Stem Cell Therapy Reverses Opioid Tolerance Effects

Jianguo Cheng, MD

Stem cell therapy may be able to prevent and reverse opioid tolerance (OT) and opioid-induced hyperalgesia (OIH) — key issues faced by patients prescribed to opioid therapy.

In a study conducted by researchers at the Cleveland Clinic, mesenchymal stem cell transplantation (MSC-TP) showed long-lasting and consistent effects on OT and OIH in rat and mouse models. The procedure has previously shown “remarkable anti-inflammatory properties,” researchers noted, lending credence to the idea that opioids could one day be prescribed without fear of abuse or addiction.

Jianguo Cheng, MD, Professor and Director, President-elect, American Academy of Pain Medicine, and study corresponding author, told MD Magazine the key question to the study was whether there was a way to mitigate opioid tolerance.

When patients develop tolerance, their response to the opioid dose is reduced, driving them to increase their dose to get the same effect. But when doses increase, so does the prevalence of adverse effects.

“That’s how people get in trouble: the high doses,” Cheng said. “If we can find a way to keep people treated at low doses, that can solve a huge problem.”

After inducing OT in models through daily subcutaneous morphine injections over 4 weeks, researchers harvested, expanded, and characterized MSCs from rat bone marrow and administered the therapy routinely.

Daily injections significantly and consistently diminished the development of OT in models, with one-time MSC-TP preventing development of OT for up to 34 days. It also significantly restored models’ sensitivity to morphine injection therapy, providing OT reversal effects within 2 days of administration and lasting for the duration of the trial period.

Researchers also developed OIH in the animal models with daily morphine injections, taking on average 5 to 7 days to develop. MSC-TP substantially diminished the development of OIH, rapidly reversing its clinical effects by about 70% to 80% after it reached full development. Its reversal of OIH implies an ability to allow pain treatment patients to feel a more realistic rate of pain, diminishing the need for opioids.

Patients also become more susceptible to lethal respiratory issues at greater dosage rates, Cheng told MD Magazine.

“Patients with OIH tend to seek more opioids to treat ‘increased pain,’ leading to a spiral of vicious cycles and deterioration of pain control,” researchers wrote. “These facts underscore the need to find new solutions for OT and OIH, as part of a national effort to combat chronic pain as a public health issue and the opioid epidemic as a national crisis.”

The researchers concluded that MSC-TP had “powerful preventive and therapeutic effects” on OT and OIH in the models, while also retaining safety.

“MSC-TP is emerging as an innovative, safe, and efficacious therapy for OT and OIH,” researchers wrote. “It has enormous potential to profoundly impact clinical practice and improve opioid efficacy and safety.”

Cheng advocated for a different take on addressing the opioid epidemic: ensuring the patient receives effective treatment that does not compromise safety. Opioid safety, he noted, is closely correlated to the dosage rate.

“There are many ways to address it, from policies, to preventive measures, making naloxone available in schools and to first responders,” Cheng said. “Those are good for people already in trouble. It’s much better to prevent it from happening in the first place.”

The study, "The Use of Stem Cell Therapy to Reverse Opioid Tolerance," was published online in Clinical Pharmacology & Therapeutics lasth month.

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