title: 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.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Su
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Yinbin
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Shiren
authors.initials: S
authors.lastname: Shen
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000235:genetics*; D062109:Dermatologic Surgical Procedures; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D054086:KATP Channels / Q000096:biosynthesis; D008297:Male; D055806:Microvessels / Q000254:growth & development* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000096:biosynthesis; D010149:Postoperative Pain / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020110:Pinacidil / Q000008:administration & dosage*; D051381:Rats
chemical_list: D051272:Glucose Transporter Type 1; D054086:KATP Channels; C495679:Slc2a1 protein, rat; D020110:Pinacidil; D020932:Nerve Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases