Background : Antidepressants are being used as supplemental therapy in neuropathic and inflammatroy pain. The mechanism of their inhibitory effect on experimental animal inflammation is not clear. Studies during the past few years clearly indicate an important role for nitric oxide (NO) in the inflammation and pain-processing system. We evaluated the effects of amitriptyline, desipramine and paroxetine on NO production in primary Schwann cell cultures. Methods : Primary cultures of the Schwann cell were prepared from dorsal root ganglia of 1-to 3-day old Spraque-Dawley rats. Schwann cells were cultured in the presence or absence of interferon-?? (500 ng/㎖) plus tumor necrosis factor-α (500 ng/㎖), amitriptyline, desipramine or paroxetine. Production of NO was determined in the supernatant of the culture media. Results : Amitriptyline (10 ㎍/㎖), desipramine (10 ㎍/㎖) and paroxetine (10 ㎍/㎖) inhibited NO release by 29.8%, 51.4%, and 66.8%, respectively. No drug had a toxic effect on cultured cells, which was determined by an LDH assay. Conclusions : Inhibition of NO production by Schwann cells may be a mechanism by which some antidepressant medications affect inflammatory and neuropathic pain. (Korean J Anesthesiol 2002; 42: 221~227)