New type of opioid targets pain areas directly avoiding negative side effects

March 3, 2017 by Bob Yirka report
NFEPP activates opioid receptors in injured, but not normal, tissue. Credit: G C. Stein

(Medical Xpress)—A team of researchers with the Free University of Berlin and Zuse-Institut Berlin has developed a type of opioid that was shown to target pain in rats without causing negative side effects. In their paper published in the journal Science, the team describes the new opioid, how well it worked in rats and the side effects that were eliminated.

Most everyone knows about the positive and negative attributes of opioids—they are used to dull but are also highly addictive and have side effects such as constipation and respiratory distress. In this new effort, the researchers have developed a type of opioid they have named NFEPP that is works only on the part of the that is in pain, while not affecting other parts, thus averting side effects.

As part of their research, the group noted that the parts of the body that hurt typically result in inflammation as the body tries to repair itself. They further noted that body parts experiencing inflammation tend to be more acidic than other parts. Because of that, they set about developing an opioid that would bind only to nerve receptors that exist in acidic environments. Opioids binding to untargeted parts of the body are what cause side effects, after all—binding to nerve cells in the gastrointestinal tract, for example, causes constipation and binding to nerve cells in the brain is what leads to feelings of euphoria and addiction.

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Molecular dynamics simulation of opioid receptor in complex with NFEPP at low pH. Credit: V. Durmaz

The researchers tested the new opioid on rats, and found that it was comparable to the commonly prescribed opioid fentanyl in relieving pain, but it did not cause constipation, addiction, breathing problems, heart rate increases or changes to . In short, it appeared the new opioid alleviated pain as well as current opioids, but did not cause any noticeable .

More research is required to test both the efficacy and safety of the opioid in rats and other test animals before it can be tested in humans, but if the opioid turns out to work in humans the way it does in , it could mark a truly transformative moment in medical science—a true breakthrough in pain mitigation and management.

Credit: G. Del Vecchio & V. Spahn

Explore further: Opioids produce analgesia via immune cells

More information: V. Spahn et al. A nontoxic pain killer designed by modeling of pathological receptor conformations, Science (2017). DOI: 10.1126/science.aai8636

Abstract
Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral μ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide–binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3′,5′-monophosphate inhibition in vitro. It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential.

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dirk_bruere
3 / 5 (1) Mar 03, 2017
Works until you take an anti-inflammatory
gkam
1 / 5 (4) Mar 03, 2017
This could have saved Elvis, who had large amounts of unpassed waste stuffed in his body from his opioid addiction.. Trying to pass it, he had a heart attack.
carbon_unit
not rated yet Mar 03, 2017
This is good news for those suffering chronic pain and living in fear that the political/medical response to the opioid overdose crisis will be to make it much more difficult to get needed relief.
Works until you take an anti-inflammatory
Long term use of anti-inflammatory drugs is problematic too, so this makes it a little less of a "which way do I suffer" decision.
DonGateley
not rated yet Mar 03, 2017
Here's hoping that the drug regulatory delay gets the attention that Mr. Trump gave it in one of his appearances. This is a huge discovery which must get a fast track.
DonGateley
not rated yet Mar 03, 2017
And that it is not priced beyond the reach of so many who need it or is subsidized by popular demand.
mjom5000
5 / 5 (1) Mar 06, 2017
Might this drug help in the management of chronic intermittent neuropathic pain?
Anonym
1 / 5 (2) Mar 06, 2017
What "most everybody knows" about addiction is wrong. Opiod "addiction" arises from psychological factors, not some physical imperative. That is why most people given opiod pain meds after surgery do not go on to become heroin addicts; they are not psychologically vulnerable. Same was true of the hundreds of thousands of heroin-addicted soldiers returning from Vietnam did not become junkies after returning Stateside.

Treating the drug "addiction" without treating the life circumstances and personality disorder that led to it is a waste of time and money.

Oh, and do you suppose that maybe the "negative side effects" which these good doctors hope to eliminate provide a safety mechanism against permanent reliance? If these researchers do succeed, they will have created an even more abusable form of opiod than previously existed. Brilliant.
DonGateley
5 / 5 (3) Mar 06, 2017
@Anonym: You sir are an idiot. Opioid/opiate addiction is a real physical phenomenon with roots in it's effects on neurotransmitters. I have one of the most addictive personalities you can find but in my experience of using heroin briefly to assuage the horrible pain of a severely wrenched leg, the side effect of not being able to pass other than rock hard, massive shit boluses with huge effort was sufficient for me to overcome quickly the otherwise pleasurable effects as soon that was realistic despite the unpleasant withdrawal. Without that deterrence I know I would have been hooked. It could be that many others who would otherwise be caught in the intrinsically addictive trap of opiates and opioids have been similarly dissuaded from their pursuit of more. These researcher's seem to have eliminated even the temptation of pleasure if I read it correctly and that is huge.
qitana
not rated yet Mar 07, 2017
It's true that opioids are physically addictive. But we may add that there are also psychological effects. For example, people who move back to the environment where they used to take the drug, have a greater chance to fall back to the habit of using it.

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