following SNL or Poly(I:C) injection. Conclusions: Intrathecal triptolide can suppress the TLR3/TRIF/IL-1 β pathway in spinal microglia following SNL. This could be the underlying mechanism by which triptolide alleviate neuropathic pain induced by peripheral nerve injury.

Chinese herb
toll like receptor
peripheral nerve injury
30901400/National Natural Science Foundation of China
81270016/National Natural Science Foundation of China
2018JM7101/Natural Science Foundation of Shaan-Xi Province
XJTU1AF-CRF-2018-018/Clinical Research Award of the First Affiliated Hospital of Xi’an JiaoTong University
xjj2017128/0816- 1191329727/Fundamental Research Funds for the Central Universities
220160900005/Foundation of Chinese Medical Association
CSDE012017120009/Foundation of Chinese Medical Association
Fig. 1.
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