Researchers might have found an answer to the puzzling and sometimes controversial problem of opioid-induced hyperalgesia (OIH).
A new study shows that dexmedetomidine, a highly selective α2 agonist that boosts pain-inhibiting neurotransmitters, might hold the key to controlling OIH. This condition of heightened pain intensity is caused, paradoxically, by opioid use.
The study, presented at the American Academy of Pain Medicine (AAPM) 29th Annual Meeting, demonstrated that a high dose of opioids induces hyperalgesia, but adding dexmedetomidine efficiently alleviates the symptoms.
This addition may represent a novel therapeutic option for OIH, lead author Yeon-Dong Kim, MD, PhD, clinical professor of anesthesiology and pain medicine, Wonkwang University Hospital, Iksan City, South Korea, told Medscape Medical News.
"The study showed that dexmedetomidine may be another choice of treatment when we encounter patients with opioid induced hyperalgesia in the management of chronic pain," Dr. Kim said.
The study enrolled 90 patients undergoing laparoscopically assisted vaginal hysterectomy who received two-step dexmedetomidine (an initial dose of 1.0 μg/kg for 10 minutes, followed by a continuous infusion of 0.7 μg/kg per hour during the operation) or saline placebo 15 minutes before getting anesthesia and intraoperative remifentanil infusion.
The patients were divided into three groups, each receiving a different dose of the opioid: group C (n = 28) received placebo and remifentanil, 0.05 μg/kg per minute; group RH (n = 29) received placebo and remifentanil, 0.3 μg/kg per minute; and group DRH (n = 28) received dexmedetomidine and remifentanil, 0.3 μg/kg per minute.
The researchers found that the mechanical hyperalgesia threshold 24 hours after surgery was significantly lower in the RH group than in the other two groups (P < .05). According to a visual analogue scale, postoperative pain intensity was significantly greater in the RH group compared with the DRH group (P < .05).
As well, the time until need for postoperative analgesic was significantly shorter in group RH than in the other two groups (P < .05).
In terms of adverse effects, the study found that shivering and the incidence of postoperative nausea and vomiting were significantly lower in the DRH group than in the other groups.
Dr. Kim stressed that further studies are needed to investigate the use of dexmedetomidine as part of a "multimodal approach" to treating OIH.
According to Lynn Webster, MD, medical director, CRI Lifetree, Salt Lake City, Utah, and incoming AAPM president, dexmedetomidine has anxiolytic properties that might be an added benefit for patients because anxiety often accompanies pain.
But dexmedetomidine is not without its drawbacks. According to Dr. Kim, the drug can lead to sedation, reduction in sympathetic tone, and, at high doses, severe hypotension and bradycardia.
Although Dr. Kim estimated that hyperalgesia affects as many as 15% to 20% of opioid users in the clinical setting, Dr. Webster said the real prevalence is unclear. "Most of us have patients who have been on opioids for a while and seem to have an increased sensitivity. Is that opioid-induced sensitivity or is something else going on?"
In any case, Dr. Webster believes that genetic vulnerability plays a role and that risk is individualized. "Some individuals may be more likely to develop a hyperalgesic state when exposed to a certain type of opioid, but then the same individuals may not develop a hyperalgesic state when exposed to a different opioid."
The condition poses a treatment conundrum for physicians, noted Dr. Webster, adding that giving patients more opioids can make the situation worse and might raise the risk for overdose. "The therapeutic window is smaller in this population than in those who are opioid naive."
It has sometimes been a "real struggle" to find a workable pain relief option for patients with OIH, he said. "This abstract appears to suggest that there may be a way to help people with whom we haven't been able to be very effective in the past."
However, at least one delegate queried whether the study merely demonstrated that the drug blocked opioid-induced tolerance rather than OIH.
The authors have disclosed no relevant financial relationships.
American Academy of Pain Medicine (AAPM) 29th Annual Meeting. Abstract 117. Presented April 12, 2013.
Pauline Anderson • Medscape Medical News © 2013 WebMD, LLC