Study Finds Link Between Chronic Pain and Anxiety

By Pat Anson, Editor

A new study helps explain why so many chronic pain patients also suffer from anxiety or depression.

Researchers at the University of Vermont discovered that the body releases the same neurotransmitter in response to stress as it does to chronic neuropathic pain. The findings, published in the journal Biological Psychiatry, could lead to the development of a new and safer class of medication that could treat both pain and anxiety.

In studies on laboratory mice, researchers found that pain signals and the PACAP neurotransmitter (pituitary adenylate cyclase activating polypeptide) share the same pathway to the brain - the spino-parabrachiomygdaloid tract - which travels from the spinal cord to the amygdala, where the brain processes emotional behavior.

"Chronic pain and anxiety-related disorders frequently go hand-in-hand," says senior author Victor May, PhD, a professor of neurological sciences at the University of Vermont. "By targeting this regulator and pathway, we have opportunities to block both chronic pain and anxiety disorders."

May and his colleagues found that anxious behavior and pain hypersensitivity were significantly reduced when a PACAP receptor antagonist -- designed to block the release of the neurotransmitter -- was applied.

"This would be a completely different approach to using benzodiazepine and opioids - it's another tool in the arsenal to battle chronic pain and stress-related behavioral disorders," said May, who found in a previous study that PACAP was highly expressed in women exhibiting symptoms of post-traumatic stress disorder (PTSD).

May’s findings are important because anxiety and stress are currently treated with sedatives, benzodiazepines and other central nervous system (CNS) depressants. When taken with opioid pain medication, the combination of the drugs can lead to extreme sleepiness, respiratory depression, coma and death.

Yesterday, the U.S. Food and Drug Administration ordered new “black box” warning labels be put on all medications that contain opioids, benzodiazepines and CNS depressants, warning patients and physicians about the increased risk.

According to a 2015 study, over a third of the patients prescribed opioids for chronic musculoskeletal pain were given a sedative. And patients with a history of psychiatric and substance abuse disorders were even more likely to be co-prescribed opioids and sedatives.

Sedatives or Opioids: Which is the Bigger Problem?

By Pat Anson, Editor

New research shows that the prescribing of opioid pain medications is declining in United States, but the co-prescribing of sedatives with opioids remains a serious problem that raises the risk of an overdose.

In a study of over 35,000 patient visits for acute and chronic pain from 2001 to 2010, researchers found that the prescribing of benzodiazepines was three to four times more likely when opioids were prescribed.

Over a third of the patients prescribed opioids for chronic musculoskeletal pain were given a sedative. And patients with a history of psychiatric and substance abuse disorders were even more likely to be co-prescribed opioids and sedatives.

"Multidrug use is the trailing edge of the opioid epidemic," said Mark Sullivan, MD, a professor of psychiatry and behavioral sciences at the University of Washington School of Medicine. "We are making progress on decreasing opioid prescribing, but co-prescribing of opioids and sedatives has not decreased."

The study, published in the journal Pharmacoepidemiology and Drug Safety, estimates that opioid prescribing peaked in 2007. It’s the latest indication there has been a reversal in the growth of opioid prescribing – which has long been blamed for the so-called “epidemic” of prescription drug abuse.

In April, another study was released showing that the painkiller hydrocodone was no longer the most-widely prescribed drug in the U.S.

While opioid prescribing is in decline, researchers found no evidence that the co-prescribing of opioids and sedatives is also dropping. Opioids, benzodiazepines and muscle relaxants are all central nervous system depressants. Mixing the drugs is potentially dangerous because their interaction can slow breathing and raise the risk of an overdose death.

"Patients who are on long-term combined opioid and benzodiazepine therapy are often on a treadmill," said Sullivan. "They feel relief when they take their medications and withdrawal when they stop, so they continue this combined therapy, even though many function poorly and some will die as a result."

A study by the Centers for Disease Control and Prevention found that as much as 80 percent of unintentional overdose deaths associated with opioids may also involve benzodiazepines. Nearly 6,500 people died from overdoses involving benzodiazepines in 2010.

“We are seeing a disturbing increase in the use of benzodiazepines, mostly Xanax and Klonopin and Adderall. I call this the evil trifecta,” said Percy Menzies, president of Assisted Recovery Centers of America, which operates four addiction treatment clinics in the St. Louis, Missouri area. “To make matters worse, the use of heroin continues to grow as Mexican farmers are switching to growing the opium poppy.”

While fewer opioids are being prescribed for pain, Menzies says there has been explosion in the use of buprenorphine – a weaker opioid – to treat addiction. For many years, buprenorphine was only available under the brand name Suboxone, but now there are several other buprenorphine brands competing in the lucrative addiction treatment market. 

“We have reduced the number of prescriptions for opioids but the use of opioids (primarily buprenorphine) are growing. Never in the history of drug treatment, has the sale of a medication exceeded $2 billion,” said Menzies in an email to Pain News Network.

Recent studies by the Substance Abuse and Mental Health Services Administration (SAMHSA)  found a ten-fold increase in the number of emergency room visits involving buprenorphine. Over half of the hospitalizations were for non-medical use of buprenorphine – meaning  many users took the drug to get high.

Over 50,000 visits to ER’s in 2011 involved a combination of benzodiazepines and opioids, according to SAMHSA.