Neuroscience graduate student Allison Doyle Brackley is currently conducting research in the lab of associate professor Nathan Jeske, Ph.D., in the Department of Oral and Maxillofacial Surgery aimed at identifying novel protein-protein interactions that influence peripheral opioid analgesic competency in the presence and absence of inflammatory mediators.

Pain in America

As a pain researcher, it is important to understand that pain is multidimensional and present in many medical conditions. According to the Institute of Medicine U.S. Committee on Advancing Pain Research Care and Education, pain is the number one reason people seek medical attention. It affects more Americans than diabetes, coronary heart disease, stroke and cancer combined, and costs our society upwards of $635 billion annually. That said, the translational research conducted by the Neuropharmacology Pain Research Group is vital to public health.

Opioids: The Gold Standard

Within the Neuropharmacology Pain Research Group, my project is focused on identifying novel protein-protein interactions that govern peripheral opioid analgesic responses in pain-sensing neurons. Opioids bind to opioid receptors throughout the body and have been regarded as the most effective treatment for pain for millennia. Many substances are referred to as opioids including opiates derived from the poppy plant, like morphine and codeine, semi-synthetic and synthetic opioids, such as heroin, hydrocodone, oxycodone and fentanyl, and endorphins, the peptides our bodies produce for pain modulation. Upon binding to their receptors, opioids can reduce the perception of pain.

Prescription opioids are commonly prescribed for a variety of injury- and dental-related pain. I strongly believe prescribers, pharmacists, patients and caregivers should review the role of opioid use in pain management, as well as their potential consequences.

Currently, opioids are widely prescribed to treat severe, acute, and chronic cancer and non-cancer pain. Opioids can be highly effective for the treatment of acute pain when non-opioid analgesics are ineffective if dosed carefully in both naA¯ve and opioid tolerant individuals. Postoperative pain after major surgery can require opioid therapy in combination with non-opioid therapies.

Pharmacologic strategies for the management of chronic pain differs between cancer versus non-cancer pain. Opioid therapy is highly effective for cancer patients with severe, persistent pain. On the other hand, long-term systemic opioid treatment in non-cancer pain is generally ineffective and contraindicated due to adverse side effects.

Opioid Abuse & Misuse

According to the National Institute on Drug Abuse (NIDA), IMS Health’s National Prescription Audit data revealed that the number of opioid prescriptions dispensed across the United States tripled over a 20-year span (1991 to 2011), which paralleled the increase in opioid-related deaths during this period and suggests that opioid prescription availability is associated with increased use and overdose. Opioid prescriptions can be just as dangerous as illicit drugs with their unintended side effect profile, and can act as a gateway drug.

One of the problematic side effects that results from opioid abuse, prescription or heroin, is the development of tolerance. This occurs when a person’s response to a drug diminishes with subsequent use. As a result, the patient experiencing pain requires a higher dose to achieve the level of initial analgesic effect. When patients are repeatedly exposed to a drug, physical dependence can develop. Those who depend on opioids only function normally in the presence of opioid drugs. If the drug is taken away the patient can experience drug-specific symptoms of withdrawal, which manifest as physical disturbances. To avoid withdrawal, some individuals find themselves in an unending state of drug use.

Dependence should not be mistaken for addiction. NIDA differentiates addiction from dependence in terms of self-control. Typically, a drug user’s initial choice to take a drug is voluntary. With chronic use, the individual may become impulsively destructive in their compulsive drug seeking and drug abuse regardless of harmful consequences. Addiction, also known as substance use disorder, is a chronic disease.

In rare cases, prescription opioids even carry the risk of becoming a “gateway” drug. Given that most Food and Drug Administration (FDA)-approved prescription opioids bind the same receptors targeted by the illicit drug heroin it is not surprising that prescription opioid abuse or misuse may progress to the use of heroin, which is known to be highly available at a low cost throughout the United States.

The National Survey on Drug Use and Health illustrates the “gateway” potential for prescription opioid addicts. For example, individuals who are addicted to prescription opioids are 40 times more likely to be addicted to heroin. How does this risk compare to other substances of abuse? Alcohol addiction doubles the likelihood of being addicted to heroin, whereas marijuana addiction triples your chance of being a heroin addict. People who are addicted to cocaine are fifteen times more likely to be addicted to heroin, but cocaine carries only about one-third the risk for heroin addiction compared to prescription opioid addiction.

The Opioid Epidemic

In 2016, America is facing one of the most challenging public health crises of our time, an opioid epidemic. Nearly four times as many opioid prescriptions are filled today compared to 15 years ago. In fact, the number of overdose deaths is higher than ever. According to the latest Centers for Disease Control (CDC) statistics, drug overdose is the number one injury death for American adults 25 to 54 years of age. Opioids are to blame for over half of these deaths and, even more worrisome, one third are related to prescription opioids.

Communities all over America are affected by the opioid epidemic, including those in the Lone Star State. The CDC’s most recent data lists Texas in the top five for total number of opioid related deaths. In a state-by-state analys
is of the societal costs of prescription opioid abuse, Texas ranked second of all states for opioid abuse-related health care costs totaling a mind-blowing $1,963,632,647. You’d think everything is bigger in Texas, including the amount of money we spend combating mental health and substance abuse, right? Wrong.

