Do opioid-exposed children have the same pain sensitivity as their non-exposed peers?
Pain impacts the life of any parent whose kiddo suffers the bumps, scratches, and other boo-boos of childhood. Do opioid-exposed children have the same pain sensitivity as their non-exposed peers?
The researchers conducting this study were interested in this question, as well as how adults with prenatal opioid exposure perceive pain. It was the treatment of pain, after all, that started our country’s opioid epidemic. If opioid-exposed children experience stronger levels of pain, will they turn to opioids for relief?
The Study:
The Science in Plain English :
To answer the author’s questions, researchers took the following steps;
female mice were exposed to regular methadone use
poop from these mice was examined to determine the balance of bacteria (harmful or beneficial) in their gut
male mice were introduced
children of the methadone-using mice were subjected to heat, and their feet were poked
measurements of pain sensitivity in these mice children were compared to mice without opioid exposure
mice children were given a specialized probiotic mix
following the probiotics, the pain tolerance of these mice was remeasured
mice children brains were examined to detect genes and neural pathways
mice children poop was also examined for gut bacterial balance, both before and after probiotics were introduced
Mice Mom Results
Pregnant mice who use opioids disrupt the balance of bacteria in their gut microbiomes. This, in turn, disrupts the composition of of their child’s gut microbiome.
Mice Children Results
Prenatal methadone exposure increased sensitivity to both thermal pain (heat) and mechanical pain (poking).
Blood samples taken from the methadone-exposed mice children had higher levels of a protein that plays a role in tissue inflammation.
Analysis of their poop showed prenatal opioid exposure resulted in significant change to the balance of bacteria in their guts; necessary bacteria strains were depleted and harmful bacteria was overgrown.
After supplementing these mice with probiotics, which reset the balance of bacteria in their guts, their previous hypersensitivity to pain was gone.
Some mice children nursed from female mice who were not exposed to methadone. Exposure to a healthy balance of gut bacteria in this way also reset the mice children and relieved their pain sensitivity.
Brain examinations showed that providing probiotics to rebalance the gut resulted in gene changes related to pain signaling. This is evidence of the gut-brain-axis mediating pain sensitivity in the mice children.
Conclusions
“Prenatal methadone exposure increases sensitivity to thermal and mechanical pain…, which is mediated by the microbiome”
The higher levels of specific proteins generated, that play a role in tissue inflammation, are made better with probiotic administration.
Prenatal opioid exposure alters a total of 3,516 genes. These genes provide pathways with key roles in neurological and immune function as well as behavior. Other altered genes activate pain and inflammation signals, sensation, and sensory system development. Significant decreases were seen in neurotransmission, learning, memory, and cognition compared to control mice. However, after administering probiotics, the effects in hundreds of these same genes were reversed. This provided significant increases in lost neurotransmission, learning, memory and cognition, and significant decreases in anxiety and sensation.
The benefits of probiotics given to pregnant mom mice affect the growing offspring’s physiology and brain function. This suggests that the deficits associated with prenatal methadone exposure may in part be mediated by the gut microbiome. If not done during pregnancy, resetting the gut bacteria balance immediately after birth may induce a permanent shift.
“…[We] suggest the importance of maintaining a balanced gut microbiome during pregnancy as one arm of a comprehensive treatment strategy to help mitigate downstream effects of prenatal opioid exposure.”
Questions
Are there more answers in the gut underlying the adverse neurodevelopmental outcomes of prenatal opioid exposure?
Yes. Scientific knowledge of the gut microbiome and it’s role in the gut-brain-axis has significantly grown in recent years. As connections are made there is sure to be knowledge gained regarding the effects of prenatal opioid exposure.
Do these findings in mice apply to humans?
Yes. Mice are used for research when it’s known that the systems and processes measured in mice mimic human systems and processes. This does not mean there is always a 100% match. However, much can be gained from doing experiments with mice models when human experimentation is not viable.
Note: Opioid and methadone are used interchangeably in this summary. Methadone was the substance administered to the mice. Methadone is an opioid.
Many thanks to the authors of this article: Abu, Y. F., Singh, S., Tao, J., Chupikova, I., Singh, P., Meng, J., & Roy, S.