Pain increases hematopoiesis

Pain neurons help make blood

Kirill Stasevich, Science and Life (nkj.ru )

All our blood cells are formed from so-called hematopoietic stem cells, which sit in the bone marrow and lead erythrocytes, lymphocytes, leukocytes, etc. Naturally, stem cells listen carefully to signals that inform them about the needs of the body in certain blood cells. After receiving such a signal, the stem cell leaves its place in the bone marrow and enters the bloodstream, where it turns into a particular blood cell. The signal itself can be a special molecule that appeared in the blood, or it can be a nerve impulse. In the bone marrow there are many nerves of the autonomic nervous system, which, with the help of neurotransmitters, control the work of hematopoietic stem cells.

At the same time, it has long been known that among the nerves entering the bone marrow, there are nerves of pain sensitivity, or nerves of nociception. It could be assumed that they also play a role in hematopoiesis. The staff of the Albert Einstein Medical College recently managed to prove this. Experiments with mice have shown that if the bone marrow is deprived of painful nerves, there will be no fewer stem cells in it – but they will go out into the bloodstream worse. That is, pain nerves are needed to mobilize blood stem cells.

The research results are published in Nature (Gao et al., Nociceptive nerves regulate haematopoietic stem cell mobilization).

Neurons that feel pain use the neurotransmitter CGRP (calcitonin gene-related peptide, or a peptide related to calcitonin). CGRP acts directly, without intermediaries, on blood stem cells, prompting them to leave the bone marrow. The more pain neurons work, the more they release the neurotransmitter CGRP, and the more actively new blood cells appear. The activity of pain neurons in the bone marrow can be stimulated with capsaicin, which is contained in capsicum. It is because of capsaicin that we feel the burning peppery taste. When experimental mice were put on a diet with capsaicin supplements, neurons in the bone marrow began to intensively mobilize stem cells. Moreover, for this it was necessary that the neurons had their pain receptors working.

Another substance that activates nerves in the bone marrow is granulocyte colony stimulating factor (G-CSF). This is the name of one of the proteins that make blood stem cells divide more energetically and enter the blood more energetically. G-CSF is one of the internal signals of the body that stimulates hematopoiesis. Based on it, the drugs filgrastim and lenograstim have been created, which help restore the immune system, for example, after chemotherapy. It turned out that, at least in part, G-CSF acts through pain neurons – like capsaicin.

The researchers also conducted experiments with mice that received cisplatin, one of their anti–cancer chemotherapy drugs. After cisplatin therapy, blood stem cells are extremely reluctant to enter the bloodstream. However, with the help of the neurotransmitter CGRP, which is used by pain neurons, the hematopoietic activity of stem cells after cisplatin was restored.

Now there are various means to enhance the activity of blood stem cells – such as drugs with colony-stimulating protein G-CSF. But these tools do not always work, and their effectiveness is limited by various factors, such as age, genetic characteristics, etc. And it's not just about cancer patients – there are many diseases when hematopoiesis needs to be spurred. Perhaps, with new data on the work of pain neurons in the bone marrow, it will become much easier to treat such patients.

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