Abstract
Chronic postsurgical pain (CPSP) is a chronic pain state that is difficult to be treated clinically. A series of complicated changes have been produced from nociceptive stimulation to the occurrence and development of postsurgical pain. Many mechanisms remain unclear. In order to study the role of intercellular gap junctions in inducing inflammatory microenvironment at the beginning of nociceptor after operation, the model of skin/muscle incision and retraction (SMIR) was established. We observed the changes of the expression of exchange proteins directly activated by cAMP-1 (Epac1) and p120 catenin (p120), the quantities of macrophages and endothelial cells, vascular endothelial permeability, and mechanical withdrawal threshold (MWT). It was found that macrophages and endothelial cells were functionally coupled through Epac1-p120. Adhesive linkage disorder remodeled the chronic, inflammatory, and eutrophic microenvironment at the beginning of nociceptor after operation through macrophages, endothelial cells, and endothelial paracellular pathways. It might be an early event and a key step in peripheral sensitization of CPSP. The expression of p120 in muscle tissue around the incision might become a prognostic marker for the conversion of acute postsurgical pain into CPSP. Targeted intervention of Epac1-p120 might be a clinical strategy for inhibiting the conversion of acute postsurgical pain into CPSP.