Antidepressants as Preventive Analgesics for Chronic Post-Surgical Pain

Up to 50% of patients who have undergone any form of surgery may later develop persistent pain. In many cases, chronic pain can be extremely difficult to manage. While the extent of the pain experienced varies depending on the type of surgery, the high incidence of chronic pain has given rise to the need for more effective treatments and preventive measures. One factor that is involved in the development of chronic pain is nerve injury at the surgical site. Amitriptyline, an antidepressant, is presently prescribed to manage chronic pain, and has also been identified as a potential preventive analgesic. Recent experiments in rodents have showed that amitriptyline, if given at a critical time in relation to a surgically-induced nerve injury, can prevent the long-term development of chronic post-surgical pain. In order to understand how amitriptyline and other antidepressants exert such preventive analgesic effects, the proposed research aims to study the changes in the nervous system that are elicited by a nerve injury. Specifically, the proposed project will use a rodent model to identify the alterations in nerve growth and pain signaling that occur in the spinal cord after a nerve injury. The effects of amitriptyline and other antidepressants on these neuronal processes will also be investigated. Understanding the mechanisms that underlie a specific antidepressant administration schedule will lead to the development of an appropriate human treatment regimen, allowing health practitioners to efficiently maximize the beneficial drug effects, while also promoting a longer-lasting method of chronic pain treatment. Furthermore, this research may aid in identifying specific antidepressants that can be considered in future clinical trials for preventive analgesia.