Date of Degree
PhD (Doctor of Philosophy)
Timothy J. Brennan
Postoperative pain constitutes a common form of acute and persistent pain. The current approaches for postoperative pain control are inadequate and problematic. A better understanding of mechanisms for postoperative pain is necessary to improve pain management. Pain at rest is a major complaint of patients after surgery. Such ongoing pain is transmitted by increased spontaneous activity (SA) in nociceptive pathways. Using the rodent plantar incision model, guarding behavior after incision has been found as a correlate to pain at rest in patients after surgery. Similar to the time course change in pain at rest after operation, guarding behavior is the greatest immediately after plantar incision and then gradually resolves over several days. When SA in nociceptive pathways was examined previously, however, SA in both dorsal horn neurons (DHNs) and primary nociceptors was not evident immediately after plantar incision. One day after incision, great SA was present. The underlying reason for the disagreement between ongoing guarding behavior and SA in nociceptive pathways is still unknown.
Here we hypothesize that incised skin has a minimal effect on the ongoing pain genesis, whereas incised deep muscle tissue produces strong ongoing pain and SA in nociceptive pathways after incision. In the first experiment, we found that skin incision induced moderate guarding on the day of incision only, whereas skin plus deep tissue incision caused guarding for 5 days. Mechanical and heat hyperalgesia were similar in both incised groups. On postoperative day (POD) 1, greater SA was present in DHNs in the skin plus deep tissue incision group than in the skin incision group. Seven days after skin plus deep tissue incision, the amount of SA in DHNs was the same as the sham control. In the second experiment, we found that on POD1 skin incision produced a similar prevalence of SA in nociceptors as sham control, whereas skin plus deep tissue incision generated a greater prevalence of SA. Seven days after skin plus deep tissue incision, the SA was similar as sham control. In the third experiment, we found that under normal conditions group III and IV muscle afferents have little SA in vitro. Incision increased the prevalence of SA. Incision also caused a greater percentage of lactic acid-responsive fibers and reduced heat and mechanical response threshold. In the fourth experiment, anti-nerve growth factor (NGF) and capsaicin were found to be effective in inhibiting ongoing pain after skin plus deep tissue incision. Taken together, we propose that deep muscle tissue rather than skin plays a central role in the genesis of ongoing pain and SA in nociceptive pathways after incision, whereas incised skin is sufficient to induce mechanical and heat hyperalgesia. We further propose increased lactic acid in incised muscle tissue may contribute to the development of SA in muscle afferents.
Copyright 2009 Jun Xu