We aimed in this study to evaluate the effects of capsaicinoids on the cellular concentration of substance P(SP) and substance P-mRNA in rat spinal cord. This study was based on the fact that longlasting analgesic, capsaicin caused depletion of SP from primary afferent neurons in dorsal root ganglia. After administration of 6-paradol (80, 500, 1000 ㎎/㎏) or capsaicin (80 ㎎/㎏) in rats, the cellular concentration of SP and its mRNA in spinal cord were analyzed by radioimmunoassay and slot blot hybridization analysis respectively. 6-Paradol, like capsaicin, reduced in dose-dependent manner the content of SP in rat spinal cord. Additionaliv, SP-mRNA concentration was also reduced to 61% of the control level at 3 h after capsaicin administration and was restored to the control level after 1 day. In 6-paradol treated group, substance P-mRNA concentration was not detectably reduced at 3 hours but significantly reduced to 49% of the control level at 1 day after 6-paradol treatment. These results support for the previous notion suggesting that the action mechanism of capsaicinoid analgesia may be primarily based on the depletion of SP from primary afferent neurons. These results also suggest that capsaicinoid analgesics may play a role at the transcription level of SP synthesis in rat spinal neurons.