Of the 47 states that reported state spending on mental health agencies, Texas ranks second-to-last in state mental health agency expenditures per capita. Texas has lagged behind the rest of the nation, ranking in the bottom five states for mental health agency expenditures per capita consistently over the last ten years.

Responding to the Opioid Epidemic

With such a rapidly evolving crisis, our government is constantly strategizing and implementing laws to tackle the epidemic. It’s hard to keep up with the many changing policies, but the response looks promising:

The White House is dedicated to addressing the opioid overdose epidemic through funding for treatment and prevention. In 2010, the Patient Protection and Affordable Care Act (PPACA), commonly referred to as the Affordable Care Act or Obama Care, was signed into law by President Obama (Public Law No: 111-148). Importantly, the PPACA includes substance use disorders as an essential health benefit. This guaranteed that services for substance use disorders were included for individuals with Medicaid and those who purchased health insurance on Health Insurance Exchanges.

In 2011, the White House Administration outlined goals to address America’s prescription drug abuse crisis in the Prescription Drug Abuse Prevention Plan. This strategy focuses on educating the public and health care providers on prescription drug abuse, increased monitoring for prescription drug use, and the development of simple and safe prescription drug disposal programs.

The opioid epidemic faces new enforcement and supply reduction with an unprecedented network of law enforcement and public health partnerships. The Drug Enforcement Administration has collected over five-and-a-half million pounds of unused prescription medication through National Take Back Days. In collaboration with the Department of Justice, the plan also implemented efforts that shut down “pill mills” and Internet prescription drug traffickers. Efforts with the Drug Enforcement Agency have led to hundreds of arrests.

The Administration has also been focused on community prevention and overdose response, including local community-based coalitions and mandatory prescriber education and training. Protection extends beyond our civilian population benefitting our military members and Veterans. The Department of Defense (DOD) now screens pharmacy data to identify prescription drug use patterns in our military population and their families. The DOD has also been providing training on opioid overdose reversal kits provided to all on-base first responders.

In addition to those who currently serve, our Veteran community is being protected. The Department of Veterans Affairs have armed Veterans with over 12,000 naloxone kits that can reverse opioid overdose. Another community that will benefit from evidence-based approaches, prevention and treatment are pregnant women with opioid disorders and their infants, who are susceptible to Neonatal Abstinence Syndrome displaying symptoms of drug withdrawal. Bipartisan legislation to address problems related to prenatal opioid use, the Protecting Our Infants Act, was signed into law last year (Public Law No: 114-91). This legislation ensures that affected pregnant women have access to prenatal care and evidence-based treatment, also focusing on the “Treating for Two” initiative for prescribers for dependent pregnant women.

Treatment is imperative to the correcting the opioid crisis. Responsible for overseeing pharmaceutical safety, quality and efficacy, the FDA recently outlined a reassessment of prescription opioid policies in response to this epidemic. This year, the Health Resources and Services Administration has $100 million available to improve substance use disorder treatment facilities across our nation.

In Fiscal Year 2016, the Substance Abuse and Mental Health Services Administration funded grants supporting medication-assisted treatment for opioid use disorders in 22 states, which the Administration hopes to increase to 45 states in Fiscal Year 2017 if approved by Congress. Committed to treatment, the Department of Health and Human Services recently announced an evidence-based, bipartisan effort called the Secretary’s Opioid Initiative, which aims to tackle the opioid epidemic focusing on three areas. The first priority is to combat the over-prescribing of opioids by providing training and resources, including updated prescriber guidelines, to prescribers and health professionals.

The second priority is aimed at reducing the number of opioid-related deaths by supporting the development and distribution of the life-saving drug naloxone, an opioid antagonist that works by blocking the effects of opioids. The third priority encourages and expands medication-assisted treatment, which combines medication and counseling/behavioral therapies to treat addiction. Last year, Senator Sheldon Whitehouse (D-RI) and Representative Jim Sensenbrenner (R-WI5) introduced Capitol Hill to the Comprehensive Addiction and Recovery Act (CARA), an act that would authorize the Attorney General and Secretary of Health and Human Services to award grants to address the prescription opioid abuse and heroin use crisis. This rare bipartisan, bicameral legislation was passed by the Senate and House of Representatives this summer and, on July 22, 2016, President Obama signed CARA into law (Public Law No: 114-198).

This Administration been diligent in their fight to curb prescription opioid abuse, but the President recognizes that the nation needs more help. The President’s Fiscal Year 2017 Budget proposed $1.1 billion in new funding to address the opioid epidemic, with $920 million for states to fund expanded access to opioid use disorder treatment in all states, $50 million for National Health Service Corps funding for substance use disorder treatment providers, and $30 million to evaluate and improve treatment for patients struggling with opioid use disorder.

The remaining $500 million in the proposed Budget will focus on prevention, medication assisted treatment, improve access to naloxone, and support enforcement strategies. Under this proposal, Texas
would be eligible to receive up to $48 million over a two-year period. This funding would expand access to treatment of opioid use disorders. Of course, this depends on Congressional approval of the proposed budget, as well as Texas’ application and plan to combat prescription opioid abuse and heroin use epidemic.

The “Beyond The Bench” series features articles written by students, alumni, and postdoctoral fellows at the Graduate School of Biomedical Sciences at The University of Texas Health Science Center San Antonio.