Plantar incision with severe muscle injury can be a cause of long-lasting postsurgical pain in the skin.

Aims: Although chronic local inflammation in deeper tissues after skin wound healing might produce chronification of acute postsurgical pain, its mechanisms have not been fully elucidated. We hypothesized that muscle injury and severe inflammation would prolong acute postsurgical pain by its central nervous system mechanisms.

Main Methods: After approval of the Animal Care Committee, experiments were performed in Male Sprague-Dawley rats weighing 250-300 g. Plantar incision and plantar incision combined with cryoinjury of the plantar flexor digitorum brevis muscle were made in the plantar incision group and muscle injury group, respectively. Pain-related behaviors were assessed, and inflammatory cells were isolated from injured muscle and analyzed by flow cytometry. Spinal microglial activation was assessed with Iba-1 staining.

Key Findings: Mechanical hyperalgesia from day 5 to day 8 and spontaneous pain-related behavior from day 3 to day 7 were significantly greater in the muscle injury group than in the plantar incision group (P < 0.05), whereas there was no significant difference between the two groups in thermal hyperalgesia. In the muscle injury group, the number of inflammatory cells on day 4 was significantly larger and spinal Iba-1 expression levels on days 4 and 7 were significantly higher than those in the plantar incision group (P < 0.05).

Significance: Surgical injury in deep tissues accompanying severe muscle inflammation induced prolonged postsurgical pain in the healing wound of the skin not by the persistence of muscle inflammation but by a central mechanism involving microglial activation at the level of the spinal cord.