Could neuropathic pain be treated by modulation of immune cells?

Written by Alice Bough (Future Science Group)

Scientists from Boston Children’s Hospital (MA, USA) and Seoul National University (Seoul, South Korea) have collaborated to determine that immune cells play a role in the repair of peripheral nerve damage. The paper, which has been published in Cell, presents the immune system as a potential therapeutic target for the treatment of neuropathic pain.
Preliminary in vitro experiments demonstrated that natural killer (NK) cells could degenerate the axons of neurons. Neuronal cells were cultured in petri dishes and it was determined that dissociated neurons expressed large amounts of the NK ligand RAE1. When the neurons were co-cultured with active NKs, the immune cells targeted the axons of the dissociated nerve cells.

“We found that the NK cells would eat away at the axons of the neurons, but wouldn’t destroy their cell bodies,” commented one of the senior authors Michael Costigan (Boston Children’s Hospital). “This was exciting as it allowed for the possibility that new, healthy axons could grow from them.”

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From these promising results, the study began in vivo experiments in mice to further analyze the response of NKs to nerve damage. Mice in which NK cell activity was enhanced had their sciatic nerve partially crushed. The recovery of the mice was then monitored and compared with that of the control mice with no immune enhancement.

The affected paws of the immune-stimulated mice had significantly reduced sensation. However, once the damaged axons had been removed by the enhanced immune response, new axons began to grow and after 2 weeks, sensation was regained.

“It was as if the neurons knew what happened,” stated Costigan. “They started to express the receptors that leave them susceptible to a NK cell attack. And the NK cells were responding, coming into the nerve and clearing those damaged axons.”

Control mice still displayed touch-sensitive pain 30 days following the nerve crush. This is representative of neuropathic pain in humans; damaged nerves that do not have the axons fully removed can continue to communicate pain signals to the brain.

This work presents modulation of NK cell activity as a potential new therapy for the treatment of chronic neuropathic pain. Further work may also help us obtain a better understanding of the mechanisms of peripheral nerve damage and repair.

Source: EurekAlert. A new approach to peripheral nerve injury? Press release: