The Expression Changes Of SNAP-25, CGRP, GluA1 In Skin, Muscle And Its Relationship With Acute Postoperative Pain After Plantar Incision Injury In Rats

Objectives:Acute postoperative pain (APOP) is a serious global concern, as it can result in postoperative complications, serious impact on patient outcomes, postoperative rehabilitation and quality of life. The aim of this study was to evaluate the change of mechanical withdrawal threshold at different time points after plantar incision. We also analyzed the gene expression of SNAP-25, CGRP and GluAl in skin and muscle around the injury site, and explore the relationship between these genes and APOP.Methods:SD adult male rats were randomly divided into sham group and plantar incision group. The mechanical withdrawal threshold of rats was assessed at 2 h,6 h, 12 h, 1d,2d,3d,4d and 5d after injury. The mRNA expression of SNAP-25, CGRP and GluAlwas detected by using Real-Time PCR at 6 h,2 d and 5 d in skin and muscle around the injury site after surgery.Results:1) Hindlimb behavioral assessment showed that the mechanical withdrawal thresholds of rats were significantly less than that of sham group within 5 day post-injury (dpi). The threshold was lowest at 6 h, slightly fluctuated except 12 h and 1 d, and gradually increased. The threshold at 4 dpi was significantly higher than these of 6 h,1 d,2 d (P=0.006, P=0.010, P=0.023).And then it was further increased at 5 dpi, and was statistically significant difference (P=0.018) compared with that at 3 dpi. But there was no significant difference (P=0.581) between that at 5 dpi and 4 dpi. 2) Real-Time PCR showed that, in skin, compared to the sham group, the expression of SNAP-25 mRNA was not significant difference at 6 h after injury, was obviously up-regulation at 2 dpi (P=0.005) but markedly down-regulation at 5dpi (P=0.000). The expression of CGRP and GluA1 mRNA were significantly higher than the sham group (P<0.05), then decreased gradually, and both of them were significantly lower than that of sham group (P<0.05).3) In muscle, the SNAP-25 mRNA expression at 6 h after surgery were significantly higher than that of sham group (P=0.000), then decreased to normal levels at 2 dpi and lower than sham group at 5 dpi. The CGRP mRNA expression was similar to SNAP-25 at 6 h (P=0.000), followed by a gradual decline, even were still significantly higher than these in sham group (P>0.05). Nevertheless, the expression of CGRP mRNA at 2 dpi,5 dpi was significantly lower than that at 6 h (P=0.000, P=0.000), and was distinctly reduced further at 5 dpi. There was no significant difference of GluA1 mRNA expression at 6 h between sham group and plantar incision group. However, GluA1 mRNA expression at 2 dpi was significantly increased (P=0.000) but remarkably decreased at 5 dpi (P=0.000), compared with sham group.Conclusion:SNAP-25 may impact the process of acute postoperative pain via mediating the release of two kinds of neurotransmitter CGRP and GluA1 synergistically after plantar incision injury in rat, which provides a new idea for molecule combination therapy on acute postoperative pain.