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Complex regional pain syndrome (CRPS), or reflex sympathetic dystrophy (RSD), is a condition characterized by trophic skin changes, swelling, bone loss, contracture, vasomotor and sudomotor instability, as well as allodynic pain. CRPS is also associated with excessive sympathetic response. The condition often is the result of trauma, but it can occur from infection, inflammation, metabolic disorders, or vascular disease. CRPS affects around 14 per 100,000 per life-year. Of CRPS patients, 4% have a nerve lesion, and 40% have had tissue trauma. CRPS is also associated with an inflammatory response, which makes stem cell therapy a good solution for treatment.
Mesenchymal stem cells (MSCs) have been found to differentiate into several lineages, such as bone cells, cartilage cells, tendon cells, and fat cells. They have been studied in musculoskeletal pain conditions for years. MSCs are thought to offer structural repair to disease and damaged tissue. In addition, the exert cytokine-mediated paracrine effects, which contribute to tissue repair and recruit local cells for the repair process. MSCs are also considered immune privileged, and modulate allogeneic immune responses by inhibiting maturation of dendritic cells.
The immunomodulatory properties of SCs make them useful in treating post-traumatic inflammatory pain. In addition, MSC transplantation from mice to rats have shown evidence of anti-inflammatory and immune-modulatory properties, which can be transferred between species. One pre-clinical study found that stem cells produced anti-tolerance and analgesic effects.
MSCs are used as anti-inflammatory agents for pain relief in CRPS. MSCs were proven beneficial for treating arthritis pain in animal models. In a current study, the cells were tested in comparison to hyaluronic acid, and found to offer functional improvement and significant pain reduction. In this study, there was alteration of intra-articular and serum cytokine levels, which provide a basis for pain control. In a large review of studies, stem cell treatment was proven to be safe for pain control in patients with knee arthritis. In another case study, autologous stem cells were found to have angiogenic activity when grafted into the patient’s calf. The patient enjoyed improvement of the condition following stem cell transplantation.
Complex regional pain syndrome is associated with nerve pain (called neuropathic pain). This type of pain is complex, and involves many molecular pathways. Neuropathic pain is associate with neuro-inflammation and IL-17. Stem cells were used in mouse models with neuropathic pain. The cells were found to offer long-lasting improvement of nerve-related pain, with increased anti-inflammatory IL-10. Stem cells injected into the lumbar dorsal root ganglia of mice with nerve injury was found to prevent mechanical and thermal allodynia. Other studies showed axonal growth stimulation and neuroprotection from stem cell therapy.
A recent clinical study involved 10 people with neuropathy pain. The subjects underwent liposuction to obtain adipose tissue for stem cells. The autologous stem cells were processed in the laboratory and transferred via local injections into the pain areas. The patients were followed for six months and pain was assessed on a numerical scale. In the study, autologous stem cells were found to significantly reduce pain intensity at the six-month evaluation, and were deemed safe and well-tolerated. Also, a case report showed that stem cell therapy could improve CRPS symptoms and allow for weight-bearing on the affected extremity. Recent clinical studies show that adipose stem cells are able to recruit local body cells to induce tissue repair.
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