How researchers are devising innovative strategies to help bring us to the next-generation of pain medications
Nearly every week a new report or study touches on the opioid epidemic and the headlines are not generally encouraging. In December the National Center for Health Statistics, part of the US Centers for Disease Control and Prevention (CDC), released data attributing a two-year decline in US life expectancy in part to a 21% rise in opioid-related deaths.
The CDC estimates that about 40% of all U.S. opioid overdose deaths involve a prescription opioid. And many opioid addicts start off with prescription painkillers before switching to heroin, the synthetic opioid fentanyl and other more potent drugs. There is a clear unmet medical need for drug researchers to produce a next generation of pain medications that have the same analgesic properties in the absence of the addictive ones.
Opioids work by targeting mu-opioid receptors, which are a key component of our perception of pain. Not only do opioids produce analgesia, they trigger learned associations between taking the drug and the physiological and perceptual effects of the drug, a New England Journal of Medicine study notes. In other words, the same receptors that are critical for the efficacy of opioids are also the culprits with respect to their addictive properties.
A new generation of drugs that offered the pain relief of opioids, but didn’t carry the risk of addiction, would address this enormous societal need, which is why there is a substantial research effort across the CNS Drug Discovery community to discover and develop the next generation of pain medications.
One alternative therapeutic strategy to identify novel pain non-opioidal medication, i.e, medications that bind to targets in the brain other than the mu opioid receptor. Multiple such putative non-opioidal mechanisms have been identified and there is a substantial effort to turn this research into marketed therapeutic. Therapeutics that target many of these mechanisms have demonstrated efficacy in animal models with multiple disparate pain endpoints (e.g., neuropathic pain, post-surgical pain, chemotherapy-induced pain, etc.), and as these medications progress, it would seem inevitable that we will find one, or more, that will serve as the next generation of pain treatments.
Another strategy has been to produce drugs that target the opioid receptor but that engage them in a manner that maintains the analgesic efficacy, but that does not produce the addictive, or desensitization effects. Executing this strategy presents certain challenges in the Drug Discovery process and the identification and development of such molecules that are biased to the analgesic properties of opioids remains challenging
A third approach researchers are exploring is the development of drugs that can work in parallel with opiates to boost the analgesic efficacy of opioids and/or to reduce their addictive/rewarding and tolerance properties. Such adjunct medications would allow prescribers to lower the dose of opioids a patient receives or to deliver them to patients in such a way to minimize the concern for addiction.
The field is also made strides in reformulating current drugs used to treat opioid addiction, notably with last year’s US Food and Drug Administration approval of a once-monthly formulation of buprenorphine for moderate-to-severe opioid disorder. Doctors hope the new version of the drug, which is injected monthly rather than taken daily in pill form, will help reduce relapses in patients.
Collectively, these approaches, among others, provide optimism that we can improve our treatment options to our overwhelming societal problem. The NIH’s National Center for Complementary and Integrate Health estimates 100 million Americans suffer from chronic pain—about a third of the population. It’s clear that relief is sorely needed.