https://painphysicianjournal.com/current/pdf?article=MTgwMw%3D%3D&journal=71
Authors: Li Prof. Yun-Qing 
Published: March 2021

Background: Current treatments for neuropathic pain are far from satisfactory. Considering the
essential contribution of central immune factors to the pathogenesis of neuropathic pain, targeting
inflammatory response is well accepted as an effective strategy for treating neuropathic pain.
Triptolide has a long history in traditional Chinese medicine for treating inflammatory diseases and
has been proven to inhibit cytokines released from glial cells.
Objective: In the present study, we tested whether systemic treatment with triptolide could
prevent or attenuate nocifensive behaviors associated with neuropathic pain. We further tried to
explore the underlying mechanism of the potential anti-allodynia effect of triptolide.
Study Design: A randomized, double blind, controlled animal trial.
Methods: Triptolide was administered systemically in a rat model of neuropathic pain induced
by spinal nerve ligation (SNL) in the single bolus and repeated treatment manners. In the single
bolus treatment experiment, triptolide (30 μg/kg, 100 μg/kg, 300 μg/kg) or vehicle was given to
SNL and sham-operated rats once on day 1 or on day 10 after surgery (n = 6 each). In the repeated
treatment study, prophylactic treatment with triptolide (30 μg/kg, 100 μg/kg, 300 μg/kg) was given
to rats during the period of day -3 (3 days prior to SNL) to day 7 (7 days post-SNL) inclusively (n
= 6 each). Another set of SNL and sham rats on postoperative day 10 received treatment with
triptolide (30 μg/kg, 100 μg/kg, 300 μg/kg) or vehicle during the period of days 11–20 inclusively
(n = 6 each), to assess potential reversal of established pain behavior. Mechanical allodynia of the
rats was tested with von Frey filaments. Astrocytic and microglial activation in the spinal dorsal
horn was evaluated with immunofluorescent histochemistry. Phosphorylation of mitogen-activated
protein kinases (MAPKs), and expression of inflammatory cytokines (interleukin-6, interleukin-1beta,
monocyte chemotactic protein-1, and tumor necrosis factor-alpha) were examined with Western
blot analysis and real-time reverse transcription polymerase chain reaction study.
Results: A single bolus treatment with triptolide could neither prevent the induction nor reverse the
maintenance of SNL-induced mechanical allodynia. However, repeated administration of triptolide
dose-dependently inhibited neuropathic pain behavior in both preventative and interventional
paradigms. Triptolide hampered SNL-induced activation of glial cells (astrocytes and microglia) in the
spinal dorsal horn without influencing neurons. In addition, SNL-induced phosphorylation of MAPKs
could be inhibited by triptolide. Furthermore, up-regulated expression of inflammatory cytokines in
neuropathic pain states could be remarkably blocked by triptolide.
Limitations: The direct target site (such as a specific receptor) of triptolide is still to be determined.
In addition, triptolide could not completely block the SNL-induced mechanical allodynia.
Conclusions: Our data suggest that triptolide may be a potential novel treatment for neuropathic
pain through modulating immune response in the spinal dorsal horn.
Key words: Triptolide, neuropathic pain, spinal dorsal horn, astrocyte, microglia, MAPK.