The human brain is a marvelous, complex organ. It controls so much of the body, and yet so little is known about it. But every day, new research opens doors to the brain’s inner workings, shedding light on the intricacies of diseases and disorders that affect it.
The PRA Health Sciences Brain Talk series zeroes in on three areas of mental health that have a significant impact on brain research today. Read on for part II of the series, pain and substance abuse.
With more than 42,000 opioid-related deaths in 2016 — of which 15,000-17,000 involved a prescription opioid — and an economic burden estimated at more than $78 billion annually, it’s no wonder that the opioid crisis is making daily headlines in the US. The crisis having now reached epic proportions, healthcare and government organizations are battling the detrimental effects of abuse, and are working tirelessly to decrease the ever-rising number of daily overdoses.
While the opioid crisis has brought to light the overuse and abuse of these drugs, the fact remains that there are still patients out there who suffer from pain and are responsibly using opioids as treatment. For many clinicians, this presents a conflict: battling the crisis vs. treating patients.
New approaches toward treatment are urgently needed, with an understanding of the patient perspective, in order to effectively treat patients while simultaneously tackling the issue of abuse and overdose.
New approaches for more effective solutions
Thankfully, there are other viable options that exist to combat the detrimental effects of opioid use, and more are in the process of development.
"Some very standard approaches [to pain treatment] include NSAIDs or anti-inflammatories to relieve pain," says Ryan Turncliff, of the Scientific Affairs Clinical Pharmacology Group of PRA Health Sciences. "These are common practices in countries outside of the US where opioids are infrequently used and that treatment option is successful."
Within opioid development, pharmaceutical companies are working both within and outside of the opioid space for solutions to pain relief. Several companies, Turncliff notes, are investigating specific subjective pathways of pain, signaling and targeting those that may not result in opioid abuse but still provide an analgesic effect. "Another avenue of ongoing research is exploring ways to limit the amount of opioid entering the body, to make opioids safer and potentially less addictive," he adds.
Pain research trials are on the rise, and those trials are providing insight into new treatment possibilities. However, one of the common issues that researchers encounter within these trials can potentially hinder the research — the need to treat patients, and the use of rescue medication for those not experiencing the desired pain relief effect.
"Within pain trials, all individuals’ pain thresholds vary, so it causes significant variability in the response to those medications," Turncliff explains. "Those two factors really influence the ability to determine whether a new medication is in fact imparting pain relief as desired in the study."
Lynn Webster, MD vice president of scientific affairs, neuroscience, for PRA Health Sciences, and past president of the American Academy of Pain Medicine, is well-known for his development of the Opioid Risk Tool, as well as his widespread public campaign to reduce overdose deaths. Webster says that the major harm from opioids is two-fold: one is addiction and abuse, and the other is overdose. These can cause respiratory depression, which is an avenue for research that needs to be considered in developing more effective treatment solutions.
All central nervous system analgesics have the potential to depress respiration, and when opioids are used in combination with other CNS depressants, there’s an increased risk of suppressing the respiratory drive. "That," Webster says, "places people at risk of apnea or death."
"The problem is that drugs that have been developed in the past have never been studied well enough to know what effect they have on respiratory depression by themselves or in combination," Webster says. "The future, I believe, is going to require studies that examine the effects on respiratory depression within the therapeutic range of a drug by itself and in combination with other central nervous system depressants." That way, he adds, clinicians who prescribe one or more drugs that have the potential to depress respirations can be educated on the risks. One new exciting development is the Ventilator Hypercapnic Response (VHR) system, which could non-invasively test for the effect of medication on respiratory drive.
Understanding the patient is the first line of treatment
Getting a prescription for pain medication can be a complicated process for some patients. While they may be using the opioid responsibly to manage their pain, their regular use of the drug may flag them needlessly as an addict.
Patients can also be misled into thinking that opioids should be the first line of treatment. Providers need to comprehensively understand a patient in order to determine their best treatment. Multiple factors should be considered, note both Turncliff and Webster, before prescribing any type of treatment or providing any intervention. Providers also have to consider comorbidity issues, time duration, and intensity of pain when a treatment of any kind is being prescribed.
Ultimately, better and safer treatments are needed, notes Webster, and digging deeper, understanding a patient’s pain on a molecular level is helping drive innovative treatments. What’s been uncovered toward that end are new mechanisms of action that cause pain in the first place.
"We now know of many different pathologies, and many different targets that the industry can go after to help overcome pain," he says. "So research is about identifying the pathology and the ways in which we might be able to reduce pain and improve function." And while there has been a flood of research in that area, he says, more is needed.
The battle continues
While the nation continues to fight against the opioid epidemic, novel approaches and new research are helping patients treat their pain now. By understanding the patient, the mechanics of pain, and how new solutions can create better outcomes, the complications that often surround pain can be mitigated and relieved for good.
Next up: Part III of the Brain Talk series—Alzheimer’s and the Brain
In case you missed it: Part I of the Brain Talk series—Depression and Bipolar Disorders