Sortilin in microglia reactivity:Investigating the mechanism underlying the impairment of neuropathic pain in sortilin knockout mice

Neuropathic pain is a serious neurological disease affecting patients with peripheral nerve injuries and neuropathies. Unfortunately, the existing treatments are insufficient in giving patients pain relieve and preventing the development of neuropathic pain.Neuroinflammation is a major contributing factor in the development of neuropathic pain. It has been well accepted that activation of microglia is essential in the spinal neuroinflammatory process underlying development of neuropathic pain after peripheral nerve injury. Unpublished data from sortilin knockout mice shows that the lack of the neuronal receptor, Sortilin, decreases development of neuropathic pain after peripheral nerve injury. Because Sortilin influences the inflammatory response in macrophages, it may also affect the response in microglia and the spinal neuroinflammation. Therefore, the aim of this project is to understand how Sortilin influences the spinal microglial response following peripheral nerve injury.We plan to investigate cultures of spinal microglia from wild type and Sortilin knockout mice by comparing the cytokine profiles in culture medium, gene expression and intracellular protein levels of cytokines. Understanding the response in microglia might contribute to the knowledge of neuroinflammatory diseases in general and hopefully prove Sortilin as a potential drug target in the development of future treatments for neuropathic pain.