PMID- 25760986 OWN - NLM STAT- MEDLINE DCOM- 20160115 LR - 20181113 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 12 IP - 1 DP - 2015 Jul TI - 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. PG - 829-36 LID - 10.3892/mmr.2015.3465 [doi] AB - 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. FAU - Cao, Su AU - Cao S AD - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China. FAU - Qin, Yinbin AU - Qin Y AD - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China. FAU - Chen, Junjie AU - Chen J AD - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China. FAU - Shen, Shiren AU - Shen S AD - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China. LA - eng PT - Journal Article DEP - 20150310 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Glucose Transporter Type 1) RN - 0 (KATP Channels) RN - 0 (Slc2a1 protein, rat) RN - 7B0ZZH8P2W (Pinacidil) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Cellular Microenvironment/*genetics MH - Dermatologic Surgical Procedures MH - Disease Models, Animal MH - Gene Expression/drug effects MH - Glucose Transporter Type 1/biosynthesis MH - Humans MH - Inflammation/*drug therapy/genetics/surgery MH - JNK Mitogen-Activated Protein Kinases/biosynthesis MH - KATP Channels/biosynthesis MH - Male MH - Microvessels/*growth & development/metabolism MH - Nerve Growth Factor/biosynthesis MH - Pain, Postoperative/*drug therapy/genetics/pathology MH - Pinacidil/*administration & dosage MH - Rats PMC - PMC4438946 EDAT- 2015/03/12 06:00 MHDA- 2016/01/16 06:00 PMCR- 2015/03/10 CRDT- 2015/03/12 06:00 PHST- 2013/11/22 00:00 [received] PHST- 2014/07/23 00:00 [accepted] PHST- 2015/03/12 06:00 [entrez] PHST- 2015/03/12 06:00 [pubmed] PHST- 2016/01/16 06:00 [medline] PHST- 2015/03/10 00:00 [pmc-release] AID - mmr-12-01-0829 [pii] AID - 10.3892/mmr.2015.3465 [doi] PST - ppublish SO - Mol Med Rep. 2015 Jul;12(1):829-36. doi: 10.3892/mmr.2015.3465. Epub 2015 Mar 10.