Is Long-Term Opioid Therapy Effective for Patients with Polyneuropathy?

Polyneuropathy is a debilitating pain syndrome usually caused by acute injury or disease that causes damage to peripheral nerves. For some patients, the cause is unknown. Polyneuropathy is most common among older persons, often resulting in significant functional impairment. In a recent article by Hoffman et al, published in JAMA Neurology (2017), researchers, using a retrospective cohort design, examined the association of long-term opioid therapy with functional status, morbidity and mortality in an outpatient care setting between January 1, 2006, and December 31, 2010. Additional follow-up data was collected through November 2016.

This highly powered study included 1,364 women and 1,528 men with polyneuropathy and 14,435 controls. The average age of the participants was approximately 67.5 years.

The findings revealed:

  1. A diagnosis of polyneuropathy increased the use of long-term opioid therapy by physicians.
  2. Patients receiving long-term opioids for polyneuropathy had multiple functional status markers. Self-reported functional status measures were either unimproved or worsened among those patients receiving long-term opioid therapy even after adjusting for medical comorbidity (adjusted odds ratio,1.9; 95% CI, 1.4-2.6).
  3. Opioid dependence, depression and opioid overdose were statistically significant adverse outcomes associated with the long-term use of opioids for patients with polyneuropathy.

Why Does This Matter?

Dr. Hoffman, the principle investigator concluded, “In general, opioid chronic therapy did not tend to have benefits for patients with peripheral neuropathy in our study, and if anything, it was associated with negative outcomes.”

In an accompanying JAMA editorial, my friend and colleague, Dr. Nora Volkow, who is the director of the National Institute on Drug Abuse (NIDA), and Dr. Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke, elaborate on the findings that cast additional doubt on the efficacy of long-term opioid therapy for polyneuropathy and other neurogenic pain syndromes. Furthermore, Volkow and Koroshetz point out that the limited options for managing chronic pain, underscores the urgency to develop new therapeutics.

Although current opioid analgesics that exclusively target mu opioid receptors (MORs) continue to be vital in the treatment of many forms of chronic pain, but as in the current study, most cause bothersome and dangerous side-effects ranging from constipation to dependence, overdose, addiction and opioid-induced hyperalgesia (OIH).

Some good news…

The delta opioid receptor (DOPr) is a promising target for the treatment of chronic pain, via a novel use of β-arrestin-2. Animal studies show that targeting DOPr may provide equivalent pain relief with less tolerance and fewer adverse effects.

As the prevalence of both chronic pain and opioid use disorder escalate in the US, we are still using a 50-year-old treatment strategy. At the same time, we cannot overlook that most persons receiving long-term opioid therapy, managed by doctors with expertise in pain management and addiction medicine, seldom abuse their medication, nor become addicted to them, based upon the American Society of Addiction Medicine (ASAM) criteria. Regardless, more basic research is needed to develop less-addicting or non-addicting pain treatments. Until that time, training physicians about chronic pain and the principles of addiction medicine is imperative.