Nefopam is a non-opioid analgesic drug, used widely in European countries to control postoperative pain. However, its mechanism of action remains unclear. In this study, the effects of intrathecal nefopam on spinal nerve-ligated induced neuropathic pain in rats were examined and the involvement of the 5-HT7 receptor at the spinal level was determined. Next, a 5-HT7 receptor antagonist (SB-269970) or descending serotonergic pathway ablation agent (5,7-DHT) was administered intrathecally before delivery of the nefopam to determine the contribution of spinal 5-HT7 receptors or descending serotonergic pathway to the activity of nefopam. The concentrations of 5-HT were measured. Intrathecal nefopam dose-dependently produced the antiallodynic effect. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of the nefopam. 5,7-DHT failed to affect the effect of nefopam. The concentrations of 5-HT in the spinal cord and plasma were decreased in neuropathic pain. Intrathecal nefopam increased the levels of 5-HT in the spinal cord and plasma. Intrathecal nefopam is effective in the attenuation of neuropathic pain induced by spinal nerve ligation and nefopam increases the level of 5-HT. Additionally, the 5-HT7 receptor is involved in the antiallodynic action of nefopam in the spinal cord.