Study: Long-term opioid treatment might not be answer for managing sickle cell pain

Johns Hopkins researchers find those treated long term with opioids often fare worse in measures of pain, fatigue, curtailed daily activities

Opioids may not be the best long-term solution for managing pain in sickle cell patients, according to new research from the Johns Hopkins School of Medicine.

In a small study of adults with sickle cell disease, researchers found that those treated long term with opioids often fared worse than others in measures of pain, fatigue, and curtailed daily activities. Their findings are published online in the American Journal of Preventive Medicine.

"We need to be careful and skeptical about giving increasing doses of opioids to patients with sickle cell disease who are in chronic pain if it isn't effective," says C. Patrick Carroll, director of psychiatric services for the Johns Hopkins Sickle Cell Center for Adults. "Too little is known about the effects of long-term opioid management of chronic pain."

Sickle cell disease, a rare genetic blood disorder, predominantly affects African-Americans in the United States. The frequency of hospitalizations for pain treatment makes the disease one of the most expensive to treat in the American medical system.

"We need to be careful and skeptical about giving increasing doses of opioids to patients with sickle cell disease who are in chronic pain if it isn't effective. Too little is known about the effects of long-term opioid management of chronic pain."
C. Patrick Carroll, Johns Hopkins

The disease is caused by a mutation in the gene responsible for hemoglobin that causes red blood cells to take on a sickle-like shape and clog blood vessels. The clogged vessels can cut off oxygen to tissues and cause episodes of severe pain, known as crises, which often drive patients to emergency rooms to receive treatment with intravenous opioids.

Sickle cell patients can also develop chronic pain over time, an issue that has shifted more to the forefront as treatments have advanced and more patients are living well into adulthood. For chronic pain as well as for crisis pain, a common pain management strategy is opioids, through long-term prescriptions that often escalate to higher doses.

The Johns Hopkins team's research, however, casts doubt on the effectiveness of long-term opioid therapy for a number of medical conditions and discovered that in some cases opioid use is associated with a paradoxical increase in pain sensitivity.

For the new study, the team recruited 83 adults with sickle cell disease—29 who were prescribed daily long-acting opioids to manage pain, and 54 who weren't on long-term opioids. For three months, the patients self-reported their daily levels of pain, physical activity, and fatigue, among other quality of life factors.

Overall, the study found that patients on long-term opioid treatment were more impaired. On days of non-crisis pain, they reported three times greater pain interference in their activities and twice the fatigue. In addition, the patients on opioids reported pain intensities over three times higher than those not taking opioids on non-crisis days, and 32 percent higher on crisis days.

The research team also examined the phenomenon of central sensitization, in which the central nervous system amplifies pain sensations. Central sensitization is thought to be one way that opioids might increase pain sensitivity, and may play a role in how sickle cell disease causes chronic pain, says Carroll.

Investigating that angle, the researchers measured how intensely the participants experienced unpleasant heat and pressure. Overall, patients on long-term opioid therapy showed higher levels of central sensitization, with an index of 0.34, than those who were not, with an index of -0.10.

In participants who were not on long-term opioid therapy, the level of central sensitization correlated with levels of non-crisis pain. However, that correlation essentially vanished in the opioid-taking patients who also had higher levels of central sensitization and crisis pain. Carroll says this surprising result suggests the pain mechanisms in opioid-taking patients may differ in unexpected ways from patients who don't take opioids regularly.

Carroll cautions that the research is preliminary and that physicians shouldn't stop prescribing opioids to sickle cell patients who need to control chronic pain.

"We need to better understand how long-term opioid use affects pain sensitization and determine if certain people are more sensitive to these effects so we can prescribe the best treatment option for each individual patient," Carroll says. "We also need to learn more about how sickle cell disease may sensitize the nervous system."

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