Role of nitric oxide in cutaneous blood flow increases in the rat hindpaw during dorsal column stimulation

John E. Croom, Robert D. Foreman, Margaret J. Chandler, Michael C. Koss, Kirk W. Barron

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


OBJECTIVE: Dorsal column stimulation (DCS) increases blood flow to the extremities and may produce a limb-saving effect in addition to treatment of refractory chronic pain in patients with peripheral vascular disease. The purpose of this study was to examine the importance of nitric oxide in cutaneous vasodilation caused by DCS. METHODS: Male Sprague-Dawley rats were anesthetized with pentobarbital (60 mg/kg, intraperitoneally). A unipolar ball electrode was placed on the left-side of the exposed spinal cord at approximately L1-L2. Blood flow was concurrently recorded from both hindpaw foot pads with laser doppler flowmeters. 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 groups of animals were examined. The first and second groups involved examination of the effects of DCS after 2 and 10 mg/kg L-NAME, respectively. In the third group, the effect of another nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (10 mg/kg), was examined on the responses 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 presence of hexamethonium and L-NAME (10 mg/kg). RESULTS: L-NAME markedly attenuated 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 DCS response. CONCLUSION: Our results demonstrated that nitric oxide played a significant role in producing the DCS-induced increase in rat cutaneous hindpaw blood flow. The involvement of nitric oxide does not require the presence of autonomic efferent function; however, ganglionic blockade may unmask a mechanism for vasodilation during DCS that is independent of nitric oxide release.

Original languageEnglish
Pages (from-to)565-571
Number of pages7
Issue number3
StatePublished - Mar 1997


  • Dorsal column stimulation
  • Laser doppler flowmetry
  • Microcirculation
  • Skin vasodilation
  • Spinal cord
  • Spinal cord stimulation


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