NPY and pain as seen from the histochemical side

The expression of neuropeptide tyrosine (NPY) and two of its receptors (Y1- and Y2Rs) in different types of rodent dorsal root ganglion (DRG) and spinal cord neurons, and their regulation by peripheral nerve injury, have suggested a role in neuropathic pain. Here we present the spinal NPYergic system from an immunohistochemical perspective based on recent studies using two specific antibodies recognizing the Y1- and Y2Rs, respectively, as well as on data from a study on a Y1R knock-out mouse. We have, for example, defined seven different neuron populations of Y1R-expressing neurons in the rat spinal cord, representing multiple targets for spinally released NPY. The differential distribution of NPY receptors probably explains both the pro- and antinociceptive effects of NPY previously reported in the literature. One system possibly responsible for antinociception is a group of Y1R-positive, presumably glutamatergic interneurons in the superficial dorsal horn laminae. We also discuss the possibility that NPY released within DRGs can act in a paracrine fashion on NPY receptors on adjacent neurons, perhaps contributing to the so-called cross excitation, a concept advanced by Devor, Amir and collaborators. Taken together with behavioral and electrophysiological results summarized by Smith et al. in this volume, histochemical analyses have advanced the knowledge on the role of NPY in pain processing.