ROLE OF NITRIC-OXIDE IN CUTANEOUS BLOOD-FLOW INCREASES IN THE RAT HINDPAW DURING DORSAL COLUMN STIMULATION

OBJECTIVE: Dorsal column stimulation (DCS) increases blood flow to the extremities and may produce a limb-saving effect in addition to treat ment of refractory chronic pain in patients with peripheral vascular d isease. The purpose of this study was to examine the importance of nit ric oxide in cutaneous vasodilation caused by DCS. METHODS: Male Sprag ue-Dawley rats were anesthetized with pentobarbital (60 mg/kg, intrape ritoneally). A unipolar ball electrode was placed on the left-side of the exposed spinal cord at approximately L1-L2. Blood flow was concurr ently recorded from both hindpaw foot pads with laser doppler flowmete rs. Blood flow responses were assessed during 1 minute of DCS (0.6 mA at 50 Hz, 0.2-ms pulse) at 10-minute intervals. Nitric oxide synthase was inhibited with N-G-nitro-L-arginine methyl ester (L-NAME). Four gr oups of animals were examined. The first and second groups involved ex amination of the effects of DCS after 2 and 10 mg/kg L-NAME, respectiv ely. In the third group, the effect of another nitric oxide synthase i nhibitor, N-G-monomethyl-L-arginine (10 mg/kg), was examined on the re sponses to DCS. The fourth group of animals entailed comparison of the effects of DCS under control conditions, after the nicotinic receptor antagonist, hexamethonium (10 mg/kg), and during the combined presenc e of hexamethonium and L-NAME (10 mg/kg). RESULTS: L-NAME markedly att enuated the cutaneous blood flow increases caused by DCS at doses of 2 or 10 mg/kg. Similarly, N-G-monomethyl-L-arginine also attenuated the DCS response. Hexamethonium did not affect the cutaneous vasodilation caused by DCS. After hexamethonium, L-NAME no longer attenuated the D CS response. CONCLUSION: Our results demonstrated that nitric oxide pl ayed a significant role in producing the DCS-induced increase in rat c utaneous hindpaw blood flow. The involvement of nitric oxide does not require the presence of autonomic efferent function; however, ganglion ic blockade may unmask a mechanism for vasodilation during DCS that is independent of nitric oxide release.