Drug overdose deaths continue to impact communities all across the United States. According to the CDC, nearly 70% of the 67,367 drug overdose deaths in 2018 involved use of an opioid.

Opioids are a class of drugs that are used to treat pain. Prescription opioids are prescribed by doctors to treat moderate to severe pain. The most common prescription opioids include oxycodone, hydrocodone, morphine and methadone. Users may be familiar with the names Percocet® or OxyContin® and Vicodin® or Norco®, which are brand names for oxycodone and hydrocodone, respectively. Fentanyl is one of the more powerful opioids and is used in severe cases, such as advanced cancer pain, but is also used for chronic non-cancer pain. Heroin is an illegal opioid, and its use has increased in the U.S. across all socioeconomic levels.

The National Institute on Drug Abuse (NIDA) reports that 21 to 29% of chronic pain patients misuse prescription opioids, displaying a strong association between chronic pain and opioid misuse.

However, chronic pain may not be directly causal to opioid addiction. Catherine Cahill, an opioid neuropharmacologist at the Hatos Center of Neuropharmacology at UCLA, leads a pain and addiction lab that aims to understand how chronic pain changes reward and motivation in an effort to reduce addiction to prescription opioid medications.

Chronic pain, unlike acute pain, is defined as pain that lasts for three months or more. Yet, most chronic pain patients suffer for years. The pain persists even after the cause of injury or illness has gone away. The stress that accompanies this consistent pain can contribute to emotional side effects such as depression, anger and anxiety.

Chronic pain patients are subject to two types of pain: physical and emotional. According to Cahill, it is this dual component of pain that makes chronic pain patients more susceptible to opioid misuse than others. 

Opioids are effective at being able to treat mood disorders, and many pain patients may have negative mood states,” Cahill said. “Instead of taking them for treating their [physical] pain, it becomes important for treating their mood disorder. And that’s where a lot of the opioid addiction has come from.” 

In essence, focus on the emotional component of pain may lead to better treatments and quality of life for these impacted individuals.

To tackle the emotional component of the pain experience, Cahill shared that she is currently researching kappa opioid receptors (KOR). Opioid receptors are proteins in the brain that act as communication links between the external environment and brain cells in response to opioids. 

Within the family of opioid receptors, KOR is associated with dysphoric and negative emotional states, including precipitating anxiety and depressive-like symptoms as well as fear. The KOR are expressed in many areas of the brain important for stress and emotion, including their expression on the terminals of dopaminergic neurons and serotonin neurons, brain cells that are responsible for the control of mood, reward, addiction and stress. As inhibitory receptors, KOR dampens dopaminergic signals. Because of the strong overlap between pain processing and emotional/motivational systems in the KOR neurocircuitry, the KOR system has become a popular area of research interest.

According to a recent article published in The Journal of Neuroscience, Cahill’s lab discovered that there is a significant increase in the expression of KORs in chronic pain states, specifically in areas important for emotion and reward. Her team identified that this increase in KOR function causes disruption of normal reward processing, that involved changes in dopamine signaling in the brain. Inhibiting KORs not only alleviated anxiety and depressive-like effects in the chronic pain animals, but also reduced the aversive component of pain. The significance of this research is highlighted by the finding that the emotional or bothersome component of the pain experience is a better predictor of quality of life.

As of today, opioids remain as one of the most effective pharmacotherapeutic agents in treating pain. However, the drugs’ ability to blunt both sensory and emotional components of pain has led to marked levels of dependence and addiction throughout the United States. The implications of the discoveries in neurocircuitry including that of the KOR system are crucial for the development of novel treatments that can address the emotional component of the chronic pain experience, which is significantly responsible for drug-dependence in this affected population. 

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