Negative side effects of opioids could be coming from users' own immune systems

Date:
August 17, 2020
Source:
American Chemical Society
Summary:
In addition to possibly developing opioid use disorder, those
who take opioids long term can develop chronic inflammation and
heightened pain sensitivity. Scientists now report that some of
those side effects might be influenced by the body's own immune
system, which can make antibodies against the drugs.



FULL STORY ==========================================================================
In addition to possibly developing opioid use disorder, those who take
opioids long term, including patients who have been prescribed the
drugs for pain relief, can develop chronic inflammation and heightened
pain sensitivity.

Scientists now report in a pilot study that some of those side effects
might be influenced by the body's own immune system, which can make
antibodies against the drugs.


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The researchers will present their results today at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo.

A brand-new video on the research is available at
http://www.acs.org/fall2020- opioids.

"Extrapolating from previous work on opioid vaccines, we started thinking
that the patient's own immune system could be responsible for some of
the negative effects of long-term opioid use," says Cody J. Wenthur,
Pharm.D., Ph.D., who led the study. "We thought the body could be
mounting an immune response and making antibodies against the drugs."
The researchers, who are at the University of Wisconsin-Madison School of Pharmacy, Scripps Research and Scripps Clinic, realized that one issue
with this hypothesis is that commonly prescribed opioids for back pain,
such as hydrocodone or oxycodone, are not large enough molecules for the
immune system to recognize as antigens. From their past studies, however,
they knew that an immune response could be triggered if something larger
were bound to the drugs.

This could happen in the body when a protein in the bloodstream
reacts with the opioid to create a larger molecule in a process called haptenization.

To find out whether long-term opioid users produced antibodies against
the drugs, the team performed an enzyme-linked immunosorbent assay
(ELISA). Blood samples were obtained from 19 patients who used either hydrocodone or oxycodone for chronic back pain and from three control
patients who used over-the-counter remedies (OTCs) or non-pharmacologic approaches. Jillian Kyzer, Ph.D., a postdoc in Wenthur's lab, along
with Hyeri Park, Ph.D., a postdoc in the laboratory of Kim Janda, Ph.D., developed new techniques to synthesize hydrocodone and oxycodone haptens, linking them with a common blood protein to form bioconjugates. These bioconjugates were then coated on the surface of ELISA plates, and the patients' blood samples were added. If antibodies against the haptens
were present in the patients' blood, they would stick to the surface
of the plate and would be detected by another antibody that binds and
creates a colorful dye through an enzyme-linked reaction.

Anti-opioid antibodies were found in the plasma of 10 people who regularly
took prescription opioids for chronic lower back pain and almost none
were found in those who used OTCs. The larger the dose of opioid, the
larger the antibody response. "This was surprising," Kyzer says. "We saw antibody responses in people who were taking large doses for as little
as 6 months." The scientists are now working on isolating the key
opioid antigenic intermediates in the body that prompt the generation
of antibodies. One possibility is that the intermediates are modified
proteins known as advanced glycation end products (AGEs), which could form
when hydrocodone or oxycodone metabolites react with a carbohydrate. AGEs
have been implicated in diseases such as atherosclerosis, cancer and Alzheimer's disease, and they might help explain chronic inflammation in long-term opioid users. The researchers have observed preliminary signals
of hydrocodone-associated AGE formation under conditions relevant to
those found in the human body, and they are planning to validate these
results soon.

Wenthur says the findings support undertaking a broader study to determine
the prevalence of antibodies in people based on race, age and sex. "The research could also be helpful in identifying efficacy biomarkers for
opioid vaccines that are entering clinical trials," Kyzer says. "If our findings hold up in subsequent research, you would expect individuals with higher levels of these antibodies to be poor candidates for anti-opioid
vaccine therapy."

========================================================================== Story Source: Materials provided by American_Chemical_Society. Note:
Content may be edited for style and length.


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Link to news story: https://www.sciencedaily.com/releases/2020/08/200817104329.htm

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