PSA-NCAM in an siRNA-mediated Knockdown of Spinal PST/STX: An Examination of its Role in Persistent Inflammatory Pain

Persistent pain is a debilitating pathology. It is associated with a neural-plasticity based process known as central sensitization, in which synaptic changes at the level of the dorsal horn of the spinal cord manifest in allodynia, hyperalgesia and secondary hyperalgesia. Researchers have indicated similarities between central sensitization and long term potentiation (LTP), a functionally plastic process related to memory formation. Neural cell adhesion molecule (NCAM) may play a role in central sensitization due to its known involvement in mediating LTP. PSA is highly hydrated and anionic, and thus it increases the space within the synapse. As such, the binding of polysialic acid (PSA) to NCAM decreases stable adhesion and may allow for the mechanisms of neurite outgrowth, plasticity, and thus LTP. The aim of this thesis is to investigate the role of the major and minor polysialyltransferase isoforms, PST and STX, in the regulation of the attachment of polysialic acid, a sugar moiety in the immunoglobulin super-family, to the neural cell adhesion molecule. Previous results in our laboratory have indicated that spinal siRNA knockdown of the polysialyltransferase isoform, PST, is correlated with a down-regulation of spinal PSA-NCAM and attenuation of inflammatory pain in a mouse model of peripheral inflammation. Here we show that spinal siRNA knockdown of PST also results in significant down-regulation of PSA-NCAM and attenuation of inflammatory pain. Taken together, these findings may have implications in the development of novel approaches to attenuate persistent inflammatory pain in a clinical setting