Intravenous mononuclear marrow cells reverse neuropathic pain from experimental mononeuropathy

BACKGROUND: Stem cells mediate neuroprotection in a variety of nervous system injury models. In this study, we evaluated a potential role for stem cells in pain therapies. Marrow mononuclear cells containing mixed stem cell populations were used because of wide experience with these cells in experimental and clinical transplantation. METHODS: After sciatic nerve chronic constriction injury (CCI), adult male Sprague Dawley rats were treated with freshly isolated marrow mononuclear cells (10(7) cells in 0.5 mL IV) from the same strain, or with carrier. The major end points of analysis were thermal and mechanical hypersensitivity using paw withdrawal latency (PWL) to a calibrated heat source and paw withdrawal response to von Frey filaments, evaluated by a blinded investigator. RESULTS: Marrow transplantation did not prevent pain, and 5 days after CCI all animals were equivalently lesioned. However, 10 days after CCI, rats that received marrow transplants demonstrated paw withdrawal response and PWL patterns indicating recovery from pain, whereas untreated rats continued to have significant pain behavior patterns. For example, PWL values for marrow-treated animals were similar to baseline pre-CCI values (P = 0.54) but significantly shorter latency to withdrawal indicative of continuing pain was seen in untreated rats compared with pre-CCI values (P < 0.001). CONCLUSIONS: These studies suggest that stem or progenitor cell-mediated therapies may be useful for the treatment of pain after nerve injury, and deserve further study to elucidate the mechanisms of analgesia.