Cell transplants and pharmacologic treatment for reducing chronic neuropathic pain in spinal cord injury

Spinal cord injury (SCI) is a major cause of chronic disability in young patients. Chronic pain is one of the main complications secondary to SCI; approximately two thirds of SCI patients suffer from chronic neuropathic pain. The combination of different strategies seems nowadays the most rational approach for attempting the repair of SCI, including therapies focusing on neuroprotection, axonal regeneration and modulation of neuronal plastic changes. This project is directed to the study and development of new therapies for the repair of the injured tissue with special attention to their contribution for reducing chronic pain following SCI. First, a drug screening will be performed in a contusion model of SCN in rates to evaluate potential neuroprotective and antinociceptive agents, and their effects on molecular and cellular processes underlying neuronal hyperexcitability and development of pain. In parallel, olfactory ensheathing glia (OEG) and embryonic stem cells (ESC) will be prepared to perform co-transplants in the animal SCI models. The effects of OEG transplants alone and in combination with effective pharmacological agents will be assessed, regarding functional recovery and neuropathic pain. ESCs will be pre-differentiated in vitro to neuronal phenotypes, either cholinergic or serotoninergic. ESC grafts may generate benefitial effects by neuroprotection, generation of new neuronal cells and also by influencing the disrupted spinal circuitry and descending inhibition by secreting serotonin. Finally cotransplantation of OEGs and ESCs will be performed and compared with single transplants. In all animal studies, functional recovery after SCI will be evaluated by behavioural, electrophysiological and inmunohistological methods. The results will shed light into the future of combined therapeutic strategies after SCI for improving functional repair and relieving neuropathic pain, and likely accelerate the translation of basic research to (...)