ScienceDaily (Jan. 21, 2005) — Women recovering from hysterectomies require less morphine to combat pain and are able to recover their lung function more quickly when they receive a combination of two non-morphine-like or “non-opioid” drugs as part of their treatment, a new Queen’s study shows.

In combination the two drugs also reduce pain more consistently than when either of the drugs is administered alone, reports lead researcher Dr. Ian Gilron, Director of Clinical Pain Research for Queen’s Departments of Anesthesiology, and Pharmacology & Toxicology.

“This is exciting because there aren’t many non-opioid treatments available to complement morphine in relieving movement-related pain,” Dr. Gilron says.

Results of the study are published on-line in the January 2005 issue of PAIN, the official journal of the International Association for the Study of Pain. Also on the team from Queen’s are Elizabeth Orr and Jorge Zamora (Anesthesiology), Dongsheng Tu (Mathematics and Statistics), and Peter O’Neill (Obstetrics and Gynecology); and from the University of Toronto Faculty of Medicine, Allan Bell.

One of the biggest issues for post-operative recovery from abdominal or chest surgery is that people tend to lie still and take shallow breaths to avoid pain. As a result, their lungs don’t re-expand quickly enough after the partial lung collapse that occurs during the operation.

While morphine works well at reducing pain when patients are at rest, it is not as effective during movement or when the patient takes a deep breath or coughs, explains Dr. Gilron. An epidural with local anesthetic that partially numbs the nerves to the affected site will prevent the pain caused by deep breaths or coughing, and allow the lungs to recover better. Epidurals are currently the best pain treatment option after many major surgeries. However, this is a fairly invasive procedure, which has some risk and also requires more medical resources.

“We continue to search for new approaches to using non-opioid treatments that could complement drugs like morphine for pain relief,” he says. “Our study is the first to thoroughly examine the strategy of combining these two different non-opioid drugs. We were looking for two drugs that bolster each other’s effects.”

In the study, funded by the Physicians’ Services Incorporated Foundation of Ontario (PSI), hysterectomy patients were given a combination of an anti-seizure drug called gabapentin and an anti-inflammatory COX-2 inhibitor drug called rofecoxib, in addition to self-administered morphine. The patients were asked to rate their pain while at rest (lying in bed), sitting up and coughing. There was also one measure of lung function, which assessed air flow after patients took a deep breath and blew out as hard as they could.

The results showed that patients receiving both gabapentin and rofecoxib, compared to those who received either drug alone: · Used significantly less morphine; · Had higher postoperative lung performance; and · Had more consistent pain reduction at rest and with movement.

Despite the recent worldwide withdrawal of rofecoxib by Merck Frosst, the results of this trial provide new evidence for using non-opioid analgesic combinations for post-operative pain management, says Dr. Gilron, pointing out that safety issues for Vioxx (rofecoxib) have been associated with long-term chronic use of the medication.

“In our study the drugs were given for three days, and usually post-operative analgesics are administered for no more than three weeks,” he continues. “While rofecoxib will obviously no longer be used, we feel there is great potential for other non-opioid drug combinations in treating post-operative pain. Our study provides a trial design to look at these.”

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