Bone Marrow Stem Cells Relieve Chronic Pain

Duke University researchers working under the guidance of Professor Ru-Rong Ji have demonstrated that injecting bone marrow stem cells into the cerebrospinal fluid relieves the symptoms of chronic neuropathic pain. Such pains often do not respond to traditional analgesics and can accompany nerve damage in various conditions, including type 2 diabetes, amputations and chemotherapy.

In their work, the authors used bone marrow stromal cells, known for their ability to produce a wide range of signaling molecules that promote tissue regeneration and transform into other types of cells. The effects of the introduction of these cells have already been studied in small clinical trials involving patients with inflammatory bowel disease, heart muscle damage and stroke. Bone marrow stromal cells have also demonstrated the ability to relieve pain, but the mechanisms of this action have so far been unclear.

As part of the study, the authors injected stromal cells isolated from the bone marrow of donor mice into the cerebrospinal fluid of mouse models of chronic neuropathic pain by lumbar puncture. Chronic compression of the sciatic nerve and sparing damage to the tibial and common fibular nerves were used as simulated conditions.

Experiments have shown that a single injection of stem cells significantly reduced the susceptibility of animals to pain stimuli compared with the sensitivity of untreated animals of the control group. At the same time, the analgesic effect persisted for 4-5 weeks.

In order to understand the mechanisms by which stem cells weaken the severity of pain syndrome, the researchers measured the levels of anti-inflammatory molecules associated with pain in one way or another. As a result, they identified one molecule – transforming growth factor-beta-1 (TGF-beta1), the level of which was increased in the cerebrospinal fluid of animals who received stem cell injections, compared with animals of the control group.

Transforming growth factor-beta-1 is a protein normally secreted by immune cells and found in all tissues of the body. Earlier studies have shown that its concentration is significantly reduced in the body of people suffering from chronic pain.

The authors demonstrated that chemical neutralization of transforming growth factor-beta-1 eliminates the pain-relieving effect of stem cell injection. Based on this, they suggested that the secretion of this protein is the main mechanism of the analgesic action of stem cells.

The introduction of the drug transforming growth factor-beta-1 directly into the cerebrospinal fluid brings relief, but not for more than a few hours. At the same time, donor stromal stem cells remain viable in the body for almost three months after administration. The authors note that the duration of this period is optimal, since a longer stay of donor stem cells in the body increases the risk of their malignancy.

Moreover, additional experiments have demonstrated that stem cells do not dull the so-called physiological pain, which performs an important protective function in the body. Thus, the introduction of bone marrow stromal cells did not change pain thresholds either under mechanical or thermal exposure.

At the next stage of the work, the authors plan to increase the effectiveness of the procedure they have developed by increasing the production of transforming growth factor-beta-1 stem cells. They are also searching for other molecules synthesized by stem cells that have the ability to relieve pain.

Article by Gang Chen et al. Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-β secret is published in The Journal of Clinical Investigation.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru Based on materials from Duke University: Stem Cells Provide Lasting Pain Relief in Mice.