Neuropathic Pain Treated with Stem Cells

Researchers from the University of Sydney have discovered a new, safe method for combating chronic neuropathic pain. They created neurons with analgesic effects from a special type of human stem cells, with a single injection providing long-term pain relief in mice without any side effects. If these encouraging results are confirmed in human trials, the discovery by the Australian scientists could help develop new – non-opioid – methods of pain therapy that selectively target the affected area.

“Nerve damage can lead to debilitating neuropathic pain, and most patients are unable to receive effective treatment from doctors,” explains Gregory Nilly, a leading pain researcher at the School of Medical Biology at the University of Sydney. “Our discovery suggests that an alternative solution for such patients could be the introduction of ‘analgesic’ transplants made from their own cells, which can address the underlying cause of pain.”

The cause of neuropathic pain is pathological excitation of neurons in the peripheral or central nervous system, which respond to physical damage. It can be constant or episodic, sharp or resembling electric shocks (shooting pains). This type of pain is often characterized by burning, tingling, numbness, and itching sensations.

Neuropathic pain can arise as a complication of diabetes, trigeminal neuralgia, radicular syndrome, nerve injuries, stroke, shingles, post-surgical conditions, and can accompany oncological diseases. It can often progress to a chronic stage and become a serious problem. In such cases, patients may have to take strong medications, including opioids, which often lead to addiction and become ineffective. As a result, treatment does not provide relief and has negative side effects, further diminishing the patient's quality of life.

A key mechanism in the development of neuropathic pain is the disruption of gamma-aminobutyric acid (GABA) production, the most important inhibitory neurotransmitter. Previously, scientists found that this type of pain could be managed using precursors of GABAergic neurons from the fetus. However, the source of these cells, for obvious reasons, makes their use for therapeutic purposes impossible. Researchers at the University of Sydney have shown for the first time that they can be obtained from induced pluripotent stem cells (iPSCs), for which the Nobel Prize was awarded in 2012.

In their recent study published in the prestigious journal Pain, the scientists used iPSCs taken from human bone marrow, reprogrammed them in the laboratory into “analgesic” neurons, and then transplanted them into the bone marrow of mice suffering from neuropathic pain. As a result, the transplants successfully integrated with the other neurons of the animals, providing them with long-term pain relief without side effects. This indicates that the transplantation of such neurons could become an effective treatment for neuropathic pain, the authors note.

“The ability to choose the area for the introduction of ‘analgesic’ neurons allows for targeted action on the body parts where pain is concentrated,” says lead author John Manion. “This approach minimizes the negative side effects of therapy, and this is one of the greatest advantages of such treatment.”

The researchers explained that they introduced the created neurons with analgesic effects into the spinal cord of the test rodents, as this is where pain impulses are first directed before reaching the brain. Simultaneously, injections of “pain-relieving” cells were made into mice without neuropathic pain, on which they had no effect. This, according to the researchers, confirms the specificity of the new treatment, which ensures its safety.

“A single injection is enough to alleviate pain sensations,” says Gregory Nilly. “It has been six months since we completed our experiment, and the analgesic effect in the mice continues to this day.” The presence of neuropathic pain in the animals was checked by lightly touching their paws. Healthy mice showed no reaction to this action, while their counterparts with injured nerves twitched their limbs after being touched.

The team notes that all the stem cells they used were taken from samples of blood from adult individuals. The researchers plan to conduct comprehensive safety trials of their method on larger rodents and pigs. If these are successful, the researchers will be able to move on to clinical trials in patients suffering from neuropathic pain. This is expected to occur within the next five years.