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Leptin Provides Effective Pain Relief for Sleep Apnea Patients

— July 15, 2020

Leptin may be a safer pain management option for patients with sleep apnea in trauma centers, according to new study.

In 2018, researchers at Johns Hopkins Medicine researchers demonstrated that delivering the hunger-suppressing hormone leptin into the nose could “ease breathing problems in sleeping obese mice.”  It has been known for some time that “obesity leads to dramatic increases in circulating levels of leptin, a hormone produced in adipose tissue.”  While leptin speeds up the metabolic rate of most individuals, “obese individuals are resistant to metabolic effects of leptin…Hyperleptinemia and leptin resistance may upregulate generation of reactive oxygen species, increasing oxidative stress and promoting inflammation.”  This causes sleep apnea to occur.  “Leptin resistance per se can contribute to development of respiratory sleep disorders.”

In other words, in addition to its role in metabolism, leptin also stimulates breathing.  Now, in a new study published in the July 1, 2020, issue of the American Journal of Respiratory Cell and Molecular Biology, the researchers report that the “same nasal delivery method for leptin also can stimulate respiration in obese mice that stop breathing when on morphine.”

Photo by Bill Oxford on Unsplash

It is known that individuals with sleep apnea are likely to have more breathing pauses while having opioids in their system than they do without medication.  This can lead to overdose, and potentially, death.  A patient with sleep apnea admitted into the emergency room with signs of trauma could be given high doses of opioids for pain relief, which can have irreparable consequences.  Doctors can offer naloxone, but this does not help with pain management.  As the researchers noted, “Naloxone, a μ-opioid receptor blocker, is an effective antidote, but it reverses analgesia.”

In the current study, researchers concluded, “Morphine dramatically increased the frequency of apneas and greatly increased severity of hypoventilation and obstructive sleep apnea.  Leptin decreased the frequency of apneas, improved obstructive sleep apnea and completely reversed hypoventilation, whereas morphine analgesia was enhanced.”  The patient would still be able to have some pain relief without the risk life-threatening complications.

In their experiments, the researchers showed “obese mice on morphine given leptin nasally had more airflow and their airways opened wider than control mice not given the hormone.  When a mouse was given enough morphine to stop breathing, a single injection of leptin to the nose restarted the animal’s respiration.  Additionally, the mice given leptin retained morphine’s pain-suppressing effects as measured by a flick to the tail.”

The new findings allow for options when sleep apnea patients seek medical treatment and demonstrate that they can still receive pain management.  This is especially critical in hospital trauma centers where split-decisions are commonly made with regards to pain protocols and the wrong decision can be fatal.

“We believe that if we can confirm our mouse study findings in human trials, applying leptin nasally would be highly useful in hospital trauma settings to keep patients safe while at the same time still treating their pain,” said Vsevolod Polotsky, M.D., Ph.D., professor of medicine at the Johns Hopkins University School of Medicine.


Hunger-blocking hormone reverses opioid overdose in mice

Intranasal Leptin Prevents Opioid Induced Sleep Disordered Breathing in Obese Mice

Leptin and Leptin Resistance in the Pathogenesis of Obstructive Sleep Apnea: A Possible Link to Oxidative Stress and Cardiovascular Complications

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