Spantide inhibits up-regulation of NOS in the pericentral canal region of the spinal cord in the rat formalin test

AIM: The present study was designed to observe the effect of ［D-Arg1, D-Trp7,9, Leu11］-substance P (spantide), a non-selective antagonist of NK receptors, on the up-regulation of nitric oxide synthase (NOS) induced by formalin test. METHODS: Formalin (5%, 0.2 mL) was subcutaneously injected into the plantar side of the right hind paw to produce persistent pain and hyperalgesia. The pain response was determined by spontaneous flinch reflex test. NOS expression was examined using NADPH-d histochemical staining. Spantide was intrathecally injected via L5-L6 intervertebral space 5 min prior to the formalin injection. RESULTS: Injection of formalin resulted in a characteristic behavioral response consisting of vigorous scratching, biting, licking and lifting of the injected hind paw from the box's bottom. Following these behavioral responses, the NOS expression was up-regulated in the pericentral canal region of the L5 segment of the spinal cord. Pre-treatment with spantide depressed the spontaneous flinches of the injected paw in the second phase of the formalin test. At the same time, the up-regulation of NOS was substantially inhibited. CONCLUSION: It might be concluded that substance P played an important role in the up-regulation of NOS in the pericentral canal region of the spinal cord in the formalin test.