Abstract
Background: Opioids can induce a state of nociceptive sensitization, also known as opioid-induced hyperalgesia. Nevertheless, the exact mechanism is still unclear. The following study investigates the role of Toll-like receptor 4 (TLR4) in the microglia activation during remifentanil—induced hyperalgesia in rats’ model of incisional pain.
Methods: Mechanical allodynia induced by remifentanil was established in adult male Sprague–Dawley rats with incisional pain. Paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWTL) were performed to evaluate mechanical and thermal hyperalgesia. The 32-G catheter intrathecal placement was used to deliver a specific TLR4 antagonist (LPS-RS).Western blot analysis was performed to measure the expression of the TLR4 and Iba-1, while Immunofluorescence staining was used to investigate the cell type and cell activation.
Results:Incisionalpain-remifentanil decreased the PWT and PWTL, upregulated the expression of TLR4 and microglia activation in the spinal cord. On the contrary, the intrathecal delivery of LPS-RS at the dose of 25 μg significantly decreased mechanical allodynia and prevented the upregulation of TLR4 induced by incisional pain-remifentanil
Conclusion: These findings suggest that TLR4 signaling pathway has an important role in incisional pain-remifentanil hyperalgesia, and that it could serve as the therapeutic target for persistent postsurgical pain