Spantide Prevents Up-regulation of Nitric Oxide Synthase Expression and Nitric Oxide Production in the Spinal Cord Induced by Fomaldehyde in Rats

AIM To study the effect of spantide {[D-Arg^1,D-Trp^(7.9),Leu^11]-substance P}, an antagonist of substance P (SP), on the up-regulation of nitric oxide synthase (NOS) and nitric oxide (NO) in the spinal cord of rat during inflammatory pain and hyperalgesia. METHODS The inflammatory pain and hyperalgesia were induced by subcutaneous injection of 5% fomaldehyde 0.2 mL into the right hind paw of the rats. NOS expression level was determined using NADPH-diaphorase histochemistry, and NO production was determined by nitrate reductase method. RESULTS The fomaldehyde injection significantly increased NOS expression level and NO production in the dorsal horn of the L5 segment of the spinal cord following pain and hyperalgesia. The increases reached its peak 24 h after the injection. Intrathecal injection of spantide (5 μg, 10 μL) 5 min prior to the fomaldehyde injection substantially inhibited the increases in NOS expression and NO production. CONCLUSION The release of SP resulted from nociceptive afferents plays an important role in the increases in NOS expression and NO production in the spinal cord of rat with pain and hyperalgesia induced by the fomaldehyde injection.