To Solve Opioid Addiction, We Still Need to Solve Pain
We know a whole lot about painkillers, but not much about pain itself.
Pain exists. Thundering, unbearable pain exists. It's not just something made up by drug companies and sold to corruptible doctors. Making opioids more difficult to obtain—in some cases—and ensuring that their dangers are widely publicized are good starts, but there still exists this fundamental tension between a patient in pain and a doctor's atomic role in treating that patient. Opioids could be full-on banned in 50 states, but we're still left with the pain.
This is why opioids won't be full-on banned, nor should they be, despite their role in the United States' devastating opioid addiction epidemic. But perhaps we're focusing too much on the pharmaceutical angle, and not on the thing itself. If we're to really solve the opioid problem, we need to be devoting more of our efforts to understanding what pain even is. As a syndrome affecting literally everyone at some point, it remains under-researched.
This is the essence of an argument made by University of Pennsylvania pharmacologist Tilo Grosser and colleagues in the current issue of Science: We need to be able to treat pain in non-addictive ways, pharmaceutical or otherwise, and this means understanding pain. When it comes to developing new painkillers, we're in a deep lull, with the most recent analgesic (painkilling) drug hitting the market five years ago. Many basic questions remain.
"Given the origins of the opioid epidemic, the pharmaceutical industry has a societal obligation to contribute."
These include, according to Grosser, whether or not neuropathic (nerve-based) and inflammatory (injury-based) pain are really distinct; how chronic pain arises absent a clear physiological cause; how acute pain becomes chronic; what effect sex and age have on pain; and what the relationship between sleep and pain is. Biomarkers for pain and pain relief are urgently needed, he says, as are truly comprehensive models of it. In hospitals that often feel like the inside of spaceships, we're somehow left quantifying how we feel with this thing:
There are some interesting ideas already in the pipeline, Grosser notes. These include developing opioid variants that are less immediately dangerous—that is, they have less of a depressant effect on respiration—and are less prone to to abuse, as well as NSAID painkillers (aspirin, classically) that just work better. There are also a whole bunch of new or relatively unexplored pain-related channels, like cannabinoid receptors, that may be targeted by new classes of pharmaceuticals. But Grosser is also looking beyond classical drugs.
"For emerging and existing analgesics, it would be beneficial to explore two other areas," he writes. "There is a need to understand the biology of the placebo response, so as to maximally exploit it. Complementary approaches to analgesia, such as acupuncture, yoga, cognitive behavioral and mindfulness techniques, and meditation, should be rigorously assessed to determine whether they provide value beyond placebo, and to determine their efficacy at an individual level."
We treat pain as though patients all respond to painkillers and pain in the same way. But there are diverse pain phenotypes to be explored. Your pain is not my pain, even though we're pretty similar people experiencing the same pain stimuli. Grosser thinks we should be harnessing electronic health records and crowdsourcing tools to better understand this diversity.
None of this comes free, of course. Grosser thinks $10 billion over 10 years should about cover the new research described above.
"Given the origins of the opioid epidemic, the pharmaceutical industry has a societal obligation to contribute," Grosser writes. "The lawsuit filed in 2014 by the city of Chicago against five opioid manufacturers, and the recent settlement reached by the city with Pfizer, suggests that the industry bears some legal responsibility for misleading marketing claims."
"Legal liability aside, however, a substantial investment by the industry at large would not only create good will," he continues, "but would likely serve its own collective financial interest, given the potential market for novel nonaddictive analgesics."
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