SUBSTANCE-P IN INTERVERTEBRAL DISKS - BINDING-SITES ON VASCULAR ENDOTHELIUM OF THE HUMAN ANNULUS FIBROSUS

The annulus fibrosus of the human intervertebral disc is sparsely inne rvated, some of the fibers containing substance P. We could demonstrat e, by autoradiography, binding sites for substance P localized on the endothelium of small blood vessels in the annulus fibrosus of human in tervertebral discs removed during anterior fusion for back pain. In bi nding inhibition studies, binding of I-125-Bolton Hunter-substance P w as inhibited by unlabeled substance P and the related tachykinins neur okinin A and neurokinin B with a rank order of potency substance P>NKA >NKB. Specific binding was reduced >75 percent by 5'-guanylylimidodiph osphate, indicating G-protein coupling. These features are characteris tic of an NK1 receptor through which vascular effects, i.e., vasodilat ion, plasma extravasation and angiogenesis of substance P, are mediate d. The presence of NK1 receptors on blood vessels in the annulus fibro sus may indicate a role for substance P in tissue repair although acut e proinflammatory effects may contribute to discogenic pain.