Objective: Post-operative chronic post-thoracotomy pain (CPTP) has been linked to restrictions
in mobility and daily activities. However, its potential causes and optimal therapy have
not been well characterized. Here, the purpose of this study was to investigate the role of Toll-like
receptor 4 (TLR4) in CPTP rats and its underlying mechanism.
Methods: Initially, rat models of CPTP were established. Then, the mechanical withdrawal threshold
(MWT) was measured after intrathecal injection of TLR4 antagonist (LPS-RS), TLR4 agonist
(LPS-PG), or caspase-1 inhibitor (Ac-YVAD-CMK) in CPTP rats. Levels of TNF-α, IL-6 and
IL-1β in the spinal dorsal horn (SDH) were measured by ELISA. TLR4 and caspase-1 were located
by immunofluorescence double staining. TLR4 and caspase-1 levels were assessed by qRT-PCR
and Western blot.
Results: TLR4 and caspase-1 were up-regulated in SDH of CPTP rats. Compared with Sham and
non-CPTP groups, MWT was effectively decreased while TNF-α, IL-6 and IL-1β in SDH were increased
in CPTP group. Moreover, intrathecal injection of TLR4 antagonist or caspase-1 inhibitor
significantly elevated MWT expression and reduced levels of TNF-α, IL-6 and IL-1β in SDH. Additionally,
high expression of TLR4 promoted mechanical hyperalgesia and inflammatory response,
while intrathecal injection of a mixture of caspase-1 inhibitor and TLR4 agonist reversed
the alleviation of caspase-1 inhibitor on the mechanical hyperalgesia and inflammatory response.
TLR4 and caspase-1 were co-located in neurons.
Conclusion: TLR4 aggravated CPTP in rats by mediating activation of caspase-1 in SDH.