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.