Abstract

In the dorsal horn of the spinal cord, activation of small fibre nociceptive afferents leads to the release of nitric oxide and enkephalins by interneurons. In this work we encountered unexpected relationships among local spinal cord dorsal horn blood flow, specific forms of afferent input, nitric oxide and intrinsic opioids. Selective rises in rat lumbar dorsal cord blood flow using laser Doppler flowmetry and microelectrode hydrogen clearance polarography were generated by ipsilateral, 'nociceptive' low (3 Hz) frequency stimulation of sciatic afferents. Inhibitors of nitric oxide synthase (NOS) prevented rises in flow during stimulation without influencing baseline flow. Ipsilateral hindpaw intradermal injection of capsaicin, a nociceptive activator, also generated large rises in flow sensitive to NOS inhibition. During NOS blockade or morphine administration there were unexpected acute declines in the dorsal cord blood flow strictly confined to low frequency stimulation epochs. This acute vasoconstrictive effect was prevented by administration of an opioid receptor antagonist. Using immunohistochemistry, terminals apparently innervating dorsal spinal cord blood vessels were labelled with antibodies against neuronal NOS and met-enkephalin. We conclude that local nitric oxide and opioids, probably from interneurons, have competitive actions on dorsal horn microvessels once interneurons are activated during a nociceptive barrage. Collateral innervation of blood vessels may explain this property.