Background: Tianeptine is an antidepressant drugs. It has structural similarities to the tricyclic antidepressants drugs used for treating major depressive episodes. Recently, it is reported that tianeptine has antinociceptive effect on various nociception. Both 5-HT7 receptor and potassium channels are involved in the nociceptive modulation. This study examined the antiallodynic effect of tianeptine in neuropathic pain rats and determined the involvement of 5-HT7 receptors and potassium channels at the spinal level.Method: Intrathecal catheters were placed into the subarachnoid space of spinal nerve ligated-rats. Withdrawal thresholds following the application of a von Frey filament were measured. After observation of the effect of intrathecal tianeptine, a 5-HT7 receptor antagonist (SB-269970, 100 ?g), an ATP-sensitive potassium channel blocker (glibenclamide, 100 ?g), a voltage-gated potassium channel blocker (4-aminopyridine, 3 ?g), a calcium-activated potassium channel blocker (iberiotoxin, 100 ng), an inwardly rectifying potassium channel blocker (barium chloride, 30 ng) were administered intrathecally 10 min before delivery of the tianeptine to determine the contribution of spinal 5-HT7 receptors and potassium channels on the activity of tianeptine.Results: Intrathecal tianeptine dose-dependently attenuated mechanical allodynia induced by spinal nerve ligated-rats. Pre-treatment with intrathecal SB-269970 and glibenclamide reversed the antiallodynic effect of tianeptine. However, pre-treatment with intrathecal 4-aminopyridine, iberiotoxin and barium chloride did not reverse the antiallodynic effect of tianeptine.Conclusions: Intrathecal tianeptine reduced neuropathic pain. 5-HT7 receptor and ATP-sensitive potassium channel play a role in the activity of tianeptine at the spinal level.