Effects of pinacidil on changes to the microenvironment around the incision site, of a skin/muscle incision and retraction, in a rat model of postoperative pain

Abstract

The aim of the present study was to evaluate the influence of the microenvironment around an incision site, on peripheral and central sensitization. The effects of pinacidil activation of ATP-sensitive potassium (KATP) channels prior to skin/muscle incision and retraction (SMIR) surgery were assessed. A total of 24 male Sprague Dawley rats were randomly assigned to four groups: Control, sham (incision operation), SMIR (incision plus retraction 1 h after the skin/muscle incision) and pinacidil (SMIR plus pinacidil). The rats in the pinacidil group were intraperitoneally injected with pinacidil prior to the SMIR procedure. The mechanical withdrawal threshold (MWT) was determined at each time point. The microvessel density (MVD) value was determined by immunohistochemistry, and western blotting was performed to analyze the relative protein expression levels of nerve growth factor (NGF), glucose transporter protein-1 (GLUT1) and C-jun N-terminal kinases. There was a significant reduction in the levels of MVD, GLUT1 and MWT following SMIR surgery as compared with the incision alone, and a significant increase in the NGF protein expression levels. In the SMIR group, the MVD value was significantly increased seven days after surgery, as compared with three days after surgery. Additionally, intraperitoneal administration of pinacidil prior to the SMIR surgery inhibited the SMIR-induced reduction in MWT and MVD and attenuated the SMIR-induced GLUT1 reduction. The results of the present study suggest that the microenvironment around an incision site may affect the development of peripheral and central sensitization. In addition, pinacidil had an inhibitory effect on the formation of the inflammatory microenvironment around the incision site through activation of KATP channels, thereby inhibiting peripheral and central sensitization.

Effects of the ATP-dependent K ( )-channel effectors pinacidil and glibenclamide on liver tissue in an experimental model of epilepsy: A histopathological study

“…Pinacidil has been reported to have cardioprotective impacts by protecting the cardiac tissues from mitochondrial damage in ischemia reperfusion that occurs in vivo and in vitro [19]. In addition, pinacidil suppressed the inflammation around the incision line, as seen in a study conducted with rats [20]. However, the literature did not have data on the morphological effects of pinacidil on liver.…”

The peripheral Epac1/p-Cav-1 pathway underlies the disruption of the vascular endothelial barrier following skin/muscle incision and retraction-induced chronic postsurgical pain

“…Additionally, the low expression of p-Cav-1 was similar to that of Epac1 on 7 d after SMIR. Previously, we found a secondary inflammatory injury caused by I/R at the injury site ( 48 ). It seemed that the local microenvironment protected the body after acute injury.…”

Skin/muscle incision and retraction regulates the persistent postoperative pain in rats by the Epac1/PKC-βII pathway

“…Glut1 expression is positively correlated with microvessel density in postoperative pain [ 28 , 29 ]. SMIR surgery induces the increased Glut1 protein around the incision site in rats [ 30 ]. PKCβII promotes PGP9.5 and VEGF proteins in DRG of the SMIR-operated rats [ 31 ].…”