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Background and Aims The purpose of this study was to evaluate the relationship between remifentanil-induced hyperalgesia(RIH) and p21 activated kinase4(PAK4) in the spinal dorsal horn of rats with incisional pain.
Methods Sprague-Dawley rats weighing 280-300g aged 9-11 weeks were divided into four groups (n = 12 each): control group(C), incisional pain group(I), incisional pain+remifentanil group(IR), incisional pain+remifentanil+PAK4 inhibitor group(IRP). Groups I and C received intravenous saline, while Group IR and IRP received intravenous remifentanil at dose of 1.2 μg·kg-1·min-1 for 90 minutes. PAK4 inhibitor PF3758309 10 nmol was intrathecally injected 30 minutes before surgery and once daily for five days after incision in group IRP, while the same intrathecal injection with DMSO in the other groups. The paw mechanical withdrawal threshold (PMWT) was measured respectively at 30 min before surgery and at 2 hours, 1 to 5 days after surgery. NLRP3 in spinal dorsal horn was detected by Western Blot.
Results PMWT decreased at 2 hours after surgery in the incisional side. PMWT of healthy foot only decreased in group I and IR at 2 hours after surgery. Compared with group IR, PMWT increased in group IRP at 3 days after surgery in incisional side, while at 2 hours in healthy side. This study indicates that PF3758309 could cut off the formation of RIH since 2 hours after surgery by modulating NLRP3 inflammasome activation conducted by PAK4 in spinal dorsal horn.
Conclusions PAK4 inhibitor could be effective to decrease the development and maintenance of RIH and increase pain threshold in rats.
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