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UI researcher unraveling mechanisms for postoperative pain

IOWA CITY, Iowa -- Imagine having an operation and recuperating without the usual discomfort or even being pain-free after surgery.

Sound impossible? Maybe not.

But before researchers can find ways to minimize or eliminate the painful aftereffects of surgery, they first must understand how incisions cause pain. A University of Iowa researcher is taking the once sore subject that has evaded scientists and is beginning to unravel it.

While pain research has expanded greatly over the last 15 years, few investigators really have focused on surgical incision pain even though it is a common, costly and poorly understood form of acute pain. Some 80 to 90 percent of surgical procedures involve some type of discomfort, said Timothy Brennan, M.D., Ph.D., UI associate professor of anesthesia. The worst pain is after thoracotomies, total knee replacements and major abdominal surgery.

"Postoperative pain is an unrecognized pain problem from a basic science point of view," Brennan said.

Basic research has concentrated on pain signaling pathways. More recently, mechanisms for hypersensitivity or exaggerated response phenomena after injury have been emphasized, Brennan said. Injury from incisions in postoperative patients is a common cause of hypersensitivity, and for Brennan, an anesthesiologist with a background in pain research, postoperative incision-induced pain became an obvious problem that needed to be addressed from a basic science perspective.

"Not only is surgery the most common cause of acute pain, but finding ways to reduce pain or stop it completely will improve patient satisfaction, reduce morbidity and perhaps decrease mortality following surgery," said Brennan, who has been looking at postoperative pain for the last five years.

Brennan has developed an animal model to investigate postoperative pain and hopes that his work eventually leads to intraoperative and postoperative pain management changes for patients. So far, Brennan and his colleagues have found a group of spinal neurotransmitter receptors that may be key in transmitting the hypersensitivity that incisions cause. Brennan anticipates new drug discoveries that block these particular excitatory amino acid neurotransmitter receptors may greatly reduce or eliminate some patients' postoperative pain.

Brennan also has described which particular groups of neurons in the spinal cord become activated and sensitized by a surgical incision and thus transmit postoperative pain.

"We will continue to search for the pathways that become sensitized by incisions," Brennan said. "As we characterize the responses of the nerves, potential new therapeutics should follow."

The medical community currently treats most postoperative pain with opioids; however, studies have shown that drugs like morphine do not greatly reduce post-surgical pain induced by activities as simple as deep breathing, coughing or walking, Brennan said. Plus, there are side effects: nausea and vomiting, delayed gastric emptying and prolonged recovery of bowel function.

Pharmaceutical companies, as well as other basic science laboratories, are taking notice of Brennan's model and the results learned from it.

"We anticipate a strong effort by a number of groups to try to solve this puzzle, and in the future, we hope to eliminate the problem," Brennan said.

New drugs for postoperative pain currently are undergoing trials, said Brennan, who expects trials to escalate in the next five years.