Neuropathic pain: How 'natural killer' cells can be a treatment

  • Scientists are being urged to look at the body’s “natural killer” cells as a potential treatment for neuropathic pain.
  • They point out that these cells are already utilized by the body to battle cancer.
  • Experts say the research is in its early stages and it is too soon to tell whether natural killer cells can be used for pain management.

Some scientists are looking at “natural killer” cells as a treatment for neuropathic pain, according to a report published today in the journal Trends in Neuroscience.

The body uses these cells to battle cancer, but Seog Bae Oh, a neurobiologist at Seoul National University in South Korea and senior author of the study, wanted to look at them in the context of pain. He points out that first, he needs a better understanding of how NK cells work and how to minimize side effects.

“These cells were named natural killer cells based on one of their functions or destroying infected, old, or cancerous cells in the body, said Dr. Matt Burford, a clinical professor of neurology in the Department of Neurology at The Ohio State University Wexner Medical Center who was not involved in the study.

“Their less exciting name is large granular lymphocytes,” he told Medical News Today.

How ‘natural killer’ cells work

Natural killer cells might reduce pain because of their involvement in the pruning of nerve cells.

Pruning is the targeted elimination of functional synapses, according to an article in the Proceedings of the National Academy of Sciences (PNAS).

Elimination of neural synapses works to form a healthy, adaptive brain.

When damaged or diseased, neurons can stop functioning as intended, causing pain. Natural killer cells could help to prune the neurons, removing the damage.

“The natural killer cells in our body target and remove unwanted cells, such as cancer cells or infected cells,” explained Alexander Davies, Ph.D., a UKRI Future Leaders fellow and one of the study’s authors.

“More recently, there has been greater interest in how [natural killer] cells interact with the nervous system during injury or disease,” he told Medical News Today. “In our article, we have collected the most recent evidence for a possible role of [natural killer] cells in neuropathic pain. One way in which [natural killer] cells may be useful for neuropathic pain is in pruning sensory nerves that are damaged as a result of injury.”

Natural killer cells and pain management

Previous experiments using mice found that when a neuron is in distress, the portion responsible for sending messages displays a stress molecule signaling that pruning is needed.

“[Natural killer] cells may additionally target other cells at the site of injury to help resolve painful injury,” Davies said. “However, as we point out in our article, there are also cases where [natural killer] cells may mistakenly attack healthy cells of the body. Therefore, we must be cautious targeting [natural killer] cells for neuropathic pain.”

The researchers point out that they need further research before determining when they could introduce natural killer cells to treat nerve pain and damage.

“This review summarizes the current understanding of the role of immune cells in neuropathic pain,” said Dr. Santosh Kesari, a neurologist at Providence Saint John’s Health Center in California and the regional medical director for the Research Clinical Institute of Providence Southern California.

“In particular, highlighting the role of specific immune cells called natural killer cells and how they contribute to causing neuropathic pain but also how they can be manipulated to fix the problem,” Kesari, who was not involved in the study, told Medical News Today. “Inflammation and fibrosis are thought to lead to pathologic processes and symptoms such as pain. [Natural killer] cells can potentially influence this and help alleviate neuropathic pain.”

Dealing with neuropathic pain

Neuropathic pain occurs as shooting or stabbing sensations around nerve damage.

“[Natural killer] cells rely in part on receptors to distinguish between healthy cells and other cells in the body that have undergone pathological changes,” Davies said. “We know of some signals on damaged nerve cells that are detected by [natural killer] cells. Immunotherapies are one way in which these signals on target cells may be detected with more sensitivity by [natural killer] cells.”

But this research is new and researchers are still looking for ways to harness the natural killer cells to relieve pain.

“A better understanding of [natural killer} cell interaction with the nervous system as well as complex interplay with other parts of the immune system may provide us with potential treatment targets to help manage, or even prevent, neuropathic pain,” Burford said. “Pathways associated with [natural killer] cell function could also be important in other inflammatory conditions of the nervous system as well.”

Currently, doctors treat nerve pain with opioids and antidepressants. However, these do not treat the underlying causes of the pain, and both have their side effects.

“Natural killers are the first line of defense for the innate immune system,” Kesari said. “On first exposure to foreign cell (e.g., tumor cells, virus-infected cells) they can eliminate them, unlike T-cells which are part of the adaptive immune system and require prior exposure to foreign antigens (cancer or viruses, etc.) and time in order mature to kill foreign/abnormal cells.”

“[Natural killer] cells are always present in the body and represent 5 to 20 percent of all lymphocytes in the blood,” Kesari continued. “They can get mobilized from the blood to organs where they are needed (infections, tumors, etc.) to fight off invaders. So, they can be increased during infections, injury, and tumor formation. Loss of [natural killer] cells can contribute to various diseases such as increased risk of infections and cancer and, as shown in this article, neuropathic pain.”

There is still a long way before natural killer cells can help with neuropathic pain.

“This area of research is still at a very early stage. Our article points out that the evidence case builds for [natural killer] cells playing a potentially beneficial role in neuropathic pain,” Davies said. “However, there are many facets to pain and [natural killer] cells may not be effective in all cases of neuropathic pain. There is still much to learn about [natural killer] cells that may be used in future therapy.”

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