April 2, 2009 — Long-term use of opioids to manage chronic pain increases patients' sensitivity to certain types of pain, and similar hyperalgesia develops with methadone-maintained drug abusers, researchers from the University of Adelaide, in Australia, report.
"There is a low ceiling dose for opioids in the treatment of persistent nonmalignant pain. Increasing doses may be causing more pain, not less pain. So use opioids sparingly," coauthor Andrew A. Somogyi, MD, told Medscape Psychiatry.
"If methadone-managed opioid-dependent patients need acute analgesia, the dose of opioid may need to be much higher due to the well-known phenomenon of tolerance and also hyperalgesia," he added.
The observational study by Justin L. Hay, MD, and colleagues is in the March issue of the Journal of Pain.
Growing Body of Evidence
The investigators compared pain sensitivity in patients with noncancer chronic pain taking either methadone (n = 10) or morphine (n = 10) with those maintained on methadone due to opioid dependence (n = 10) and with a control group (n = 10).
The outcome variables were hyperalgesia (enhanced pain in response to a normally painful stimulus) and allodynia (pain due to a stimulus that does not normally cause pain). These were measured using cold-pressor tolerance and electrical stimulation for hyperalgesia and von Frey hairs–stimulation testing for allodynia.
Results showed that the methadone-maintained group and both of the chronic pain groups were hyperalgesic measured by the cold-pressor test but not measured by electrical stimulation. None of the groups had allodynia.
"We did not expect that chronic noncancer pain patients on morphine or methadone would have similar cold-pressor–induced hyperalgesia. Perhaps it will occur in all patients on any opioid," Dr. Somogyi speculated.
"These results add to the growing body of evidence that chronic opioid exposure increases sensitivity to some types of pain. They also demonstrate that in humans, this hyperalgesia is not associated with allodynia," the authors write.
Evidence "Not Terribly Encouraging"
David Clark, MD, from the Palo Alto VA Health Care System, in California, has also studied opioid-induced hyperalgesia. According to Dr. Clark, "[An] important finding in this study was that not only addicts have this type of sensitization. Chronic-pain patients have it as well, so this problem goes beyond the boundaries of what is unique to drug abusers."
Dr. Clark said the finding that long-term use of opioids might sensitize patients to pain itself suggests factors that could both limit the clinical utility of opioids used to control chronic pain and add to pain problems in those being treated for addiction.
"The emerging experience regarding the long-term use of opioids for chronic pain is not terribly encouraging, and opioid-induced hyperalgesia is 1 explanation for why this therapy might have limited success," he said.
The researchers' data on allodynia have both clinical and research implications. "Allodynia is perhaps the most commonly followed feature of opioid-induced hyperalgesia in animal populations," Dr. Clark said.
"The authors very reasonably conclude that particular types of pain might be more altered than others after long-term opioid use. The trouble is that no one knows which of these pain models might be the best index of anything experienced by a human with clinical pain," he added.
Dr. Somogyi said that this study also raises new questions about opioid-related hyperalgesia. "Is it dose related? How quickly might it start? Why does it occur only for cold-pressor pain and not electrical-stimulation–induced pain? What nonneuronal mechanism might be involved?" he said.
0 σχόλια:
Δημοσίευση σχολίου