Methods for treating carpal tunnel syndrome and tarsal tunnel syndrome in a subject involve providing an effective amount of an anti-cytokine agent at or near inflammation in the carpal or tarsal tunnel. Anti-cytokine agents, such as, TNF-a inhibitors, NF-κB inhibitors, IL-1 inhibitors, IL-6 inhibitors, IL-8 inhibitors, IL-12 inhibitors, IL-15 inhibitors, IL-10, Interferon-gamma (IFN-gamma) act to prevent further inflammation initiated by cytokine factors. One embodiment includes, adding with the anti-cytokine agent one or more of an antibiotic or analgesic. Delivery of the anti-cytokine agent may be provided to the inflamed tissue of the carpal or tarsal tunnel by injection, implantation, or a transdermal patch. These agents, individually or in combination, directly address the underlying inflammation that causes the discomfort, pain, and restricted movement associated with carpal and tarsal tunnel syndrome.